Cicad 29

This report contains the collective views of an international group of experts and does not
necessarily represent the decisions or the stated policy of the United Nations Environment
Programme, the International Labour Organization, or the World Health Organization.
Concise International Chemical Assessment Document 29
VANADIUM PENTOXIDE AND

OTHER INORGANIC VANADIUM COMPOUNDS
Note that the layout and pagination of this pdf file are not identical to the printed CICAD
First draft prepared by

Dr M. Costigan and Mr R. Cary, Health and Safety Executive, Liverpool, United Kingdom,
and
Dr S. Dobson, Centre for Ecology and Hydrology, Huntingdon, United Kingdom
Published under the joint sponsorship of the United Nations Environment Programme, the
International Labour Organization, and the World Health Organization, and produced within the
framework of the Inter-Organization Programme for the Sound Management of Chemicals.
World Health Organization

Geneva, 2001
The International Programme on Chemical Safety (IPCS), established in 1980, is a joint venture
of the United Nations Environment Programme (UNEP), the International Labour Organization (ILO),
and the World Health Organization (WHO). The overall objectives of the IPCS are to establish the
scientific basis for assessment of the risk to human health and the environment from exposure to
chemicals, through international peer review processes, as a prerequisite for the promotion of chemical
safety, and to provide technical assistance in strengthening national capacities for the sound management
of chemicals.
The Inter-Organization Programme for the Sound Management of Chemicals (IOMC) was
established in 1995 by UNEP, ILO, the Food and Agriculture Organization of the United Nations, WHO,
the United Nations Industrial Development Organization, the United Nations Institute for Training and
Research, and the Organisation for Economic Co-operation and Development (Participating
Organizations), following recommendations made by the 1992 UN Conference on Environment and
Development to strengthen cooperation and increase coordination in the field of chemical safety. The
purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating
Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human
health and the environment.
WHO Library Cataloguing-in-Publication Data
Vanadium pentoxide and other inorganic vanadium compounds.
(Concise international chemical assessment document ; 29)
1.Vanadium compounds - adverse effects 2.Risk assessment
3.Environmental exposure I.International Programme on Chemical Safety
II.Series
ISBN 92 4 153029 4
ISSN 1020-6167
(NLM Classification: QV 290)
The World Health Organization welcomes requests for permission to reproduce or translate its
publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications,
World Health Organization, Geneva, Switzerland, which will be glad to provide the latest information on
any changes made to the text, plans for new editions, and reprints and translations already available.
World Health Organization 2001
Publications of the World Health Organization enjoy copyright protection in accordance with the
provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.
The designations employed and the presentation of the material in this publication do not imply the
expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization
concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the
delimitation of its frontiers or boundaries.
The mention of specific companies or of certain manufacturers products does not imply that they are
endorsed or recommended by the World Health Organization in preference to others of a similar nature
that are not mentioned. Errors and omissions excepted, the names of proprietary products are
distinguished by initial capital letters.
The Federal Ministry for the Environment, Nature Conservation and Nuclear Safety, Germany,
provided financial support for the printing of this publication.
Printed by Wissenschaftliche Verlagsgesellschaft mbH, D-70009 Stuttgart 10
TABLE OF CONTENTS
FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.
EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.
IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.
ANALYTICAL METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.1
3.2
3.3
Workplace air monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Biological monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Environmental monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
4.
SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
5.
ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION . . . . . . . . . . . . . . . . . . . . . . 9

5.1
5.2
5.3
5.4
6.
Chemical speciation of vanadium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Essentiality of vanadium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Bioaccumulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Leaching and bioavailability in soils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9
9
9
10
ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

6.1
6.2
Environmental levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1.2 Surface waters and sediments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1.3 Biota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
6.1.4 Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Human exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
10
10
11
11
12
12
7.
COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND

HUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
8.
EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS . . . . . . . . . . . . . . . . . . . . . . . . . . 14

8.1
8.2
8.3
8.4
8.5
8.6
Single exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.1.4 Trivalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Irritation and sensitization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Effects of inhaled vanadium compounds on the respiratory tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Other short-term exposure studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Medium-term exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.5.1 Vanadium pentoxide and other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Long-term exposure and carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.6.1 Vanadium pentoxide and other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iii
15
15
15
15
15
15
16
17
17
17
18
18
18
19
19
19
8.7
8.8
8.9
9.

Genotoxicity and related end-points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.1 Studies in prokaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.1.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.1.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.1.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.1.4 Trivalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.2 In vitro studies in eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.2.4 Trivalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.3 Sister chromatid exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.4 Other in vitro studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.5 In vivo studies in eukaryotes (somatic cells) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.6 In vivo studies in eukaryotes (germ cells) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.6.2 Other pentavalent and tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.7.7 Supporting data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Reproductive toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.8.1 Effects on fertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.8.1.1 Vanadium pentoxide and other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . .
8.8.2 Developmental toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Immunological and neurological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
19
19
19
19
19
19
19
19
19
20
21
21
21
21
21
21
22
22
22
22
22
22
22
23
23
23
23
23
24
24
24
24
25
25
25
26
26
EFFECTS ON HUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
9.1
9.2
9.3
Studies on volunteers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical and epidemiological studies for occupational exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epidemiological studies for general population exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iv
26
26
27
27
27
27
29
29
Vanadium pentoxide and other inorganic vanadium compounds
10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

10.1
10.2
Aquatic environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Terrestrial environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
11. EFFECTS EVALUATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

11.1
11.2
Evaluation of health effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

11.1.1 Hazard identification and doseresponse assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11.1.2 Criteria for setting tolerable intakes or guidance values for vanadium pentoxide . . . . . . . . . . . . . . . . . .
11.1.3 Sample risk characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
11.1.4 Uncertainties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Evaluation of environmental effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
32
32
33
33
34
34
12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
APPENDIX 1 SOURCE DOCUMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
APPENDIX 2 CICAD PEER REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
APPENDIX 3 CICAD FINAL REVIEW BOARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
INTERNATIONAL CHEMICAL SAFETY CARDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
RSUM DORIENTATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
RESUMEN DE ORIENTACIN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
FOREWORD
provided as guidance only. The reader is referred to EHC

1701 for advice on the derivation of health-based
tolerable intakes and guidance values.
Concise International Chemical Assessment

Documents (CICADs) are the latest in a family of
publications from the International Programme on
Chemical Safety (IPCS) a cooperative programme of
the World Health Organization (WHO), the International
Labour Organization (ILO), and the United Nations
Environment Programme (UNEP). CICADs join the
Environmental Health Criteria documents (EHCs) as
authoritative documents on the risk assessment of
chemicals.
While every effort is made to ensure that CICADs

represent the current status of knowledge, new information is being developed constantly. Unless otherwise
stated, CICADs are based on a search of the scientific
literature to the date shown in the executive summary. In
the event that a reader becomes aware of new information that would change the conclusions drawn in a
CICAD, the reader is requested to contact IPCS to inform
it of the new information.
International Chemical Safety Cards on the

relevant chemical(s) are attached at the end of the
CICAD, to provide the reader with concise information
on the protection of human health and on emergency
action. They are produced in a separate peer-reviewed
procedure at IPCS. They may be complemented by
information from IPCS Poison Information Monographs
(PIM), similarly produced separately from the CICAD
process.
Procedures
The flow chart shows the procedures followed to
produce a CICAD. These procedures are designed to
take advantage of the expertise that exists around the
world expertise that is required to produce the highquality evaluations of toxicological, exposure, and other
data that are necessary for assessing risks to human
health and/or the environment. The IPCS Risk Assessment Steering Group advises the Co-ordinator, IPCS, on
the selection of chemicals for an IPCS risk assessment,
whether a CICAD or an EHC is produced, and which
institution bears the responsibility of the document
production, as well as on the type and extent of the
international peer review.
CICADs are concise documents that provide summaries of the relevant scientific information concerning
the potential effects of chemicals upon human health
and/or the environment. They are based on selected
national or regional evaluation documents or on existing
EHCs. Before acceptance for publication as CICADs by
IPCS, these documents undergo extensive peer review
by internationally selected experts to ensure their
completeness, accuracy in the way in which the original
data are represented, and the validity of the conclusions
drawn.
The first draft is based on an existing national,

regional, or international review. Authors of the first
draft are usually, but not necessarily, from the institution
that developed the original review. A standard outline
has been developed to encourage consistency in form.
The first draft undergoes primary review by IPCS and
one or more experienced authors of criteria documents in
order to ensure that it meets the specified criteria for
CICADs.
The primary objective of CICADs is characterization of hazard and doseresponse from exposure to a
chemical. CICADs are not a summary of all available data
on a particular chemical; rather, they include only that
information considered critical for characterization of the
risk posed by the chemical. The critical studies are,
however, presented in sufficient detail to support the
conclusions drawn. For additional information, the
reader should consult the identified source documents
upon which the CICAD has been based.
The draft is then sent to an international peer

review by scientists known for their particular expertise
and by scientists selected from an international roster
compiled by IPCS through recommendations from IPCS
national Contact Points and from IPCS Participating
Institutions. Adequate time is allowed for the selected
experts to undertake a thorough review. Authors are
required to take reviewers comments into account and
revise their draft, if necessary. The resulting second draft
Risks to human health and the environment will

vary considerably depending upon the type and extent
of exposure. Responsible authorities are strongly
encouraged to characterize risk on the basis of locally
measured or predicted exposure scenarios. To assist the
reader, examples of exposure estimation and risk
characterization are provided in CICADs, whenever
possible. These examples cannot be considered as
representing all possible exposure situations, but are
International Programme on Chemical Safety (1994)

Assessing human health risks of chemicals: derivation
of guidance values for health-based exposure limits.
Geneva, World Health Organization (Environmental
Health Criteria 170).
1
CICAD PREPARATION FLOW CHART
SELECTION OF PRIORITY CHEMICAL
SELECTION OF HIGH QUALITY

NATIONAL/REGIONAL
ASSESSMENT DOCUMENT(S)
FIRST DRAFT
PREPARED
PRIMARY REVIEW BY IPCS

( REVISIONS AS NECESSARY)
REVIEW BY IPCS CONTACT POINTS/

SPECIALIZED EXPERTS
R E V I E W O F C O M M E N T S ( PRODUCER/RESPONSIBLE OFFICER),
PREPARATION
OF SECOND DRAFT 1
FINAL REVIEW BOARD
FINAL DRAFT
EDITING
APPROVAL BY DIRECTOR, IPCS
PUBLICATION
1 Taking into account the comments from reviewers.

2 The second draft of documents is submitted to the Final Review Board together with the reviewers comments.
3 Includes any revisions requested by the Final Review Board.
is submitted to a Final Review Board together with the

reviewers comments.
A consultative group may be necessary to advise
on specific issues in the risk assessment document.
The CICAD Final Review Board has several
important functions:
to ensure that each CICAD has been subjected to

an appropriate and thorough peer review;
to verify that the peer reviewers comments have
been addressed appropriately;
to provide guidance to those responsible for the
preparation of CICADs on how to resolve any
remaining issues if, in the opinion of the Board, the
author has not adequately addressed all comments
of the reviewers; and
to approve CICADs as international assessments.
Board members serve in their personal capacity, not as

representatives of any organization, government, or
industry. They are selected because of their expertise in
human and environmental toxicology or because of their
experience in the regulation of chemicals. Boards are
chosen according to the range of expertise required for a
meeting and the need for balanced geographic
representation.
Board members, authors, reviewers, consultants,
and advisers who participate in the preparation of a
CICAD are required to declare any real or potential
conflict of interest in relation to the subjects under
discussion at any stage of the process. Representatives
of nongovernmental organizations may be invited to
observe the proceedings of the Final Review Board.
Observers may participate in Board discussions only at
the invitation of the Chairperson, and they may not
participate in the final decision-making process.
1. EXECUTIVE SUMMARY
64 000 tonnes of vanadium that are emitted to the atmosphere each year from both natural and anthropogenic
sources comes from oil combustion.
This CICAD on vanadium pentoxide and other

inorganic vanadium compounds was based on a review
of human health concerns (primarily occupational)
prepared by the United Kingdoms Health and Safety
Executive (HSE, in press). This review focuses on
exposures via routes relevant to occupational settings,
but it also contains environmental information. Data
identified as of November 1998 were covered. A further
literature search was performed up to May 1999 to
identify any additional information published since this
review was completed. An Environmental Health Criteria
monograph (IPCS, 1988) was used as a source document
for environmental information. As no more recent source
document was available for environmental fate and
effects, the literature was searched for additional
information. Information on the nature of the peer review
and availability of the source documents is presented in
Appendix 1. Information on the peer review of this
CICAD is presented in Appendix 2. This CICAD was
approved as an international assessment at a meeting of
the Final Review Board, held in Helsinki, Finland, on
2629 June 2000. Participants at the Final Review Board
meeting are listed in Appendix 3. The International
Chemical Safety Cards on vanadium trioxide (ICSC 0455)
and vanadium pentoxide (ICSC 0596), produced by the
International Programme on Chemical Safety (IPCS,
1999a,b), have also been reproduced in this document.
The environmental chemistry of vanadium is complex. In minerals, the oxidation state of vanadium may be
+3, +4, or +5. Dissolution in water rapidly oxidizes V3+
and V4+ to the pentavalent state, the most usual form of
the metal in the environment. Vanadate, the pentavalent
species in solution, may polymerize (mainly to dimeric
and trimeric forms), particularly at higher concentrations
of the salts. Within tissues of organisms, V3+ and V4+
predominate because of largely reducing conditions; in
plasma, V5+ predominates.
Vanadium is probably essential to enzyme systems
that fix nitrogen from the atmosphere (bacteria) and is
concentrated by some organisms (tunicates, some polychaete annelids, some microalgae), but its function in
these organisms is uncertain. Whether vanadium is
essential to other organisms remains an open question.
There is no evidence of accumulation or biomagnification in food chains in marine organisms, the best studied
group.
There is very limited leaching of vanadium through
soil profiles.
Higher levels of vanadium have been reported in
air close to industrial sources and oil fires. Representative deposition rates are 0.110 kg/ha per annum for
urban sites affected by strong local sources, 0.01
0.1 kg/ha per annum for rural sites and urban ones with
no strong local source, and <0.0010.01 kg/ha per annum
for remote sites.
Vanadium (CAS No. 7440-62-2) is a soft silverygrey metal that can exist in a number of different oxidation states: !1, 0, +2, +3, +4, and +5. The most common
commercial form is vanadium pentoxide (V2O5; CAS No.
1314-62-1), and this exists in the pentavalent state as a
yellow-red or green crystalline powder.
Most surface fresh waters contain less than 3 g

vanadium/litre; higher levels of up to about 70 g/litre
have been reported in areas with high geochemical
sources. Data on levels of vanadium in surface water
close to industrial activity are few; most reports suggest
levels approximately the same as the highest natural
ones. Seawater concentrations in the open ocean range
from 1 to 3 g/litre, and sediment concentrations range
from 20 to 200 g/g; the highest levels are in coastal
sediments.
Vanadium is an abundant element with a very wide

distribution and is mined in South Africa, Russia, and
China. During the smelting of iron ore, a vanadium slag
is formed that containvanadium pentoxide, which is used
for the production of vanadium metal. Vanadium pentoxide is also produced by solvent extraction from uranium
ores and by a salt roast process from boiler residues or
residues from elemental phosphate plants. During the
burning of fuel oils in boilers and furnaces, vanadium
pentoxide is present in the solid residues, soot, boiler
scale, and fly ash.
A few organisms concentrate vanadium, with up to

10 000 g/g in ascidians and 786 g/g in polychaete
annelids. Most other organisms contain generally less
than 50 g/g and usually much lower concentrations.
Atmospheric emissions from natural sources have

been estimated at 8.4 tonnes per annum globally (range
1.549.2 tonnes). By far the most important source of
environmental contamination with vanadium is combustion of oil and coal; about 90% of the approximately
Estimates of total dietary intake of humans range

from 11 to 30 g/day. Levels in drinking-water range up
to 100 g/litre. Some groundwater sources supplying
potable water show concentrations above 50 g/litre.

Levels in bottled spring water may be higher.
pentoxide dust and fume. Overall, there are insufficient

data to reliably describe the exposureresponse relationship for the respiratory effects of vanadium pentoxide
dust and fume in humans.
In humans, there is limited toxicokinetic information suggesting that vanadium is absorbed following
inhalation and is subsequently excreted via the urine
with an initial rapid phase of elimination, followed by a
slower phase, which presumably reflects the gradual
release of vanadium from body tissues. Following oral
administration, tetravalent vanadium is poorly absorbed
from the gastrointestinal tract. There were no dermal
studies available.
Pentavalent and tetravalent forms of vanadium

have produced aneugenic effects in vitro in the presence
and absence of metabolic activation. There is evidence
that these forms of vanadium as well as trivalent vanadium can also produce DNA/chromosome damage in
vitro, both positive and negative results having emerged
from the available studies. The weight of evidence from
the available data suggests that vanadium compounds
do not produce gene mutations in standard in vitro tests
in bacterial or mammalian cells.
In inhalation and oral studies in laboratory animals,

absorbed vanadium in either pentavalent or tetravalent
states is distributed mainly to the bone, liver, kidney,
and spleen, and it is also detected in the testes. The main
route of vanadium excretion is via the urine. The pattern
of vanadium distribution and excretion indicates that
there is potential for accumulation and retention of
absorbed vanadium, particularly in the bone. There is
evidence that tetravalent vanadium has the ability to
cross the placental barrier to the fetus.
In vivo, both pentavalent and tetravalent vanadium

compounds have produced clear evidence of aneuploidy
in somatic cells following exposure by several different
routes. The evidence for vanadium compounds also
being able to express clastogenic effects is, as with in
vitro studies, mixed, and the overall position on clastogenicity in somatic cells is uncertain. A positive result
was obtained in germ cells of mice receiving vanadium
pentoxide by intraperitoneal injection. However, the
underlying mechanism for this effect (aneugenicity;
clastogenicity) is uncertain. It is also unclear how these
findings can be generalized to more realistic routes of
exposure or to other vanadium compounds.
The one acute inhalation study available reported

an LC67 of 1440 mg/m3 (800 mg vanadium/m3) following a
1-h exposure of rats to vanadium pentoxide dust. Oral
studies in rats and mice resulted in LD 50 values in the
range 10160 mg/kg body weight for vanadium pentoxide and other pentavalent vanadium compounds, while
tetravalent vanadium compounds have LD 50 values in
the range 448467 mg/kg body weight. No information is
available concerning dermal toxicity.
The nature of the genotoxicity database on vanadium pentoxide and other vanadium compounds is such
that it is not possible to clearly identify the threshold
level, for any route of exposure relevant to humans,
below which there would be no concern for potential
genotoxic activity.
Eye irritation has been reported in studies in

vanadium workers. No skin irritation was reported in
100 human volunteers following skin patch testing with
10% vanadium pentoxide, although patch testing in
workforces has produced two isolated reactions. No
clear information is available from animal studies with
regard to the potential of vanadium compounds to
produce skin or eye irritation or skin sensitization.
No useful information is available on the carcinogenic potential of any form of vanadium via any route of
exposure in animals 1 or in humans.
A fertility study in male mice, involving exposure
to sodium metavanadate in drinking-water, suggests the
possibility that oral exposure of male mice to sodium
metavanadate at 60 and 80 mg/kg body weight directly
caused a decrease in spermatid/spermatozoal count and
in the number of pregnancies produced in subsequent
matings. However, significant general toxicity (decreased
body weight gain) was also evident at 80 mg/kg body
weight.
In a group of human volunteers, a single 8-h

exposure to 0.1 mg vanadium pentoxide dust/m3 caused
delayed but prolonged bronchial effects involving excessive production of mucus. At 0.25 mg/m3, a similar
pattern of response was seen, with the addition of cough
for some days post-exposure. Exposure to 1.0 mg/m3
produced persistent and prolonged coughing after 5 h.
A no-effect level for bronchial effects was not identified
in this study.
Repeated inhalation exposure to the dust and fume
of vanadium pentoxide is associated with irritation of the
eyes, nose, and throat. Wheeze and dyspnoea are
commonly reported in workers exposed to vanadium
The authors of this document are aware that a 2-year

inhalation bioassay in rodents has recently been
completed at the US National Toxicology Program.
However, results are not available at this time.
5
There are a number of developmental studies on

pentavalent and tetravalent vanadium compounds, and a
consistent observation is that of skeletal anomalies.
Interpretation of these studies is difficult because of
unconventional routes of exposure and evidence of
maternal toxicity that may itself contribute to the effects
seen in pups.
provides some physicochemical properties of vanadium

compounds that are referred to in this review.
Vanadium (CAS No. 7440-62-2) is a soft silverygrey metal with a relative molecular mass of 50.9.
Vanadium pentoxide (CAS No. 1314-62-1) is the
most commonly used vanadium compound and exists in
the pentavalent state as a yellow-red or green crystalline
powder of relative molecular mass 181.9. Other common
synonyms include vanadic anhydride and divanadium
pentoxide.
The toxicological end-points of concern for

humans are genotoxicity and respiratory tract irritation.
Since it is not possible to identify a level of exposure
that is without adverse effect, it is recommended that
levels be reduced to the extent possible.
Vapour pressures (and hence Henrys law constants) and octanol/water partition coefficients are not
available for vanadium compounds.
Acute LC50 values for aquatic organisms range

from 0.2 to about 120 mg/litre, with the majority lying
between 1 and 12 mg/litre. More ecotoxicologically
relevant end-points were development of oyster larvae
(significantly reduced at 0.05 mg vanadium/litre) and
reproduction of Daphnia (21-day no-observed-effect
concentration at 1.13 mg/litre). There are few terrestrial
studies. Most plant studies have been on hydroponic
cultures where effects occurred at 5 mg/litre and higher;
these studies are difficult to interpret in relation to plants
growing in soil.
3. ANALYTICAL METHODS
3.1
Workplace air monitoring
Airborne monitoring is largely based on measurement of vanadium, rather than vanadium pentoxide. The
Health and Safety Executive has published MDHS 91
Metals and metalloids in workplace air by X-ray
fluorescence spectrometry (HSE, 1998). This method can
be used for measuring vanadium and vanadium
compounds in workplace air, but no method performance
data are available for vanadium.
Concentrations in environmental media are substantially lower than reported toxic concentrations. Few
data are available on concentrations at specific industrial
sites, and it is not possible to conduct a risk assessment
on this basis. However, reported concentrations appear
to be similar to the highest natural concentrations,
suggesting that risk would be low. Local measurements
must be carried out to assess risk in any particular
circumstance.
The US National Institute of Occupational Safety

and Health (NIOSH, 1994) and the US Occupational
Safety and Health Administration (OSHA, 1991) have
published methods that are suitable for measuring
vanadium and vanadium compounds in workplace air.
Both are generic methods for metals and metalloids in
which samples are collected by drawing air through a
membrane filter mounted in a cassette-type filter holder,
dissolved in acid on a hotplate, and analysed by inductively coupled plasma atomic emission spectrometry
(ICP-AES). For both methods, the lower limit of the
working range is approximately 0.005 mg/m3 for a 500-litre
air sample, although these methods are not widely
available.
2. IDENTITY AND PHYSICAL/CHEMICAL

PROPERTIES
Vanadium can exist in a number of different

oxidation states: !1, 0, +2, +3, +4, and +5. The most
common commercial form of vanadium is vanadium
pentoxide (V2O5), in which vanadium is in the +5
oxidation state. Other forms of vanadium in the +5
oxidation state mentioned in this review derive from the
vanadate ion (VO 3) and include ammonium metavanadate (NH4VO3), sodium metavanadate (NaVO 3), and
sodium orthovanadate (Na3VO4). Compounds in the +4
oxidation state are derived from the vanadyl ion (VO 2+)
for example, vanadyl dichloride (VOCl2) and vanadyl
sulfate (VOSO 4). Compounds containing vanadium in the
+3 oxidation state include vanadium oxide (V2O3). Table 1
3.2
Biological monitoring
The measurement of vanadium in end-of-shift urine

samples is appropriate for biological monitoring of
vanadium exposure and has been widely used to monitor
occupational exposure to vanadium compounds in a
number of industrial activities (Angerer & Schaller,
1994).
Table 1: Physical/chemical properties of vanadium and selected inorganic vanadium compounds.

Solubility (g/litre)
CAS
number
Molecular/
atomic mass
Melting
point (C)
Boiling
point (C)
Cold water
(2025 C)
Vanadium, V
7440-62-2
50.942
1890 10;
1917
Hot water
Other solvents
3380
Insoluble
Insoluble
Not attacked by hot or

cold hydrochloric acid
or cold sulfuric acid,
but soluble in
hydrofluoric acid, nitric
acid, and aquaregia
Vanadium
pentoxide,
V 2O5
1314-62-1
181.9
690
1750
No data
Soluble in acid/alkali;
insoluble in absolute
alcohol
Sodium metavanadate,
NaVO3
13718-268
121.93
No data
No data
211
388 (at 75
C)
No data
Sodium orthovanadate,
Na 3VO4
13721-396
183.91
850856
No data
Soluble
No data
Soluble in alcohol
Ammonium
metavanadate,
NH4VO3
7803-55-6
116.98
200
(decomposes)
No data
58
Decomposes
Soluble in ammonium
carbonate
Vanadium
oxytrichloride,
VOCl 3
7727-18-6
Soluble,
decomposes
No data
Soluble in alcohol,
ether, acetic acid
Vanadyl
sulfate,
VOSO4
27774-136
Very soluble
No data
No data
Vanadyl
oxydichloride,
VOCl 2
10213-099
Decomposes
No data
Soluble in dilute nitric

acid
Vanadium
trioxide, V 2O3
1314-34-7
Slightly
soluble
Soluble
Soluble in nitric acid,

hydrofluoric acid,
alkali
Compound
Vanadium is eliminated in the urine with a half-life

of 1540 h (Sabbioni & Moroni, 1983). Pre-shift and
post-shift urine vanadium levels measured at the
beginning and the end of a working week will, therefore,
give a measure of daily absorption and accumulated
dose from exposures over the preceding days. A further
study of workers exposed to vanadium pentoxide (Kawai
et al., 1989) demonstrated the utility of measuring midshift urinary vanadium as an indicator of exposure.
Blood vanadium levels were also determined but offered
no advantage over urine measurements. As noninvasive sampling is normally preferred for routine
biological monitoring, the measurement of vanadium in
urine is generally recommended.
spectrophotometry (AAS), with pre-concentration by

chelation and solvent extraction, is the most widely used
analytical method for the determination of vanadium in
urine, and validated methods have been described in the
literature. This analytical method gives typical detection
limits of 0.1 g/litre for vanadium in urine, with analytical
precisions of 11% relative standard deviation at 1 g/litre
and 4% at 10 g/litre.
3.3
Environmental monitoring
Various methods have been described for analysis

of vanadium in air, surface waters, and biota (e.g.,
Ahmed & Banerjee, 1995). Flameless AAS (NIOSH, 1977)
gives a detection limit of 1 ng/ml in air, corresponding to
an absolute sensitivity of 0.1 ng vanadium. ICP-AES has
a working range of 52000 g/m3 for a 500-litre air sample
(NIOSH, 1994). Direct aspiration and graphite furnace
AAS methods for determining vanadium compounds in
water were reported in US EPA (1983). The detection
limits for these two methods are 200 and 4 g/litre,
respectively (US EPA, 1986). Instrumental neutron
activation analysis gave detection limits of 0.01 g/g in
In biological monitoring studies of occupational

vanadium exposure, urinary levels of vanadium associated with airborne exposures have been measured (see
Table 4 in section 6.2).
Urinary vanadium may be determined accurately
by several analytical techniques (Hauser et al., 1998;
HSE, in press). Electrothermal atomic absorption
7
the context of sea mammal tissues (Mackey et al., 1996).

