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 (NLM Classification: QV 290)

ISSN 1020-6167

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 TABLE OF CONTENTS

FOREWORD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1. EXECUTIVE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

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

3. ANALYTICAL METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

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

3.2 Biological monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.3 Environmental monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

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

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

5.1 Chemical speciation of vanadium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

5.2 Essentiality of vanadium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
5.3 Bioaccumulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
5.4 Leaching and bioavailability in soils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

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

6.1 Environmental levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

6.1.1 Air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
6.1.2 Surface waters and sediments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
6.1.3 Biota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
6.1.4 Soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
6.2 Human exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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 Single exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

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

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Concise International Chemical Assessment Document 29

8.6.2 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

8.7 Genotoxicity and related end-points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.1 Studies in prokaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.1.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.1.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.1.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.1.4 Trivalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.2 In vitro studies in eukaryotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.2.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8.7.2.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
8.7.2.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
8.7.2.4 Trivalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
8.7.3 Sister chromatid exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
8.7.4 Other in vitro studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
8.7.4.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
8.7.4.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
8.7.4.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8.7.5 In vivo studies in eukaryotes (somatic cells) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8.7.5.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8.7.5.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8.7.5.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8.7.6 In vivo studies in eukaryotes (germ cells) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8.7.6.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
8.7.6.2 Other pentavalent and tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
8.7.7 Supporting data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
8.8 Reproductive toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
8.8.1 Effects on fertility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
8.8.1.1 Vanadium pentoxide and other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . 23
8.8.1.2 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
8.8.2 Developmental toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
8.8.2.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
8.8.2.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
8.8.2.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
8.9 Immunological and neurological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
8.9.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
8.9.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
8.9.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

9. EFFECTS ON HUMANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

9.1 Studies on volunteers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

9.1.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
9.1.2 Other pentavalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
9.1.3 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
9.2 Clinical and epidemiological studies for occupational exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
9.2.1 Vanadium pentoxide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
9.2.2 Tetravalent vanadium compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
9.3 Epidemiological studies for general population exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

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 Vanadium pentoxide and other inorganic vanadium compounds

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

10.1 Aquatic environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

10.2 Terrestrial environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

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

11.1 Evaluation of health effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

11.1.1 Hazard identification and dose–response assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
11.1.2 Criteria for setting tolerable intakes or guidance values for vanadium pentoxide . . . . . . . . . . . . . . . . . . 33
11.1.3 Sample risk characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
11.1.4 Uncertainties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
11.2 Evaluation of environmental effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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

RÉSUMÉ D’ORIENTATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

RESUMEN DE ORIENTACIÓN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51

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 Vanadium pentoxide and other inorganic vanadium compounds
FOREWORD
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.
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.
CICADs are concise documents that provide sum-
maries 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 primary objective of CICADs is characteri-
zation of hazard and dose–response 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.
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
1
provided as guidance only. The reader is referred to EHC
1701 for advice on the derivation of health-based
tolerable intakes and guidance values.
While every effort is made to ensure that CICADs
represent the current status of knowledge, new informa-
tion 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 informa-
tion that would change the conclusions drawn in a
CICAD, the reader is requested to contact IPCS to inform
it of the new information.
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 high-
quality evaluations of toxicological, exposure, and other
data that are necessary for assessing risks to human
health and/or the environment. The IPCS Risk Assess-
ment 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.
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 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
1
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).
 Concise International Chemical Assessment Document 29

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 2

FINAL DRAFT 3

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.

2
 Vanadium pentoxide and other inorganic vanadium compounds

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.

3
Concise International Chemical Assessment Document 29
1. EXECUTIVE SUMMARY
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 Kingdom’s 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
26–29 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.
Vanadium (CAS No. 7440-62-2) is a soft silvery-
grey metal that can exist in a number of different oxida-
tion 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.
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 pentox-
ide 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.
Atmospheric emissions from natural sources have
been estimated at 8.4 tonnes per annum globally (range
1.5–49.2 tonnes). By far the most important source of
environmental contamination with vanadium is combus-
tion of oil and coal; about 90% of the approximately
4
64 000 tonnes of vanadium that are emitted to the atmos-
phere each year from both natural and anthropogenic
sources comes from oil combustion.
The environmental chemistry of vanadium is com-
plex. 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 poly-
chaete 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 biomagnifica-
tion 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. Representa-
tive deposition rates are 0.1–10 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 <0.001–0.01 kg/ha per annum
for remote sites.
Most surface fresh waters contain less than 3 µg
vanadium/litre; higher levels of up to about 70 µg/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 µg/litre, and sediment concentrations range
from 20 to 200 µg/g; the highest levels are in coastal
sediments.
A few organisms concentrate vanadium, with up to
10 000 µg/g in ascidians and 786 µg/g in polychaete
annelids. Most other organisms contain generally less
than 50 µg/g and usually much lower concentrations.
Estimates of total dietary intake of humans range
from 11 to 30 µg/day. Levels in drinking-water range up
to 100 µg/litre. Some groundwater sources supplying
 Vanadium pentoxide and other inorganic vanadium compounds
potable water show concentrations above 50 µg/litre.
Levels in bottled spring water may be higher.
In humans, there is limited toxicokinetic informa-
tion 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.
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.
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 10–160 mg/kg body weight for vanadium pentox-
ide and other pentavalent vanadium compounds, while
tetravalent vanadium compounds have LD 50 values in
the range 448–467 mg/kg body weight. No information is
available concerning dermal toxicity.
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.
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 exces-
sive 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
5
pentoxide dust and fume. Overall, there are insufficient
data to reliably describe the exposure–response relation-
ship for the respiratory effects of vanadium pentoxide
dust and fume in humans.
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 vana-
dium 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 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 clasto-
genicity 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 nature of the genotoxicity database on vana-
dium 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.
No useful information is available on the carcino-
genic 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.
1
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.
Concise International Chemical Assessment Document 29
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.
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.
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.
Concentrations in environmental media are sub-
stantially 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.
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 meta-
vanadate (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
6
provides some physicochemical properties of vanadium
compounds that are referred to in this review.
Vanadium (CAS No. 7440-62-2) is a soft silvery-
grey 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.
Vapour pressures (and hence Henry’s law con-
stants) and octanol/water partition coefficients are not
available for vanadium compounds.
3. ANALYTICAL METHODS
3.1 Workplace air monitoring
Airborne monitoring is largely based on measure-
ment 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.
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 induc-
tively 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.
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).
 Vanadium pentoxide and other inorganic vanadium compounds

Table 1: Physical/chemical properties of vanadium and selected inorganic vanadium compounds.