The instrumental detection limit was 0.1 ng/ml using
inductively coupled plasma mass spectrometry (Saeki
et al., 1999).
outside the United Kingdom, is used in very small quantities for research purposes.
Vanadium pentoxide is used as the catalyst for a
variety of gas-phase oxidation processes, particularly
the conversion of sulfur dioxide to sulfur trioxide during
the manufacture of sulfuric acid. The most frequently
used vanadium pentoxide catalyst contains 46%
vanadium as vanadium pentoxide on a silica base.
4. SOURCES OF HUMAN AND

ENVIRONMENTAL EXPOSURE
Vanadium pentoxide is also used in some pigments

and inks used in the ceramics industry to impart a colour
ranging from brown to green. Pigments and inks are
made containing up to about 15% vanadium pentoxide,
the higher-concentration ones being supplied in an oil
base rather than as a dry powder.
Vanadium is a relatively abundant element with a

very wide distribution; however, workable deposits are
very rare. Vanadium occurs in the minerals vanadinite,
chileite, patronite, and carnotite. It constitutes about
0.01% of the crust of the Earth (Budavari et al., 1996). It
is derived mainly from titaniferous magnetites containing
1.52.5% vanadium pentoxide, which are mined in South
Africa, Russia, and China (HSE, in press). During the
smelting of iron ore, a vanadium slag is formed that
contains 1224% vanadium pentoxide, which is used for
the production of vanadium metal. Worldwide production of vanadium was stable at just over 27 000 tonnes
per annum between 1976 and 1990. Estimated production
in 1990 was 30 700 tonnes, comprising approximately
15 400 tonnes from South Africa, 4100 tonnes from
China, 8200 tonnes from the former USSR, 2100 tonnes
from the USA, and under 900 tonnes from Japan (Hilliard,
1992). Vanadium pentoxide is also produced by solvent
extraction from uranium ores and by a salt roast process
from boiler residues or residues from elemental
phosphate plants. Ferrovanadium can be obtained from
vanadium pentoxides or vanadium slags by the aluminothermic process.
Vanadium pentoxide can be used as a colouring

agent and to provide ultraviolet filtering properties in
some glasses. Normally, the vanadium content in the
batch materials is less than 0.5%.
Atmospheric emissions of vanadium from natural
sources have been estimated at 8.4 tonnes per annum
globally (range 1.549.2 tonnes). Natural sources, in
order of importance, are continental dusts, volcanoes,
seasalt spray, forest fires, and biogenic processes
(Nriagu, 1990).
By far the most important source of environmental
contamination with vanadium is combustion of oil, with
coal combustion as the second most important. Of the
estimated total global emissions from both natural and
anthropogenic sources of 64 000 tonnes per annum to
the atmosphere, 58 500 tonnes come from oil
combustion, with more than 33 500 tonnes of this
accounted for by the developing economies in Asia and
just under 14 500 tonnes by Eastern Europe and the
former USSR. There are considerable regional variations
in vanadium emissions. For example, emissions to the
Great Lakes area fell between 1980 and 1995, whereas
those to the Mediterranean basin have continued to rise,
dominated by emissions from a few countries (Turkey
20%, Egypt 19%, and Lebanon 15% of the total) (Nriagu
& Pirrone, 1998).
All crude oils contain metallic impurities, including

vanadium, which is present as an organometallic
complex. The vanadium concentration in the oils varies
greatly, depending on their origin. The concentration of
vanadium in crude oil ranges from 3 to 260 g/g and in
residual fuel oil from 0.2 to 160 g/g (NAS, 1974). During
the burning of fuel oils in boilers and furnaces, the
vanadium is left behind as vanadium pentoxide in the
solid residues, soot, boiler scale, and fly ash. The vanadium content of these residues varies from less than 1%
up to almost 60%. Vanadium is also present in coal,
typically at a concentration between 14 and 56 ppm
(mg/kg).
Vanadium is used in the United Kingdom in certain ferrovanadium alloys, being added in relatively small
proportions at the refining stage of steelmaking.
Titanium-boron-aluminium (TiBAl) rod, containing less
than 1% vanadium, is used by the secondary aluminium
industry as a grain refiner. The hard metals industry uses
small amounts of vanadium carbide in the production of
tungsten carbide tool bits. Pure vanadium, imported from
5. ENVIRONMENTAL TRANSPORT,
DISTRIBUTION, AND TRANSFORMATION
5.1
atmospheric nitrogen to ammonia. The best characterized

nitrogenase is molybdenum-dependent, and its detailed
structure has been published (Chan et al., 1993).
Although it has been known for a long time (Bortels,
1936) that vanadium could substitute for molybdenum as
a trace element in nitrogen-fixing bacteria, only recently
has it been studied in detail. The structure of the
vanadium-dependent enzyme is not fully known but is
assumed to be similar to the molybdenumiron protein
(Chan et al., 1993). The vanadium enzyme has been
shown to function under conditions of low molybdenum,
but it may also operate under all conditions; genetic
variants lacking the molybdenumiron enzyme and
relying exclusively on the vanadiumiron enzyme are
known.
Chemical speciation of vanadium
The chemistry of vanadium is extremely complex,

and the reader is referred elsewhere for detailed discussion of the origin, speciation, bioaccumulation, and
complex-forming chemistry of the metal related to the
environment and biological systems (Crans et al., 1998).
A simple summary of vanadium chemistry is presented
here.
Under environmental conditions, vanadium may
exist in oxidation states +3, +4, and +5. V3+ and V4+ act as
cations, but V5+, the most common form in the aquatic
environment, reacts both as a cation and anionically as
an analogue of phosphate.
Vanadium-dependent haloperoxidases have been

found in marine macroalgae and also in a lichen and
fungus. Amavadin, a complex molecule centred on
vanadium, is found in fungi of the genus Amanita; its
function is not known, but it may act as a mediator in
electron transfer. In ascidians (Tunicata; Protochordata),
commonly called sea squirts, it has been suggested that
vanadium interacts with tunichromes, oligopeptides that
are the building blocks of the tunic. In fan worms
(Polychaeta; Annelida), a function for vanadium in
oxygen absorption and storage has been suggested.
In minerals, the oxidation state of vanadium may be

+3, +4, or +5, but all mineral dissolution rapidly oxidizes
V3+ and V4+ to the pentavalent state. Dry weathering
produces dusts that may be distributed over great
distances; deposition of dust into water will also lead to
exclusively pentavalent vanadium. Vanadium is a nonvolatile metal, and atmospheric transport is via
particulates. In fuel oils and coal, vanadium is present as
very stable porphyrin and non-porphyrin complexes
(Yen, 1975; Fish & Komlenic, 1984) but is emitted as
oxides when these fossil fuels are burned. The native
oxides are sparingly soluble in water but undergo
hydrolysis to generate vanadate in solution. Vanadate
is often used as a generalized term for vanadium species
in solution. Speciation of vanadium in solution is complex and highly dependent on vanadium concentration.
Under most common environmental conditions of pH
and redox potential, and at the low concentrations
reported for vanadium in natural waters, the vanadate is
largely monomeric. At higher concentrations, such as
those used in toxicity testing, dimeric and trimeric forms
may predominate, and this can have an effect on how the
vanadium compounds interact with biological systems
(Crans et al., 1998).
Recent reviews on the role of vanadium in biological systems include those by Rehder & Jantzen (1998),
Wever & Hemrika (1998), Chasteen (1990), and Sigel &
Sigel (1995), where details of the chemistry of vanadium
in biological systems can be found.
Whether vanadium is an essential trace element for
mammals remains an open question. Deficiency states
have been described for goats and chicks, consisting of
reproductive anomalies and deleterious effects on bone
growth (Nielsen & Uthus, 1990). However, there is
disagreement on results, and, if vanadium is essential,
requirement levels of the order of a few nanograms per
day are likely (Mackey et al., 1996).
5.3
Ascidians have been known to accumulate large

residues of vanadium since a first report in 1911 (Henze,
1911). The metal accumulates in blood cells (vanadocytes). The highest reported concentration is 350 mmol/
litre in the blood cells of Ascidia gemmata (Michibata et
al., 1991), a concentration factor above that in seawater
of 107. Recent reviews of accumulation and the significance of vanadium in these organisms include those by
Kustin & Robinson (1995), Michibata (1996), and
Michibata & Kanamori (1998). Recently (Ishii et al., 1993),
high vanadium accumulation was demonstrated for
Within tissues in organisms, V3+ and V4+ predominate because of largely reducing conditions; in plasma,
however, which is high in oxygen, V5+ is formed (Crans
et al., 1998).
5.2
Bioaccumulation
Essentiality of vanadium
Vanadium has been characterized as a constituent

of several enzyme systems and complexes within living
organisms. Nitrogen-fixing bacteria and cyanobacteria
contain nitrogenases, which catalyse the reduction of
polychaetes of the genus Pseudopotamilla; polychaetes

of other genera did not accumulate the metal.
Pseudopotamilla occelata showed concentrations in
whole soft body ranging from 320 to 1350 mg/kg dry
weight. Distribution, speciation, and possible physiological roles of the metal are discussed in Ishii (1998).
the Alaskan marine environment as possible

explanations (Mackey et al., 1996).
Marine biota are thought to contribute to the
sedimentation of vanadium from seawater via shells,
faecal pellets, and moult. Coastal sediments appear to be
a sink for vanadium (Miramand & Fowler, 1998).
Apart from the specific accumulators mentioned

above, organisms generally do not concentrate or accumulate vanadium from environmental media to a high
degree, and there is no indication of biomagnification in
food chains. Miramand & Fowler (1998) reviewed
reported levels of vanadium in marine organisms and
calculated concentration factors for components of a
typical marine food chain based on average seawater
concentrations of 2 ng/g. Concentration factors for
primary producers ranged from 40 to 560, for primary
consumers from 40 to 150, for secondary consumers from
approximately 20 to 150, and for tertiary consumers from
approximately 2 to 400. Although vanadium
concentrations are higher in sediment than in open
seawater, only one study has attempted to quantify
uptake from sediment using 48V; the ragworm Nereis
diversicolor accumulated vanadium from the sediment
with a low transfer factor of about 0.02 (Miramand, 1979).
Using labelled food, assimilation coefficients have been
calculated for several marine organisms. For the
carnivorous invertebrates Marthasterias glacialis,
Sepia officianalis, Carcinus maenus, and Lysmata
seticaudata, assimilation coefficients of 88% (Miramand
et al., 1982), 40% (Miramand & Fowler, 1998), 38%, and
25% (Miramand et al., 1981) were reported, respectively.
Biological half-lives in the same organisms were 57, 7, 10,
and 12 days, respectively. A high proportion of the
vanadium was present in the digestive gland (6398.8%).
For a single fish species (Gobius minutus), assimilation
was much lower, at 23%, with a half-life of 3 days
(Miramand et al., 1992), and accumulation was also low
in a bivalve feeding on suspended matter (Mytilus
galloprovincialis), at 7%, with a half-life of 7 days
(Miramand et al., 1980). Comparison of uptakes via food
and directly from water showed that invertebrates
accumulated much of the vanadium from food
(Miramand & Fowler, 1998). Recent studies on bioaccumulation of vanadium in pinnipeds and cetaceans in
Swedish (Frank et al., 1992), northern Pacific (Saeki et al.,
1999), and Alaskan/Atlantic (Mackey et al., 1996) waters
have shown a correlation of residues with age,
comparable to other metal residues. Liver showed the
highest accumulation of the metal of all tissues analysed.
However, bone, which might be expected to accumulate
the element, was not analysed. Alaskan sea mammals
showed the highest levels, ranging up to 1.2 g/g wet
weight. The authors suggest a unique dietary source, a
unique geochemical source, or anthropogenic input to
5.4
Leaching and bioavailability in soils
A field study conducted over 30 months examined

movement of vanadium added to the top 7.5 cm of
coastal plain soil and its availability to bean plants. Less
than 3% of applied metal moved down the soil profile.
Extractable concentrations decreased over the first
18 months of the study and remained constant thereafter.
Uptake of vanadium into the roots and upper parts of the
bean plants did not change significantly between
18 months and the end of the experiment but was
reduced during the initial period, suggesting reduced
bioavailability over time as a result of binding to soil
materials (Martin & Kaplan, 1998).
6. ENVIRONMENTAL LEVELS AND

HUMAN EXPOSURE
6.1
Environmental levels
A very substantial literature exists on environmental levels of vanadium. The metal has been monitored in
geographical areas with naturally high occurrence of the
metal (mainly volcanic regions) where local water contributes to drinking supplies, and vanadium has been
used to monitor general industrial contamination, since it
is a common component of oil and coal. In addition,
accumulation of the metal has been studied intensively
for marine organisms, since vanadium is known to
accumulate in a few species (section 5). In this section,
representative levels are presented. The reader is referred
to several recent reviews for more detailed coverage of
the literature in each of the subsections following.
6.1.1
Air
Earlier measurements of vanadium in air were

reviewed by Schroeder et al. (1987); most measurements
were performed in the 1970s, with a few in the early
1980s. A review of later measurements and comparison
with the earlier review were conducted by Mamane &
Pirrone (1998). The ranges they reported are presented in
Table 2, together with reported concentrations downwind of the Kuwait oil fires in 19911992. The ranges are
very large, and there is no simple explanation for the
10
Table 2: Ranges of concentrations of vanadium in air.

Atmospheric
concentration
(ng/m3)
Area
Reference
Urban air
Rural air
Remote areasa
0.41460
2.797
0.00114
Schroeder et al., 1987
Urban air
Rural air
Remote areas
0.51230
0.4500
0.012
Mamane & Pirrone,

1998
2.41170 (in
the PM 10
fraction)
Sadiq & Mian, 1994
Dhahran, Saudi
Arabia, during
Kuwait oil fires
1969). A wider survey of Wyoming, Idaho, Utah, and

Colorado in the USA showed vanadium concentrations
of 2.09.0 g/litre (Parker et al., 1978). Unfiltered water
from the source area of the Yangtze River in China contained between 0.24 and 64.5 g/litre, whereas concentrations in filtered water ranged from 0.02 to 0.46 g/litre
(Zhang & Zhou, 1992). The highest levels reported are in
surface waters in the area of Mount Fuji in Japan. Two
springs had 14.8 and 16.4 g/litre, and five river samples
showed between 17.7 and 48.8 g/litre (Hamada, 1998).
Data on concentrations of vanadium in wastewater
and local surface water are few, and studies are old;
reliability for present-day operations is questionable. A
single concentration of 2 mg/litre for surface water from
1961, reported in IPCS (1988), seems much higher than
other more recent reports, where levels of up to 60 g/litre in industrial areas seem more likely.
Includes the Arctic and oceanic islands in the Atlantic and

Pacific.
variation; possible causes are reviewed by Mamane &

Pirrone (1998), although they can draw no firm conclusions.
Seawater concentrations have been reviewed by

Miramand & Fowler (1998). Most reported concentrations in the open ocean have been in the range 13 g/litre, with the highest reported value at 7.1 g/litre. Sediment concentrations range from 20 to 200 g/g dry
weight, with higher levels in coastal sediments.
Vanadium in air from oil combustion tends to be in

smaller particulate fractions. In arid areas with dust
storms, high levels of vanadium have been reported;
here, particle size tends to be much larger (Mamane &
Pirrone, 1998).
6.1.3
Bulk precipitation concentration ranges have been
reported at 4.113 g/litre for the rural United Kingdom
(Galloway et al., 1982) and 0.120.65 g/litre (mean 0.45
g/litre) in Switzerland (Atteia, 1994). Wet deposition in
an area of New England remote from anthropogenic
input showed concentrations of vanadium ranging from
0.2 to 1.16 g/litre (average 0.67 g/litre) and in Bermuda
ranging from 0.049 to 0.111 g/litre (average 0.096
g/litre) (Church et al., 1984). Ice and snow levels in
northern Norway and Alaska were 0.31 and 0.13 g/litre,
respectively (Galloway et al., 1982), and two ice core
levels in Greenland were reported at 0.022 and 0.016
g/litre. Levels in rain ranged from 1.1 to 46 g/litre for
rural and urban sites in North America and Europe
(Galloway et al., 1982).
Ranges of concentrations of vanadium in marine

organisms are given in Table 3, based on a review of the
literature in Miramand & Fowler (1998), where the
original references can be found. The ranges include
values from areas of likely local contamination from
industrial sources. With the exception of ascidians
(tunicates), some annelids, and molluscs, concentrations
of vanadium in marine organisms are low. The range for
planktonic species is heavily influenced by a single
study showing accumulation up to 290 mg/kg dry
weight; this was mainly into shells of planktonic forms of
molluscs. Generally, planktonic organisms show
concentrations of vanadium around 1 mg/kg.
There are fewer data for freshwater organisms. The
most comprehensive study of organisms was conducted
in the Mount Fuji area of Japan, where concentrations in
organisms from water with high (43.4 g/litre) and lower
(0.72 or 0.4 g/litre) concentrations of vanadium were
compared. Water plants from the high-vanadium area
contained 21.8 11.3 g/g dry weight of the metal (range
5.643.7 g/g), compared with 0.79 0.52 g/g (range
0.221.91 g/g) in the low-vanadium area. A green
microalga in the high-concentration area contained the
highest reported concentration of the metal, at 118168
g/g dry weight. The vanadium concentration in rainbow
trout (Oncorhynchus mykiss) farmed in water from these
areas was measured: bone concentrations
Based on these reported concentrations, Mamone

& Pirrone (1998) calculated representative total deposition rates of vanadium at 0.110 kg/ha per annum for
urban sites affected by strong local sources, 0.01
0.1 kg/ha per annum for rural sites and urban ones with
no strong local source, and <0.0010.01 kg/ha per annum
for remote sites.
6.1.2
Biota
Surface waters and sediments
Most surface fresh waters contain less than 3 g

vanadium/litre (Hamada, 1998). The vanadium content of
water from the Colorado River basin (USA) ranged from
0.2 to 49.2 g/litre, with the highest levels associated
with uraniumvanadium mining (Linstedt & Kruger,
11
Table 3: Concentrations of vanadium in marine organisms.a

Concentration of vanadium
(mg/kg dry weight)
Organism
Phytoplankton
0.07290
Macroalgae
0.48.9
Ascidians
2510 000
Annelids
0.7786
Other invertebrates
The main activity where workers can be exposed to

vanadium in the United Kingdom is the cleaning of oilfired boilers and furnaces where vanadium pentoxide is a
major component of the boiler residues. It is estimated
that 1000 workers in the United Kingdom are employed
by specialist boiler maintenance contractors, although
they probably spend less than 20% of their time cleaning
oil-fired boilers. Measured vanadium exposures (total
inhalable fraction) can approach 20 mg/m3 (during task),
but can be lower than 0.1 mg/m3. The lowest results are
obtained where wet cleaning methods are used. Respiratory protective equipment is usually worn during boiler
cleaning operations.
0.00445.7
Fish
0.083
Mammals
<0.011.04 (fresh weight)
From Miramand & Fowler (1998).
were 0.87, 4.77, and 17.2 g/g and kidney concentrations

were 0.43, 2.38, and 4.63 g/g for water concentrations of
0.72, 43.4, and 82.7 g/litre, respectively. In all cases,
muscle concentrations were low and did not differ
between areas (0.0160.024 g/g) (Hamada, 1998). A
pooled sample of 279 larval razorback sucker (Xyrauchen
texanus) from the Green River in Utah, USA, showed a
vanadium concentration of 1.7 mg/kg dry weight. The
Green River receives irrigation drainage and typically
shows higher concentrations of a range of elements
compared with the input streams (Hamilton et al., 2000).
Handling of catalysts in chemical manufacturing

plants is carried out by specialist contractors. Fewer
than 50 workers in the United Kingdom are exposed to
vanadium pentoxide during such activities. Exposure
depends on the type of operations being carried out.
During the removal and replacement of the catalyst,
exposures can be between 0.01 and 0.67 mg/m3. Sieving
of the catalyst can lead to higher exposures, and results
of between 0.01 and 1.9 mg/m3 (total inhalable vanadium)
have been obtained. Air-fed respiratory protective
equipment is normally worn during catalyst removal and
replacement and sieving.
A single study detected vanadium in 19 out of

120 canvasback ducks (Aythya valisineria) wintering in
Louisiana, USA; the maximum concentration in duck
liver was 0.94 g/g dry weight (Custer & Hohman, 1994).
The mean vanadium concentration in four species of
Japanese waterfowl ranged from 3.69 to 8.11 g/g dry
weight in kidney and from 0.39 to 3.69 g/g in liver tissue
(Mochizuki et al., 1999).
6.1.4
Human exposure
The quantitative data available to the authors of

this document are restricted mainly to the occupational
environment (HSE, in press). Information on control
measures has been derived from industry sources in the
United Kingdom.
1.54.7
Zooplankton
6.2
Fewer than 200 workers in the United Kingdom are

exposed to vanadium during the manufacture of
ferrovanadium alloys and TiBAl rod. The limited
exposure data available indicate exposures below the
limit of detection of 0.01 mg/m3. No data have been
found to quantify exposures during the manufacture of
TiBAl rod.
Soil
At distances of 6002400 m from a metallurgical

plant producing vanadium pentoxide, to a depth of
10 cm, the surface layer of the soil contained 18136 mg
vanadium/kg dry weight (Lener et al., 1998). The background concentration for the area is not stated, although
levels at 600 m from the plant are clearly elevated compared with those at greater distances. Concentrations in
soil globally are very variable. Schacklette et al. (1971)
found concentrations in soils in the USA ranging from
<7 to 500 mg/kg, with the median at around 60 mg/kg and
the 90th percentile at 130 mg/kg. The average worldwide
soil concentration is around 100 mg/kg (Hopkins et al.,
1977).
There are fewer than 50 workers who are exposed

to vanadium compounds in the United Kingdom during
the manufacture of vanadium-containing pigments for
the ceramics industry. Exposure is controlled by the use
of local exhaust ventilation, and measured data indicate
that levels are normally below 0.2 mg/m3 (total inhalable
fraction).
Occupational exposure data are also available from
Finland, including personal monitoring data from a range
of work processes in a vanadium refining plant (Kiviluoto, 1981). Generally, two samples were taken per person
over a 2-month period. The mean respirable fraction
12
Table 4: Biological monitoring studies of occupational vanadium exposure.

Sample
matrix
No. of subjects
Measured air V
(mg/m3) (TWA)
Urine V (g/litre)
(range)
V 2O5 production
Urine
58
Up to 5
28.3 (3762)
Boiler cleaning
Urine
2.318.6
(0.16.3)
210.5
White et al., 1987
Incinerator workers
Urine
43
Not known
<0.12
Wrbitsky et al., 1995
Boiler cleaners
Urine
10 (!RPE)
10 (+RPE)
Not known
92 (20270)
38
Todaro et al., 1991
Boiler cleaners
Urine
30
0.0488.7
(0.1322)
V alloy production
Urine
Not known
3.6 (0.58.9)
Arbouine, 1990
Pigment
manufacture
Urine
Not known
2.3 (0.86.3)
Arbouine, 1990
V 2O5 staining
Urine
(<0.040.13)
<4124
Kawai et al., 1989
Unexposed (general
population)
Urine
213 012
0.22 (0.070.5)
<0.4
<0.1
Kucera et al., 1992

White et al., 1987
Smith, 1992
Industry
Reference
Kucera et al., 1992
Smith et al., 1992
RPE = respiratory protective equipment.
(particle size 5 m or less) of the dust was 20%. The

highest values (expressed as total inhalable vanadium)
were obtained in the laboratory (range 0.254.7 mg/m3,
mean shift length exposure 1.7 mg/m3) and the smelting
room (0.0550.47 mg/m3, mean 0.21 mg/m3), but were
usually much lower for other processes (around 0.002
0.18 mg/m3, mean 0.0050.037 mg/m3).
to a vanadium slag processing plant in the Czech

Republic showed concentrations ranging from 0.01 to
0.44 g/litre; the local municipal supply contained
0.01 g/litre (Lener et al., 1998). Groundwater in the
vicinity of Mount Fuji in Japan contains high vanadium
levels from leaching of larval flows rich in the metal;
measured concentrations in deep wells were between 89
and 147 g/litre, levels higher than those measured in
spring water (Hamada, 1998). A sample of drinking-water
from Kanagawa Prefecture in Japan contained a
vanadium concentration of 22.6 g/litre, the highest
value in a survey of Japanese cities and 21 cities in the
USA (Tsukamoto et al., 1990). The water here was
influenced by Mount Fuji groundwater. Groundwater in
the region of Mount Etna in Sicily has been used as a
source of drinking-water. The western basin showed the
highest levels of vanadium; 33% of samples had concentrations between non-detectable and 20 g/litre, 54%
between 20 and 50 g/litre, and 13% higher than 50 g/litre (Giammanco et al., 1996). Older studies summarized in
IPCS (1988) report drinking-water concentrations up to
70 g/litre, although the majority of samples contained
less than 10 g/litre, and in many the metal was
undetectable. Levels in bottled waters from mineral
springs may contain much higher levels of vanadium;
one study of bottled waters from Switzerland reported a
range of 4290 g/litre (Schlettwein-Gzell & MommsenStraub, 1973).
Biological monitoring studies of occupational

vanadium exposure also indicate the magnitude of
airborne exposures (Table 4). A further recent example is
detailed (Kucera et al., 1992, 1994, 1998; see also sections
7 and 9): a group of workers from the Czech Republic
involved in the manufacture of vanadium pentoxide from
slag rich in vanadium for periods of 0.533 years (mean
duration of exposure 9.2 years) was exposed to airborne
vanadium concentrations of 0.0164.8 mg/m3. Urinary
vanadium content was 3.02769 ng/ml, compared with
0.06653.4 ng/ml in controls. In blood, vanadium levels
were 3.1217 ng/ml, compared with 0.0320.095 ng/ml in
controls. The vanadium content in the hair of exposed
and non-exposed persons was in the range of 0.103203
mg/kg and 0.0093.03 mg/kg, respectively, and the
vanadium content in the fingernails was in the range of
0.260614 mg/kg and 0.01716.5 mg/kg, respectively.
Determinations of the vanadium content were carried out
by both radiochemical and instrumental neutron
activation analyses in all instances.
Estimates given in IPCS (1988) for total dietary
intake of the general population in food range from 11 to
30 g/day (adults). The mean vanadium concentration in
drinking-water in Cleveland, USA, was 5 g/litre, with a
maximum of 100 g/litre (Strain et al., 1982). Wells close
The mean concentration of vanadium in cigarettes

was 1.11 0.35 g/g, and the mean concentration in
cigarette smoke was 0.33 0.06 g/g (Adachi et al., 1998).
13
Following the major contamination of the marine

environment with oil in the Gulf War, levels of vanadium
in seafood (six species of fish and two species of shrimp)
were measured. Mean daily consumption of seafood by
people in five districts of Kuwait ranged from 0.15 to 1.16
g seafood/kg body weight; the mean vanadium content
of seafood edible tissues ranged from 0.48 to 1.48 g/g
dry weight (Bu-Olayan & Al-Yakoob, 1998).
Oral studies (Parker & Sharma, 1978; Conklin et al.,

1982; Ramanadham et al., 1991; summarized by HSE, in
press) indicate that vanadium compounds are poorly
absorbed from the gastrointestinal tract (approximately
3% of the administered dose).
No dermal studies are available.
Absorbed vanadium in either pentavalent or tetravalent states is distributed mainly to the bone (around
1025% of the administered dose 3 days after administration) and to a lesser extent to the liver (about 5%),
kidney (about 4%), and spleen (about 0.1%), while small
amounts are also detected in the testes (about 0.2%)
(Sabbioni et al., 1978; Ramanadham et al., 1991; Sanchez
et al., 1998; HSE, in press). Distribution studies in which
rats received a total of approximately 224 and 415 mg
vanadium pentoxide/kg in drinking-water over a period of
1 and 2 months indicated that the vanadium content
(assessed in 13 specific tissues) was greatest in the
kidneys, spleen, tibia, and testes (Kucera et al., 1990).
Similar distribution was seen in a study conducted using
vanadyl sulfate (tetravalent vanadium) (Kucera et al.,
1990). Further evidence for the distribution of vanadium
to testes comes from genotoxicity studies in germ cells
(section 8.7) and reproductive studies (section 8.8).
7. COMPARATIVE KINETICS AND

METABOLISM IN LABORATORY ANIMALS
AND HUMANS
Human exposure data suggest that vanadium

(chemical form unknown) is absorbed following inhalation exposure to 0.030.77 mg vanadium/m3 and is subsequently excreted via the urine with an initial rapid
phase of elimination, followed by a slower phase, which
presumably reflects the gradual release of vanadium from
body tissues (Kiviluoto et al., 1981a).
Following oral administration of 50125 mg/day,
ammonium vanadyl tartrate (tetravalent vanadium) is
poorly absorbed from the gastrointestinal tract in
humans (Dimond et al., 1963). Less than 1% of the
administered dose was eliminated in the urine within the
first 24 h post-administration. No other information is
available in humans.
The main route of vanadium excretion is via the

urine (HSE, in press). Following oral (drinking-water)
administration of vanadyl sulfate (tetravalent vanadium),
the half-time for elimination via urine in rats was calculated to be around 12 days (this is in contrast to the
initial short half-time seen in humans, presumably
reflecting post-exposure clearance from the bloodstream,
followed by a more gradual release from other body
compartments). The pattern of vanadium distribution
and excretion indicates that there is potential for
accumulation and retention of absorbed vanadium,
particularly in the bone. One oral study in which groups
of 22 pregnant mice received vanadyl sulfate
pentahydrate at doses of 0, 38, 75, or 150 mg/kg body
weight per day by oral gavage (Paternain et al., 1990)
indicates that tetravalent vanadium has the ability to
cross the placental barrier to the fetus.
Groups of two rats were exposed to ammonium

metavanadate (pentavalent vanadium, median mass
aerodynamic diameter [MMAD] 0.32 m) at a concentration of 2 mg/m3 for 8 h/day for 4 days (Cohen et al.,
1996b). There was a tendency for vanadium to accumulate in the lung; lung levels increased by around 44%
over the first 2 days, followed by an additional 10% on
each of days 3 and 4. Twenty-four hours after the final
exposure, lung vanadium levels decreased by about 39%
(from 27 to 17 g/g lung).
Intratracheal studies in animals (Oberg et al., 1978;
Conklin et al., 1982; Rhoads & Sanders, 1985; Sharma et
al., 1987) indicate that vanadium, from either vanadium
pentoxide or other pentavalent and tetravalent vanadium
compounds, is absorbed to a significant extent from the
lungs. Following intratracheal instillation of 40 g
vanadium pentoxide, 72% of the administered dose was
absorbed from the lungs within 11 min (Rhoads &
Sanders, 1985). The remaining 28% was absorbed over 2
days. Forty per cent of the administered dose was
retained within the carcass after 14 days (12% in bones),
and 40% was eliminated via urine and faeces. Similar
results were obtained by the other authors.
8. EFFECTS ON LABORATORY
MAMMALS AND IN VITRO TEST SYSTEMS
Where data on vanadium pentoxide are lacking,

information on properties of other pentavalent or tetravalent vanadium compounds is utilized. There is no
toxicological information on elemental vanadium and
negligible information on the trivalent forms.
14
In this section, reference is made to a review of the

toxicity of vanadium compounds (including vanadium
pentoxide) by Sun (1987). However, it has not been
possible to trace the majority of the primary references
from which the review is constructed, and so it has not
been possible to perform a critical evaluation of the
quality of the information presented.
8.1
Single exposure
8.1.1
Vanadium pentoxide
and decreased sensitivity to pain. At the highest doses

(not clearly defined), intense diarrhoea, irregular respiration, and increased cardiac rhythm and ataxia were
reported. The effects had mostly disappeared in survivors at 48 h after treatment. No histopathology was
performed.
The MAK (1992) review cites rat oral LD 50 values
in the range 18160 mg/kg body weight for ammonium
metavanadate. No further details are available.
An oral LD 50 value of 75 mg/kg body weight in
male mice was reported for sodium metavanadate (Llobet
& Domingo, 1984). No deaths were reported at 41 mg/kg
body weight. Clinical signs of toxicity reported were the
same as those seen in rats.
The one acute inhalation study available reported

an LC67 of 1.44 mg/litre (1440 mg/m3) following a 1-h
exposure of rats to vanadium pentoxide dust (US EPA,
1992). Additional inhalation data are cited in the MAK
(1992) review. Two out of four rabbits exposed to
205 mg/m3 for 2 h (30% of particles had a diameter less
than 5 m) died within 1224 h. Clinical signs of toxicity
included respiratory distress, mucosal irritation
(tissues unstated), and diarrhoea.
8.1.3 Tetravalent vanadium compounds

An oral LD 50 value of 448 mg/kg body weight in
male rats exposed to vanadyl sulfate pentahydrate was
reported (Llobet & Domingo, 1984). No deaths were
reported at 296 mg/kg body weight. Signs of toxicity
were similar to those reported following treatment with
sodium metavanadate, although to a lesser degree.
Further information relating to single inhalation

exposures is presented in section 8.3. No information on
single exposures via the dermal route is available.
Oral studies in rats and mice demonstrate greater
toxicity of vanadium as oxidation state increases. The
review by Sun (1987) cites a study by Yao et al. (1986b)
in which rat oral LD 50 values for vanadium pentoxide in
the range 86137 mg/kg body weight are reported.
Clinical signs of toxicity included lethargic behaviour,
lacrimation, and diarrhoea, and histological examination
revealed necrosis of liver cells and cloudy swelling of
renal tubules. The doseresponse characteristics of
these effects were not described.
For mice, the oral LD 50 value reported for vanadyl

sulfate pentahydrate was 467 mg/kg body weight (Llobet
& Domingo, 1984). No deaths were reported at 186 mg/kg
body weight. Clinical signs of toxicity reported were the
same as those seen in rats.
A study by Paternain et al. (1990) investigating
developmental toxicity in mice reported an LD 50 for
vanadyl sulfate pentahydrate of 450 mg/kg body weight.
8.1.4
A further review of vanadium pentoxide cites oral

LD 50 values of around 10 mg/kg body weight for rats and
23 mg/kg body weight for mice (MAK, 1992). No further
details are available.
The MAK (1992) review cites a rat oral LD 50 value

of 350 mg/kg body weight and a mouse LD 50 value of
around 23 mg/kg body weight for vanadium trichloride
and a mouse oral LD 50 of 130 mg/kg body weight for
vanadium trioxide. No further details are available.
For mice, oral LD 50 values for vanadium pentoxide

were in the range 64117 mg/kg body weight (Yao et al.,
1986b). Similarly, an oral LD 50 of 64 mg/kg body weight
for vanadium pentoxide administered to male rabbits was
reported. For both rabbits and mice, the signs of toxicity
reported were the same as those observed in rats.
8.1.2
Trivalent vanadium compounds
8.2
Irritation and sensitization
No information is available from animal studies

with regard to the potential of vanadium compounds to
induce skin or eye irritation.
Other pentavalent vanadium compounds

The primate inhalation studies by Knecht et al.
1992 (see section 8.3) also included an unconventional
evaluation of skin sensitization; this investigation gave a
negative response for immediate and delayed skin
reactions to vanadium only or in combination with a
carrier protein.
Groups of 10 male rats received aqueous sodium

metavanadate by gavage (Llobet & Domingo, 1984). The
LD 50 value reported was 98 mg/kg body weight. No
deaths were reported at 39 mg sodium metavanadate/kg
body weight. Clinical signs of toxicity reported were
decreased locomotor activity, paralysis of the hind legs,
15
8.3
Effects of inhaled vanadium

compounds on the respiratory tract
the percentage rise in nitrogen at 25% vital capacity (VC;

167% of baseline values), an indication of narrowing of
the dependent, peripheral small airways. No significant
changes were reported in forced vital capacity (FVC),
total lung capacity (TLC), or diffusion capacity for
carbon monoxide (DL50), indicating the absence of
parenchymal dysfunction. However, although
statistically significant, the magnitude of the observed
changes was small.
Presumably owing to the serious nature and rapid

onset of the respiratory effects that have been observed
in humans in occupational settings (see also section 9),
the following series of single and repeated inhalation
studies was conducted in an attempt to further elucidate
the possible mechanisms and doseresponse relationships.
BAL analysis revealed statistically significant

increases in numbers of polymorphonuclear leukocytes
and decreases in mast cells following exposure to 5.0 mg
vanadium pentoxide/m3. Numbers of macrophages and
lymphocytes were unaltered by exposure.
A study by Knecht et al. (1985) investigated

pulmonary responses to inhaled vanadium pentoxide
dust and sodium vanadate aerosols (thought to contain
the polymeric vanadium species most likely to be present
in the respiratory mucosa after inhalation of vanadium
pentoxide) in a group of 16 cynomolgus monkeys. The
study design attempted to simulate exposure patterns
and their consequences in humans. Animals were given
sequential exposures to 0, 19, and 39 mg vanadium/m3 in
the form of sodium vanadate aerosol (characteristics not
reported) for 1 min, at 30-min intervals (duration unclear).
Two weeks later, the animals were exposed, whole body,
to 0.5 and then to 5.0 mg vanadium pentoxide dust/m3
(0.28 and 2.8 mg vanadium/m3; particle size 0.590.61 m)
for 6 h, with a 1-week interval between the two
exposures. Pulmonary function was evaluated before
any exposures began and then immediately after
exposure to sodium vanadate and 1821 h after exposure
to vanadium pentoxide. The reason for this pattern of
investigating was that experience in humans suggested
that respiratory effects had appeared approximately 1
day after exposure to vanadium pentoxide; the
pulmonary investigations made immediately after sodium
vanadate exposure were explained on the basis that it
was known that inhalation of soluble zinc salt can
produce an immediate irritant response. Bronchoalveolar
lavage (BAL) was performed pre-exposure and following
exposure to 5.0 mg vanadium pentoxide/m3.
Another study in monkeys by Knecht et al. (1992)

compared bronchial reactivity following challenge with
vanadium pentoxide dust, both before and after subchronic exposure to vanadium pentoxide dust. Both
before and after subchronic exposure, the animals
underwent 6-h whole-body challenges with vanadium
pentoxide aerosol (stated to be generally 15 micrometres) at concentrations of 0.5 and 3.0 mg/m3 (0.28 and
1.68 mg vanadium/m3), separated by a 2-week interval.
Two weeks later, the animals were challenged with
methacholine to assess non-specific bronchial reactivity.
The subchronic exposure regime involved exposure to
vanadium pentoxide 6 h/day, 5 days/week, for 26 weeks.
Two vanadium pentoxide-exposed groups (n = 9 each)
received equal weekly exposures (concentration time)
with different exposure profiles. One vanadium
pentoxide-exposed group received a constant
concentration of 0.1 mg/m3 (0.06 mg vanadium/m3) for
3 days/week and an exposure at a constant
concentration of 1.1 mg/m3 (0.62 mg vanadium/m3) for 2
days/week. The other vanadium pentoxide-exposed
group received a constant daily concentration of 0.5
mg/m3. A control group (n = 8) received filtered,
conditioned air. The animals were allowed a 2-week
recovery period before being retested as before.
Evidence of slight impairment of pulmonary function was reported following the single 6-h inhalation of
5.0 mg vanadium pentoxide dust/m3, but not 0.5 mg/m3.
This was based on statistically significant decreases in
peak expiratory flow rate (PEFR; median 89% of baseline
values), forced expiratory volume (FEV0.5; 95% of
baseline values), and forced expiratory flow (FEF 50; 92%
of baseline values), these changes giving an indication
of airflow limitation in the large central airways; a statistically significant decrease in FEF 25 (77% of baseline
values), which gives an indication of airflow limitation in
the peripheral airways; and statistically significant
increases in functional residual volume (FRV; 124% of
baseline values), residual volume (133% of baseline
values), closing volume (127% of baseline values), and
Blood cytological and immunological analysis was

carried out before both sets of acute challenges with
vanadium pentoxide. Pulmonary function testing was
carried out pre-exposure, the day after each acute
challenge with vanadium pentoxide, and immediately
after challenge with methacholine. BAL fluid was
collected for cytological and immunological analysis
before each series of challenges and after challenge with
3.0 mg/m3.
Respiratory distress developed in three monkeys
from the subchronic exposure group, which received the
intermittent peaks of 1.1 mg vanadium pentoxide/m3,
characterized by audible wheezing and coughing, which
16
8.4.1
occurred only on peak exposure days during the first few

weeks of exposure. Pre-subchronic exposure
provocation challenges with vanadium pentoxide
produced statistically significant changes in average
flow resistance (RL; mean, 103% and 114% of baseline
values at 0.5 and 3.0 mg/m3, respectively) and FVC (96%
and 97% of baseline values, respectively) at both dose
levels used, while statistically significant differences
were observed only at 3.0 mg/m3 for FEF 50/FVC (99% and
87% of baseline values, respectively) and residual
volume (RV; 105% and 114% of baseline values,
respectively), which indicates an obstructive pattern of
impaired pulmonary function. No statistically significant
change in dynamic compliance (CLdyn) was observed.
Short-term immunotoxicity studies are described

briefly in section 8.9.1.
8.4.2
Groups of 10 male rats received 0, 5, 10, and

50 ppm (mg/litre) sodium metavanadate in drinking-water
for 3 months, which corresponded to 0, 2.1, 4.2, and 21
ppm vanadium. This intake was equivalent to about 0,
0.3, 0.6, and 3 mg sodium metavanadate/kg body weight
per day, assuming 350 g body weight and 20 ml/day
water consumption (Domingo et al., 1985). Limited
numbers of animals were selected for liver and renal
function tests and organ weight analysis (liver, kidneys,
heart, spleen, and lungs only). Histological examination
was performed on only three animals of each group.
At the second challenge, after subchronic exposure, the pattern of findings was similar to that from the
first challenge, but none of the changes was statistically
significantly different from baseline values, nor was
there any statistically significant difference between the
controls, the peak exposure group, or the constant
group. Large, statistically significant increases in RL and
FEF 50/FVC were observed following challenge with
methacholine, but this reactivity was not significantly
increased following subchronic exposure to vanadium
pentoxide.
There was no effect on weight gain, consumption

of water, urine volume, or urinary protein levels during
the treatment period. No significant difference was
reported in the relative organ weights of the groups.
Plasma concentrations of urea, uric acid, and creatinine
were reported to be within the normal range for all
groups of animals, except in 50 ppm animals, in which
urea and uric acid values were significantly greater than
in concurrent controls. No effect on liver function was
apparent from the results. Dose-dependent histological
changes, including hypertrophy and hyperplasia in the
white pulp of spleen, corticomedullary microhaemorrhagic foci in kidneys, and mononuclear cell infiltration,
mostly perivascular, in lungs, were apparent in all treated
animals. Hence, no no-observed-adverse-effect level
(NOAEL) could be derived from this study, although
changes at the lowest exposure level were considered by
the authors to be minimal.
A significant increase in the total number of

respiratory cells in BAL fluid was observed following
pre-subchronic exposure challenge with 3.0 mg vanadium pentoxide/m3. The increase in the total number of
cells occurred through a highly significant increase in
the number of neutrophils (393% of baseline values).
The number of eosinophils recovered from the lung was
also increased (170% of baseline values), while the
numbers of lymphocytes, macrophages, and mast cells
were not. Significant challenge responses were not
observed for total protein, albumin, leukotriene C4, or the
immunoglobulins IgG and IgE, despite the significant
cellular response to vanadium pentoxide challenge. A
similar pattern of cellular and immunological response
was observed after subchronic exposure. Post-exposure
challenge responses for neutrophils were greater than
400% of baseline values. A post-exposure trend
(statistically significant for eosinophils) towards
decreased responses was observed in the vanadium
pentoxide-exposed groups as compared with the control
group. The number of circulating neutrophils and
eosinophils in venous blood was not affected by subchronic vanadium pentoxide exposure. Similarly, serum
immunoglobulins were unchanged throughout the
study.
8.4
Vanadium pentoxide
Groups of eight male rats were administered 0 or

about 9.7 mg vanadium/kg body weight per day as
ammonium metavanadate via the drinking-water for
12 weeks (Dai et al., 1995). Before the start of the study
and at weeks 1, 2, 4, 8, and 12 following vanadium treatment, haematological indices (haematocrit, haemoglobin
concentration, erythrocyte count, leukocyte count,
platelet count, reticulocyte count, and erythrocyte
osmotic fragility) of the peripheral blood were investigated in all animals. There were no other investigations.
No difference in food intake or body weight was apparent between the groups. There were no differences in
haematological parameters between the groups.
Groups of 1516 male and female rats were administered 0, 1.5, or 56 mg vanadium/kg body weight per
day as ammonium metavanadate in drinking-water for
4 weeks (Zaporowska et al., 1993). No differences in
Other short-term exposure studies
Oral studies are described below; no dermal

studies are available.
17
external appearance or locomotor behaviour were

reported between the groups. Body weight increase in
the treated groups was lower than in control animals, but
this was not dose-related. Slight, but statistically significant, decreases in erythrocyte number and haemoglobin
concentration (top dose only, all about 10% less than
control) were observed. Similarly, a slight but statistically significant decrease in haematocrit was reported
in treated males (mean value was 98% of controls). No
significant differences in leukocyte numbers were
reported between the groups. No clinically significant
changes in biochemical parameters were reported.
Overall, the changes were slight.
the reduction in total distance travelled could have been

related to other factors such as palatability that may
have affected behaviour and movement. Also, given the
extremely limited range of observations, substantial
interindividual variation, and absence of histopathology,
it is impossible to draw any firm conclusions from this
study.
8.4.3
Tetravalent vanadium compounds
As previously described for sodium metavanadate

(section 8.4.2), Dai et al. (1995) also investigated the
potential effect of 7.7 mg vanadium/kg body weight per
day as vanadyl sulfate (+4) and 9.2 mg vanadium/kg
body weight per day in the form of bis(maltolato)oxovanadium (+4) on haematological parameters. No
difference in food intake or body weight was apparent
between the groups (control and vanadium in valency
states +4 and +5). There were no differences in haematological parameters between the groups.
Groups of 1213 male and female Wistar rats were

administered 0 or about 13 mg ammonium metavanadate/
kg body weight per day in drinking-water for 4 weeks
(Zaporowska & Wasilewski, 1992). Investigations
included water and food consumption, body weight, and
a range of haematological parameters; there were no
further investigations conducted.
There was a marked decrease in water consumption
with concomitant decreases in food consumption and
body weight gain. Although there were statistically
significant reductions in some of the haematological
parameters measured (as above), it is impossible to draw
any conclusions regarding the toxicological significance
due to the limited study design and confounding due to
impaired water consumption (which may have been
related to unpalatability).

8.5
Medium-term exposure
8.5.1
Vanadium pentoxide and other

pentavalent vanadium compounds
Medium-term oral and dermal exposures to

vanadium pentoxide have not been studied.
Groups of 12 male Sprague-Dawley rats received 0,

4, 8, or 16 mg aqueous sodium metavanadate/kg body
weight per day by oral gavage for 8 weeks (Sanchez et
al., 1998). Investigations were limited to body weight,
open field activity, avoidance of electrical stimulus
(recorded over a 3-week period, starting after the 8-week
treatment period), and a limited range of tissues removed
for analysis of vanadium content (see section 7).
Groups of six male rats received 0, 10, or 40 g/ml

as sodium metavanadate (about 0, 0.6, or 2.4 mg/kg body
weight per day, assuming 20 ml water consumed per day
and 350 g body weight) in drinking-water for 210 days
(Boscolo et al., 1994). In the second experiment, groups
of six male rats received 0 or 1 g sodium
metavanadate/ml (approximately 0.06 mg/kg body weight
per day using the same assumptions) in drinking-water
for 180 days. Investigations included urinalysis,
haemodynamic measurements, and histopathology.
Reduced body weight gain was noted only at

16 mg/kg body weight per day (20% lower than
controls). There was no observable effect on rearing
counts. However, a statistically significant reduction in
total distance travelled in the open field activity
investigation (recorded 3 weeks after cessation of
treatment only) was recorded in the first 5 min at 8 and 16
mg/kg body weight per day, but not at 510 or 10
15 min. Decreased avoidance compared with controls
was noted among all vanadium-exposed animals over
3 consecutive days, although there was no clear dose
response relationship and no indication of other results
for the 3-week testing period. Hence, this would seem to
be a rather selective presentation of results. There was
no discussion of whether or not the transient nature of
No treatment-related effect on cardiovascular

function was reported. Histopathological investigation
showed no change in the brain, liver, lungs, heart, or
blood vessels of treated animals. An increase (5 times
greater than controls) in urinary kininase I (measured to
assess arterial hypertension) and II (twice control
values) activities was reported in treated rats at 40 g/ml,
although the significance of this is unclear. No effect
was reported on urinary excretion of creatinine, total
nitrogen, protein, or sodium. Urinary potassium
decreased with dose, whereas urinary calcium was
18
reduced at 10 g/ml only. Again, this study did not

reveal any clearly toxicologically significant changes
attributable to vanadium exposure.
8.7.1.2
8.5.2
8.7.1.3
There are no data available.
Long-term exposure and

carcinogenicity
8.6.1
Vanadium pentoxide and other

pentavalent vanadium compounds
8.7.1.4
In a study conducted by Yao et al. (1986a) and

cited by Sun (1987), groups of 6284 male and female
mice were exposed to 0, 0.5, 2, or 8 mg vanadium
pentoxide dust/m3 (particle size not reported) for 4 h/day
for 1 year. Papillomatous and adenomatous tumours in
the lungs were reported in 2 of 79 and 3 of 62 mice at 2
and 8 mg/m3, respectively. No tumours were reported in
controls or at 0.5 mg/m3. No further information is
available.
Long-term inhalation and dermal exposures to

tetravalent vanadium compounds have not been studied.
8.7.1
Studies in prokaryotes
8.7.1.1
Vanadium pentoxide
In vitro studies in eukaryotes
8.7.2.1
Vanadium pentoxide
Mitotic index was statistically significantly

decreased (74, 41, and 42% of control value at 2, 4, and 6
g/ml, respectively). The frequency of structural chromosome aberrations did not increase in the presence of
vanadium pentoxide. However, a statistically significant
increase in the frequency of polyploid cells was reported
at all dose levels, which did not show a clear dose
response relationship (4/226, 10/224, 8/200, and 10/218,
respectively). This study also reported a dose-related
increase in the number of cells with satellite associations (a tendency for satellite-bearing chromosomes to
lie side by side, with their satellite regions facing each
other). This finding, along with the induction of polyploidy, is indicative of vanadium pentoxide exerting its
effects at the level of spindle formation.
As part of a study related to the investigation of

diabetes, groups of 823 male Wistar rats received
approximately 0, 34, 54, or 90 mg vanadyl sulfate/kg body
weight per day in drinking-water for up to 52 weeks (Dai
& McNeill, 1994; Dai et al., 1994a,b). Investigations were
extensive and included blood biochemistry,
haematology, blood pressure and pulse rate,
ophthalmoscopy, organ weights, and microscopic
pathology. The only adverse effect observed was
reduced body weight gain (around 33% reduction at
90 mg/kg body weight per day and 10% at 34 and
54 mg/kg body weight per day).
Genotoxicity and related end-points
8.7.2
Vanadium pentoxide was added, at concentrations

of 0, 2, 4, and 6 g/ml (0, 1, 2, and 3 g vanadium/ml), in
replicate experiments, to cultures of human lymphocytes
(Roldan & Altamirano, 1990). Cells were incubated in the
absence of metabolic activation with vanadium
pentoxide for 48 h. A minimum of 100 well-spread firstdivision metaphases were analysed for structural and
numerical aberrations (polyploid only).
8.7
One Ames test has been performed with vanadium

(+3) trichloride. Negative results were obtained, in the
presence and absence of metabolic activation, at concentrations between 1 and 200 g/plate with Salmonella
typhimurium strains TA98, TA100, TA1535, TA1537,
and TA1538 and Escherichia coli WP2uvrA (JETOC,
1996).
Long-term oral and dermal exposures to vanadium

pentoxide and other pentavalent vanadium compounds
have not been studied.
8.6.2

8.6
The potential of vanadium pentoxide exposure to

induce micronuclei and centromere-positive micronuclei
in vitro was investigated in Chinese hamster V79 cells, in
the absence of metabolic activation (Zhong et al., 1994).
Studies of cytotoxicity were performed in cells exposed
to concentrations of vanadium pentoxide up to 12 g/ml
(6.7 g vanadium/ml) for 24 h. In each group, the
numbers of mononucleated and binucleated cells per
1000 cells were determined for cell cycle kinetics. The
investigation of centromere-positive micronuclei was
Only very limited data are available (see section

8.7.7).
19
Significant increases were reported in the numbers

of chromosome aberrations (excluding gaps) induced
compared with solvent control values in both the
presence and absence (up to 8 times controls in each
case) of metabolic activation. The positive controls gave
appropriate responses.
performed in cells cultured with vanadium pentoxide

concentrations of 0, 1, 2, or 3 g/ml (0, 0.6, 1.1, or 2.2 g
vanadium/ml) for 24 h. Binucleated cells were scored and
numbers of micronuclei determined.
Cytotoxic effects of vanadium pentoxide, as
defined by a reduced number of binucleated cells, were
apparent at all doses. A dose-related, statistically
significant increase in micronucleus induction was
reported at all vanadium dose levels tested (2.4, 4.2, 6.2,
and 7.6% of cells, for solvent control, 1, 2, and 3 g/ml,
respectively). This doseresponse relationship was also
observed in the numbers of centromere-positive micronuclei (49, 70, 82, and 89% of micronuclei, respectively).
Migliore et al. (1993) investigated the potential of

three pentavalent vanadium compounds sodium
metavanadate, ammonium metavanadate, and sodium
orthovanadate to induce micronuclei in human
lymphocytes in vitro. The aneugenic potential was
investigated using fluorescence in situ hybridization
(FISH), the number of micronuclei with fluorescent spots
(centromere-positive micronuclei) being reported. The
final concentrations tested were 0 and 2.5160 mol/litre
(approximately 0 and 0.138.0 g vanadium/ml) in all
experiments, apart from the study involving in situ
hybridization, where only 0, 10, 40, and 80 mol/litre
(approximately 0, 0.5, 2.1, and 4.2 g vanadium/ml) were
used. Cells were incubated with the test substances for
48 h. Two thousand binucleated cells (when possible),
100 clear first metaphases, and 25 clear second
metaphases were analysed for micronuclei.
Induction of gene mutation at the HPRT locus was

investigated following exposure of Chinese hamster V79
cells, in the absence of metabolic activation, to 0, 1, 2, 3,
or 4 g vanadium pentoxide/ml (0, 0.6, 1.1, 1.7, or 2.2 g
vanadium/ml) for 24 h (Zhong et al., 1994). No significant
increase in the frequency of gene mutation was reported
following treatment with vanadium pentoxide.
8.7.2.2
Human lymphocyte cells were incubated in the

absence of metabolic activation for 24 h with sodium
metavanadate, ammonium metavanadate, and sodium
orthovanadate at concentrations of 0, 2.5, 5, 10, 20, 40,
80, or 160 mol/litre (approximately 0, 0.138.0 g
vanadium/ml), and the induction of structural and
numerical chromosome aberrations was investigated
(Migliore et al., 1993).
The highest dose of vanadium used, 160 mol/litre,

was found to be toxic to the cells in all studies.
Ammonium metavanadate (up to 6% at the highest
dose), sodium metavanadate (up to 4.6% at the highest
dose), and sodium orthovanadate (up to 2.4% at the
highest dose) all induced a dose-related, statistically
significant number of micronuclei at 10 mol/litre and
above, although the increases were in general relatively
small. Dose-related decreases in the number of
binucleated cells were also reported for all compounds,
which could be due to general toxicity or specific
inhibition of cell cytokinesis. A dose-related increase in
the number of micronuclei was reported in the cells used
for the FISH technique, although the increases were, as
before, relatively small. Statistically significant increases
in the numbers of centromere-positive micronuclei were
reported at all dose levels for all the compounds, which
were comparable with the positive control values.
The highest dose of vanadium compounds used,

160 mol/litre, was found to be toxic to the cells in all
studies. There was no significant difference in the
incidences of chromosome aberrations (excluding gaps,
although the nature of the aberrations was not defined)
induced by any of the three compounds, for any of the
dose levels used. A statistically significant number of
hypoploid cells (missing chromosomes) was reported at
all doses following treatment with sodium metavanadate
and sodium orthovanadate and at the top two doses
with ammonium metavanadate. No significant increases
in the numbers of hyperploid or polyploid cells were
reported.
The ability of ammonium metavanadate to induce

mutations, with exogenous metabolic activation, at the
HPRT locus in V79 cells in Chinese hamster ovary was
investigated using concentrations of 0, 5, 10, 20, 25, 40,
and 50 mol/litre (Cohen et al., 1992). No treatmentrelated increase in mutation frequency was reported,
with testing up to cytotoxic concentrations of ammonium
metavanadate.
Chinese hamster ovary cells were exposed to 0, 4,