Solubility (g/litre)

CAS Molecular/ Melting Boiling Cold water

Compound number atomic mass point (°C) point (°C) (20–25 °C) Hot water Other solvents

Vanadium, V 7440-62-2 50.942 1890 ± 10; 3380 Insoluble Insoluble Not attacked by hot or
1917 cold hydrochloric acid
or cold sulfuric acid,
but soluble in
hydrofluoric acid, nitric
acid, and aquaregia

Vanadium 1314-62-1 181.9 690 1750 8 No data Soluble in acid/alkali;

pentoxide, insoluble in absolute
V 2O5 alcohol

Sodium meta- 13718-26- 121.93 No data No data 211 388 (at 75 No data
vanadate, 8 °C)
NaVO3

Sodium ortho- 13721-39- 183.91 850–856 No data Soluble No data Soluble in alcohol
vanadate, 6
Na 3VO4

Ammonium 7803-55-6 116.98 200 No data 58 Decomposes Soluble in ammonium

meta- (decom- carbonate
vanadate, poses)
NH4VO3

Vanadium 7727-18-6 Soluble, No data Soluble in alcohol,

oxytrichloride, decomposes ether, acetic acid
VOCl 3

Vanadyl 27774-13- Very soluble No data No data

sulfate, 6
VOSO4

Vanadyl 10213-09- Decomposes No data Soluble in dilute nitric

oxydichloride, 9 acid
VOCl 2

Vanadium 1314-34-7 Slightly Soluble Soluble in nitric acid,

trioxide, V 2O3 soluble hydrofluoric acid,
alkali

Vanadium is eliminated in the urine with a half-life
of 15–40 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 mid-
shift urinary vanadium as an indicator of exposure.
Blood vanadium levels were also determined but offered
no advantage over urine measurements. As non-
invasive sampling is normally preferred for routine
biological monitoring, the measurement of vanadium in
urine is generally recommended.
In biological monitoring studies of occupational
vanadium exposure, urinary levels of vanadium asso-
ciated 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
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 µg/litre for vanadium in urine, with analytical
precisions of 11% relative standard deviation at 1 µg/litre
and 4% at 10 µg/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 5–2000 µg/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 µg/litre,
respectively (US EPA, 1986). Instrumental neutron
activation analysis gave detection limits of 0.01 µg/g in

7
Concise International Chemical Assessment Document 29
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).
4. SOURCES OF HUMAN AND
ENVIRONMENTAL EXPOSURE
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
1.5–2.5% 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 12–24% vanadium pentoxide, which is used for
the production of vanadium metal. Worldwide produc-
tion 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 alumino-
thermic process.
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 µg/g and in
residual fuel oil from 0.2 to 160 µg/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 vana-
dium 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 cer-
tain 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
8
outside the United Kingdom, is used in very small quan-
tities 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 4–6%
vanadium as vanadium pentoxide on a silica base.
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 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 1.5–49.2 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).
 Vanadium pentoxide and other inorganic vanadium compounds
5. ENVIRONMENTAL TRANSPORT,
DISTRIBUTION, AND TRANSFORMATION
5.1 Chemical speciation of vanadium
The chemistry of vanadium is extremely complex,
and the reader is referred elsewhere for detailed dis-
cussion 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.
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 non-
volatile 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 com-
plex 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).
Within tissues in organisms, V3+ and V4+ predom-
inate because of largely reducing conditions; in plasma,
however, which is high in oxygen, V5+ is formed (Crans
et al., 1998).
5.2 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
9
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 molybdenum–iron 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 molybdenum–iron enzyme and
relying exclusively on the vanadium–iron enzyme are
known.
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.
Recent reviews on the role of vanadium in biologi-
cal 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 Bioaccumulation
Ascidians have been known to accumulate large
residues of vanadium since a first report in 1911 (Henze,
1911). The metal accumulates in blood cells (vanado-
cytes). 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 signifi-
cance 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
Concise International Chemical Assessment Document 29
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 physio-
logical roles of the metal are discussed in Ishii (1998).
Apart from the specific accumulators mentioned
above, organisms generally do not concentrate or accu-
mulate 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 (63–98.8%).
For a single fish species (Gobius minutus), assimilation
was much lower, at 2–3%, 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 bioaccu-
mulation 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 µg/g wet
weight. The authors suggest a unique dietary source, a
unique geochemical source, or anthropogenic input to
10
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).
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 environmen-
tal levels of vanadium. The metal has been monitored in
geographical areas with naturally high occurrence of the
metal (mainly volcanic regions) where local water con-
tributes 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 down-
wind of the Kuwait oil fires in 1991–1992. The ranges are
very large, and there is no simple explanation for the
 Vanadium pentoxide and other inorganic vanadium compounds

Table 2: Ranges of concentrations of vanadium in air. 1969). A wider survey of Wyoming, Idaho, Utah, and
Colorado in the USA showed vanadium concentrations
Atmospheric
concentration of 2.0–9.0 µg/litre (Parker et al., 1978). Unfiltered water
Area (ng/m3) Reference from the source area of the Yangtze River in China con-
Urban air 0.4–1460 Schroeder et al., 1987 tained between 0.24 and 64.5 µg/litre, whereas concentra-
Rural air 2.7–97 tions in filtered water ranged from 0.02 to 0.46 µg/litre
Remote areasa 0.001–14 (Zhang & Zhou, 1992). The highest levels reported are in
Urban air 0.5–1230 Mamane & Pirrone, surface waters in the area of Mount Fuji in Japan. Two
Rural air 0.4–500 1998 springs had 14.8 and 16.4 µg/litre, and five river samples
Remote areas 0.01–2 showed between 17.7 and 48.8 µg/litre (Hamada, 1998).
Dhahran, Saudi 2.4–1170 (in Sadiq & Mian, 1994
Arabia, during the PM 10 Data on concentrations of vanadium in wastewater
Kuwait oil fires fraction) and local surface water are few, and studies are old;
aIncludes the Arctic and oceanic islands in the Atlantic and reliability for present-day operations is questionable. A
Pacific. 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 µg/li-
variation; possible causes are reviewed by Mamane & tre in industrial areas seem more likely.
Pirrone (1998), although they can draw no firm conclu-
sions. Seawater concentrations have been reviewed by
Miramand & Fowler (1998). Most reported concentra-
Vanadium in air from oil combustion tends to be in tions in the open ocean have been in the range 1–3 µg/li-
smaller particulate fractions. In arid areas with dust tre, with the highest reported value at 7.1 µg/litre. Sedi-
storms, high levels of vanadium have been reported; ment concentrations range from 20 to 200 µg/g dry
here, particle size tends to be much larger (Mamane & weight, with higher levels in coastal sediments.
Pirrone, 1998).
6.1.3 Biota
Bulk precipitation concentration ranges have been
reported at 4.1–13 µg/litre for the rural United Kingdom Ranges of concentrations of vanadium in marine
(Galloway et al., 1982) and 0.12–0.65 µg/litre (mean 0.45 organisms are given in Table 3, based on a review of the
µg/litre) in Switzerland (Atteia, 1994). Wet deposition in literature in Miramand & Fowler (1998), where the
an area of New England remote from anthropogenic original references can be found. The ranges include
input showed concentrations of vanadium ranging from values from areas of likely local contamination from
0.2 to 1.16 µg/litre (average 0.67 µg/litre) and in Bermuda industrial sources. With the exception of ascidians
ranging from 0.049 to 0.111 µg/litre (average 0.096 (tunicates), some annelids, and molluscs, concentrations
µg/litre) (Church et al., 1984). Ice and snow levels in of vanadium in marine organisms are low. The range for
northern Norway and Alaska were 0.31 and 0.13 µg/litre, planktonic species is heavily influenced by a single
respectively (Galloway et al., 1982), and two ice core study showing accumulation up to 290 mg/kg dry
levels in Greenland were reported at 0.022 and 0.016 weight; this was mainly into shells of planktonic forms of
µg/litre. Levels in rain ranged from 1.1 to 46 µg/litre for molluscs. Generally, planktonic organisms show
rural and urban sites in North America and Europe concentrations of vanadium around 1 mg/kg.
(Galloway et al., 1982).
There are fewer data for freshwater organisms. The
Based on these reported concentrations, Mamone most comprehensive study of organisms was conducted
& Pirrone (1998) calculated representative total depo- in the Mount Fuji area of Japan, where concentrations in
sition rates of vanadium at 0.1–10 kg/ha per annum for organisms from water with high (43.4 µg/litre) and lower
urban sites affected by strong local sources, 0.01– (0.72 or 0.4 µg/litre) concentrations of vanadium were
0.1 kg/ha per annum for rural sites and urban ones with compared. Water plants from the high-vanadium area
no strong local source, and <0.001–0.01 kg/ha per annum contained 21.8 ± 11.3 µg/g dry weight of the metal (range
for remote sites. 5.6–43.7 µg/g), compared with 0.79 ± 0.52 µg/g (range
0.22–1.91 µg/g) in the low-vanadium area. A green
6.1.2 Surface waters and sediments microalga in the high-concentration area contained the
highest reported concentration of the metal, at 118–168
Most surface fresh waters contain less than 3 µg µg/g dry weight. The vanadium concentration in rainbow
vanadium/litre (Hamada, 1998). The vanadium content of trout (Oncorhynchus mykiss) farmed in water from these
water from the Colorado River basin (USA) ranged from areas was measured: bone concentrations
0.2 to 49.2 µg/litre, with the highest levels associated
with uranium–vanadium mining (Linstedt & Kruger,

11
Concise International Chemical Assessment Document 29
Table 3: Concentrations of vanadium in marine organisms.a
Concentration of vanadium
Organism (mg/kg dry weight)
Phytoplankton 1.5–4.7
Zooplankton 0.07–290
Macroalgae 0.4–8.9
Ascidians 25–10 000
Annelids 0.7–786
Other invertebrates 0.004–45.7
Fish 0.08–3
Mammals <0.01–1.04 (fresh weight)
a From Miramand & Fowler (1998).
were 0.87, 4.77, and 17.2 µg/g and kidney concentrations
were 0.43, 2.38, and 4.63 µg/g for water concentrations of
0.72, 43.4, and 82.7 µg/litre, respectively. In all cases,
muscle concentrations were low and did not differ
between areas (0.016–0.024 µg/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).
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 µg/g dry weight (Custer & Hohman, 1994).
The mean vanadium concentration in four species of
Japanese waterfowl ranged from 3.69 to 8.11 µg/g dry
weight in kidney and from 0.39 to 3.69 µg/g in liver tissue
(Mochizuki et al., 1999).
6.1.4 Soil
At distances of 600–2400 m from a metallurgical
plant producing vanadium pentoxide, to a depth of
10 cm, the surface layer of the soil contained 18–136 mg
vanadium/kg dry weight (Lener et al., 1998). The back-
ground concentration for the area is not stated, although
levels at 600 m from the plant are clearly elevated com-
pared 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).
12
6.2 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.
The main activity where workers can be exposed to
vanadium in the United Kingdom is the cleaning of oil-
fired 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. Respira-
tory protective equipment is usually worn during boiler
cleaning operations.
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.
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.
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 (Kivilu-
oto, 1981). Generally, two samples were taken per person
over a 2-month period. The mean respirable fraction
 Vanadium pentoxide and other inorganic vanadium compounds

Table 4: Biological monitoring studies of occupational vanadium exposure.

Sample Measured air V Urine V (µg/litre)

Industry matrix No. of subjects (mg/m3) (TWA) (range) Reference

V 2O5 production Urine 58 Up to 5 28.3 (3–762) Kucera et al., 1992

Boiler cleaning Urine 4 2.3–18.6 2–10.5 White et al., 1987

(0.1–6.3)

Incinerator workers Urine 43 Not known <0.1–2 Wrbitsky et al., 1995

Boiler cleaners Urine 10 (!RPE) a Not known 92 (20–270) Todaro et al., 1991
10 (+RPE) 38

Boiler cleaners Urine 30 0.04–88.7 (0.1–322) Smith et al., 1992

V alloy production Urine 5 Not known 3.6 (0.5–8.9) Arbouine, 1990

Pigment Urine 8 Not known 2.3 (0.8–6.3) Arbouine, 1990

manufacture

V 2O5 staining Urine 2 (<0.04–0.13) <4–124 Kawai et al., 1989

Unexposed (general Urine 213 012 0.22 (0.07–0.5) Kucera et al., 1992
population) <0.4 White et al., 1987
<0.1 Smith, 1992

a RPE = respiratory protective equipment.

(particle size 5 µm or less) of the dust was 20%. The
highest values (expressed as total inhalable vanadium)
were obtained in the laboratory (range 0.25–4.7 mg/m3,
mean shift length exposure 1.7 mg/m3) and the smelting
room (0.055–0.47 mg/m3, mean 0.21 mg/m3), but were
usually much lower for other processes (around 0.002–
0.18 mg/m3, mean 0.005–0.037 mg/m3).
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 0.5–33 years (mean
duration of exposure 9.2 years) was exposed to airborne
vanadium concentrations of 0.016–4.8 mg/m3. Urinary
vanadium content was 3.02–769 ng/ml, compared with
0.066–53.4 ng/ml in controls. In blood, vanadium levels
were 3.1–217 ng/ml, compared with 0.032–0.095 ng/ml in
controls. The vanadium content in the hair of exposed
and non-exposed persons was in the range of 0.103–203
mg/kg and 0.009–3.03 mg/kg, respectively, and the
vanadium content in the fingernails was in the range of
0.260–614 mg/kg and 0.017–16.5 mg/kg, respectively.
Determinations of the vanadium content were carried out
by both radiochemical and instrumental neutron
activation analyses in all instances.
to a vanadium slag processing plant in the Czech
Republic showed concentrations ranging from 0.01 to
0.44 µg/litre; the local municipal supply contained
0.01 µg/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 µg/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 µg/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 concen-
trations between non-detectable and 20 µg/litre, 54%
between 20 and 50 µg/litre, and 13% higher than 50 µg/li-
tre (Giammanco et al., 1996). Older studies summarized in
IPCS (1988) report drinking-water concentrations up to
70 µg/litre, although the majority of samples contained
less than 10 µg/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 4–290 µg/litre (Schlettwein-Gzell & Mommsen-
Straub, 1973).