8, or 16 g ammonium metavanadate/ml (0, 1.7, 3.3, or 6.7
g vanadium/ml) for 2 h in the presence and absence of
metabolic activation, and then for a further 22 h in fresh
medium (Owusu-Yaw et al., 1990). At least 100
metaphases per flask were scored for chromosome
aberrations (experiment carried out in duplicate).
Ammonium metavanadate induced both mitotic

gene conversion and reverse point mutation in the D7
strain of Saccharomyces cerevisiae at dose levels of
20
between 80 and 210 mmol/litre in both the presence and

absence of metabolic activation (Bronzetti et al., 1990).
sulfate/litre in both the presence and absence of metabolic activation (Galli et al., 1991).
Cell transformation and gap junctional intercellular

communication were assessed in Syrian hamster embryo
cells exposed to 0, 0.2, 0.4, 1.9, 2.3, or 6.9 mol sodium
orthovanadate/litre (Rivedal et al., 1990; Kerckaert et al.,
1996). A marked increase in cell transformation was
noted only at the highest concentration, although there
were no effects on cloning efficiency, indicating a
positive result for genotoxicity in this system. There was
no observed effect on gap junctional intercellular
communication.
Vanadyl chloride did not produce an increased

incidence of transformations in the C3H10T1/2 mouse
fibroblast cell line at dose levels up to 5 g/ml (Doran et
al., 1998).
8.7.2.3
8.7.2.4
Using protocols similar to that previously ascribed

to these authors, Chinese hamster ovary cells were
exposed to 12 or 18 g vanadium oxide/ml (8.2 or 12.2 g
vanadium/ml) (Owusu-Yaw et al., 1990). Significant
increases in induction of chromosome aberrations were
reported in both the presence (up to 4 times controls)
and absence (up to 6 times controls) of metabolic
activation.
Migliore et al. (1993) also investigated the ability of

vanadyl sulfate to induce structural and numerical
chromosome aberrations in human lymphocytes in the
absence of exogenous metabolic activation. No significant difference in the incidence of chromosome aberrations (excluding gaps) was induced. A statistically
significant number of hypoploid cells was reported at the
top three doses (2080 mol/litre).
8.7.3
Sister chromatid exchange
Vanadium pentoxide did not increase incidences of

sister chromatid exchange, while studies with other
pentavalent, tetravalent, and trivalent compounds did, in
a number of different cell systems, over a range of concentrations (0.319.2 g/ml) (Owusu-Yaw et al., 1990;
Roldan & Altamirano, 1990; Migliore et al., 1993; Zhong
et al., 1994).
Owusu-Yaw et al. (1990) also exposed Chinese

hamster ovary cells to 6, 12, or 24 g vanadyl sulfate/ml
(1.9, 3.7, or 7.4 g vanadium/ml) for investigation of
chromosome aberrations. Significant increases in
induction of chromosome aberrations were reported in
both the presence (up to 6 times controls) and absence
(up to 13 times controls) of metabolic activation.
8.7.4
Other in vitro studies
8.7.4.1
Vanadium pentoxide
A study by Rojas et al. (1996) investigated the

induction of DNA strand breaks in human lymphocytes
by vanadium pentoxide using the Comet assay. At dose
levels of 0.5, 5.5, and 546 g vanadium pentoxide/ml, a
statistically significant increase in DNA migration was
reported, indicating the DNA-damaging potential of
vanadium pentoxide. There was no cytotoxicity detected.
Migliore et al. (1993) also investigated the potential

of vanadyl sulfate to induce micronuclei in human
lymphocytes. Dose-related decreases in the number of
binucleated cells were also reported, although these
were less pronounced than those observed with
pentavalent vanadium compounds. A dose-related,
statistically significant increase in the number of
micronuclei was reported at 10 mol/litre and above,
although the increases were in general relatively small.
Statistically significant increases in the numbers of
centromere-positive micronuclei were reported at all dose
levels.
8.7.4.2
Chinese hamster V79 cells and human leukaemic Tlymphocyte (MOLT4) cells were exposed to ammonium
metavanadate to investigate the formation of
DNAprotein cross-links (Cohen et al., 1992). Doserelated increases in cross-links were reported following
24-h exposure to ammonium metavanadate in both cell
types.
Vanadyl sulfate induced no convertants or revertants in the D7 strain of S. cerevisiae at dose levels of
between 420 and 1000 mmol/litre in both the presence
and absence of metabolic activation (Galli et al., 1991).
Also, no mutagenic activity was detected in hamster V79
cells at dose levels between 0 and 7.5 mmol/litre in both
the presence and absence of metabolic activation.
Ammonium vanadate gave positive results in a

transformation assay in BALB/3T3 mouse embryo cells
at doses of 5 and 10 mol/litre (Sabbioni et al., 1993).
No mutagenic activity was detected in hamster V79

cells at dose levels between 0 and 7.5 mmol vanadyl
21
8.6.4.3
Vanadyl sulfate gave negative results in a transformation assay in BALB/3T3 mouse embryo cells at
doses of 5 and 10 mol/litre (Sabbioni et al., 1993). For
this study and the above-mentioned work on ammonium
metavanadate by these authors (section 8.7.4.2), cytotoxicity, as evidenced by about a 50% reduction in
colony-forming efficiency compared with controls, was
seen at a concentration of 5 mol/litre.
Polychromatic erythrocyte/normochromatic
erythrocyte (PCE/NCE) ratios were lower in the test
animals (down to 50% of control values at some time
points), indicating that the vanadium compounds had
reached the bone marrow and expressed cytotoxicity.
Compared with negative controls, there was a small but
statistically significant increase (at least twice control
values) in the percentage of PCEs with micronuclei for
sodium orthovanadate at 24, 30, and 48 h and with
ammonium metavanadate at 18, 24, and 30 h.
8.7.5
In vivo studies in eukaryotes (somatic

cells)
8.7.5.3
8.7.5.1
Vanadium pentoxide
Ciranni et al. (1995) also investigated the ability of

vanadyl sulfate to induce chromosome aberration and
aneuploidy in the bone marrow of male mice. Male mice
were administered a single dose, intragastrically, of 0 or
100 mg vanadyl sulfate/kg body weight (0 or 31 mg vanadium/kg body weight). A statistically significant increase
in the number of aberrant cells (excluding gaps) was
found at 24 and 36 h (4.3 and 2.7%, respectively, compared with 0.6% in negative controls). Statistically significant increases in cells with hypoploidy were reported
following treatment at both sampling times and in cells
with hyperploidy 24 h post-treatment. No significant
induction of polyploidy was reported.
Only very limited data are available (see section

8.7.7).
8.7.5.2
Ciranni et al. (1995) investigated the ability of

sodium orthovanadate and ammonium metavanadate to
induce chromosome aberration and aneuploidy in the
bone marrow of male mice. Male mice (three per
experimental group or four per control group) were
administered a single dose, intragastrically, of either 0 or
75 mg sodium orthovanadate/kg body weight (21 mg
vanadium/kg body weight) or 50 mg ammonium metavanadate/kg body weight (42 mg vanadium/kg body
weight) dissolved in sterile water. Groups of animals
were sacrificed at 24 and 36 h post-dose.
Groups of male mice were administered a single

dose of 0 or 100 mg vanadyl sulfate/kg body weight (0 or
31 mg vanadium/kg body weight) intragastrically
(Ciranni et al., 1995). There was a small but statistically
significant increase (at least twice control values) in the
percentage of PCEs with micronuclei at 6, 12, 18, 24, 30,
36, and 48 h.
Although increases in chromosome aberrations

were reported after 36 h with sodium orthovanadate and
ammonium metavanadate, these were not statistically
significant. No increases were seen at 24 h. Clear and
statistically significant increases in cells with
hypoploidy and with hyperploidy were apparent at one
or both sampling times with both vanadium compounds.
Statistically significant, dose-related increases in cells
with hypoploidy were reported following treatment with
sodium orthovanadate and ammonium metavanadate.
Statistically significant increases in cells with hyperploidy were reported 24 h post-treatment with sodium
orthovanadate and at both 24 and 36 h post-treatment
with ammonium metavanadate. No significant induction
of polyploidy was reported.
8.7.6
In vivo studies in eukaryotes (germ cells)
8.7.6.1
Vanadium pentoxide
As part of a larger study (not performed to current

standard Organisation for Economic Co-operation and
Development [OECD] guidelines) to investigate other
reproductive and genotoxic end-points, a dominant
lethal-type assay was reported by Altamirano-Lozano et
al. (1996). On the basis of deaths reported following
repeated administration of 17 mg vanadium pentoxide/kg
body weight by intraperitoneal injection in a previous
study by the same authors, male mice (1520 per group)
received 0 or 8.5 mg vanadium pentoxide/kg body weight
in saline by intraperitoneal injection every third day for
60 days. From day 61, each male had five overnight
matings with two untreated females, and successful
copulation was determined by the presence of a copulation plug or sperm in the vagina.
Groups of 34 male mice were administered a single

dose, intragastrically, of either 0 or 75 mg sodium
orthovanadate/kg body weight (21 mg vanadium/kg
body weight) or 50 mg ammonium metavanadate/kg
body weight (42 mg vanadium/kg body weight)
dissolved in sterile water (Ciranni et al., 1995). Bone
marrow cells were sampled at 6, 12, 18, 24, 30, 36, 42, 48,
and 72 h post-treatment and assessed for induction of
micronuclei.
A statistically significantly reduced body weight in

treated animals at the end of the treatment period was
22
reported (79% of control value). The study did not refer

to any other signs of toxicity in male mice. Whereas 34 of
40 (85%) of the females mated with controls became
pregnant, the rate for the treated group was 33% (10/30).
There was a statistically significant reduction in implantation sites per dam for the treatment groups compared
with controls (10.9 and 5.8 in the control and treated
groups, respectively). A statistically significant increase
in the number of resorptions per litter (0.2 and 2.0 in the
control and treated groups, respectively) and a statistically significant reduction in the number of live fetuses
per litter (10.5 and 3.4 in the control and treated groups,
respectively) were apparent in the vanadium pentoxide
group. There was no statistically significant difference in
the numbers of dead fetuses per litter. Post-implantation
loss (number of dead fetuses per number of liveborn
pups) was approximately 10 times greater in the treatment
group than in controls (0.41 and 0.04, respectively).
pentoxide was tested at concentrations of 0, 10, 50, 100,

500, 1000, and 2000 g/plate in both the presence and
absence of S9. A highly significant, dose-related
increase in the number of revertants was reported at 10,
50, and 100 g/plate in strains WP2, WP2uvrA, and
CM891 in both the presence and absence of S9. Above
these dose levels, vanadium pentoxide produced
toxicity. No significant increase was reported in strains
ND-160 and MR 102.
Vanadium pentoxide did not increase incidences of
sister chromatid exchange in vitro over a range of concentrations (0.330 g/ml) (Sun, undated).
Bone marrow micronucleus tests on vanadium
pentoxide via the intraperitoneal, subcutaneous, inhalation, and oral routes in mice are briefly reported (Si et al.,
1982; Yang et al., 1986b,c; Sun et al., undated). A
statistically significant increase (approximately doubled)
in the frequency of micronucleus formation was reported
at all dose levels in mice administered 0, 0.2 (or 0.7), 2, or
6 mg vanadium pentoxide/kg body weight intraperitoneally daily for 5 days. A positive result was also
reported in mice following subcutaneous administration
of 0.25, 1.0, or 4.0 mg vanadium pentoxide/kg body
weight, 6 days/week, for 5 weeks, although no further
details were provided. An increase in the frequency of
micronuclei was reported following exposure of mice to
0, 0.5, 2.0, or 8.0 mg vanadium pentoxide dust/m3 (no
details of dust characteristics given). No increase in
induction of micronuclei was reported in mice orally
administered 1, 3, 6, or 11 mg vanadium pentoxide/kg
body weight in a 3% starch suspension for 6 weeks.
Given that vanadium pentoxide is poorly absorbed

following oral exposure and well absorbed and widely
distributed when inhaled, the use of the intraperitoneal
route in this assay is considered a valid surrogate for
relevant exposure routes in this instance. Overall, while
this study is of limited quality in view of the nonstandard protocol, poor reporting, and clearly reduced
pregnancy rate in females mated with treated males, the
clear increases in resorptions per litter and postimplantation losses in the vanadium pentoxide group are
indicative of a dominant lethal effect.
8.7.6.2
Other pentavalent and tetravalent vanadium

compounds
8.8
Reproductive toxicity
8.8.1
Effects on fertility
The following studies cited in a review prepared by

Sun (1987) have been included here as they provide
further supporting evidence of genotoxic activity of
vanadium pentoxide. However, no firm conclusions can
be drawn from the results due to the limited reporting.
8.8.1.1
Vanadium pentoxide and other pentavalent

vanadium compounds
An Ames test using S. typhimurium strains TA98,

TA100, TA1535, TA1537, and TA1538 is briefly reported
(Si et al., 1982). Vanadium pentoxide at 0, 50, 100, and 200
g/plate was tested in both the absence and presence of
S9 mix. The numbers of induced revertants at all test
levels were less than 2-fold greater than control
numbers; hence, vanadium pentoxide gave a negative
result under the conditions of the test.
Groups of 24 male mice received sodium metavanadate in drinking-water for 64 days at concentrations
of 0, 20, 40, 60, or 80 mg/kg body weight per day (Llobet
et al., 1993). At the end of the exposure period, each
group was divided into two subgroups: a group of
8 animals for a mating trial and a group of 16 animals for
pathology and sperm examinations (utilizing postmortem
samples). In the fertility study, each male was mated with
two untreated females for 4 days. The females were
sacrificed 10 days after the end of the mating period and
their uterine contents examined.
8.7.7
Supporting data
No fertility studies are available on vanadium

pentoxide.
In an E. coli reversion assay using strains WP2,

WP2uvrA, CM891 (base pair substitutions), ND-160, and
MR 102 (frameshift mutations) (Si et al., 1982), vanadium
23
A 13% reduction in male body weight was apparent in the 80 mg/kg body weight group, compared with
the controls, immediately after the exposure period.
Decreases relative to the controls in the number of
pregnant females were reported in some of the vanadium-treated group, but no doseresponse relationship
was observed. No information was given on mating
behaviour. There were no significant differences
between the groups regarding the numbers of implantations, early or late resorptions, or dead or live fetuses.
In males, no significant differences were observed in
testes weights. Absolute epididymis weight was reduced
at 80 mg/kg body weight (88% of control value),
although no difference was observed in relative weight,
reflecting the reduced body weight in animals of this
dose group. A significant 30% reduction in spermatid
count was reported at 80 mg/kg body weight, and a
significant decrease in spermatozoal count was reported
at 60 and 80 mg/kg body weight, although this was not
clearly dose-related (99%, 104%, 56%, and 69% of
control values in the 20, 40, 60, and 80 mg/kg body
weight groups, respectively). There were no significant
differences in sperm motility or sperm abnormalities
between the groups. No histopathological changes were
reported between the groups.
Statistically significant decreases in maternal body

weight gain were reported in animals of the 9 and
18 mg/kg body weight groups (75% and 40% of control
values, respectively). No treatment-related increases in
the numbers of resorptions or dead fetuses were
observed, although the results were not reported on a
per litter basis. Fetal body weight, body length, and tail
length were all statistically significantly decreased in the
top dose group (87%, 92%, and 94% of control values,
respectively).
Delayed occipital ossification (top-dose animals)
and non-ossification or delayed ossification of the
sternum (all dose groups) were reported; however, these
results were not given on a per litter basis, and so their
significance is unclear. It was also observed that skeletal
abnormalities were statistically significantly increased in
the top two dose groups, but again these findings were
not reported on a per litter basis. No visceral abnormalities were reported.
Although the reported increase in skeletal abnormalities at 18 mg/kg body weight is a concern, interpretation is hindered by the evidence of significant
maternal toxicity. Furthermore, bearing in mind the nature
of the abnormalities seen and data not having been
related to the litter as a unit, no decision can be made
regarding the reliability of the reported findings.
This study suggests the possibility that oral exposure of male mice to sodium metavanadate at 60 and
80 mg/kg body weight directly caused a decrease in
spermatid/spermatozoal count and in the number of
pregnancies produced in subsequent matings. However,
the results are not convincing, and significant general
toxicity, reflected in decreased body weight gain, was
also evident at 80 mg/kg body weight. Overall, the
results do not provide convincing evidence that oral
exposure to sodium metavanadate produced specific
fertility effects in this study.
8.8.1.2
8.8.2.2
Groups of 20 mated, presumed pregnant, rats were

administered 0, 5, 10, or 20 mg sodium metavanadate/kg
body weight (0, 2.1, 4.2, and 8.4 mg vanadium/kg body
weight) in distilled water, intragastrically, on days 614
of gestation (Paternain et al., 1987). The fetuses were
removed on day 20 by caesarean section.
No information regarding maternal toxicity was

reported. The numbers of litters produced were 14, 14,
12, and 8 at 0, 5, 10, and 20 mg/kg body weight, respectively. There was no statistical difference in the numbers
per litter of corpora lutea, implantations, resorptions, or
live fetuses between the groups. A non-dose-related
increase in the number of abnormal fetuses was reported.
No visceral or skeletal abnormalities were reported.
Although fetal dermal haemorrhage (haematoma) in the
facial area, dorsal area, thorax, and extremities was
reported, this is a common background finding in
developmental toxicology studies and is not considered
to be an indicator of specific developmental toxicity.
Hydrocephaly was reported in 2 of 98 fetuses at
20 mg/kg body weight compared with none in other
groups. No significant difference was reported for fetal
body weight or body length. Overall, there is no clear
evidence of direct developmental toxicity following
exposure to sodium metavanadate.
No data are available.

8.8.2
Developmental toxicity
8.8.2.1
Vanadium pentoxide
Groups of 1821 pregnant Wistar rats received 0, 1,

3, 9, or 18 mg vanadium pentoxide/kg body weight per
day in vegetable oil by oral gavage on days 615 of
gestation (Yang et al., 1986a). Animals were sacrificed on
day 20 of gestation and the uterine contents examined.
The numbers of implantations, resorptions, and live and
dead fetuses were recorded. Fetuses were examined for
gross anomalies, and fetal body weight and length were
measured. One-third were subsequently examined for
visceral abnormalities, and two-thirds for skeletal
abnormalities.
24
Groups of 1820 pregnant mice were administered

0, 7.5, 15, 30, or 60 mg sodium orthovanadate/kg body
weight (0, 2.1, 4.2, 8.3, or 16.6 mg vanadium/kg body
weight) in deionized water by oral gavage on days 615
of pregnancy (Sanchez et al., 1991). The animals were
sacrificed on day 18 of pregnancy.
150 mg/kg body weight (4 fetuses in 3 litters and

58 fetuses in 12 litters, respectively) and micrognathia
at 37.5, 75, and 150 mg/kg body weight (2 fetuses in
1 litter, 3 fetuses in 1 litter, and 12 fetuses in 3 litters,
respectively). The only visceral abnormality reported
was hydrocephaly at 75 and 150 mg/kg body weight
(2 fetuses in 2 litters and 4 fetuses in 3 litters, respectively). Delayed ossification was reported in all groups,
including controls.
Severe maternal toxicity resulted from the dosing

with 30 and 60 mg/kg body weight (4/18 and 17/19 dams,
respectively, died as a result of treatment). The two
remaining dams at 60 mg/kg body weight were not
included in the final evaluation. Body weight gain was
significantly reduced (approximately 20%) at 15 mg/kg
body weight. However, no significant difference was
reported at the end of the study. No differences were
reported in final body weight, gravid uterine weight, or
corrected body weight. There were no differences in the
number of total implants per dam, number of live fetuses
per dam, sex ratio, average fetal body weight, or the
number of stunted fetuses. There were also no differences between the groups in the incidences of skeletal
or visceral abnormalities. There was some evidence of
delayed ossification at 30 mg/kg body weight; this is
considered to be a secondary consequence of the
pronounced maternal toxicity produced at this dose
level. Overall, sodium orthovanadate did not produce
developmental toxicity in this thorough investigation.
8.8.2.3
The effects on fetal development (cleft palate,

micrognathia, hydrocephaly) reported in this study
occurred in the presence of significant maternal toxicity
as defined by decreased body weight gain. It is possible
that the fetal effects were secondary to maternal toxicity.
Unfortunately, the study did not include a dose level at
which there was no maternal toxicity.
A number of other studies have been reported in
which vanadium compounds have been administered via
intraperitoneal, subcutaneous, and intravenous routes
(Carlton et al., 1982; Wide, 1984; Sun, 1987; Zhang et al.,
1991, 1993a,b; Gomez et al., 1992; Bosque et al., 1993).
Effects were observed on the developing fetus,
including (but not in every report) increased skeletal
abnormalities, increased numbers of resorbed/dead
fetuses, increased incidences of delayed ossification,
and decreased fetal body weight and length. However,
given the routes of exposure used, no conclusion can be
drawn from these studies in relation to the potential
developmental toxicity of vanadium compounds in
humans exposed occupationally.
Groups of 22 pregnant mice were administered

vanadyl sulfate pentahydrate at 0, 37.5, 75, or 150 mg/kg
body weight per day by gavage on days 615 of gestation (Paternain et al., 1990). The animals were sacrificed
on day 18 of gestation. Three fetuses from each dam
were used for whole-body analyses of vanadium. After
external examination, one-third of the remaining fetuses
were examined for visceral abnormalities and the rest for
skeletal abnormalities.
8.9
Immunological and neurological

effects
8.9.1
Vanadium pentoxide
Groups of 68 female rats received a solution of 0,

0.042, or 0.42 mg vanadium pentoxide in phosphatebuffered saline by single intratracheal administration
(Pierce et al., 1996). Cells were collected by BAL and
subsequently lysed for RNA isolation. Hybridization
studies were conducted to determine the expression of
cytokines. BAL indicated a significant, dose-related
influx of neutrophils in the lungs, and the Northern blot
analysis demonstrated increased mRNA expression of
macrophage inflammatory protein-2 and another cytokine, KC. The results demonstrate an inflammatory
response in the lungs associated with exposure to
vanadium pentoxide.
Over the study period, there was a dose-related

decrease in body weight gain down to 62% of control
values at 150 mg/kg body weight, with no corresponding
difference in food consumption. Final body weights were
significantly reduced (81%, 83%, and 80% of controls,
respectively), and corrected body weights, minus the
gravid uterine weight, were also significantly reduced
(88%, 84%, and 83% of controls, respectively). There
were no differences in the mean numbers of total
implants per dam, live fetuses per dam, late resorptions
per dam, or dead fetuses per dam. Fetal body weight was
significantly reduced at all dose levels (87%, 87%, and
79% of control values, respectively), as was fetal body
length (97%, 85%, and 82% of control values, respectively). The major dose-related effects externally were
increased incidence of cleft palate (an abnormality with a
significant background incidence in mice) at 75 and
Groups of 10 male Wistar rats received vanadium

pentoxide in drinking-water for a period of 6 months at
concentrations of 0, 1, or 100 mg vanadium/litre. Similarly, 10 male and 10 female ICR mice were given 0 or
25
6 mg vanadium pentoxide/kg body weight by gavage,

5 days/week for 6 weeks. The study focused on
assessing the immunotoxicity of vanadium and recorded
the weight of the spleen and thymus, spleen cellularity,
leukocyte count in peripheral blood, indicators of nonspecific immunity (phagocytosis, natural killer cell
activity), and humoral as well as cell-mediated immunity
(Mravcova et al., 1993).
(Pierce et al., 1996). Procedures were as with the work on

vanadium pentoxide (section 8.9.1).
The study demonstrated an enlargement of the

spleen in rats exposed to vanadium at a concentration of
100 mg/litre, the same finding as in mice, although with
diminished spleen cellularity in mice. Thymus weight
was not influenced. The leukocyte count in peripheral
blood was increased significantly in both rats and mice.
In rats and mice, a decrease in phagocytosis, which was
dose-dependent in rats, was found. In exposed mice,
there appeared signs of intense response to mitogens
and high stimulation of B-cells in the plaque-forming
cells assay. Activation of T- and B-cells and the
magnitude of the response to concanavalin A indicate
potential vanadium-related hypersensitivity.
There are no data specifically relating to neurological end-points.
Results were similar to those obtained with vanadium pentoxide, but occurred earlier and lasted longer.
The results demonstrate an inflammatory response, more
potent than with vanadium pentoxide, associated with
exposure to sodium metavanadate.
8.9.3
As part of the study summarized above (sections

8.9.1 and 8.9.2), groups of 68 female rats received a
solution of 0, 0.021, or 0.21 mg vanadyl sulfate in
phosphate-buffered saline by single intratracheal
administration (Pierce et al., 1996). Procedures were as
with the work on vanadium pentoxide (section 8.9.1).
Results were similar to those obtained with vanadium pentoxide, but occurred earlier and lasted longer
than with either vanadium pentoxide or sodium metavanadate, indicating that, in this assay, this substance
was the most potent in an inflammatory response.

8.9.2

Male rats (numbers not given) were exposed nose

only 8 h/day for 4 days to atmospheres containing either
filtered air or approximately 2 mg vanadium/m3 in the
form of ammonium metavanadate aerosol (0.32 m
MMAD) (Cohen et al., 1996a,b). Twenty-four hours after
the final exposure, BAL was performed on the rats. Cells
gathered in this process were used to assess the effects
of vanadium on tumour necrosis factor alpha (TNF-")
production, radical oxygen ion production, interferon-(induced Class II/I-A antigen expression, and phagocytic
activity.
9. EFFECTS ON HUMANS
9.1
Studies on volunteers
9.1.1
Vanadium pentoxide
Nine healthy volunteers were exposed to vanadium

pentoxide dust (98% <5 m) in an exposure chamber
(Zenz & Berg, 1967). Each subject underwent a complete
physical evaluation, chest X-ray, haematological and
urine analysis, and pulmonary function tests prior to and
immediately after exposure.Two volunteers were exposed
to 0.1 mg/m3 for 8 h. No symptoms occurred during or
immediately after exposure. Within 24 h, considerable
mucus had formed. This was easily cleared by slight
coughing, increased after 48 h, subsided within 72 h, and
completely disappeared after 4 days. Five volunteers
were exposed to 0.25 mg/m3 for 8 h. All developed a
loose, productive cough the following morning. All
subjects had stopped coughing by the tenth day.
Physical examination revealed nothing of clinical
significance, and pulmonary function tests showed no
change compared with pre-exposure values. Two
volunteers were exposed to 1 mg vanadium pentoxide
There was no significant difference in the numbers

of alveolar macrophages in the BAL fluid taken from
exposed and control animals. Induced production of
TNF-" by these macrophages was decreased following
vanadium exposure, as was the ability to increase cell
surface Class II/I-A antigen expression induced by
interferon-(. The ability of the macrophages to produce
radical oxygen anions in response to stimulation was
also reduced following vanadium exposure. The report
suggests that vanadium exposure could alter host
immunocompetence through an inhibitory effect on
macrophage function.
Groups of 68 female rats received a solution of 0,
0.021, or 0.21 mg sodium metavanadate in phosphatebuffered saline by single intratracheal administration
26
dust/m3 for 8 h. Sporadic coughing developed after 5 h,

and more frequent coughing developed by the end of
the 7th hour. Persistent cough remained for 8 days.
Chest examinations revealed clear lung fields, and no
differences were reported in pulmonary function tests
performed before, immediately after, or once weekly for
3 weeks after exposure. Three weeks after the initial
exposure, the same volunteers were accidentally exposed
to a heavy cloud of vanadium pentoxide dust (unknown
concentration) for a 5-min period while waiting for
another test, resulting in marked coughing (which persisted for about 1 week), production of sputum, rales,
and expiratory wheezes. Pulmonary function was alleged
to be normal, although the reliability of this claim is
considered doubtful in view of the severity of the clinical
observations.
abdominal pain, anorexia, nausea, and weight loss.