Estimates given in IPCS (1988) for total dietary
intake of the general population in food range from 11 to
30 µg/day (adults). The mean vanadium concentration in
drinking-water in Cleveland, USA, was 5 µg/litre, with a
maximum of 100 µg/litre (Strain et al., 1982). Wells close
The mean concentration of vanadium in cigarettes
was 1.11 ± 0.35 µg/g, and the mean concentration in
cigarette smoke was 0.33 ± 0.06 µg/g (Adachi et al., 1998).

13
Concise International Chemical Assessment Document 29
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 µg/g
dry weight (Bu-Olayan & Al-Yakoob, 1998).
7. COMPARATIVE KINETICS AND
METABOLISM IN LABORATORY ANIMALS
AND HUMANS
Human exposure data suggest that vanadium
(chemical form unknown) is absorbed following inhala-
tion exposure to 0.03–0.77 mg vanadium/m3 and is sub-
sequently 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 50–125 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.
Groups of two rats were exposed to ammonium
metavanadate (pentavalent vanadium, median mass
aerodynamic diameter [MMAD] 0.32 µm) at a concen-
tration of 2 mg/m3 for 8 h/day for 4 days (Cohen et al.,
1996b). There was a tendency for vanadium to accumu-
late 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 µg/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 µg
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.
14
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 tetra-
valent states is distributed mainly to the bone (around
10–25% of the administered dose 3 days after admin-
istration) 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).
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 calcu-
lated 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.
8. EFFECTS ON LABORATORY
MAMMALS AND IN VITRO TEST SYSTEMS
Where data on vanadium pentoxide are lacking,
information on properties of other pentavalent or tetra-
valent vanadium compounds is utilized. There is no
toxicological information on elemental vanadium and
negligible information on the trivalent forms.
 Vanadium pentoxide and other inorganic vanadium compounds
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
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 µm) died within 12–24 h. Clinical signs of toxicity
included respiratory distress, “mucosal irritation”
(tissues unstated), and diarrhoea.
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 86–137 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 dose–response characteristics of
these effects were not described.
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.
For mice, oral LD 50 values for vanadium pentoxide
were in the range 64–117 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 Other pentavalent vanadium compounds
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
and decreased sensitivity to pain. At the highest doses
(not clearly defined), intense diarrhoea, irregular res-
piration, and increased cardiac rhythm and ataxia were
reported. The effects had mostly disappeared in sur-
vivors at 48 h after treatment. No histopathology was
performed.
The MAK (1992) review cites rat oral LD 50 values
in the range 18–160 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.
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.
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 Trivalent vanadium compounds
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.
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.
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.
Concise International Chemical Assessment Document 29
8.3 Effects of inhaled vanadium
compounds on the respiratory tract
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 dose–response relation-
ships.
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 0.59–0.61 µm)
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 18–21 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.
Evidence of slight impairment of pulmonary func-
tion 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 statis-
tically 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
16
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.
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.
Another study in monkeys by Knecht et al. (1992)
compared bronchial reactivity following challenge with
vanadium pentoxide dust, both before and after sub-
chronic 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 1–5 micro-
metres”) 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.
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
 Vanadium pentoxide and other inorganic vanadium compounds
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.
At the second challenge, after subchronic expo-
sure, 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.
A significant increase in the total number of
respiratory cells in BAL fluid was observed following
pre-subchronic exposure challenge with 3.0 mg vana-
dium 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 sub-
chronic vanadium pentoxide exposure. Similarly, serum
immunoglobulins were unchanged throughout the
study.
8.4 Other short-term exposure studies
Oral studies are described below; no dermal
studies are available.
17
8.4.1 Vanadium pentoxide
Short-term immunotoxicity studies are described
briefly in section 8.9.1.
8.4.2 Other pentavalent vanadium compounds
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.
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 microhaemor-
rhagic 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.
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 treat-
ment, haematological indices (haematocrit, haemoglobin
concentration, erythrocyte count, leukocyte count,
platelet count, reticulocyte count, and erythrocyte
osmotic fragility) of the peripheral blood were investi-
gated in all animals. There were no other investigations.
No difference in food intake or body weight was appar-
ent between the groups. There were no differences in
haematological parameters between the groups.
Groups of 15–16 male and female rats were admin-
istered 0, 1.5, or 5–6 mg vanadium/kg body weight per
day as ammonium metavanadate in drinking-water for
4 weeks (Zaporowska et al., 1993). No differences in
Concise International Chemical Assessment Document 29
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 signif-
icant, decreases in erythrocyte number and haemoglobin
concentration (top dose only, all about 10% less than
control) were observed. Similarly, a slight but statis-
tically 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.
Groups of 12–13 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).
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).
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 5–10 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
18
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.
Short-term immunotoxicity studies are described
briefly in section 8.9.2.
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)oxo-
vanadium (+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 haema-
tological parameters between the groups.
Short-term immunotoxicity studies are described
briefly in section 8.9.3.
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 six male rats received 0, 10, or 40 µg/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 µg 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.
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 µg/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
 Vanadium pentoxide and other inorganic vanadium compounds
reduced at 10 µg/ml only. Again, this study did not
reveal any clearly toxicologically significant changes
attributable to vanadium exposure.
8.5.2 Tetravalent vanadium compounds
There are no data available.
8.6 Long-term exposure and
carcinogenicity
8.6.1 Vanadium pentoxide and other
pentavalent vanadium compounds
Long-term oral and dermal exposures to vanadium
pentoxide and other pentavalent vanadium compounds
have not been studied.
In a study conducted by Yao et al. (1986a) and
cited by Sun (1987), groups of 62–84 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.
8.6.2 Tetravalent vanadium compounds
Long-term inhalation and dermal exposures to
tetravalent vanadium compounds have not been studied.
As part of a study related to the investigation of
diabetes, groups of 8–23 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).
8.7 Genotoxicity and related end-points
8.7.1 Studies in prokaryotes
8.7.1.1 Vanadium pentoxide
Only very limited data are available (see section
8.7.7).
19
8.7.1.2 Other pentavalent vanadium compounds
There are no data available.
8.7.1.3 Tetravalent vanadium compounds
There are no data available.
8.7.1.4 Trivalent vanadium compounds
One Ames test has been performed with vanadium
(+3) trichloride. Negative results were obtained, in the
presence and absence of metabolic activation, at concen-
trations between 1 and 200 µg/plate with Salmonella
typhimurium strains TA98, TA100, TA1535, TA1537,
and TA1538 and Escherichia coli WP2uvrA (JETOC,
1996).
8.7.2 In vitro studies in eukaryotes
8.7.2.1 Vanadium pentoxide
Vanadium pentoxide was added, at concentrations
of 0, 2, 4, and 6 µg/ml (0, 1, 2, and 3 µg 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 first-
division metaphases were analysed for structural and
numerical aberrations (polyploid only).
Mitotic index was statistically significantly
decreased (74, 41, and 42% of control value at 2, 4, and 6
µg/ml, respectively). The frequency of structural chro-
mosome 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 associa-
tions” (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 poly-
ploidy, is indicative of vanadium pentoxide exerting its
effects at the level of spindle formation.
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 µg/ml
(6.7 µg 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
Concise International Chemical Assessment Document 29
performed in cells cultured with vanadium pentoxide
concentrations of 0, 1, 2, or 3 µg/ml (0, 0.6, 1.1, or 2.2 µg
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 µg/ml,
respectively). This dose–response relationship was also
observed in the numbers of centromere-positive micro-
nuclei (49, 70, 82, and 89% of micronuclei, respectively).
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 µg vanadium pentoxide/ml (0, 0.6, 1.1, 1.7, or 2.2 µg
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 Other pentavalent vanadium compounds
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 µmol/litre (approximately 0, 0.13–8.0 µg
vanadium/ml), and the induction of structural and
numerical chromosome aberrations was investigated
(Migliore et al., 1993).
The highest dose of vanadium compounds used,
160 µmol/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.
Chinese hamster ovary cells were exposed to 0, 4,
8, or 16 µg ammonium metavanadate/ml (0, 1.7, 3.3, or 6.7
µg 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).
20
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.
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 2.5–160 µmol/litre
(approximately 0 and 0.13–8.0 µg vanadium/ml) in all
experiments, apart from the study involving in situ
hybridization, where only 0, 10, 40, and 80 µmol/litre
(approximately 0, 0.5, 2.1, and 4.2 µg 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.
The highest dose of vanadium used, 160 µmol/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 µmol/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 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 µmol/litre (Cohen et al., 1992). No treatment-
related increase in mutation frequency was reported,
with testing up to cytotoxic concentrations of ammonium
metavanadate.
Ammonium metavanadate induced both mitotic
gene conversion and reverse point mutation in the D7
strain of Saccharomyces cerevisiae at dose levels of
 Vanadium pentoxide and other inorganic vanadium compounds
between 80 and 210 mmol/litre in both the presence and
absence of metabolic activation (Bronzetti et al., 1990).
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 µmol 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.
8.7.2.3 Tetravalent vanadium compounds
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 signifi-
cant difference in the incidence of chromosome aberra-
tions (excluding gaps) was induced. A statistically
significant number of hypoploid cells was reported at the
top three doses (20–80 µmol/litre).
Owusu-Yaw et al. (1990) also exposed Chinese
hamster ovary cells to 6, 12, or 24 µg vanadyl sulfate/ml
(1.9, 3.7, or 7.4 µg 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.
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 µmol/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.
Vanadyl sulfate induced no convertants or rever-
tants 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.
No mutagenic activity was detected in hamster V79
cells at dose levels between 0 and 7.5 mmol vanadyl
21
sulfate/litre in both the presence and absence of meta-
bolic activation (Galli et al., 1991).
Vanadyl chloride did not produce an increased
incidence of transformations in the C3H10T1/2 mouse
fibroblast cell line at dose levels up to 5 µg/ml (Doran et
al., 1998).
8.7.2.4 Trivalent vanadium compounds
Using protocols similar to that previously ascribed
to these authors, Chinese hamster ovary cells were
exposed to 12 or 18 µg vanadium oxide/ml (8.2 or 12.2 µg
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.
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 con-
centrations (0.3–19.2 µg/ml) (Owusu-Yaw et al., 1990;
Roldan & Altamirano, 1990; Migliore et al., 1993; Zhong
et al., 1994).
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 µg 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.
8.7.4.2 Other pentavalent vanadium compounds
Chinese hamster V79 cells and human leukaemic T-
lymphocyte (MOLT4) cells were exposed to ammonium
metavanadate to investigate the formation of
DNA–protein cross-links (Cohen et al., 1992). Dose-
related increases in cross-links were reported following
24-h exposure to ammonium metavanadate in both cell
types.
Ammonium vanadate gave positive results in a
transformation assay in BALB/3T3 mouse embryo cells
at doses of 5 and 10 µmol/litre (Sabbioni et al., 1993).
Concise International Chemical Assessment Document 29
8.6.4.3 Tetravalent vanadium compounds
Vanadyl sulfate gave negative results in a trans-
formation assay in BALB/3T3 mouse embryo cells at
doses of 5 and 10 µmol/litre (Sabbioni et al., 1993). For
this study and the above-mentioned work on ammonium
metavanadate by these authors (section 8.7.4.2), cyto-
toxicity, as evidenced by about a 50% reduction in
colony-forming efficiency compared with controls, was
seen at a concentration of 5 µmol/litre.
8.7.5 In vivo studies in eukaryotes (somatic
cells)
8.7.5.1 Vanadium pentoxide
Only very limited data are available (see section
8.7.7).
8.7.5.2 Other pentavalent vanadium compounds
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 meta-
vanadate/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.
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 hyper-
ploidy 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.
Groups of 3–4 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.
22
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.
8.7.5.3 Tetravalent vanadium compounds
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 vana-
dium/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, com-
pared with 0.6% in negative controls). Statistically sig-
nificant 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.
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.
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 (15–20 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 copula-
tion plug or sperm in the vagina.
A statistically significantly reduced body weight in
treated animals at the end of the treatment period was
 Vanadium pentoxide and other inorganic vanadium compounds
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 implan-
tation 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 statis-
tically 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).
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 non-
standard protocol, poor reporting, and clearly reduced
pregnancy rate in females mated with treated males, the
clear increases in resorptions per litter and post-
implantation losses in the vanadium pentoxide group are
indicative of a dominant lethal effect.
8.7.6.2 Other pentavalent and tetravalent vanadium
compounds
There are no data available.
8.7.7 Supporting data
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.
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
µg/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.
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
pentoxide was tested at concentrations of 0, 10, 50, 100,
500, 1000, and 2000 µg/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 µg/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 con-
centrations (0.3–30 µg/ml) (Sun, undated).
Bone marrow micronucleus tests on vanadium
pentoxide via the intraperitoneal, subcutaneous, inhala-
tion, 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 intra-
peritoneally 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.
8.8 Reproductive toxicity
8.8.1 Effects on fertility
8.8.1.1 Vanadium pentoxide and other pentavalent
vanadium compounds
No fertility studies are available on vanadium
pentoxide.
Groups of 24 male mice received sodium meta-
vanadate 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.
Concise International Chemical Assessment Document 29
A 13% reduction in male body weight was appar-
ent 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 vana-
dium-treated group, but no dose–response relationship
was observed. No information was given on mating
behaviour. There were no significant differences
between the groups regarding the numbers of implan-
tations, 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.
This study suggests the possibility that oral expo-
sure 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 Tetravalent vanadium compounds
No data are available.
8.8.2 Developmental toxicity
8.8.2.1 Vanadium pentoxide