These symptoms improved when dosing was stopped or
reduced. Five men developed green tongue and one
other pharyngitis with marginal ulceration of the tongue.
9.1.2 Other pentavalent vanadium compounds
Eye irritation has been reported in studies in vanadium workers (see Lewis, 1959; Zenz et al., 1962; Lees,
1980; Musk & Tees, 1982). Patch testing in workforces
has produced two isolated reactions, although no skin
irritation was reported in 100 human volunteers following
skin patch testing with 10% vanadium pentoxide in
petrolatum. The underlying reason for the skin
responses in workers is unclear (Motolese et al., 1993).
A group of six subjects was administered 50

125 mg ammonium vanadyl tartrate/day orally for 45
94 days (Dimond et al., 1963). No haematological or
biochemical indication of toxicity and no effect on
circulating lipids were reported. There were no other
investigations conducted.
Five male medical students received an oral

administration of 100 or 125 mg diammonium oxytartratovanadate/day (approximately 1.7 mg/kg body
weight per day, assuming 70 kg body weight) for
6 weeks (Curran et al., 1959). No overt evidence of
toxicity was reported in any of the men. No change in
complete blood counts, including platelets, routine
urinalyses, blood urea nitrogen, blood glucose, serum
cholesterol esters, serum alkaline phosphatase, serum
transaminase, or serum bilirubin was reported
throughout the study. No further investigations were
conducted.
9.1.3
9.2
Clinical and epidemiological studies

for occupational exposure
9.2.1
Vanadium pentoxide
Zenz et al. (1962) reported on 18 workers exposed

to varying degrees to vanadium pentoxide dust (mean
particle size <5 m) in excess of 0.5 mg/m3 (apparently
measured over a 24-h period) during a pelletizing
process. Three of the most heavily exposed men developed symptoms, including sore throat and dry cough.
Examination of each on the third day revealed markedly
inflamed throats and signs of intense persistent
coughing, but no evidence of wheezing or rales. The
three men also reported burning eyes, and physical
examination revealed slight conjunctivitis. Upon
resumption of work after a 3-day exposure-free period,
the symptoms returned within 0.54 h, with greater
intensity than before, despite the use of respiratory
protective equipment. After 2 weeks of the process, all 18
workers, including those primarily assigned to office and
laboratory duties, developed symptoms and signs of
varying degrees, including nasopharyngitis, hacking
cough, and wheezing. This study confirms that
vanadium pentoxide exposure can produce respiratory
and also eye irritation.
Vanadyl sulfate is apparently used by some

weight-training athletes in an attempt to improve
performance, as it has been claimed to lower blood
cholesterol levels. A double-blind trial by Fawcett et al.
(1996, 1997) investigated the effects of administration of
vanadyl sulfate on haematological indices, blood
viscosity, and biochemistry in weight-training athletes.
The treatment group (11 males; 4 females) was orally
administered 0.5 mg/kg body weight per day for 12
weeks, and a control group (12 males; 4 females) received
placebo capsules. At the end of the study, there were no
significant differences between the groups in terms of
body weight, blood pressure, standard haematological
indices, blood viscosity, or standard blood biochemistry
measurements.
Lees (1980) reported signs of respiratory irritation

(cough, respiratory wheeze, sore throat, rhinitis, and
nosebleed) and eye irritation in a group of 17 boiler
cleaners. However, as there was no control group and it
was unclear whether other compounds were present, no
conclusions can be drawn regarding the cause or significance of these symptoms. However, the findings are
compatible with other studies on inhalation of vanadium
pentoxide.
A group of 12 volunteers received 75 mg diammonium vanadotartrate/day orally for 2 weeks, followed by

125 mg/day for the remaining 5.5 months (Somerville &
Davies, 1962). Two subjects withdrew due to toxic
gastrointestinal effects.
There was no significant effect on serum cholesterol levels. However, five patients had persistent upper
27
A study by Kiviluoto (1980), using a respiratory

questionnaire, chest radiography, and tests of
ventilatory function (FVC and FEV1), investigated 63
men who had worked at a factory refining vanadium
pentoxide from magnetite ore for at least 4 months.
These men were matched for age and smoking habit with
63 workers at a magnetite ore mine in the same area,
presumably not exposed or negligibly exposed to
vanadium pentoxide.
controls), injection (i.e., hyperaemia) of the pharynx and

nasal mucosa in 41.5% (4.4% in controls), and green
tongue in 37.5% (0% in controls).
Overall, on the basis of pulmonary function tests

and a questionnaire of respiratory symptomatology,
there were no indications of vanadium-induced ill-health
in this workforce.
A group of 69 workers in the Czech Republic was

exposed for periods ranging from 0.5 to 33 years (mean
duration of exposure 9.2 years) in the manufacture of
vanadium pentoxide from slag rich in vanadium (Kucera
et al., 1994). The concentration of vanadium in the
ambient air at the work sites was 0.0164.8 mg/m3. For
comparison, a group of 33 adult subjects not exposed to
vanadium was investigated to assess the influence of
such exposure. The authors stated that there were no
symptoms of adverse health effects related to vanadium
reported in the workers, although it was unclear what
investigations had been conducted to support this
assertion.
It is not clear what levels or duration of exposure

were experienced by the workers who presented with
symptoms. However, the findings reinforce the picture of
exposure to vanadium pentoxide causing eye and
respiratory tract effects.
A further study, in which haematological and

biochemical analyses were performed, is reported in the
same group of workers as above by Kiviluoto et al.
(1981b). All the haematological results were within
reference values, and there were no statistical differences
between the groups. Although there were significant
differences between control and exposed groups in
serum concentrations of albumin, chloride ions, bilirubin,
conjugated bilirubin, and urea, these were not clinically
significant, as the magnitude of change was small,
subject to interindividual variation, and liable to have
arisen by chance.
Huang et al. (1989) conducted a clinical and radiological investigation of 76 workers in a ferrovanadium
works, who had worked in the plant between 2 and
28 years. In the exposed group, out of 71 examined, 89%
had a cough (10% in controls), expectoration was seen in
53% (15% in controls), 38% were short of breath (0% in
controls), and 44% had respiratory harshness or dry
sibilant rale (0% in controls). Of 66 of the exposed group
examined, hyposmia or anosmia was reported in 23% (5%
in controls), congested nasal mucosa in 80% (13% in
controls), erosion or ulceration of the nasal septum in
9% (0% in controls), and perforation of the nasal septum
in 1 subject (0 in controls). Chest X-rays of all 76
exposed subjects revealed 68% with increased, coarsened, and contorted bronchovascular shadowing (23%
in controls).
Levy et al. (1984) studied respiratory tract irritation

in a group of 74 boilermakers. Vanadium pentoxide fume
in air was measured from various parts of the boiler and
ranged between 0.05 and 5.3 mg/m3 (time period of
measurement not stated). The boilermakers worked
10 h/day, 6 days/week, and reported symptoms after
only a couple of days.
The incidence of respiratory tract symptomatology
was high, a finding that is compatible with other studies
on inhalation of vanadium pentoxide. However, it is
difficult to draw firm conclusions from this study due to
the potential for mixed exposures to have occurred (e.g.,
especially sulfur dioxide, but also chromium, nickel,
copper, iron oxide, and carbon monoxide), and also no
control group was utilized for comparison.
While exposure to vanadium compounds may have

contributed to the clinical findings and symptoms
reported, no firm conclusion can be drawn from this
study in this regard, as mixed exposures are likely to
have occurred, including possibly to hexavalent chromium used in alloy production or chromium plating
(some of the effects described, particularly nasal septum
perforation, are consistent with chromium toxicity).
A study by Lewis (1959) investigated 24 men

exposed to vanadium pentoxide for at least 6 months
from two different centres. These were age-matched with
45 control subjects from the same areas. The level of
exposure to vanadium pentoxide was between 0.2 and
0.92 mg/m3 (0.11 and 0.52 mg vanadium/m3; time period of
measurement not stated). In the exposed group, 62.5%
complained of eye, nose, and throat irritation (6.6% in
control), 83.4% had a cough (33.3% in control), 41.5%
produced sputum (13.3% in control), and 16.6% complained of wheezing (0% in control). Physical findings
included wheezes, rales, or rhonchi in 20.8% (0% in
The case histories of four men were reported by

Musk & Tees (1982). One worker was exposed to large
amounts of dry ammonium vanadate dust over a 6-h
period while shovelling powder into a bin. Within 2 h of
commencing work, retro-orbital headache, epiphora
(tears), dry mouth, and green discoloration of the tongue
28
were reported. There was a marked green discoloration of

the skin of the fingers (despite the use of gloves),
scrotum, and upper legs. His nose was reported to be
stuffy, and he was lethargic. The next day, his testicles
were swollen and tender, and, on the third day after
exposure, he developed wheezing, dyspnoea, and a
cough productive of green sputum. He had several small
haemoptyses over the following 2 weeks. Wheezing and
dyspnoea persisted for about 1 month; chest symptoms
were at their worst 3 weeks after the incident. On
examination 6 weeks after the last exposure, he was
asymptomatic, with the exception of a partially blocked
left nostril and the reddened appearance of nasal
mucosa. Chest examination revealed no abnormality.
Pulmonary function assessment showed normal lung
volume, forced expiratory flow rate, and gas transfer. He
had a mild eosinophilia of the peripheral blood.
A link between workers exposed to vanadium and

asthma/bronchial hyperresponsiveness has been claimed
(Irsigler et al., 1999). However, less than 1% of workers
showed bronchial hyperresponsiveness. Although it
was reported that some of these worked in a part of the
factory with the highest vanadium exposures, it is
unclear how many other men also worked there but were
unaffected by exposure. Indeed, details of the numbers
of men in various parts of the factory were not given.
Also, the previous medical histories of the affected men
are unclear. There does not appear to be a comparison
with a suitably matched control group. Thus, no meaningful conclusions can be drawn from this study.
The other three workers also reported broadly

similar findings (e.g., green discoloration of the tongue
and skin, respiratory difficulties) associated with
exposure to vanadium pentoxide.
9.3
9.2.2

Epidemiological studies for general
population exposure
Early correlational studies relating general concentrations of vanadium in the environment to mortality
figures are summarized in IPCS (1988); no causeeffect
relationships can be established from these studies,
which give conflicting results. A single epidemiological
study, where individual exposure could be assessed, has
been conducted of general population exposure to dusts
generated by a plant processing vanadium-rich slag. It is
estimated that an area with a radius of 3 km was exposed
to the dust from a plant in Mnisek in the Czech Republic;
the population in this area was 4850. The study concentrated on children aged between 10 and 12 years, with
sampling conducted over 2 years. Venous blood, saliva,
hair, and fingernail clippings were collected from the
children. Dust aerosol, ambient air, soil, and drinkingwater were analysed from the local environment. Health
status was assessed based on haematological
parameters (blood cell and platelet counts, haematocrit,
mean corpuscular volume, and haemoglobin), specific
immunity (IgA, IgE, IgG, secretory IgA, IgM, transferrin,
"-1-antitrypsin, $-2-microglobulin), cellular immunity
(phagocytosis of peripheral leukocytes, stimulation of Tlymphocyte mitogenic activity), cytogenic analysis
(frequency of chromosome aberrations in peripheral
lymphocytes, sister chromatid exchange), and serum
lipids (cholesterol, triglycerides). Children from the
exposed groups had lower red blood cell counts than
controls, a decrease in levels of serum and secretory
IgA, and a seasonal decrease in IgG. Marked differences
between groups were seen in natural cell-mediated
immunity, with significantly higher mitotic activity of Tlymphocytes in children from the immediate vicinity of
the plant. A higher incidence of viral and bacterial
infections was registered in children from the exposed
locality. However, the study could not control for
In a further study of workers exposed to vanadium

pentoxide, one worker exposed to up to 0.1 mg/m3 for
30 min/day on a regular basis displayed the
characteristic green tongue associated with vanadium
exposure (Kawai et al., 1989). This effect was not
observed in the two other workers regularly working
with vanadium pentoxide (albeit at much lower levels).
The limited number of samples and people in this study
precluded any assessment of a doseresponse
relationship for green tongue.
A similar, but slight, impairment of pulmonary
function (FEV1 reduced by less than 4%) was observed
over a 4-week work period in a prospective study of a
group of 26 boilermakers with personal exposures to
around 0.00160.032 mg/m3 vanadium (form unspecified) (Hauser et al., 1995). However, no firm conclusions
can be drawn owing to the mixed exposures that were
likely to have been encountered and the small magnitude
of the reported change. There was also a lack of
exposureresponse relationship.
Similarly, green tongue and irritation of the upper
respiratory tract were reported in a group of 10 boiler
maintenance workers (Todaro et al., 1991). Urinary
vanadium levels were recorded, but there was no reporting of air monitoring values or indication of other
substances that may have been present. A small range of
blood biochemistry parameters was recorded for up to
2 years after a change in the work (which presumably led
to reduced exposure), but no changes were observed.
Overall, no useful conclusions can be drawn from this
study.
29
Stendahl & Sprague (1982) reported weightadjusted 7-day LC50s ranging from 1.9 to 6 mg vanadium/
litre in tests at various levels of total hardness (30, 100,
and 355 mg/litre) and pH (5.58.8). Toxicity decreased
from low to high hardness by an average factor of 1.8.
Toxicity was greatest at pH 7.7, and the predominating
ion H2VO4 was apparently the most toxic one.
confounding by exposures to compounds other than

vanadium. Cytogenetic analysis revealed no genotoxic
effects. Vanadium levels in hair were elevated in children
living close to the plant. In another group living farther
away, those with parent(s) working at the plant had
higher levels in hair than those whose parent(s) did not,
indicating exposure in the home from dust transferred on
working clothes (Kucera et al., 1992). The overall
conclusion reached was that long-term exposure to
vanadium had no negative impact on health; differences
observed were within the range of normal values in all
cases (Lener et al., 1998).
Hilton & Bettger (1988) fed juvenile rainbow trout

(Oncorhynchus mykiss) a diet containing sodium orthovanadate at concentrations ranging from 10.2 to 8960 mg
vanadium/kg diet for 12 weeks. All levels of supplemented vanadium significantly reduced growth and
feeding response in the trout. Feed avoidance and
significantly increased mortality were reported at
>493 mg/kg diet.
10. EFFECTS ON OTHER ORGANISMS IN

THE LABORATORY AND FIELD
10.2
10.1
Terrestrial environment
Cannon (1963) reported detrimental effects on

plants at aqueous vanadium concentrations of 10
20 mg/litre; however, higher concentrations can be
tolerated by legumes that use vanadium in the nitrogen
fixation process.
Aquatic environment
The toxicity of vanadium to aquatic organisms is

summarized in Table 5.
In six of seven lakes studied, the addition of
vanadium at concentrations in the 2165 107 mol/litre
range decreased photosynthetic rates of phytoplankton.
Simple correlation analysis revealed that only biomass
and proportion of cyanobacteria were significantly
correlated (P < 0.05) with the response to vanadium. The
authors concluded that lakes characterized by high
phytoplankton biomass, high proportion of cyanobacteria, and low proportion of Bacillariophyta and
Chrysophyta are most vulnerable to inhibition of
photosynthesis by vanadium (Nalewajko et al., 1995).
The growth of flax and cabbage was reduced at a

vanadium concentration of 0.5 mg/litre (nutrient solution), especially under conditions of low iron and phosphorus (Warington, 1954; Hara et al., 1976).
Vanadium can induce iron deficiency chlorosis
(Cannon, 1963) and affect trace element nutrition
(Warington, 1954; Wallace et al., 1977). Hewitt (1953)
found that 5 mg vanadium/litre in hydroponic medium
caused iron deficiency chlorosis in sugar beet plants,
and growth was reduced by 3050%.
Ringelband & Karbe (1996) found that population

growth in the brackish water hydroid Cordylophora
caspia was significantly impaired at 2 mg vanadium/litre
over a 10-day exposure period.
In soil, the concentration of vanadium causing

toxic effects in plants may range between 10 and
1300 mg/kg, depending on plant species, the form of
vanadium, and soil type (Hopkins et al., 1977). Kaplan et
al. (1990) found that vanadium concentrations of
80 mg/kg caused significant reductions in Brassica
biomass in sandy soil; however, concentrations of up to
100 mg/kg had no effect in loamy sand. The differential
response was attributed to greater accumulation of
vanadium by plants grown in sand. Similarly, significant
reductions in dry matter yield of shoots and roots of
soybean were observed at 30 mg/kg in fluvo-aquic soil,
whereas no effect was found at 75 mg/kg in oxisols
derived from red sandstones in China (Wang & Liu,
1999).
Fichet & Miramand (1998) observed a significant

reduction in the development of normal oyster (Crassostrea gigas) larvae exposed to 0.05 mg vanadium/litre for
48 h. A significant reduction in pluteus development in
urchin (Paracentrotus lividus) larvae was found at
0.1 mg/litre, but not at 0.05 mg/litre, over the same time
period. In 8-day exposures, significant mortality was
observed in brine shrimp (Artemia salina) larvae at
0.25 mg/litre.
Van der Hoeven (1991) found a 21-day noobserved-effect concentration (NOEC), based on offspring production in Daphnia magna, of 1.13 mg
vanadium/litre.
30
Table 5: Toxicity of vanadium compounds to aquatic organisms.

Organism
End-point
Concentration (mg/litre)
Reference
15-day LC50
0.5
Miramand & nsal, 1978
15-day LC50
48-h LC50
3.1
Allen et al., 1995
48-h LC50
4.1
Beusen & Neven, 1987
23-day LC50
48-h LC50
30.8
Smith et al., 1991
Hydroid Cordylophora caspia
10-day LC50
5.8
Ringelband & Karbe, 1996
Worm Nereis diversicolor
9-day LC50
10
Mussel Mytilus galloprovincialis
9-day LC50
35
Crab Carcinus maenus
9-day LC50
65
Brine shrimp Artemia salina (larvae)
9-day LC50
0.20.3
Miramand & Fowler, 1998
Sea urchin Arbaccia lixula (pluteus)
72-h LC100
0.5
Miramand & Fowler, 1998
Rainbow trout Oncorhynchus mykiss
96-h LC50
6.422
(juvenile)
96-h LC50
11.4
Giles & Klaverkamp, 1982
(eyed egg)
96-h LC50
118
Giles & Klaverkamp, 1982
96-h LC50
5.213.2
Stendahl & Sprague, 1982
7-day LC50
2.45.6
Sprague et al., 1978
11-day LC50
1.99
Sprague et al., 1978
14-day LC50
1.95
Giles et al., 1979
Chinook salmon Oncorhynchus tshawytscha
96-h LC50
16.5
Hamilton & Buhl, 1990
Brook trout Salvelinus fontinalis
96-h LC50
724
Ernst & Garside, 1987
Flag fish Jordanella floridae (adult)
96-h LC50
11.2
Holdway & Sprague, 1979
28-day LC50
1.11.9
Holdway & Sprague, 1979
Colorado squawfish Ptychocheilus lucius (fry)
96-h LC50
7.8
Hamilton, 1995
(juvenile)
96-h LC50
3.84.3
Hamilton, 1995
Razorback sucker Xyrauchen texanus (fry)
96-h LC50
8.8
Hamilton, 1995
(juvenile)
96-h LC50
3.04.0
Hamilton, 1995
Bonytail Gila elegans (fry)
96-h LC50
5.3
Hamilton, 1995
(juvenile)
96-h LC50
2.25.1
Hamilton, 1995
Flannelmouth sucker Catostomus latipinnis

(larvae)
96-h LC50
11.5
Goldfish Carassius auratus
144-h LC50
2.58.1
Guppy Poecilia reticulata
96-h LC50
144-h LC50
0.41.1
Zebrafish Brachydanio rerio
96-h LC50
Freshwater teleost Nuria denricus
96-h LC50
2.6
Abbasi, 1998
96-h LC50
27.8
Taylor et al., 1985
Marine algae
Green alga Dunaliella marina
Marine diatom
Diatom Asterionella japonica
Freshwater invertebrates
Water flea Daphnia magna
Naidid oligochaete Pristina leidyi

Marine invertebrates
Freshwater fish
(larvae)
Giles et al., 1979
Hamilton & Buhl, 1997

Knudtson, 1979
Knudtson, 1979
Marine fish
Dab Limanda limanda
31
11. EFFECTS EVALUATION
11.1
Evaluation of health effects
11.1.1
Hazard identification and doseresponse

assessment
to pentavalent vanadium compounds have been

investigated or reported in animals and humans. The
data are of variable quality. No studies are available on
tetravalent forms of vanadium.
Inhalation studies in primates reported changes in
pulmonary function and inflammatory cell parameters
following a 6-h exposure to 3 or 5 mg vanadium pentoxide aerosol/m3 (1.7 or 2.8 mg vanadium/m3). Subchronic
exposure did not lead to an exacerbation of this acute
responsivity or to a cellular immune response as measured in BAL fluid and also in serum. Furthermore,
subchronic exposure to up to 0.5 mg/m3 (0.28 mg
vanadium/m3) did not enhance bronchial reactivity to
vanadium pentoxide or methacholine. Respiratory
distress developed in three animals from a group of nine
exposed to the intermittent peaks of 1.1 mg vanadium
pentoxide/m3 (0.62 mg/m3 vanadium) for 2 days/week.
A concentration of 1.0 mg vanadium pentoxide/m3
(0.56 mg vanadium/m3) did not produce respiratory tract
toxicity in rats and mice following exposure for 6 h/day, 5
days/week, for 13 weeks. At 2 mg vanadium pentoxide/
m3 (1 mg vanadium/m3) and above, dose-related toxicity
to the respiratory tract has been observed in rodents,
including hyperplasia and metaplasia of the respiratory
epithelium and lung fibrosis and inflammation.
In animals, pentavalent vanadium has been shown

to accumulate in the lung following repeated exposure.
There is information suggesting that inorganic vanadium
compounds are absorbed following inhalation and
subsequently excreted via the urine with an initial rapid
phase of elimination, followed by a slower phase, which
presumably reflects the gradual release of vanadium from
body tissues.
Oral studies indicate that vanadium compounds
are poorly absorbed from the gastrointestinal tract. No
dermal studies are available.
Absorbed vanadium in either pentavalent or
tetravalent states is distributed mainly to the bone, liver,
kidney, and spleen, and it is also detected in the testes.
The main route of vanadium excretion is via the urine.
The pattern of vanadium distribution and excretion
indicates that there is potential for accumulation and
retention of absorbed vanadium, particularly in the bone.
One oral study indicates that tetravalent vanadium has
the ability to cross the placental barrier to the fetus.
A study in human volunteers showed that a single

8-h exposure to 0.1 mg vanadium pentoxide dust/m3
leads to delayed but prolonged bronchial effects involving excessive production of mucus. The mechanism
underlying this response is uncertain, as no subjective
irritant symptoms were reported during exposure. At 0.25
mg/m3, a similar pattern of response was seen, with the
addition of cough for some days post-exposure. Exposure to 1.0 mg/m3 produced persistent and prolonged
coughing after 5 h. A no-effect level for bronchial effects
was not identified in this study.
An LC67 of 1440 mg/m3 (800 mg vanadium/m3) has

been reported following 1-h inhalation exposure of rats
to vanadium pentoxide dust. Oral studies in rats and
mice produced LD 50 values in the range 10160 mg/kg
body weight (690 mg/kg body weight as vanadium) for
vanadium pentoxide and other pentavalent vanadium
compounds, whereas tetravalent vanadium compounds
have LD 50 values in the range 448467 mg/kg body
weight (9094 mg/kg body weight as vanadium). No
information is available concerning dermal toxicity.
The workplace studies available lack information

on the nature and extent of past occupational exposure
and provide only limited information on exposures at the
time of the study. There is the likelihood that mixed
exposures may have occurred, although the appearance
of green coloration of the tongue indicates that exposure
to vanadium pentoxide is likely. The generally poorquality data available indicate that repeated inhalation
exposure to the dust and fume of vanadium pentoxide is
associated with irritation of the eyes, nose, and throat.
Wheeze and dyspnoea are commonly reported in workers exposed to vanadium pentoxide dust and fume.
Overall, there are insufficient data to reliably describe the
exposureresponse relationship for the respiratory
effects of vanadium pentoxide dust and fume in humans.
Eye irritation has been reported in studies in

vanadium workers. Patch testing in workforces has
produced two isolated reactions. No skin irritation was
reported in 100 human volunteers following skin patch
testing with 10% vanadium pentoxide. No information is
available from animal studies with regard to the potential
of vanadium compounds to produce skin or eye irritation. Overall, the potential for vanadium and vanadium
compounds to produce skin irritation on direct contact is
unclear. No conventional animal skin sensitization
studies have been reported.
The effects on the respiratory tract of single and
repeated inhalation exposure (and combinations thereof)
32
Oral studies involving repeated exposure, although

of poor quality, are available for both pentavalent and
tetravalent forms of vanadium in both humans and
animals, although vanadium pentoxide has not been
studied. No dermal studies are available, although it is
not expected that vanadium will be absorbed across the
skin to any significant extent. The limitations of the
repeated oral dosing studies are such that it is not possible to characterize a doseresponse relationship for the
toxicity of any form of vanadium in animals or in
humans; one study in rats produced evidence of spleen
and kidney toxicity with a drinking-water intake of
2.1 ppm (mg/litre) vanadium and above, as sodium
metavanadate.
The potential for vanadium compounds to exert

effects on fertility has been very poorly investigated. A
fertility study in male mice involving exposure to sodium
metavanadate in drinking-water suggests the possibility
that oral exposure of male mice to sodium metavanadate
at 60 and 80 mg/kg body weight directly caused a
decrease in spermatid/spermatozoal count and in the
number of pregnancies produced in subsequent matings.
However, significant general toxicity, reflected in
decreased body weight gain, was also evident at
80 mg/kg body weight.
There are a number of developmental studies on
pentavalent and tetravalent vanadium compounds, and a
consistent observation is that of skeletal anomalies.
Interpretation of these studies is difficult because of
unconventional routes of exposure and evidence of
maternal toxicity that may itself contribute to the effects
seen in pups.
Pentavalent and tetravalent forms of vanadium

have produced aneugenic effects in vitro. There is evidence that these forms of vanadium as well as trivalent
vanadium can also produce DNA/chromosome damage
in vitro, both positive and negative results having
emerged from the available studies. The weight of evidence from the available data suggests that vanadium
compounds do not produce gene mutations in standard
in vitro tests in bacterial or mammalian cells.
11.1.2
Criteria for setting tolerable intakes or

guidance values for vanadium pentoxide
The toxicological end-points of concern are

genotoxicity and respiratory tract irritation. Vanadium
pentoxide is considered to be a somatic and germ cell
mutagen, and there is some, although not conclusive,
evidence to indicate the involvement, at least in part, of
aneugenicity. It is not possible to clearly identify the
threshold level, for any route of exposure relevant to
humans, below which there would be no concern for
potential genotoxic activity. In addition, repeated
inhalation exposure to the dust and fume of vanadium
pentoxide is associated with irritation of the eyes, nose,
and throat and impaired pulmonary function. Similarly,
there are insufficient data to reliably describe the
effects of vanadium pentoxide dust and fume in humans.
Since it is not possible to identify a level of exposure
that is without adverse effect, it is recommended that
levels be reduced to the extent possible.
In vivo, both pentavalent and tetravalent vanadium

compounds have produced clear evidence of aneuploidy
in somatic cells. There is some limited evidence for
vanadium compounds also being able to express clastogenic effects. Only one study is available on the
potential of vanadium compounds to produce germ cell
mutagenicity. A positive result was obtained in mice
receiving vanadium pentoxide by intraperitoneal
injection, indicating the potential for vanadium to act as
a germ cell mutagen. However, the underlying
mechanism for this effect (aneugenicity; clastogenicity)
is uncertain. It is also unclear how these findings can be
generalized to more realistic routes of exposure or to
other vanadium compounds.
Although aneugenicity is, in principle, a form of
genotoxicity that can have an identifiable threshold, the
nature of the mutagenicity database on vanadium compounds is such that it is not possible to clearly identify
the threshold level, for any route of exposure relevant to
humans, below which there would be no concern for
potential mutagenic activity.
11.1.3
Sample risk characterization
Risks to human health and the environment will

vary considerably depending upon the type and extent
of exposure. Responsible authorities are strongly
encouraged to characterize risk on the basis of locally
measured or predicted exposure scenarios. To assist the
reader, examples of exposure estimation and risk
characterization are provided in CICADs, whenever
possible. These examples cannot be considered as
representing all possible exposure situations, but are
provided as guidance only. The reader is referred to EHC
170 (IPCS, 1994) for advice on the derivation of healthbased tolerable intakes and guidance values.
No useful information is available regarding the

carcinogenic potential of any form of vanadium via any
route of exposure in animals 1 or in humans.
The authors of this document are aware that a 2-year

inhalation bioassay in rodents has recently been
completed at the US National Toxicology Program.
However, results are not available at this time.
33
The scenario chosen as a specific example is occupational exposure in the United Kingdom. There are only
two forms of vanadium of occupational significance in
the United Kingdom vanadium metal (impure and
alloyed forms) and vanadium pentoxide. No toxicology
data are available on metallic vanadium (valency state 0).
There is no means of extrapolating data from vanadium
compounds to predict the properties of vanadium metal.
Therefore, in the absence of a hazard assessment on
vanadium metal, no risk assessment can be performed.
term effects as a result of sequestration in body tissues

such as bone. Furthermore, the significance of effects
seen in developmental toxicity studies using vanadium
pentoxide is not well understood. At present, studies are
generally poorly reported or poorly conducted. Skeletal
anomalies have been seen in a number of studies with
pentavalent and tetravalent vanadium compounds,
although it is difficult to ascertain the role of the severe
maternal toxicity that has also been evident. It is plausible that the skeletal anomalies in pups may be related to
the disturbance of calcium balance (Younes & Strubelt,
1991) and interference with phosphate metabolism.
The other occupationally relevant form is vanadium pentoxide. Vanadium pentoxide is a demonstrable
somatic and presumed germ cell mutagen and produces
an unusual profile of respiratory tract effects. Delayed
and persistent respiratory effects (production of mucus
and cough) have been reported following human exposure to 0.1 mg vanadium pentoxide dust/m3, although no
threshold was established for these effects. Impaired
pulmonary function is reported following repeated
exposure to vanadium pentoxide dust and fume, and
there are insufficient data to reliably describe the
effects in humans. Thus, toxicity to the respiratory tract
will be a concern at all levels of occupational exposure.
11.2
Vanadium is found in both fresh water and seawater in a natural background range of approximately
13 g/litre. Locally high concentrations of the metal, up
to about 70 g/litre, have been reported in fresh waters,
often associated with leaching from volcanic lava flows
and uranium deposits. Data on concentrations in surface
waters influenced by industrial waste are few, but mainly
fall within the natural range (up to about 65 g/litre). A
single early reported concentration in surface waters
receiving industrial waste of 2 mg/litre may be unreliable.
Inhalation is the dominant route of concern for

vanadium pentoxide exposure. There is substantial
absorption of inorganic vanadium compounds following
inhalation exposure. Given the genotoxic properties of
vanadium and the inability to identify a threshold, there
is concern at every level of exposure.
Vanadium is an essential trace element in some

organisms (e.g., nitrogen-fixing bacteria). Its essentiality
in other organisms (e.g., for humans and other mammals)
remains an open question.
Vanadium is bioaccumulated by a few species of
biota, notably ascidians and some polychaete annelids.
Most organisms show low concentrations of the metal.
There is no evidence for biomagnification in food chains
in marine organisms; there are no data for freshwater
organisms.
There are no oral exposure data on vanadium

pentoxide.
Following dermal exposure, it is unlikely that skin
irritation or sensitization will be of concern in humans.
Given the green staining of the skin that is occasionally
seen as a result of excessive exposure to vanadium
pentoxide, it would seem that there is potential for some,
perhaps limited, dermal absorption. However, there are
no data relating to potential systemic toxicity via dermal
exposure. Given the overall lack of information in relation
to dermal exposure, it is not possible to assess the risks
to human health following exposure by this route.
11.1.4
Evaluation of environmental effects
Toxicity values for vanadium in freshwater and

marine organisms generally range between 0.2 and
120 mg/litre. Reports of sublethal effects at around
10 g/litre for algal photosynthesis, 50 g/litre for oyster
larval development, and 1130 g/litre for Daphnia
reproduction have been reported.
For natural waters, most toxic effects of vanadium
occur only at concentrations substantially higher than
those reported in the field. Most reported concentration
in industrial areas are also substantially lower than those
required to produce adverse effects. A single, possibly
unreliable, older high value for an industrial scenario
does exceed toxic concentrations (Fig. 1).
Uncertainties
Overall, the toxicokinetic and toxicological database on vanadium and vanadium pentoxide is limited,
and attempts to utilize information from other inorganic
vanadium compounds are not entirely satisfactory. Of
particular concern is the limited understanding of the
potential for dermal absorption and the potential long-
34
10
Log concentration of vanadium (g/litre)
10
Single reported
concentration
for industrial waters
(reliability uncertain)
10
10
10
Highest reported
concentration in natural
water
10
Normal range for surface waters
10
-1
10
Figure 1. Range of reported toxic concentrations of vanadium compared with concentrations in water. Triangles represent
reported LC50 values for a range of organisms in seawater and fresh water, squares represent the 21-day NOEC for Daphnia
magna reproduction, and circles represent the LOEC for the development of oyster larvae.
There are insufficient data on toxicity to terrestrial

organisms to draw risk conclusions.
There are too few data to assess risk in specific
industrial contexts.
12. PREVIOUS EVALUATIONS BY