Groups of 18–21 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 6–15 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
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 abnormal-
ities were reported.
Although the reported increase in skeletal abnor-
malities at 18 mg/kg body weight is a concern, inter-
pretation 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.
8.8.2.2 Other pentavalent vanadium compounds
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 6–14
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, respec-
tively. 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.
 Vanadium pentoxide and other inorganic vanadium compounds
Groups of 18–20 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 6–15
of pregnancy (Sanchez et al., 1991). The animals were
sacrificed on day 18 of pregnancy.
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 differ-
ences 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 Tetravalent vanadium compounds
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 6–15 of gesta-
tion (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.
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, respec-
tively). The major dose-related effects externally were
increased incidence of cleft palate (an abnormality with a
significant background incidence in mice) at 75 and
25
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, respec-
tively). Delayed ossification was reported in all groups,
including controls.
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.
8.9 Immunological and neurological
effects
8.9.1 Vanadium pentoxide
Groups of 6–8 female rats received a solution of 0,
0.042, or 0.42 mg vanadium pentoxide in phosphate-
buffered 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 cyto-
kine, KC. The results demonstrate an inflammatory
response in the lungs associated with exposure to
vanadium pentoxide.
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. Simi-
larly, 10 male and 10 female ICR mice were given 0 or
Concise International Chemical Assessment Document 29
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 non-
specific immunity (phagocytosis, natural killer cell
activity), and humoral as well as cell-mediated immunity
(Mravcova et al., 1993).
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 neuro-
logical end-points.
8.9.2 Other pentavalent vanadium compounds
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 µm
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.
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 6–8 female rats received a solution of 0,
0.021, or 0.21 mg sodium metavanadate in phosphate-
buffered saline by single intratracheal administration
26
(Pierce et al., 1996). Procedures were as with the work on
vanadium pentoxide (section 8.9.1).
Results were similar to those obtained with vana-
dium 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.
There are no data specifically relating to neuro-
logical end-points.
8.9.3 Tetravalent vanadium compounds
As part of the study summarized above (sections
8.9.1 and 8.9.2), groups of 6–8 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 vana-
dium pentoxide, but occurred earlier and lasted longer
than with either vanadium pentoxide or sodium meta-
vanadate, indicating that, in this assay, this substance
was the most potent in an inflammatory response.
There are no data specifically relating to neuro-
logical end-points.
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 µm) 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
 Vanadium pentoxide and other inorganic vanadium compounds
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 per-
sisted 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.
9.1.2 Other pentavalent vanadium compounds
Five male medical students received an oral
administration of 100 or 125 mg diammonium oxy-
tartratovanadate/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 Tetravalent vanadium compounds
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.
A group of 12 volunteers received 75 mg diammo-
nium 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 choles-
terol levels. However, five patients had persistent upper
27
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.
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.
9.2 Clinical and epidemiological studies
for occupational exposure
9.2.1 Vanadium pentoxide
Eye irritation has been reported in studies in vana-
dium 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).
Zenz et al. (1962) reported on 18 workers exposed
to varying degrees to vanadium pentoxide dust (mean
particle size <5 µm) 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 devel-
oped 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 0.5–4 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.
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 signifi-
cance of these symptoms. However, the findings are
compatible with other studies on inhalation of vanadium
pentoxide.
Concise International Chemical Assessment Document 29
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.
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 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.
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.
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% com-
plained of wheezing (0% in control). Physical findings
included wheezes, rales, or rhonchi in 20.8% (0% in
28
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).
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 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 0.016–4.8 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.
Huang et al. (1989) conducted a clinical and radio-
logical 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, coars-
ened, and contorted bronchovascular shadowing (23%
in controls).
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 chro-
mium used in alloy production or chromium plating
(some of the effects described, particularly nasal septum
perforation, are consistent with chromium toxicity).
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
 Vanadium pentoxide and other inorganic vanadium compounds
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.
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.
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 dose–response
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 0.0016–0.032 mg/m3 “vanadium” (form unspec-
ified) (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
exposure–response 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 report-
ing 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
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 mean-
ingful conclusions can be drawn from this study.
9.2.2 Tetravalent vanadium compounds
There are no data available.
9.3 Epidemiological studies for general
population exposure
Early correlational studies relating general concen-
trations of vanadium in the environment to mortality
figures are summarized in IPCS (1988); no cause–effect
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 concen-
trated 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 drinking-
water 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 T-
lymphocyte 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 T-
lymphocytes 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
Concise International Chemical Assessment Document 29
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).
10. EFFECTS ON OTHER ORGANISMS IN
THE LABORATORY AND FIELD
10.1 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 2–165 ×10–7 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 cyano-
bacteria, and low proportion of Bacillariophyta and
Chrysophyta are most vulnerable to inhibition of
photosynthesis by vanadium (Nalewajko et al., 1995).
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.
Fichet & Miramand (1998) observed a significant
reduction in the development of normal oyster (Crassos-
trea 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 no-
observed-effect concentration (NOEC), based on off-
spring production in Daphnia magna, of 1.13 mg
vanadium/litre.
30
Stendahl & Sprague (1982) reported weight-
adjusted 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 (5.5–8.8). 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.
Hilton & Bettger (1988) fed juvenile rainbow trout
(Oncorhynchus mykiss) a diet containing sodium ortho-
vanadate at concentrations ranging from 10.2 to 8960 mg
vanadium/kg diet for 12 weeks. All levels of supple-
mented vanadium significantly reduced growth and
feeding response in the trout. Feed avoidance and
significantly increased mortality were reported at
>493 mg/kg diet.
10.2 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.
The growth of flax and cabbage was reduced at a
vanadium concentration of 0.5 mg/litre (nutrient solu-
tion), especially under conditions of low iron and phos-
phorus (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 30–50%.
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).
 Vanadium pentoxide and other inorganic vanadium compounds

Table 5: Toxicity of vanadium compounds to aquatic organisms.

Organism End-point Concentration (mg/litre) Reference

Marine algae

Green alga Dunaliella marina 15-day LC50 0.5 Miramand & Ünsal, 1978

Marine diatom
Diatom Asterionella japonica 15-day LC50 2 Miramand & Ünsal, 1978

Freshwater invertebrates

Water flea Daphnia magna 48-h LC50 3.1 Allen et al., 1995

48-h LC50 4.1 Beusen & Neven, 1987

23-day LC50 2 Beusen & Neven, 1987

Naidid oligochaete Pristina leidyi 48-h LC50 30.8 Smith et al., 1991

Marine invertebrates
Hydroid Cordylophora caspia 10-day LC50 5.8 Ringelband & Karbe, 1996

Worm Nereis diversicolor 9-day LC50 10 Miramand & Ünsal, 1978

Mussel Mytilus galloprovincialis 9-day LC50 35 Miramand & Ünsal, 1978

Crab Carcinus maenus 9-day LC50 65 Miramand & Ünsal, 1978

Brine shrimp Artemia salina (larvae) 9-day LC50 0.2–0.3 Miramand & Fowler, 1998

Sea urchin Arbaccia lixula (pluteus) 72-h LC100 0.5 Miramand & Fowler, 1998

Freshwater fish
Rainbow trout Oncorhynchus mykiss 96-h LC50 6.4–22 Giles et al., 1979

(juvenile) 96-h LC50 11.4 Giles & Klaverkamp, 1982

(eyed egg) 96-h LC50 118 Giles & Klaverkamp, 1982

96-h LC50 5.2–13.2 Stendahl & Sprague, 1982

7-day LC50 2.4–5.6 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 7–24 Ernst & Garside, 1987

Flag fish Jordanella floridae (adult) 96-h LC50 11.2 Holdway & Sprague, 1979

(larvae) 28-day LC50 1.1–1.9 Holdway & Sprague, 1979

Colorado squawfish Ptychocheilus lucius (fry) 96-h LC50 7.8 Hamilton, 1995

(juvenile) 96-h LC50 3.8–4.3 Hamilton, 1995

Razorback sucker Xyrauchen texanus (fry) 96-h LC50 8.8 Hamilton, 1995

(juvenile) 96-h LC50 3.0–4.0 Hamilton, 1995

Bonytail Gila elegans (fry) 96-h LC50 5.3 Hamilton, 1995

(juvenile) 96-h LC50 2.2–5.1 Hamilton, 1995

Flannelmouth sucker Catostomus latipinnis 96-h LC50 11.5 Hamilton & Buhl, 1997
(larvae)

Goldfish Carassius auratus 144-h LC50 2.5–8.1 Knudtson, 1979

Guppy Poecilia reticulata 96-h LC50 8 Beusen & Neven, 1987

144-h LC50 0.4–1.1 Knudtson, 1979

Zebrafish Brachydanio rerio 96-h LC50 4 Beusen & Neven, 1987

Freshwater teleost Nuria denricus 96-h LC50 2.6 Abbasi, 1998

Marine fish

Dab Limanda limanda 96-h LC50 27.8 Taylor et al., 1985

31
Concise International Chemical Assessment Document 29
11. EFFECTS EVALUATION
11.1 Evaluation of health effects
11.1.1 Hazard identification and dose–response
assessment
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.
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 10–160 mg/kg
body weight (6–90 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 448–467 mg/kg body
weight (90–94 mg/kg body weight as vanadium). No
information is available concerning dermal toxicity.
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 irrita-
tion. 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
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 pentox-
ide 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 mea-
sured 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.
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 involv-
ing 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. Expo-
sure 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.
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 poor-
quality 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 work-
ers exposed to vanadium pentoxide dust and fume.
Overall, there are insufficient data to reliably describe the
exposure–response relationship for the respiratory
effects of vanadium pentoxide dust and fume in humans.
 Vanadium pentoxide and other inorganic vanadium compounds
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 pos-
sible to characterize a dose–response 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.
Pentavalent and tetravalent forms of vanadium
have produced aneugenic effects in vitro. There is evi-
dence 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 evi-
dence from the available data suggests that vanadium
compounds do not produce gene mutations in standard
in vitro tests in bacterial or mammalian cells.
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 clasto-
genic 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 com-
pounds 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.
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.
1
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 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.
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
exposure–response relationship for the respiratory
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.
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 health-
based tolerable intakes and guidance values.
Concise International Chemical Assessment Document 29
The scenario chosen as a specific example is occu-
pational 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.
The other occupationally relevant form is vana-
dium 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 expo-
sure 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
exposure–response relationship for the respiratory
effects in humans. Thus, toxicity to the respiratory tract
will be a concern at all levels of occupational exposure.
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.
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 Uncertainties
Overall, the toxicokinetic and toxicological data-
base 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
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 plaus-
ible that the skeletal anomalies in pups may be related to
the disturbance of calcium balance (Younes & Strubelt,
1991) and interference with phosphate metabolism.
11.2 Evaluation of environmental effects
Vanadium is found in both fresh water and sea-
water in a natural background range of approximately
1–3 µg/litre. Locally high concentrations of the metal, up
to about 70 µg/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 µg/litre). A
single early reported concentration in surface waters
receiving industrial waste of 2 mg/litre may be unreliable.
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.
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 µg/litre for algal photosynthesis, 50 µg/litre for oyster
larval development, and 1130 µg/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).
 Vanadium pentoxide and other inorganic vanadium compounds

6
10
5
10

Log concentration of vanadium (µg/litre)

4 Single reported
10 concentration
for industrial waters
(reliability uncertain)
3
10
Highest reported
2 concentration in natural
10 water

1
10 Normal range for surface waters

0
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 Organization’s air quality
guideline for vanadium is 1 µg/m3, which is based on a
lowest-observed-adverse-effect level (LOAEL) of 20
µg/m3 from studies on occupationally exposed
individuals, using an overall uncertainty factor of 20
(WHO, 1987).