INTERNATIONAL BODIES
A published review of vanadium is available (IPCS,

1988). Information on international hazard classification
and labelling is included in the International Chemical
Safety Cards (ICSCs 0455 and 0596) reproduced in this
document. The World Health Organizations air quality
guideline for vanadium is 1 g/m3, which is based on a
lowest-observed-adverse-effect level (LOAEL) of 20
g/m3 from studies on occupationally exposed
individuals, using an overall uncertainty factor of 20
(WHO, 1987).
35
Cannon H (1963) The biogeochemistry of vanadium. Soil

science, 96(3):196204.
REFERENCES
Carlton B, Beneke M, Fisher G (1982) Assessment of the teratogenicity of ammonium vanadate using Syrian golden hamsters.
Environmental research, 29:256262.
Abbasi S (1998) Water quality criteria for vanadium with

reference to impact studies on the freshwater teleost Nuria
dendricus (Hamilton). In: Nriagu J, ed. Vanadium in the
environment. Part 1: Chemistry and biochemistry. New York, NY,
John Wiley & Sons, pp. 125130.
Chan M, Kim J, Rees D (1993) The nitrogenase FeMo-cofactor

and P-cluster pair: 2.2 resolution structure. Science,
260:792794.
Adachi A, Asai K, Koyama Y, Matsumoto Y, Kobayashi T (1998)

Vanadium content of cigarettes. Bulletin of environmental
contamination and toxicology, 61:276280.
Chasteen N (1990) Vanadium in biological systems . Dordrecht,

Kluwer Academic Press, 225 pp.
Ahmed M, Banerjee A (1995) Non-extractive spectrophotometric

determination of vanadium in alloys and environmental,
biological and soil samples using 5,7-dibromo-8hydroxyquinoline. Analyst, 120:20192023.
Church T, Tramontano J, Scudlark J, Jickells T, Tokos J, Knap A

(1984) The wet deposition of trace metals to the western Atlantic
Ocean at the mid Atlantic coast and on Bermuda. Atmospheric
environment, 18:26572664.
Allen Y, Calow P, Baird D (1995) A mechanistic model of

contaminant-induced feeding inhibition in Daphnia magna.
Environmental toxicology and chemistry, 14(9):16251630.
Ciranni R, Antonetti M, Migliore L (1995) Vanadium salts induce

cytogenetic effects in in vivo treated mice. Mutation research,
343:5360.
Altamirano-Lozano M, Alvarez-Barrera L, Basurto-Alcantara F,

Valverde M, Rojas E (1996) Reprotoxic and genotoxic studies of
vanadium pentoxide in male mice. Teratogenesis,
carcinogenesis, mutagenesis, 16:717.
Cohen M, Klein B, Costa M (1992) Forward mutations and

DNAprotein crosslinks induced by ammonium metavanadate in
cultured mammalian cells. Mutation research, 269:141148.
Angerer J, Schaller K-H, eds. (1994) Analyses of hazardous

substances in biological materials. Deutsche Forschungsgemeinschaft (DFG). Weinheim, VCH.
Cohen M, McManus T, Yang Z, Qu Q, Schlesinger R, Zelikoff J

(1996a) Vanadium affects macrophage interferon-(-binding and
-inducible responses. Toxicology and applied pharmacology,
138:110120.
Arbouine M (1990) The determination of vanadium in urine and

its application to the biological monitoring of occupationally
exposed workers. Sudbury, Suffolk, Health and Safety Executive
(Research Reports IR/L/TM/90/01 and IR/L/TM/90/020).
Cohen M, Yang Z, Zelikoff J, Schlesinger R (1996b) Pulmonary

immunotoxicity of inhaled ammonium metavanadate in Fischer
344 rats. Fundamental and applied toxicology, 33:254263.
Atteia O (1994) Major and trace elements in precipitation on

western Switzerland. Atmospheric environment, 28:36173624.
Conklin A, Skinner C, Felten T, Sanders C (1982) Clearance and

distribution of intratracheally instilled 48Vanadium salts in the rat.
Toxicology letters, 11:199203.
Beusen MH, Neven B (1987) Toxicity of vanadium to different

freshwater organisms. Bulletin of environmental contamination
and toxicology, 39:194201.
Crans D, Amin S, Keramidas A (1998) Chemistry of relevance to

vanadium in the environment. In: Nriagu J, ed. Vanadium in the
Bortels H (1936) Weitere Untersuchungen uber die Bedeutung

von Molybdan, Vanadium, Wolfram und andere Erdaschenstoffe
fr stickstoffbindene und andere Mikroorganismen. Zentralblatt
fr Bakteriologie, Parasitenkunde, Infektionskrankheiten und
Hygiene, Abteilung 2, 95:193218.
Curran G, Azarnoff D, Bolinger R (1959) Effect of cholesterol

synthesis inhibition in normocholesteraemic young men. Journal
of clinical investigation, 38:12511261.
Custer T, Hohman W (1994) Trace elements in canvasbacks
(Aythya valisineria) wintering in Louisiana, USA, 19871988.
Environmental pollution, 84:253259.
Boscolo P, Carmignani M, Volpe AR, Felaco M, Del Rosso G,

Porcelli G, Giuliano G (1994) Renal toxicity and arterial hypertension in rats chronically exposed to vanadate. Occupational
and environmental medicine, 51:500503.
Dai S, McNeill JH (1994) One year treatment of non-diabetic

and streptozotocin-diabetic rats with vanadyl sulphate did not
alter blood pressure or haematological indices. Pharmacology
Bosque M, Domingo J, Llobet J, Corbella J (1993) Variability in

the embryotoxicity and fetotoxicity of vanadate with the day of
exposure. Veterinary and human toxicology, 35(1):13.
Dai S, Thompson KH, McNeill JH (1994a) One year treatment of

streptozotocin-induced diabetic rats with vanadyl sulphate.
Pharmacology and toxicology, 74:101109.
Bronzetti G, Morichetti E, Della Croce C, Del Carratore R,

Giromini L, Galli A (1990) Vanadium: Genetical and
biochemical investigations. Mutagenesis, 5(3):293295.
Dai S, Thompson K, Vera E, McNeill J (1994b) Toxicity studies

on one year treatment of non-diabetic and streptozotocindiabetic rats with vanadyl sulphate. Pharmacology and
toxicology, 75:265273.
Budavari S, ONeil MJ, Smith A, Heckelman PE, Kinneary JF,

eds. (1996) The Merck index an encyclopedia of chemicals,
drugs and biologicals, 12th ed. Whitehouse Station, NJ, Merck &
Co., Inc., pp. 16911692.
Dai S, Vera E, McNeill J (1995) Lack of haematological effects

of oral vanadium treatment in rats. Pharmacology and
Bu-Olayan A, Al-Yakoob S (1998) Lead, nickel and vanadium in

seafood: An exposure assessment for Kuwaiti consumers. The
science of the total environment, 223:8186.
36
Dimond E, Caravaca J, Benchimol A (1963) Vanadium:

Excretion, toxicity, lipid effect in man. American journal of
clinical nutrition, 12:4953.
and biochemistry. New York, NY, John Wiley & Sons, pp.
97123.
Hamilton S (1995) Hazard assessment of inorganics to three
endangered fish in the Green River, Utah. Ecotoxicology and
environmental safety, 30:134142.
Domingo J, Llobet J, Tomas J, Corbella J (1985) Short-term

toxicity studies of vanadium in rats. Journal of applied
Hamilton S, Buhl K (1990) Safety assessment of selected

inorganic elements to fry of chinook salmon (Oncorhynchus
tshawytscha). Ecotoxicology and environmental safety,
20:307324.
Doran A, Law F, Allen M, Rushton N (1998) Neoplastic

transformation of cells by soluble but not particulate forms of
metals used in orthopaedic implants. Biomaterials, 19:751759.
Ernst W, Garside E (1987) Lethal effects of vanadium to two life
stages of brook trout Salvelinus fontinalis (Mitchill). Canadian
journal of zoology, 65:628634.
Hamilton S, Buhl K (1997) Hazard evaluation of inorganics,

singly and in mixtures, to flannelmouth sucker Catostomus
latipinnis in the San Juan River, New Mexico. Ecotoxicology
and environmental safety, 38:296308.
Fawcett J, Farquhar S, Thou T, Lowe G, Golding A (1996) The

effect of oral vanadyl sulphate on body composition and performance in weight-training athletes. International journal of sport
nutrition, 6:382390.
Hamilton S, Muth R, Waddell B, May T (2000) Hazard

assessment of selenium and other trace elements in wild larval
razorback sucker from the Green River, Utah. Ecotoxicology and
environmental safety, 45:132147.
Fawcett J, Farquhar S, Walker R, Thou T, Shand B (1997) Oral

vanadyl sulphate does not affect blood cells, viscosity or
biochemistry in humans. Pharmacology and toxicology,
80:202206.
Hara T, Sonoda Y, Iwai I (1976) Growth response of cabbage

plants to transition elements under water culture conditions. I.
Titanium, vanadium, chromium, manganese, and iron. Soil
science and plant nutrition, 22(3):307315.
Fichet D, Miramand P (1998) Vanadium toxicity to three marine

invertebrates larvae: Crassostrea gigas, Paracentrotus lividus
and Artemia salina. Chemosphere , 37(7):13631368.
Hauser R, Elreedy S, Hoppin J, Christiani D (1995) Airway

obstruction in boilermakers exposed to fuel oil ash. American
journal of respiratory and critical care medicine, 152:14781484.
Fish R, Komlenic J (1984) Molecular characterization and profile

identifications of vanadyl compounds in heavy crude petroleums
by liquid chromatography/graphite furnace atomic spectrometry.
Analytical chemistry, 56:510517.
Hauser R, Elreedy S, Ryan P, Christiani D (1998) Urine

vanadium concentrations in workers overhauling an oil-fired
boiler. American journal of industrial medicine, 33:5560.
Frank A, Galgan V, Roos A, Olsson M, Petersson L, Bignert A

(1992) Metal concentrations in seals from Swedish waters.
Ambio, 21:529538.
Henze M (1911) Die vanadium Verbindung der Blutkorperchen.

Hoppe-Seylers Zeitschrift fr Physiologische Chemie,
72:494501.
Galli A, Vellosi R, Fiorio R, Della Croce C, Del Carratore R,

Morichetti E, Giromini L, Rosellini D, Bronzetti G (1991) Genotoxicity of vanadium compounds in yeast and cultured
mammalian cells. Teratogenesis, carcinogenesis, mutagenesis,
11:175183.
Hewitt E (1953) Metal interrelationships in plant nutrition. I.

Effects of some metal toxicities on sugar beet, tomato, oat,
potato, and marrowstem kale grown in sand culture. Journal of
experimental botany, 4(10):5964.
Hilliard H (1992) Vanadium. In: Bureau of Mines minerals year
book. Washington, DC, US Department of the Interior.
Galloway J, Thornton J, Norton S, Volchok H, MacLean R (1982)

Trace metals in atmospheric deposition: A review and
assessment. Atmospheric environment, 16:16771700.
Hilton J, Bettger W (1988) Dietary vanadium toxicity in juvenile

rainbow trout: A preliminary study. Aquatic toxicology,
12:6371.
Giammanco S, Valenza M, Pignato S, Giammanco G (1996)

Mg, Mn, Fe and V concentrations in the ground waters of Mount
Etna (Sicily). Water research, 30:378386.
Holdway D, Sprague J (1979) Chronic toxicity of vanadium to

flag fish. Water research, 13:905910.
Giles M, Klaverkamp J (1982) The acute toxicity of vanadium

and copper to eyed eggs of rainbow trout (Salmo gairdneri ).
Water research, 16:885889.
Hopkins LL, Cannon HL, Miesch AT, Welch RM, Nielsen FH

(1977) Vanadium. In: Geochemistry and the environment. Vol. II.
Washington, DC, National Academy of Sciences, pp. 93107.
Giles M, Klaverkamp J, Lawrence S (1979) The acute toxicity of

saline groundwater and of vanadium to fish and invertebrates.
Edmonton, Environment Alberta (Project No. AF 3.2.1; prepared
for the Alberta Oil Sands Environmental Research Program)
[cited in IPCS, 1988].
HSE (1998) Methods for the determination of hazardous

substances: Metals and metalloids in workplace air by X-ray
fluorescence spectrometry. Health and Safety Executive.
Sudbury, Suffolk, HSE Books (MDHS 91; ISBN 0 7176 1557 X).
Gomez M, Sanchez D, Domingo J, Corbella J (1992)

Embryotoxic and teratogenic effects of intraperitoneally
administered metavanadate in mice. Journal of toxicology and
environmental health, 37:4756.
HSE (in press) Vanadium pentoxide. Health and Safety

Executive. Sudbury, Suffolk, HSE Books (Risk Assessment
Document EH72/XX).
Huang R, Liu P, Yuan Z, Lin J, Liu Y (1989) Radiological
observations on workers exposed to vanadium. Zhonghua Yufang
Yixue Zazhi, 23(5):283285.
Hamada T (1998) High vanadium content in Mount Fuji

groundwater and its relevance to the ancient biosphere. In:
Nriagu J, ed. Vanadium in the environment. Part 1: Chemistry
37
IPCS (1988) Vanadium. Geneva, World Health Organization,

International Programme on Chemical Safety, 170 pp. (Environmental Health Criteria 81).
vanadium pentoxide following subchronic inhalation exposure in

a non-human primate animal model. Journal of applied
IPCS (1994) Assessing human health risks of chemicals:

derivation of guidance values for health-based exposure limits.
Geneva, World Health Organization, International Programme
on Chemical Safety (Environmental Health Criteria 170).
Knudtson B (1979) Acute toxicity of vanadium to two species of

fresh water fish. Bulletin of environmental contamination and
IPCS (1999a) International Chemical Safety Card Vanadium

trioxide. Geneva, World Health Organization, International
Programme on Chemical Safety (ICSC 0455).
Kucera J, Simkova M, Lener J, Mravcova A, Kinova L, Penev I

(1990) Vanadium determination in rat tissues and biological
reference materials by neutron activation analysis. Journal of
radioanalytical and nuclear chemistry, 141:4959.
IPCS (1999b) International Chemical Safety Card Vanadium

pentoxide. Geneva, World Health Organization, International
Programme on Chemical Safety (ICSC 0596).
Kucera J, Byrne A, Mravcova A, Lener J (1992) Vanadium levels

in hair and blood of normal and exposed persons. The science
of the total environment, 15:191205.
Irsigler G, Visser P, Spangenberg P (1999) Asthma and chemical

bronchitis in vanadium plant workers. American journal of
industrial medicine, 35:366374.
Kucera J, Lener J, Mnukova J (1994) Vanadium levels in urine

and cystine levels in fingernails and hair of exposed and normal
persons. Biological trace element research, 4345:327334.
Ishii T (1998) Characterization of vanadium in the fan worm

Pseudopotamilla occelata. In: Nriagu J, ed. Vanadium in the
Kucera J, Lener J, Mnukova J, Bayerova E (1998) Vanadium

exposure tests in humans: Hair, nails, bloods, and urine. In:
Nriagu J, ed. Vanadium in the environment. Part 2: Health
effects. New York, NY, John Wiley & Sons, pp. 5573.
Ishii T, Nakai I, Numako C, Okoshi K, Otake T (1993) Discovery of

a new vanadium accumulator, the fan worm Pseudopotamilla
occelata. Naturwissenschaften, 80:268270.
Kustin K, Robinson W (1995) Vanadium transport in animal

systems. In: Sigel H, Sigel A, eds. Metal ions in biological
systems. New York, NY, Marcel Dekker, pp. 511542.
JETOC (1996) Mutagenicity test data of existing chemical substances. Tokyo, Japan Chemical Industry Ecology-Toxicology &
Information Centre.
Lees R (1980) Changes in lung function after exposure to

vanadium compounds in fuel oil ash. British journal of industrial
medicine, 37:253256.
Kaplan D, Sajwan K, Adriano D, Gettier S (1990)

Phytoavailability and toxicity of beryllium and vanadium. Water,
air, and soil pollution, 53:203212.
Lener J, Kucera J, Kodl M, Skokanova V (1998) Health effects of

environmental exposure to vanadium. In: Nriagu J, ed.
Vanadium in the environment. Part 2: Health effects. New York,
NY, John Wiley & Sons, pp. 119.
Kawai T, Seiji K, Watanabe T, Nakatsuka H, Ikeda M (1989)

Urinary vanadium as a biological indicator of exposure to
vanadium. International archives of occupational and
Levy B, Hoffman L, Gottsegen S (1984) Boilermakers bronchitis:

Respiratory tract irritation associated with vanadium pentoxide
exposure during oil-to-coal conversion of a power plant. Journal
of occupational medicine, 26:567570.
Kerckaert G, LeBouef R, Isfort R (1996) Use of the Syrian

hamster embryo cell transformation assay for determining the
carcinogenic potential of heavy metal compounds. Fundamental
and applied toxicology, 34:6772.
Lewis C (1959) The biological actions of vanadium: II. The signs

and symptoms of occupational vanadium exposure. American
Medical Associations archives of industrial health, 19:497503.
Kiviluoto M (1980) Observations on the lungs of vanadium

workers. British journal of industrial medicine, 37:363366.
Linstedt K, Kruger P (1969) Vanadium concentrations in

Colorado river basin waters. Journal of the American Water
Works Association, 61:8588.
Kiviluoto M (1981) A clinical study of occupational exposure to

vanadium pentoxide dust. Academic thesis. Acta Universitatis
Ouluensis, Series D, Medica No. 72 (Medica Publica No. 2).
Llobet J, Domingo J (1984) Acute toxicity of vanadium

compounds in rats and mice. Toxicology letters, 23:227231.
Kiviluoto M, Pyy L, Pakarinen A (1981a) Serum and urinary

vanadium of workers processing vanadium pentoxide.
International archives of occupational and environmental health,
48:251256.
Llobet J, Colomina M, Sirvent J, Domingo J, Corbella J (1993)

Reproductive toxicity evaluation of vanadium in male mice.
Toxicology, 80:199206.
Mackey E, Becker P, Demiralp R, Greenberg R, Koster B, Wise S
(1996) Bioaccumulation of vanadium and other trace metals in
livers of Alaskan cetaceans and pinnipeds. Archives of
environmental contamination and toxicology, 30:503512.
Kiviluoto M, Pyy L, Pakarinen A (1981b) Clinical laboratory

results of vanadium-exposed workers. Archives of environmental
health, 36:109113.
Knecht E, Moorman W, Clark J, Lynch D, Lewis T (1985)
Pulmonary effects of acute vanadium pentoxide inhalation in
monkeys. American reviews of respiratory disease,
132:11811185.
MAK (1992) Occupational toxicants: Critical evaluation for MAK

values and classification of carcinogens. Weinheim, VCH
Verlagsgesellschaft mbH (ISBN 3-527-27025-6).
Mamane Y, Pirrone N (1998) Vanadium in the atmosphere. In:
Nriagu J, ed. Vanadium in the environment. Part 1: Chemistry
and biochemistry. New York, NY, John Wiley & Sons, pp. 3771.
Knecht EA, Moorman WJ, Clark JC, Hull RD, Biagini RE, Lynch
DW, Boyle TJ, Simon SD (1992) Pulmonary reactivity to
38
Martin H, Kaplan D (1998) Temporal changes in cadmium,

thallium, and vanadium mobility in soil and phytoavailability
under field conditions. Water, air, and soil pollution,
101:399410.
Musk A, Tees J (1982) Asthma caused by occupational exposure

to vanadium compounds. The medical journal of Australia,
1:183184.
Nalewajko C, Lee K, Jack T (1995) Effects of vanadium on
freshwater phytoplankton photosynthesis. Water, air, and soil
pollution, 81(12): 93105.
Michibata H (1996) The mechanics of accumulation of

vanadium by ascidians: Some progress towards an
understanding of this unusual phenomenon. Zoological
sciences, 13:489502.
NAS (1974) Medical and biological effects of vanadium.

Washington, DC, National Academy of Sciences.
Michibata H, Kanamori K (1998) Selective accumulation of

vanadium by ascidians from sea water. In: Nriagu J, ed.
Vanadium in the environment. Part 1: Chemistry and
biochemistry. New York, NY, John Wiley & Sons, pp. 217249.
Nielsen F, Uthus E (1990) The essentiality and metabolism of

vanadium. In: Chasteen N, ed. Vanadium in biological systems.
Dordrecht, Kluwer Academic Press, pp. 5162.
Michibata H, Iwata Y, Hirata J (1991) Isolation of highly acidic

and vanadium-containing blood cells from among several types
of blood cell from Ascidiidae species by density gradient
centrifugation. Journal of experimental zoology, 257:306313.
NIOSH (1977) Occupational exposure to vanadium. Washington,

DC, National Institute for Occupational Safety and Health, 142
pp. (Document No. 77-222).
NIOSH (1994) Method 7300 Elements (ICP) and Method 7504
Vanadium oxides. In: NIOSH manual of analytical methods, 4th
ed. Washington, DC, National Institute for Occupational Safety
and Health (DHHS (NIOSH) Publication 94-113; NTIS PB 85179018).
Migliore L, Bocciardi R, Macri C, Lo Jacono F (1993)

Cytogenetic damage induced in human lymphocytes by four
vanadium compounds and micronucleus analysis by
fluorescence in situ hybridisation with a centromeric probe.
Mutation research, 319:205213.
Nriagu J (1990) Global metal pollution: Poisoning the

biosphere. Environment, 32:711.
Miramand P (1979) Contribution ltude de la toxicit et des

transferts du vanadium chez quelques organismes marins.
Doctoral Thesis, Universit des Sciences et Techniques du
Languedoc, Montpellier, 115 pp.
Nriagu J, Pirrone N (1998) Emission of vanadium into the atmosphere. In: Nriagu J, ed. Vanadium in the environment. Part 1:
Chemistry and biochemistry. New York, NY, John Wiley & Sons,
pp. 2536.
Miramand P, Fowler S (1998) Bioaccumulation and transfer of

vanadium in marine organisms. In: Nriagu J, ed. Vanadium in
the environment. Part 1: Chemistry and biochemistry. New York,
Oberg S, Parker R, Sharma R (1978) Distribution and

elimination of an intratracheally administered vanadium
compound in the rat. Toxicology, 11:315323.
Miramand P, nsal M (1978) Acute toxicity of vanadium to some

marine benthic and phytoplanktonic species. Chemosphere ,
10:827832.
OSHA (1991) Method ID-125G Metal and metalloid particulates

in workplace atmospheres (ICP analysis) and Method ID 185
Confirmation of vanadium pentoxide in workplace atmospheres.
In: Analytical methods manual, 2nd ed. Washington, DC, US
Department of Labor, Occupational Safety and Health
Administration.
Miramand P, Guary J, Fowler S (1980) Vanadium transfer in the

mussel Mytilus galloprovincialis. Marine biology, 56:281293.
Miramand P, Guary J, Fowler S (1981) Uptake, accumulation,
and excretion of vanadium in the shrimp Lysmata seticaudata
(Risso), and the crab Carcinus maenus (L.). Journal of
experimental marine biology and ecology, 49:267287.
Owusu-Yaw J, Cohen M, Fernando S, Wei C (1990) An

assessment of the genotoxicity of vanadium. Toxicology letters,
50:327336.
Miramand P, Fowler S, Guary J (1982) Comparative study of

vanadium biokinetics in three species of echinoderms. Marine
biology, 67:127134.
Parker R, Sharma R (1978) Accumulation and depletion of vanadium in selected tissues of rats treated with vanadyl sulphate
and sodium orthovanadate. Journal of environmental pathology
Miramand P, Fowler S, Guary J (1992) Experimental study on

vanadium transfer in the benthic fish Gobius minutus. Marine
biology, 114:349353.
Parker R, Sharma R, Miller G (1978) Vanadium in plants, soils

and water in the Rocky Mountain region and its relationship to
industrial operations. Trace substances and environmental
health, 12:340350.
Mochizuki M, Ueda F, Sasaki S, Hondo R (1999) Vanadium

contamination and the relation between vanadium and other
elements in wild birds. Environmental pollution, 106:249251.
Paternain J, Domingo J, Llobet J, Corbella J (1987) Embryotoxic

effects of sodium metavanadate administered to rats during
organogenesis. Revista Espanola de Fisiologia, 43(2):223228.
Motolese A, Truzzi M, Giannini A, Seidenari S (1993) Contact

dermatitis and contact sensitisation among enamellers and
decorators in the ceramics industry. Contact dermatitis,
28:5962.
Paternain J, Domingo J, Gomez M, Ortega A, Corbella J (1990)

Developmental toxicity of vanadium in mice after oral administration. Journal of applied toxicology, 10(3):181186.
Mravcova A, Jirova D, Janci H, Lener J (1993) Effects of orally

administered vanadium on the immune system and bone
metabolism in experimental animals. The science of the total
environment, Supplement Part 1: 663669.
Pierce L, Alessandrini F, Godleski J, Paulauskis J (1996)

Vanadium-induced chemokine mRNA expression and pulmonary
inflammation. Toxicology and applied pharmacology, 138:111.
39
Ramanadham S, Heyliger C, Gresser M, Tracey A, McNeill J

(1991) The distribution and half-life for retention of vanadium in
the organs of normal and diabetic rats orally fed vanadium(IV)
and vanadium(V). Biological trace element research,
30:119124.
fr Vitaminforschung Beiheft Ernahrungsforschung,

43:242250 (in German).
Schroeder W, Dobson M, Cane D, Johnson N (1987) Toxic trace
elements associated with airborne particulate matter: A review.
Journal of the Air Pollution Control Association, 37:12671285.
Rehder D, Jantzen S (1998) Structure, function, and models of

biogenic vanadium compounds. In: Nriagu J, ed. Vanadium in
the environment. Part 1: Chemistry and biochemistry. New York,
Shacklette H, Hamilton J, Boerngen J, Bowles J (1971)

Elemental composition of surficial materials in the conterminous
United States. Washington, DC, US Geological Survey, 71 pp.
(Professional Paper 574).
Rhoads K, Sanders C (1985) Lung clearance, translocation and

acute toxicity of arsenic, beryllium, cadmium, cobalt, lead,
selenium, vanadium and ytterbium oxides following deposition
in rat lung. Environmental research, 36:359378.
Sharma R, Flora S, Brown D, Oberg S (1987) Persistence of

vanadium compounds in lungs after intratracheal instillation in
rats. Toxicology and industrial health, 3:321329.
Ringelband U, Karbe L (1996) Effects of vanadium on

population growth and Na-K-ATPase activity of the brackish
water hydroid Cordylophora caspia. Bulletin of environmental
contamination and toxicology, 57:118124.
Si R et al. (1982) Studies on the mutagenicity and teratogenicity

of vanadium pentoxide. Weisheng Zhuanye Cankao Ziliao,
School of Public Health, Sichuan Medical College [cited in
Sun, 1987].
Rivedal E, Roseng L, Sanner T (1990) Vanadium compounds

promote the induction of morphological transformation of
hamster embryo cells with no effect on gap junctional cell
communication. Cell biology and toxicology, 6(3):303314.
Sigel H, Sigel A, eds. (1995) Metal ions in biological systems.

Vol. 31. Vanadium and its role in life. New York, NY, Marcel
Dekker, 779 pp.
Smith D, Kennedy J, Dickson K (1991) An evaluation of a naidid
oligochaete as a toxicity test organism. Environmental toxicology
and chemistry, 10:14591465.
Rojas E, Valverde M, Herrera L, Altamirano-Lozano M, OstrotskyWegman P (1996) Genotoxicity of vanadium pentoxide

evaluated by the single gel electrophoresis assay in human
lymphocytes. Mutation research, 359:7784.
Smith MM, White MA, Ide C (1992) The biological monitoring of

occupational exposure to vanadium in boiler cleaners. Sudbury,
Suffolk, Health and Safety Executive (Research Report
IR/L/TM/92/1).
Roldan RE, Altamirano LM (1990) Chromosomal aberrations,

sister-chromatid exchanges, cell-cycle kinetics and associations
in human lymphocyte cultures exposed to vanadium pentoxide.
Mutation research, 245:6165.
Somerville J, Davies B (1962) Effect of vanadium on serum

cholesterol. American heart journal, 64(1):5456.
Sabbioni E, Moroni M (1983) A study on vanadium in workers

from oil-powered fire plants. Luxembourg, Commission of
European Communities (EU Report 005-EN).
Sprague J, Holdway D, Stendahl D (1978) Acute and chronic

toxicity of vanadium to fish. Edmonton, Environment Alberta
(Project No. AF 3.2.1; prepared for the Alberta Oil Sands
Environmental Research Program) [cited in IPCS, 1988].
Sabbioni E, Marafante E, Amantini L, Ubertalli L, Birattari C

(1978) Similarity in metabolic patterns of different chemical
species of vanadium in the rat. Bioinorganic chemistry,
8:503515.
Stendahl D, Sprague J (1982) Effects of water hardness and pH

on vanadium lethality to rainbow trout. Water research,
16:14791488.
Sabbioni E, Pozzi G, Devos S, Pintar A, Casella L, Fischbach M

(1993) The intensity of vanadium(V)-induced cytotoxicity and
morphological transformation in BALB/3T3 cells is dependent
on glutathione-mediated bioreduction to vanadium(IV).
Carcinogenesis, 14(12):25652568.
Strain W, Varnes A, Drenski T, Paxton C, McKinney B (1982)

Vanadium content of drinking water. Trace substances and
Sun M, ed. (1987) Toxicity of vanadium and its environmental
health standard . Chengdu, West China University of Medical
Sciences, 20 pp.
Sadiq M, Mian A (1994) Nickel and vanadium in air particulates

at Dhahran (Saudi Arabia) during and after Kuwait oil fires.
Atmospheric environment, 28:22492253.
Sun M et al. (undated) Study on the toxicity of vanadium

pentoxide (unpublished) [cited in Sun, 1987].
Saeki K, Nakajima M, Noda K, Loughlin T, Baba N, Kiyota M,

Tatsukawa R, Calkins D (1999) Vanadium accumulation in pinnipeds. Archives of environmental contamination and toxicology,
36:8186.
Taylor D, Maddock B, Mance G (1985) The acute toxicity of nine

grey list metals (arsenic, boron, chromium, copper, lead, nickel,
tin, vanadium and zinc) to two marine fish species: dab
(Limanda limanda) and grey mullet (Chelon labrosus). Aquatic
Sanchez D, Ortega A, Domingo J, Corbella J (1991)

Developmental toxicity evaluation of orthovanadate in the
mouse. Biological trace element research, 30:219226.
Todaro A, Bronzato R, Buratti M, Colombi A (1991) [Acute

exposure to vanadium-containing dusts: health effects and
biological monitoring in a group of boiler maintenance workers.]
Medicina del Lavoro , 82:142147 (in Italian with English
summary).
Sanchez D, Colomina M, Domingo J (1998) Effects of vanadium

on activity and learning in rats. Physiology and behaviour,
63(3):345350.
Schlettwein-Gzell D, Mommsen-Straub S (1973) [Trace
elements in foodstuffs. XI. Vanadium.] Internationale Zeitschrift
40
Tsukamoto Y, Saka S, Kumano K, Iwanami S, Ishida O, Marumo

F (1990) Abnormal accumulation of vanadium in patients on
chronic hemodialysis. Nephron, 56:368373.
mice and Kunming albino mice. Dukou Sanitary and AntiEpidemic Station [cited in Sun, 1987].
Yao D, Li S, et al. (1986a) A long-term study on the chronic
toxicity and carcinogenicity of the inhalation of vanadium
pentoxide dust on mice. Dukou Sanitary and Anti-Epidemic
Station [cited in Sun, 1987].
US EPA (1983) Methods for chemical analysis of water and

wastes. Washington, DC, US Environmental Protection Agency;
Springfield, VA, US Department of Commerce, National
Technical Information Service.
Yao D, Zhang B, et al. (1986b) Study on the acute and

subchronic toxicity of vanadium pentoxide. Dukou Sanitary and
Anti-Epidemic Station [cited in Sun, 1987].
US EPA (1986) Test methods for evaluating solid waste. Vol.

1A: Laboratory manual for physical/chemical methods.
Washington, DC, US Environmental Protection Agency, Office of
Solid Waste and Emergency Response (Document No. 7910.17911.3).
Yen TF (1975) Vanadium and its bonding in petroleum. In: Yen

TF, ed. The role of trace metals in petroleum. Ann Arbor, MI,
Ann Arbor Science Publishers, pp. 167181.
US EPA (1992) Support: Dust inhalation toxicity studies with

cover letter dated 081992. Washington, DC, US Environmental
Protection Agency, Office of Toxic Substances (Doc #89940000275; see also Doc #88-920000666, initial submission).
Younes M, Strubelt O (1991) Vanadate-induced toxicity towards

isolated perfused rat livers: The role of lipid peroxidation.
Toxicology, 66:6374.
van der Hoeven N (1991) Proceedings of the 2nd workshop on

sources of variation in ecotoxicological tests with Daphnia
magna. Sheffield, University of Sheffield [cited in Allen et al.,
1995].
Zaporowska H, Wasilewski W (1992) Haematological results of

vanadium intoxication in Wistar rats. Comparative biochemistry
and physiology, 101C(1):5761.
Zaporowska H, Wasilewski W, Slotwinska M (1993) Effect of
chronic vanadium administration in drinking water to rats.
Biometals, 6:310.
Wallace A, Alexander G, Chadhury F (1977) Phytotoxicity of

cobalt, vanadium, titanium, silver, and chromium.
Communications in soil science and plant analysis,
8(9):751756.
Zenz C, Berg B (1967) Human responses to controlled vanadium

pentoxide exposure. Archives of environmental health,
14:709712.
Wang J, Liu Z (1999) Effect of vanadium on the growth of

soybean seedlings. Plant and soil, 216:4751.
Zenz C, Bartlett J, Thiede W (1962) Acute vanadium pentoxide

intoxication. Archives of environmental health, 5:542546.
Warington K (1954) The influence of iron supply on toxic effects

of manganese, molybdenum and vanadium in soybeans, peas,
and flax. Annals of applied biology, 41(1):122.
Zhang L, Zhou K (1992) Background values of trace elements in

the source area of the Yangtze River. The science of the total
environment, 125:391404.
Wever R, Hemrika W (1998) Vanadium in enzymes. In: Nriagu J,

ed. Vanadium in the environment. Part 1: Chemistry and
biochemistry. New York, NY, John Wiley & Sons, pp. 285305.
Zhang T, Gou X, Yang Z (1991) A study on developmental

toxicity of vanadium pentoxide in NIH mice. Hua Hsi I Ko Ta
Hsueh Hsueh Pao, 22:192195.
White MA, Reeves GD, Moore S, Chandler HA, Holden HJ

(1987) Sensitive determination of urinary vanadium as a
measure of occupational exposure during cleaning of oil fired
boilers. Annals of occupational hygiene, 31(3):339343.
Zhang T, Gou X, Yang Z (1993a) Study of teratogenicity and

sensitive period of vanadium pentoxide in Wistar rats. Hua Hsi I
Ko Ta Hsueh Hsueh Pao, 24:202205.
WHO (1987) Air quality guidelines for Europe. Copenhagen,

World Health Organization, Regional Office for Europe, 426 pp.
Zhang T, Yang Z, Zeng C, Gou X (1993b) A study on developmental toxicity of vanadium pentoxide in Wistar rats. Hua Hsi I
Ko Ta Hsueh Hsueh Pao, 24:9296.
Wide M (1984) Effect of short-term exposure to five industrial

metals on the embryonic and fetal development of the mouse.
Environmental research, 33:4753.
Zhong B, Gu Z, Wallace W, Whong W, Ong T (1994)

Genotoxicity of vanadium pentoxide in Chinese hamster V79
cells. Mutation research, 321:3542.
Wrbitsky R, Goen T, Frank F, Angerer J (1995) Internal exposure

of waste incineration workers to organic and inorganic
substances. International archives of occupational and
Yang H, Yao D, Feng S, Qin J, Chen Y (1986a) [A study of the
teratogenicity of vanadium pentoxide.] Dukou Sanitary and AntiEpidemic Station, pp. 3543 (internal report) [cited in Sun,
1987].
Yang H et al. (1986b) A study on the effect of inhaling vanadium
pentoxide dust on the frequencies of micronucleus of PCE in
mice. Dukou Sanitary and Anti-Epidemic Station, pp. 4850
(internal report) [cited in Sun, 1987].
Yang H, Zhang B, et al. (1986c) Studies on the effect of
vanadium pentoxide on the micronucleus of PCE in 615 strain
41
APPENDIX 1 SOURCE DOCUMENTS
APPENDIX 2 CICAD PEER REVIEW
The draft CICAD on vanadium pentoxide and other

inorganic vanadium compounds was sent for review to
institutions and organizations identified by IPCS after contact
with IPCS national contact points and Participating Institutions,
as well as to identified experts. Comments were received from:
HSE (in press) Vanadium pentoxide. Health and

Safety Executive. Sudbury, Suffolk, HSE Books
(Risk Assessment Document EH72/XX)
The authors draft version is initially reviewed internally by
a group of approximately 10 Health and Safety Executive
experts, mainly toxicologists, but also involving other relevant
disciplines, such as epidemiology and occupational hygiene.
The toxicology section of the amended draft is then reviewed by
toxicologists from the United Kingdom Department of Health.
Subsequently, the entire Risk Assessment Document is reviewed
by a tripartite advisory committee to the United Kingdom Health
and Safety Commission, the Working Group for the Assessment
of Toxic Chemicals (WATCH). This committee comprises experts
in toxicology, occupational health, and hygiene from industry,
trade unions, and academia.
M. Baril, International Programme on Chemical Safety/

Institut de Recherche en Sant et en Scurit du
Travail du Qubec, Montreal, Quebec, Canada
R. Benson, Drinking Water Program, US Environmental
Protection Agency, Denver, CO, USA
T. Berzins, National Chemicals Inspectorate, Solna,
Sweden
R. Chhabra, Department of Health and Human Services,
Research Triangle Park, NC, USA
P. Edwards, Protection of Health Division, Department of
Health, London, United Kingdom
R. Hertel, Federal Institute for Health Protection of
Consumers and Veterinary Medicine, Berlin,
Germany
M. Kiilunen, Finnish Institute of Occupational Health,
Helsinki, Finland
J. Lener, National Institute of Public Health, Prague,
Czech Republic
I. Mangelsdorf, Fraunhofer Institute, Hanover, Germany
H. Nagy, National Institute for Occupational Safety and
Health, Washington, DC, USA
E. Ohanian, Office of Water, US Environmental
Protection Agency, Washington, DC, USA
S.A. Soliman, Alexandria University, El-Shatby,
Alexandria, Egypt
M. Sun, School of Public Health, West China University of
Medical Sciences, Chengdu, Sichuan, Peoples
Republic of China
W.F. ten Berge, DSM, Heerlen, The Netherlands
P. Yao, Institute of Occupational Medicine, Chinese
Academy of Preventive Medicine, Ministry of Health,
Beijing, Peoples Republic of China
K. Ziegler-Skylakakis, GSF-Forschungszentrum fr Umvelt
und Gesundheit, Neuherberg, Oberschleissheim,
Germany
The members of the WATCH committee at the time of the

peer review were:
Mr Steve Bailey (Independent Consultant)
Professor Jim Bridges (Robens Institute, Guildford)
Mr Robin Chapman (Chemical Industries Association)
Dr Hilary Cross (Trade Unions Congress)
Mr David Farrar (Independent Consultant)
Dr Tony Fletcher (Trade Unions Congress)
Dr Ian Guest (Chemical Industries Association)
Dr Alastair Hay (Trade Unions Congress)
Dr Len Levy (Institute for Environment and Health,
Leicester)
Dr Tony Mallet (Chemical Industries Association)
Mr Alan Moses (Chemical Industries Association)
Mr Jim Sanderson (Independent Consultant)
Dr Anne Spurgeon (Institute of Occupational Health,
Birmingham)
IPCS (1988) Vanadium. Geneva, World Health

Organization, International Programme on
Chemical Safety, 170 pp. (Environmental Health
Criteria 81)
A WHO Task Group on Environmental Health Criteria for
Vanadium met in Moscow, USSR, from 30 March to 3 April
1987. The Task Group reviewed and revised the draft criteria
document and made an evaluation of the risks for human health
and the environment from exposure to vanadium
Copies of this document may be obtained from:
International Programme on Chemical Safety
World Health Organization
Geneva, Switzerland
42
APPENDIX 3 CICAD FINAL REVIEW

BOARD
Observer
Helsinki, Finland, 2629 June 2000
Members
Dr R.J. Lewis (representative of European Centre for

Ecotoxicology and Toxicology of Chemicals), Epidemiology and
Health Surveillance, ExxonMobil Biomedical Sciences, Inc.,
Annandale, NJ, USA
Mr H. Ahlers, Education and Information Division, National

Institute for Occupational Safety and Health, Cincinnati, OH,
USA
Secretariat
Dr T. Berzins, National Chemicals Inspectorate (KEMI), Solna,

Sweden
Dr A. Aitio, International Programme on Chemical Safety, World

Health Organization, Geneva, Switzerland (Secretary)
Dr R.M. Bruce, Office of Research and Development, National

Center for Environmental Assessment, US Environmental
Protection Agency, Cincinnati, OH, USA
Dr P.G. Jenkins, International Programme on Chemical Safety,

World Health Organization, Geneva, Switzerland
Dr M. Younes, International Programme on Chemical Safety,
World Health Organization, Geneva, Switzerland
Mr R. Cary, Health and Safety Executive, Liverpool, United

Kingdom (Rapporteur)
Dr R.S. Chhabra, General Toxicology Group, National Institute
of Environmental Health Sciences, Research Triangle Park, NC,
USA
Dr H. Choudhury, National Center for Environmental Assessment,
US Environmental Protection Agency, Cincinnati, OH, USA
Dr S. Dobson, Centre for Ecology and Hydrology, Monks Wood,
Abbots Ripton, United Kingdom (Chairman)
Dr H. Gibb, National Center for Environmental Assessment, US
Environmental Protection Agency, Washington, DC, USA
Dr R.F. Hertel, Federal Institute for Health Protection of
Consumers and Veterinary Medicine, Berlin, Germany
Ms K. Hughes, Priority Substances Section, Environmental
Health Directorate, Health Canada, Ottawa, Ontario, Canada
Dr G. Koennecker, Chemical Risk Assessment, Fraunhofer
Institute for Toxicology and Aerosol Research, Hanover,
Germany
Ms M. Meek, Existing Substances Division, Environmental
Health Directorate, Health Canada, Ottawa, Ontario, Canada
Dr A. Nishikawa, Division of Pathology, Biological Safety
Research Centre, National Institute of Health Sciences, Tokyo,
Japan
Dr V. Riihimki, Finnish Institute of Occupational Health,
Helsinki, Finland
Dr J. Risher, Agency for Toxic Substances and Disease Registry,
Division of Toxicology, US Department of Health and Human
Services, Atlanta, GA, USA
Professor K. Savolainen, Finnish Institute of Occupational
Health, Helsinki, Finland (Vice-Chairman)
Dr J. Sekizawa, Division of Chem-Bio Informatics, National
Institute of Health Sciences, Tokyo, Japan
Dr S. Soliman, Department of Pesticide Chemistry, Faculty of
Agriculture, Alexandria University, Alexandria, Egypt
Ms D. Willcocks, National Industrial Chemicals Notification and
Assessment Scheme, Sydney, NSW, Australia
43
VANADIUM TRIOXIDE
0455
March 1998
CAS No: 1314-34-7

RTECS No: YW3050000
UN No: 3285
EC No:
TYPES OF
HAZARD/
EXPOSURE
FIRE
Divanadium trioxide
Vanadium sesquioxide
Vanadic oxide
Vanadium(III) oxide
V2O3
Molecular mass: 149.9
ACUTE HAZARDS/SYMPTOMS
PREVENTION
FIRST AID/FIRE FIGHTING
Combustible under specific

conditions. Gives off irritating or
toxic fumes (or gases) in a fire.
NO open flames.
In case of fire in the surroundings:

all extinguishing agents allowed.
EXPLOSION
EXPOSURE
PREVENT DISPERSION OF DUST!
Inhalation
Sore throat. Cough. Laboured

breathing. Weakness.
Local exhaust or breathing

protection.
Fresh air, rest. Half-upright

position. Refer for medical
attention.
Skin
Dry skin. Redness.
Protective gloves.
Remove contaminated clothes.

Rinse skin with plenty of water or
shower.
Eyes
Redness.
Safety goggles, or eye protection in

combination with breathing
protection if powder.
First rinse with plenty of water for

several minutes (remove contact
lenses if easily possible), then take
to a doctor.
Ingestion
Headache. Vomiting. Weakness.
Do not eat, drink, or smoke during

work.
Induce vomiting (ONLY IN

CONSCIOUS PERSONS!). Give
plenty of water to drink. Refer for
medical attention.
SPILLAGE DISPOSAL
PACKAGING & LABELLING
Sweep spilled substance into containers; if

appropriate, moisten first to prevent dusting.
Carefully collect remainder, then remove to safe
place (extra personal protection: P3 filter respirator
for toxic particles).
Symbol
R:
S:
UN Hazard Class: 6.1
UN Pack Group: III
EMERGENCY RESPONSE
STORAGE
Transport Emergency Card: TEC (R)-61G65c
Separated from food and feedstuffs.
IPCS
International
Programme on
Chemical Safety
Do not transport with food and

feedstuffs.
Prepared in the context of cooperation between the International

Programme on Chemical Safety and the European Commission
IPCS 1999
SEE IMPORTANT INFORMATION ON THE BACK.
0455
VANADIUM TRIOXIDE
IMPORTANT DATA
Physical State; Appearance

BLACK POWDER, TURNS GRADUALLY INTO INDIGO-BLUE
CRYSTALS OF VANADIUM TETROXIDE (V2O4) ON
EXPOSURE TO AIR.
Chemical Dangers
The substance decomposes on heating or on burning
producing irritating and toxic fumes (vanadium oxides).
Occupational Exposure Limits
TLV not established. MAK not established.
Routes of Exposure
The substance can be absorbed into the body by inhalation of
its aerosol and by ingestion.
Inhalation Risk
Evaporation at 20C is negligible; a harmful concentration of
airborne particles can, however, be reached quickly.
Effects of Short-term Exposure
The aerosol irritates the eyes, the skin and the respiratory tract.
Inhalation of high concentrations of aerosol of this substance
may cause conjunctivitis, rhinitis and bronchitis. The effects
may be delayed. See Notes.
Effects of Long-term or Repeated Exposure
The substance may have effects on the respiratory tract,
resulting in chronic rhinitis and chronic bronchitis.
PHYSICAL PROPERTIES
Melting point: 1970C
Density: 4.87 g/cm3 at 18C
Solubility in water: poor
ENVIRONMENTAL DATA
NOTES
Depending on the degree of exposure, periodic medical examination is indicated. The symptoms of acute exposure do not become
manifest until 1-6 days. Also consult ICSC # 0596 Vanadium pentoxide.
ADDITIONAL INFORMATION
LEGAL NOTICE
Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible
for the use which might be made of this information
IPCS 1999
VANADIUM PENTOXIDE
0596
October 1999
CAS No: 1314-62-1

RTECS No: YW2450000 (dust)
UN No: 2862
EC No: 023-001-00-8
Divanadium pentoxide
Vanadic anhydride
Vanadium(V)oxide
V2O5
Molecular mass: 181.9
TYPES OF
HAZARD/
EXPOSURE
ACUTE HAZARDS/SYMPTOMS
FIRE
Not combustible.
PREVENTION
FIRST AID/FIRE FIGHTING

In case of fire in the surroundings:
all extinguishing agents allowed.
EXPLOSION
EXPOSURE
PREVENT DISPERSION OF DUST!

STRICT HYGIENE!
Inhalation
Sore throat. Cough. Burning

sensation. Shortness of breath.
Laboured breathing. Wheezing.
Ventilation, local exhaust, or

breathing protection.
Fresh air, rest. Half-upright position.

Refer for medical attention.
Skin
Redness. Burning sensation. Pain.
Protective gloves.
Remove contaminated clothes.

Rinse skin with plenty of water or
shower.
Eyes
Pain. Redness. Conjunctivitis.
Safety goggles, or eye protection in

combination with breathing
protection if powder.
First rinse with plenty of water for

several minutes (remove contact
lenses if easily possible), then take
to a doctor.
Ingestion
Abdominal cramps. Diarrhoea.

Drowsiness. Nausea.
Unconsciousness. Vomiting.
Do not eat, drink, or smoke during

work. Wash hands before eating.
Induce vomiting (ONLY IN

CONSCIOUS PERSONS!). Give
plenty of water to drink. Refer for
medical attention.
SPILLAGE DISPOSAL
PACKAGING & LABELLING
Sweep spilled substance into containers; if

appropriate, moisten first to prevent dusting.
Carefully collect remainder, then remove to safe
place. (Extra personal protection: P3 filter respirator
for toxic particles). Do NOT let this chemical enter
the environment.
T Symbol
N Symbol
R: 20/22-37-40-48/23-51/53-63
S: (1/2-)36/37-38-45-61
UN Hazard Class: 6.1
UN Pack Group: III
EMERGENCY RESPONSE
STORAGE
Transport Emergency Card: TEC (R)-61G64c
Separated from food and feedstuffs.
IPCS
International
Programme on
Chemical Safety
Do not transport with food and

feedstuffs.
Prepared in the context of cooperation between the International

Programme on Chemical Safety and the European Commission
IPCS 2000
SEE IMPORTANT INFORMATION ON THE BACK.
0596
VANADIUM PENTOXIDE
IMPORTANT DATA
Physical State; Appearance

YELLOW TO RED CRYSTALLINE POWDER OR SOLID IN
VARIOUS FORMS.
Routes of exposure
The substance can be absorbed into the body by inhalation of
its aerosol and by ingestion.
Chemical dangers
Upon heating, toxic fumes are formed. Reacts with combustible
substances.
Inhalation risk
Evaporation at 20C is negligible; a harmful concentration of
airborne particles can, however, be reached quickly when
dispersed.
Occupational exposure limits

TLV (respirable dust or fume, as V 2O5): 0.05 mg/m3 (TWA)
(ACGIH 1999).
MAK: 0.05 mg/m3; (1996).
Effects of short-term exposure

The aerosol of this substance irritates the eyes, the skin and
the respiratory tract. Inhalation of high concentrations may
cause lung oedema, bronchitis, bronchospasm. The effects
may be delayed.
Effects of long-term or repeated exposure
Lungs may be affected by inhalation of high concentrations of
dust or fumes. The substance may cause greenish-black
discolouration of the tongue.
PHYSICAL PROPERTIES
Boiling point (decomposes): 1750C
Melting point: 690C
Relative density (water = 1): 3.4

Solubility in water, g/100 ml: 0.8
ENVIRONMENTAL DATA
The substance is harmful to aquatic organisms.
NOTES
Depending on the degree of exposure, periodic medical examination is indicated.
The symptoms of lung oedema often do not become manifest until a few hours have passed and they are aggravated by physical
effort. Rest and medical observation are therefore essential.
Immediate administration of an appropriate spray, by a doctor or a person authorized by him/her, should be considered.
ADDITIONAL INFORMATION
LEGAL NOTICE
Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible
for the use which might be made of this information
IPCS 2000
On estime que chaque anne, quelque 8,4 tonnes

de vanadium sont libres dans latmosphre partir de
sources naturelles (valeurs extrmes : 1,5-49,2 tonnes). La
source de pollution de lenvironnement par le vanadium
qui est de loin la plus importante est constitue par la
combustion du ptrole et du charbon; environ 90 % des
quelque 64 000 tonnes de vanadium libres dans
latmosphre chaque anne par des phnomnes
naturels ou par lactivit humaine ont en effet cette
source pour origine.
RSUM DORIENTATION
Ce CICAD consacr au pentoxyde de vanadium et
dautres drivs minraux du vanadium repose sur un
bilan des problmes sanitaires (principalement en milieu
professionnel) prpar par le Health and Safety
Executive du Royaume-Uni (HSE, sous presse). Ce
document vise principalement les voies dexposition
prendre en considration sur les lieux de travail, mais
contient galement des informations relatives
lenvironnement. La bibliographie utilise va jusqu
novembre 1998. Un dpouillement complmentaire de la
litterature t effectu jusqu mai 1999 afin de recueillir
toutes donnes supplmentaires publies aprs
lachvement de ce document. En ce qui concerne les
donnes environnementales, on a utilis la monographie
publie dans la srie Critres dhygine de lenvironnement (IPCS, 1988). Comme on ne disposait daucun
document plus rcent sur le devenir et les effets
environnementaux de ces composs, il a t procd
une recherche bibliographique afin dobtenir un
complment dinformation. Des renseignements sur la
nature de lexamen par des pairs et sur les sources
documentaires existantes sont donnes lappendice 1.
Lappendice 2 contient des informations sur lexamen par
des pairs du prsent CICAD. Ce CICAD a t approuv
en tant quvaluation internationale lors de la runion du
Comit dvaluation finale qui sest tenue Helsinki
(Finlande) du 26 au 29 juin 2000. La liste des participants
cette runion figure lappendice 3. Les fiches
internationales sur la scurit chimique du trioxyde
(ICSC 0455) et du pentoxyde de vanadium (ICSC 0596)
tablies par le Programme international sur la scurit
chimique (IPCS, 1999a,b) sont galement reproduites
dans le prsent CICAD.
Dans lenvironnement, le vanadium offre une

chimie complexe. Dans les minraux, le degr doxydation
du vanadium peut tre de +3, +4 ou +5. Par dissolution
dans leau, V3+ et V4+ sont rapidement oxyds au degr
+5, qui constitue la forme la plus commune du vanadium
dans lenvironnement. En solution, cette forme
correspond aux vanadates, qui peuvent se polymriser
(pour donner principalement des dimres et des
trimres), en particulier en solution concentre. Dans les
tissus, ce sont les formes V3+ et V4+ qui prdominent, du
fait que le milieu est largement rducteur; dans le plasma,
cest V5+ qui prdomine.
Le vanadium est probablement essentiel pour les
systmes enzymatiques qui fixent lazote atmosphrique
(bactries) et il est concentr par certains organismes
comme les tuniciers, quelques annlids de la classe des
polychtes et certaines algues microscopiques. On ne
sait cependant pas avec certitude quelle est sa fonction
chez ces organismes. La question de savoir si le
vanadium est essentiel pour dautres organismes reste
pose. Rien nindique quil saccumule ou subisse une
bioamplification dans la chane alimentaire des
organismes marins, qui constituent le groupe le mieux
tudi.
Le vanadium (No CAS 7440-62-2) est un mtal

ductile, de couleur gris-argent, qui peut exister sous
divers degrs doxydation : !1, 0, +2, +3, +4 et +5. Sa
forme commerciale la plus courante est le pentoxyde
V2O5 (No CAS 1314-62-1) correspondant la valence +5
et qui se prsente sous la forme dune poudre cristalline
qui peut tre jaune, rouge ou verte.
Le lessivage du vanadium dans les diffrents

profils pdologiques est trs limit.
On a signal la prsence de fortes concentrations
de vanadium dans lair proximit de sources industrielles et de feux dhydrocarbures. En ce qui concerne
les dpts, des valeurs annuelles de 0,1 10 kg/ha sont
caractristiques des zones urbaines o sont implantes
des sources importantes de vanadium; ces valeurs vont
de 0,01 0,1 kg/ha par an dans les zones rurales ou
urbaines o nexistent pas de sources de vanadium et
sabaissent <0,001-0,01 kg/ha par an dans les rgions
recules.
Le vanadium est un lment abondant et trs

largement rpandu. Le minerai est extrait en Afrique du
Sud, en Russie et en Chine. Lors de la fusion du minerai
de fer, il se forme un laitier contenant du pentoxyde de
vanadium que lon utilise pour la production du mtal.
On prpare galement le pentoxyde de vanadium en
lextrayant par solvant des minerais duranium ou par
grillage des sels prsents dans les rsidus de chaudires
ou dans ceux des usines de production de phosphore
lmentaire. La combustion des huiles lourdes dans les
chaudires et les fours conduit la formation de rsidus
solides, de suie, de tartre et de cendres volantes qui
contiennent du pentoxyde de vanadium.
Dans la plupart des eaux douces de surface, la

concentration du vanadium est infrieure 3 g/litre; des
valeurs plus leves, pouvant atteindre 70 g/litre ont
t releves dans des zones o existent dimportantes
sources gochimiques. On ne possde gure de donnes
sur la teneur en vanadium des eaux proches de sites
industriels; la plupart des publications font tat de
48
Des tudes sur des travailleurs de lindustrie du

vanadium ont mis en vidence des cas dirritation
oculaire. Chez 100 volontaires qui on avait pos un
timbre cutan contenant 10 % de pentoxyde de
vanadium, on na pas constat dirritation cutane, mais
un test analogue effectu sur des travailleurs a donn
lieu a deux ractions isoles. Lexprimentation animale
na permis de dgager aucun rsultat clair concernant le
pouvoir irritant oculaire ou cutan des composs du
vanadium ou leur action sensibilisatrice au niveau de
lpiderme.
valeurs correspondant sensiblement aux concentrations

naturelles les plus fortes. Les concentrations plagiques
vont de 1 3 g/litre, dans les sdiments, la concentration va de 20 200 g/g, les valeurs les plus leves
tant releves dans la zone littorale.
Quelques organismes concentrent le vanadium, et
la concentration de ce mtal peut atteindre 10 000 g/g
chez les ascidies et 786 g/g chez les polychtes. Chez la
plupart des tres vivants, la concentration est, dune
faon gnrale, infrieure 50 g/g et habituellement
beaucoup plus faible.
Dans un groupe de volontaires exposs pendant 8

h de la poussire contenant 0,1 mg de vanadium par m3,
on a observ des effets retards mais prolongs sur les
bronches qui se manifestaient notamment par une
production excessive de mucus. A la concentration de
0,25 mg/m3, la raction tait analogue, avec en plus de la
toux qui sest prolonge pendant les quelques jours
suivant lexposition. A la concentration de 1,0 mg/m3, la
toux est devenue permanente au bout de cinq heures et
sest maintenue longtemps. Il ne ressort de cette tude
aucune valeur de la dose maximale sans effet
bronchique.
Lexposition par la voie alimentaire est estime

chez lHomme 11-30 g par jour. Dans leau de boisson,
la concentration va jusqu 100 g/litre. Dans certaines
nappes souterraines qui alimentent les sources deau
potable, on a relev des concentrations de vanadium
suprieures 50 g/litre. Leau minrale en bouteille peut
en contenir davantage.
On possde des donnes toxicocintiques limites
selon lesquelles chez lHomme, le vanadium est rsorb
aprs inhalation puis excrt dans lurine, llimination se
faisant en deux phases, une phase initiale rapide puis
une phase plus lente qui correspond vraisemblablement
la libration progressive du vanadium retenu dans les
tissus. Aprs administration par voie orale, le vanadium
IV est mal rsorb dans les voies digestives. On ne
dispose pas dtudes sur labsorption percutane.
Linhalation rpte de vapeurs et de poussires

de pentoxyde de vanadium entrane une irritation des
yeux, du nez et de la gorge. Chez les travailleurs exposs
ces vapeurs et ces poussires, on observe
couramment une respiration sifflante et de la dyspne.
Globalement , on ne dispose pas de donnes suffisantes
pour tablir de faon fiable une relation expositionrponse relative aux effets respiratoires des poussires et
des vapeurs de vanadium chez lHomme.
Lexprimentation animale montre quaprs

exposition par la voie respiratoire ou orale le vanadium
absorb sous des formes correspondant aux degrs
doxydation IV ou V se rpartit principalement dans les
os, le foie, les reins et la rate. On en a galement dcel la
prsence dans les testicules. La principale voie
dexcrtion est la voie urinaire. Le mode de distribution
et dexcrtion du vanadium montre quune fois rsorb,
le mtal peut saccumuler et tre retenu, notamment dans
les os. Il a galement t montr que le vanadium
ttravalent est capable de franchir la barrire foetoplacentaire.
Les drivs correspondant aux valences 4 et 5 du

vanadium ont des effets aneugnes in vitro en prsence
ou en labsence dactivation mtabolique. On est fond
penser que ces drivs ainsi que ceux du vanadium III
sont capables de provoquer des lsions de lADN et des
chromosomes in vitro, mais les tudes existantes
donnent cet gard des rsultats qui sont tantt
positifs, tantt ngatifs. Il semble, la lumire des
donnes disponibles, que les composs du vanadium ne
soient pas mutagnes , en juger par les tests classiques
de mutagnicit in vitro sur des cellules bactriennes ou
mammaliennes.
Dans la seule tude de toxicit aigu par inhalation

qui soit disponible, on a obtenu une CL67 de 1440 mg/m3
(800 mg de vanadium par m3) pour des rats exposs
pendant 1 h de la poussire de pentoxyde de
vanadium. Lexposition de rats et de souris par la voie
orale a permis dobtenir une DL50 qui se situait entre 10
et 160 mg/kg de poids corporel dans le cas du pentoxyde
et dautres drivs du vanadium V, alors quavec les
drivs du vanadium IV, les valeurs taient comprises
entre 448 et 467 mg/kg de poids corporel. On ne dispose
daucune donne sur la toxicit du vanadium par la voie
percutane.
In vivo, une aneuplodie des cellules somatiques

sobserve clairement aprs exposition des drivs du
vanadium IV et du vanadium V selon diffrentes voies.
Comme dans le cas des tudes in vitro, les tests destins
mettre en vidence des effets clastognes donnent des
rsultats mitigs et dans lensemble, on reste dans
lincertitude quand au pouvoir clastogne du vanadium
vis--vis des cellules somatiques. Par contre, on a
obtenu un rsultat positif dans le cas des cellules
germinales de souris qui on avait inject du pentoxyde
49
de vanadium par voie intrapritonale. Le mcanisme qui

est la base de ces effets (aneugnes et clastognes)
nest pas connu avec certitude. On ignore galement
dans quelle mesure ces rsultats peuvent tre tendus
dautres voies dexposition et dautres drivs du
vanadium.
de vue cotoxicologique, il serait plus judicieux de

prendre en considration laction sur le dveloppement
des hutres (sensiblement rduit 0,05 mg de vanadium
par litre) et sur la reproduction des daphnies (concentration sans effet observable 21 jours : 1,13 mg/litre).
Peu dtudes ont t consacrs aux organismes
terrestres. La plupart de celles qui portent sur des
vgtaux concernent des cultures hydroponiques sur
lesquelles on observe des effets partir de 5 mg/litre.
Les rsultats de ces tudes sont difficiles transposer
aux plantes cultives en pleine terre.
Etant donn la nature de la base de donnes sur la

gnotoxicit du pentoxyde de vanadium et dautres
drivs de cet lment, il nest pas possible de dfinir
sans ambiguit le seuil au-dessous duquel, quelle que
soit la voie dexposition prendre en considration chez
lHomme, il ny aurait pas lieu de craindre un risque
dactivit gnotoxique.
Dans les divers compartiments de lenvironnement,

la concentration est sensiblement infrieure aux valeurs
toxiques. On ne possde que peu de donnes sur la
concentration au voisinage des sites industriels et il
nest pas possible de procder une valuation du
risque sur cette base. Quoi quil en soit, les valeurs dont
il est fait tat semble correspondre aux concentrations
naturelles les plus fortes, ce qui indique que le risque
devrait tre faible. Des mesures sur les lieux mmes
simposent dans chaque cas particulier.
On ne possde aucune information utile sur le

pouvoir cancrogne du vanadium chez lHomme ou
lanimal, sous quelque forme et par quelque voie
dexposition que ce soit.1
Une tude de fcondit sur des souris mles dont
leau de boisson contenait du mtavanadate de sodium,
incite penser que lexposition des animaux ce
compos aux doses de 60 et 80 mg/kg de poids corporel
a t la cause directe dune diminution du nombre de
spermatides et de spermatozodes ainsi que du nombre
de grossesses conscutives laccouplement de ces
mles avec des souris femelles. Il est vrai toutefois, qu
la dose de 80 mg/kg p.c., la toxicit gnrale du compos
tait galement vidente (diminution du gain de poids).
Un certain nombre dtudes ont t consacres
laction des composs du vanadium IV et V sur le
dveloppement. Elles rvlent systmatiquement la
prsence danomalies du squelette. Les rsultats de ces
tudes sont difficiles interprter car les voies
dexposition taient inhabituelles et la toxicit manifeste
des composs pour les mres a pu influer sur les effets
constats dans la progniture.
Chez lHomme les points daboutissement de
laction toxique prendre en considration sont la
gnotoxicit et lirritation des voies respiratoires. Comme
il nest pas possible de dfinir le seuil de concentration
partir duquel il ny a plus deffets toxiques, il est
recommand de rduire le plus possible le niveau
dexposition.
Pour les organismes aquatiques, les valeurs de la
CL50 vont de 0,2 environ 120 mg/litre, la majorit des
valeurs se situant entre 1 et 12 mg par litre. Dune point
1
Les auteurs de ce document ont connaissance dune

tude au cours de laquelle on a fait inhaler pendant 2 ans
des drivs du vanadium des rongeurs. Cette tude
vient de sachever aux Etats-Unis dans le cadre du
National Toxicology Program et les rsultats nen sont
pas encore disponibles.
50
Las emisiones atmosfricas a partir de fuentes

naturales en todo el mundo se han estimado en 8,4 toneladas al ao (gama de 1,5-49,2 toneladas). La fuente ms
importante de contaminacin ambiental por vanadio es
con diferencia la combustin de petrleo y de carbn;
alrededor del 90% de las aproximadamente 64 000 toneladas de vanadio que se liberan en la atmsfera cada ao
a partir de fuentes tanto naturales como antropognicas
procede de la combustin del petrleo.
RESUMEN DE ORIENTACIN
Este CICAD sobre el pentxido de vanadio y otros

compuestos inorgnicos de vanadio se bas en un
examen de los problemas relativos a la salud humana
(fundamentalmente profesionales) preparado por la
Direccin de Salud y Seguridad del Reino Unido (HSE,
en prensa). Este examen se concentra en las vas de
exposicin de inters para el entorno ocupacional, pero
contiene tambin informacin sobre el medio ambiente.
Figuran los datos identificados hasta noviembre de 1998.
Se realiz una ulterior bsqueda bibliogrfica hasta mayo
de 1999 para localizar cualquier informacin nueva que
se hubiera publicado desde la terminacin del examen. Se
utiliz una monografa de los Criterios de Salud
Ambiental (IPCS, 1988) como documento original para la
informacin ambiental. Puesto que no se dispona de
documentos originales ms recientes sobre el destino y
los efectos en el medio ambiente, se realiz una
bsqueda bibliogrfica para obtener ms informacin. La
informacin acerca del carcter del examen colegiado y la
disponibilidad de los documentos originales figura en el
apndice 1. La informacin sobre el examen colegiado de
este CICAD aparece en el apndice 2. Este CICAD se
aprob como evaluacin internacional en una reunin de
la Junta de Evaluacin Final celebrada en Helsinki
(Finlandia) del 26 al 29 de junio de 2000. La lista de
participantes en esta reunin figura en el apndice 3. Las
Fichas internacionales de seguridad qumica sobre el
trixido de vanadio (ICSC 0455) y el pentxido de
vanadio (ICSC 0596), preparadas por el Programa
Internacional de Seguridad de las Sustancias Qumicas
(IPCS, 1999a,b), tambin se reproducen en el presente
documento.
La qumica del vanadio en el medio ambiente es

compleja. En los minerales, el estado de oxidacin del
vanadio puede ser +3, +4 +5. La disolucin en agua
oxida rpidamente el V3+ y el V4+ al estado pentavalente,
que es la forma ms comn del metal en el medio
ambiente. El vanadato, compuesto pentavalente en
solucin, se puede polimerizar (principalmente a las
formas dimricas o trimricas), en particular a concentraciones ms altas de las sales. En los tejidos de los
organismos predominan el V3+ y el V4+, debido en gran
parte a las condiciones de reduccin; en el plasma
predomina el V5+.
El vanadio es probablemente esencial para los
sistemas enzimticos que fijan el nitrgeno de la atmsfera (bacterias) y lo concentran algunos organismos
(tunicados, algunos anlidos poliquetos, algunas microalgas), pero no se conoce bien su funcin en estos
organismos. Sigue siendo una cuestin abierta si el
vanadio es o no esencial para otros organismos. No hay
pruebas de acumulacin o bioamplificacin en las
cadenas alimentarias de los organismos marinos, que
forman el grupo mejor estudiado.
Hay una lixiviacin muy limitada del vanadio a
travs de los perfiles del suelo.
El vanadio (CAS N 7440-62-2) es un metal gris

plateado suave que puede existir en varios estados de
oxidacin diferentes: !1, 0, +2, +3, +4 y +5. La forma
comercial ms comn es el pentxido de vanadio (V2O5;
CAS N 1314-62-1) y en este estado pentavalente es un
polvo cristalino rojo-amarillento o verde.
Se han notificado niveles ms altos de vanadio en

el aire prximo a fuentes industriales e incendios de
hidrocarburos. Las tasas de deposicin representativas
son de 0,1-10 kg/ha al ao para zonas urbanas afectadas
por fuentes locales importantes, de 0,01-0,1 kg/ha al ao
para las zonas rurales y urbanas que no tienen una
fuente local importante y <0,001-0,01 kg/ha al ao para
las zonas remotas.
El vanadio es un elemento abundante, con una

distribucin muy amplia; se extrae en Sudfrica, Rusia y
China. Durante la fusin de la mena de hierro se forma
escoria de vanadio con pentxido de vanadio, que se
utiliza para la produccin de vanadio metlico. El
pentxido de vanadio se obtiene tambin por extraccin
con disolventes a partir de menas de uranio y mediante
un proceso de calcinacin de las sales de los residuos de
las calderas o de los residuos de las instalaciones de
fosfato elemental. Durante la combustin de fueloil en
calderas y hornos, hay pentxido de vanadio en los
residuos slidos, el holln, las incrustaciones de las
calderas y las cenizas voltiles.
La mayor parte de las aguas superficiales dulces

contienen menos de 3 g de vanadio/litro; se han
notificado niveles ms altos, de hasta unos 70 g/litro,
en zonas con fuentes geoqumicas grandes. Los datos
sobre los niveles de vanadio en aguas superficiales
prximas a actividades industriales son escasos; la
mayora de los informes parecen indicar niveles
aproximadamente iguales a los naturales ms elevados.
Las concentraciones en el agua marina en mar abierta
oscilan entre 1 y 3 g/litro y en los sedimentos van de 20
a 200 g/g; los niveles ms altos se observan en los
sedimentos costeros.
51
Algunos organismos concentran vanadio en cantidades que ascienden hasta 10 000 g/g en las ascidias
y 786 g/g en los anlidos poliquetos. La mayora de los
organismos suelen contener menos de 50 g/g y normalmente concentraciones mucho ms bajas.
En un grupo de voluntarios humanos, una exposicin aislada de ocho horas a 0,1 mg de polvo de
pentxido de vanadio/m3 produjo efectos bronquiales
retardados, pero prolongados, con una produccin
excesiva de moco. Con 0,25 mg/m3 se observ una pauta
de respuesta semejante, con la adicin de tos durante
algunos das despus de la exposicin. La exposicin a
1,0 mg/m3 produjo una tos persistente y prolongada
despus de cinco horas. En este estudio no se identific
un nivel sin efectos para los trastornos bronquiales.
Las estimaciones de la exposicin total de las

personas en los alimentos oscilan entre 11 y 30 g/da.
Los niveles en el agua de bebida ascienden hasta
100 g/litro. Algunas fuentes de agua fretica que
abastecen de agua potable muestran concentraciones
superiores a 50 g/litro. Los niveles en el agua de
manantial embotellada pueden ser ms altos.
La exposicin por inhalacin repetida al polvo y el

humo de pentxido de vanadio est asociada con la
irritacin de los ojos, la nariz y la garganta. En los
trabajadores expuestos al polvo y el humo de pentxido
de vanadio se suelen notificar jadeo y disnea. En conjunto, no hay datos suficientes que permitan describir de
manera fidedigna la relacin exposicin-respuesta para
los efectos respiratorios del polvo y el humo de pentxido de vanadio en las personas.
En las personas, la limitada informacin txicocinetica disponible parece indicar que se absorbe
vanadio tras la inhalacin y luego se excreta en la orina
con una fase inicial de eliminacin rpida, seguida de
una fase ms lenta, que posiblemente se debe a la
eliminacin gradual de vanadio de los tejidos del
organismo. Tras la administracin oral, la absorcin de
vanadio tetravalente a partir del sistema gastrointestinal
es escasa. No se dispona de estudios cutneos.
Las formas pentavalentes y tetravelentes del

vanadio han provocado efectos aneugnicos in vitro
con activacin metablica y sin ella. Hay pruebas de que
estas formas de vanadio, as como el vanadio trivalente,
tambin pueden producir in vitro daos en el ADN/
cromosomas, habindose obtenido en los estudios
disponibles resultados tanto positivos como negativos.
El valor probatorio de los datos disponibles parece
indicar que los compuestos de vanadio no producen
mutaciones genticas en pruebas normalizadas in vitro
en clulas de bacterias o de mamferos.
En estudios de inhalacin y de administracin oral

en animales de laboratorio, el vanadio absorbido en los
estados pentavalente o tetravalente se distribuye fundamentalmente en los huesos, el hgado, el rin y el bazo,
y tambin se detecta en los testculos. La va principal de
excrecin del vanadio es a travs de la orina. Su pauta de
distribucin y excrecin indica que es posible la
acumulacin y retencin del vanadio absorbido, sobre
todo en los huesos. Hay pruebas de que el vanadio
tetravalente puede atravesar la barrera placentara y
llegar al feto.
In vivo, tanto los compuestos de vanadio pentavalentes como los tetravalentes han dado pruebas
manifiestas de aneuploida de las clulas somticas tras
la exposicin mediante varias vas diferentes. Las
pruebas de que los compuestos de vanadio tambin
pueden producir efectos clastognicos son desiguales,
al igual que en los estudios in vitro, y la posicin global
sobre la clastogenicidad en las clulas somticas es
incierta. Se obtuvo un resultado positivo en clulas
germinales de ratones a los que se administr pentxido
de vanadio por inyeccin intraperitoneal. Sin embargo,
hay dudas acerca del mecanismo en el que se basa este
efecto (aneugenicidad; clastogenicidad). Tampoco est
claro cmo se pueden generalizar estos resultados a vas
de exposicin ms realistas o a otros compuestos de
vanadio.
En el nico estudio de inhalacin aguda disponible

se notific una CL67 de 1440 mg/m3 (800 mg de vanadio/
m3) tras la exposicin de ratas a polvo de pentxido de
vanadio durante una hora. En estudios de administracin
oral en ratas y ratones se obtuvieron valores de la DL50
del orden de 10-160 mg/kg de peso corporal para el
pentxido de vanadio y otros compuestos de vanadio
pentavalente, mientras que para los compuestos de
vanadio tetravalente los valores de la DL50 son del orden
de 448-467 mg/kg de peso corporal. No hay informacin
relativa a la toxicidad cutnea.
En estudios realizados con trabajadores del vanadio se ha notificado irritacin ocular. No se inform de
irritacin cutnea en 100 voluntarios humanos tras la
prueba del parche cutneo con un 10% de pentxido de
vanadio, aunque la prueba del parche realizada en los
trabajadores produjo dos reacciones aisladas. No hay
informacin clara disponible de estudios en animales con
respecto al potencial de los compuestos de vanadio para
producir irritacin cutnea u ocular o bien sensibilizacin
cutnea.
Las caractersticas de la base de datos sobre la

genotoxicidad del pentxido de vanadio y otros compuestos de vanadio son tales que no es posible identificar claramente el nivel umbral para ninguna va de
exposicin de inters para el ser humano por debajo del
cual no habra que preocuparse por la posible actividad
genotxica.
52
No se dispone de informacin til sobre el

potencial carcinognico de ninguna de las formas de
vanadio por ninguna de las vas de exposicin para los
animales 1 o las personas.
pocos datos sobre las concentraciones en lugares

industriales especficos y no es posible realizar una
evaluacin del riesgo sobre esta base. Sin embargo, las
concentraciones notificadas parecen ser semejantes a las
naturales ms altas, lo que parece indicar que el riesgo
sera bajo. Se deben realizar mediciones locales para
evaluar el riesgo en cualquier circunstancia determinada.
Un estudio de la fecundidad en ratones machos,

con exposicin al metavanadato de sodio en el agua de
bebida, parece indicar la posibilidad de que la exposicin
oral de los ratones machos a este compuesto a
concentraciones de 60 y 80 mg/kg de peso corporal
causara directamente una disminucin del recuento de
espermtidas/espermatozoides y del nmero de gestaciones tras el apareamiento. Sin embargo, tambin se
pudo observar una toxicidad general significativa
(disminucin del aumento del peso corporal) a 80 mg/kg
de peso corporal).
Hay algunos estudios sobre los efectos de los
compuestos de vanadio pentavalente o tetravalente en el
desarrollo, con una observacin sistemtica de anomalas esquelticas. La interpretacin de estos estudios es
difcil, debido a las vas de exposicin no tradicionales
utilizadas y a que hay pruebas de toxicidad materna, la
cual podra contribuir por s misma a los efectos detectados en las cras.
Los efectos toxicolgicos finales motivo de preocupacin para las personas son la genotoxicidad y la
irritacin de las vas respiratorias. Puesto que no es
posible determinar un nivel de exposicin sin efectos
adversos, se recomienda reducir los niveles en la medida
de lo posible.
Los valores de la CL50 para la toxicidad aguda de
organismos acuticos oscila entre 0,2 y unos 120 mg/litro, aunque para la mayora estn entre 1 y 12 mg/litro.
Otros efectos finales importantes desde el punto de vista
ecotoxicolgico se observaron en el desarrollo de las
larvas de ostras (reduccin significativa con 0,05 mg de
vanadio/litro) y en la reproduccin de Daphnia (concentracin sin efectos observados en 21 das con
1,13 mg/litro). Son pocos los estudios terrestres. La
mayora de los estudios en plantas se han realizado en
cultivos hidropnicos, donde se detectaron efectos a
concentraciones de 5 mg/litro y superiores; estos
estudios son difciles de interpretar en relacin con las
plantas cultivadas en el suelo.
Las concentraciones en los compartimentos del
medio ambiente son notablemente inferiores a las
concentraciones txicas notificadas. Se dispone de
1
Los autores de este documento tienen conocimiento de

que recientemente se ha completado en el Programa
Nacional de Toxicologa de los Estados Unidos una
biovaloracin por inhalacin de dos aos en roedores.
Sin embargo, en este momento no estn disponibles
todava los resultados.
53
THE CONCISE INTERNATIONAL CHEMICAL ASSESSMENT DOCUMENT SERIES
Azodicarbonamide (No. 16, 1999)

Benzoic acid and sodium benzoate (No. 26, 2000)
Benzyl butyl phthalate (No. 17, 1999)
Biphenyl (No. 6, 1999)
2-Butoxyethanol (No. 10, 1998)
Chloral hydrate (No. 25, 2000)
Crystalline silica, Quartz (No. 24, 2000)
Cumene (No. 18, 1999)
1,2-Diaminoethane (No. 15, 1999)
3,3'-Dichlorobenzidine (No. 2, 1998)
1,2-Dichloroethane (No. 1, 1998)
2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) (No. 23, 2000)
Diphenylmethane diisocyanate (MDI) (No. 27, 2000)
Ethylenediamine (No. 15, 1999)
Ethylene glycol: environmental aspects (No. 22, 2000)
2-Furaldehyde (No. 21, 2000)
HCFC-123 (No. 23, 2000)
Limonene (No. 5, 1998)
Manganese and its compounds (No. 12, 1999)
Methyl chloride (No. 28, 2000)
Methyl methacrylate (No. 4, 1998)
Mononitrophenols (No. 20, 2000)
Phenylhydrazine (No. 19, 2000)
N-Phenyl-1-naphthylamine (No. 9, 1998)
1,1,2,2-Tetrachloroethane (No. 3, 1998)
1,1,1,2-Tetrafluoroethane (No. 11, 1998)
o-Toluidine (No. 7, 1998)
Tributyltin oxide (No. 14, 1999)
Triglycidyl isocyanurate (No. 8, 1998)
Triphenyltin compounds (No. 13, 1999)
To order further copies of monographs in this series, please contact Marketing and Dissemination,
World Health Organization, 1211 Geneva 27, Switzerland
(Fax No.: 41-22-7914857; E-mail: bookorders@who.int)

Cicad 29

Încărcat de

Informații document

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

Cicad 29

Încărcat de

Drepturi de autor:

Formate disponibile

This report contains the collective views of an international group of experts and does not

Concise International Chemical Assessment Document 29

VANADIUM PENTOXIDE AND

First draft prepared by

World Health Organization

(NLM Classification: QV 290)

IDENTITY AND PHYSICAL/CHEMICAL PROPERTIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Workplace air monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION . . . . . . . . . . . . . . . . . . . . . . 9

Chemical speciation of vanadium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

COMPARATIVE KINETICS AND METABOLISM IN LABORATORY ANIMALS AND

EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Concise International Chemical Assessment Document 29

8.6.2 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Vanadium pentoxide and other inorganic vanadium compounds

10. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

11. EFFECTS EVALUATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Evaluation of health effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

12. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Vanadium pentoxide and other inorganic vanadium compounds

provided as guidance only. The reader is referred to EHC

Concise International Chemical Assessment

While every effort is made to ensure that CICADs

International Chemical Safety Cards on the

The first draft is based on an existing national,

The draft is then sent to an international peer

Risks to human health and the environment will

International Programme on Chemical Safety (1994)

Concise International Chemical Assessment Document 29

CICAD PREPARATION FLOW CHART

SELECTION OF PRIORITY CHEMICAL

SELECTION OF HIGH QUALITY

PRIMARY REVIEW BY IPCS

REVIEW BY IPCS CONTACT POINTS/

FINAL REVIEW BOARD

APPROVAL BY DIRECTOR, IPCS

1 Taking into account the comments from reviewers.

Vanadium pentoxide and other inorganic vanadium compounds

is submitted to a Final Review Board together with the

to ensure that each CICAD has been subjected to

Board members serve in their personal capacity, not as

Concise International Chemical Assessment Document 29

This CICAD on vanadium pentoxide and other

Most surface fresh waters contain less than 3 g

Vanadium is an abundant element with a very wide

A few organisms concentrate vanadium, with up to

Atmospheric emissions from natural sources have

Estimates of total dietary intake of humans range

Vanadium pentoxide and other inorganic vanadium compounds

potable water show concentrations above 50 g/litre.

pentoxide dust and fume. Overall, there are insufficient

Pentavalent and tetravalent forms of vanadium

In inhalation and oral studies in laboratory animals,

In vivo, both pentavalent and tetravalent vanadium

The one acute inhalation study available reported

Eye irritation has been reported in studies in

In a group of human volunteers, a single 8-h

The authors of this document are aware that a 2-year

Concise International Chemical Assessment Document 29

There are a number of developmental studies on

provides some physicochemical properties of vanadium