35
Concise International Chemical Assessment Document 29
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Concise International Chemical Assessment Document 29
APPENDIX 1 — SOURCE DOCUMENTS
HSE (in press) Vanadium pentoxide. Health and
Safety Executive. Sudbury, Suffolk, HSE Books
(Risk Assessment Document EH72/XX)
The author’s 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.
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 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:
M. Baril, International Programme on Chemical Safety/
Institut de Recherche en Santé et en Sécurité du
Travail du Québec, 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, People’s
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, People’s Republic of China
K. Ziegler-Skylakakis, GSF-Forschungszentrum für Umvelt
und Gesundheit, Neuherberg, Oberschleissheim,
Germany
 Vanadium pentoxide and other inorganic vanadium compounds

APPENDIX 3 — CICAD FINAL REVIEW

BOARD
Observer
Helsinki, Finland, 26–29 June 2000
Dr R.J. Lewis (representative of European Centre for
Ecotoxicology and Toxicology of Chemicals), Epidemiology and
Health Surveillance, ExxonMobil Biomedical Sciences, Inc.,
Members 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, Dr A. Aitio, International Programme on Chemical Safety, World
Sweden 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
Mr R. Cary, Health and Safety Executive, Liverpool, United
Kingdom (Rapporteur)
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

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. Riihimäki, 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 Divanadium trioxide
RTECS No: YW3050000 Vanadium sesquioxide
UN No: 3285 Vanadic oxide
EC No: Vanadium(III) oxide
V2O3
Molecular mass: 149.9

TYPES OF
HAZARD/ ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING
EXPOSURE

FIRE Combustible under specific NO open flames. In case of fire in the surroundings:
conditions. Gives off irritating or all extinguishing agents allowed.
toxic fumes (or gases) in a fire.

EXPLOSION

EXPOSURE PREVENT DISPERSION OF DUST!

Inhalation Sore throat. Cough. Laboured Local exhaust or breathing Fresh air, rest. Half-upright
breathing. Weakness. protection. 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 First rinse with plenty of water for
combination with breathing several minutes (remove contact
protection if powder. lenses if easily possible), then take
to a doctor.

Ingestion Headache. Vomiting. Weakness. Do not eat, drink, or smoke during Induce vomiting (ONLY IN
work. CONSCIOUS PERSONS!). Give
plenty of water to drink. Refer for
medical attention.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Sweep spilled substance into containers; if Symbol Do not transport with food and
appropriate, moisten first to prevent dusting. R: feedstuffs.
Carefully collect remainder, then remove to safe S:
place (extra personal protection: P3 filter respirator UN Hazard Class: 6.1
for toxic particles). UN Pack Group: III

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-61G65c Separated from food and feedstuffs.

Prepared in the context of cooperation between the International

IPCS Programme on Chemical Safety and the European Commission
International © IPCS 1999
Programme on
Chemical Safety 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 20
C 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: 1970
C Solubility in water: poor
Density: 4.87 g/cm3 at 18
C

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

Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible
LEGAL NOTICE
for the use which might be made of this information

© IPCS 1999
VANADIUM PENTOXIDE 0596
October 1999
CAS No: 1314-62-1 Divanadium pentoxide
RTECS No: YW2450000 (dust) Vanadic anhydride
UN No: 2862 Vanadium(V)oxide
EC No: 023-001-00-8 V2O5
Molecular mass: 181.9

TYPES OF
HAZARD/ ACUTE HAZARDS/SYMPTOMS PREVENTION FIRST AID/FIRE FIGHTING
EXPOSURE

FIRE Not combustible. In case of fire in the surroundings:

all extinguishing agents allowed.

EXPLOSION

EXPOSURE PREVENT DISPERSION OF DUST!

STRICT HYGIENE!

Inhalation Sore throat. Cough. Burning Ventilation, local exhaust, or Fresh air, rest. Half-upright position.
sensation. Shortness of breath. breathing protection. Refer for medical attention.
Laboured breathing. Wheezing.

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 First rinse with plenty of water for
combination with breathing several minutes (remove contact
protection if powder. lenses if easily possible), then take
to a doctor.

Ingestion Abdominal cramps. Diarrhoea. Do not eat, drink, or smoke during Induce vomiting (ONLY IN
Drowsiness. Nausea. work. Wash hands before eating. CONSCIOUS PERSONS!). Give
Unconsciousness. Vomiting. plenty of water to drink. Refer for
medical attention.

SPILLAGE DISPOSAL PACKAGING & LABELLING

Sweep spilled substance into containers; if T Symbol Do not transport with food and
appropriate, moisten first to prevent dusting. N Symbol feedstuffs.
Carefully collect remainder, then remove to safe R: 20/22-37-40-48/23-51/53-63
place. (Extra personal protection: P3 filter respirator S: (1/2-)36/37-38-45-61
for toxic particles). Do NOT let this chemical enter UN Hazard Class: 6.1
the environment. UN Pack Group: III

EMERGENCY RESPONSE STORAGE

Transport Emergency Card: TEC (R)-61G64c Separated from food and feedstuffs.

Prepared in the context of cooperation between the International

IPCS Programme on Chemical Safety and the European Commission
International © IPCS 2000
Programme on
Chemical Safety SEE IMPORTANT INFORMATION ON THE BACK.
0596 VANADIUM PENTOXIDE

IMPORTANT DATA
Physical State; Appearance Routes of exposure
YELLOW TO RED CRYSTALLINE POWDER OR SOLID IN The substance can be absorbed into the body by inhalation of
VARIOUS FORMS. its aerosol and by ingestion.

Chemical dangers Inhalation risk

Upon heating, toxic fumes are formed. Reacts with combustible Evaporation at 20°C is negligible; a harmful concentration of
substances. 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) Effects of short-term exposure
(ACGIH 1999). The aerosol of this substance irritates the eyes, the skin and
MAK: 0.05 mg/m3; (1996). 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): 1750°C Relative density (water = 1): 3.4
Melting point: 690°C 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

Neither the EC nor the IPCS nor any person acting on behalf of the EC or the IPCS is responsible
LEGAL NOTICE for the use which might be made of this information

©IPCS 2000
Concise International Chemical Assessment Document 29
RÉSUMÉ D’ORIENTATION
Ce CICAD consacré au pentoxyde de vanadium et
à d’autres dérivés minéraux du vanadium repose sur un
bilan des problèmes sanitaires (principalement en milieu
professionnel) préparé par le Health and Safety
Executive du Royaume-Uni (HSE, sous presse). Ce
document vise principalement les voies d’exposition à
prendre en considération sur les lieux de travail, mais
contient également des informations relatives à
l’environnement. La bibliographie utilisée va jusqu’à
novembre 1998. Un dépouillement complémentaire de la
litterature à été effectué jusqu’à mai 1999 afin de recueillir
toutes données supplémentaires publiées après
l’achèvement de ce document. En ce qui concerne les
données environnementales, on a utilisé la monographie
publiée dans la série Critères d’hygiène de l’environne-
ment (IPCS, 1988). Comme on ne disposait d’aucun
document plus récent sur le devenir et les effets
environnementaux de ces composés, il a été procédé à
une recherche bibliographique afin d’obtenir un
complément d’information. Des renseignements sur la
nature de l’examen par des pairs et sur les sources
documentaires existantes sont données à l’appendice 1.
L’appendice 2 contient des informations sur l’examen par
des pairs du présent CICAD. Ce CICAD a été approuvé
en tant qu’évaluation internationale lors de la réunion du
Comité d’évaluation finale qui s’est tenue à Helsinki
(Finlande) du 26 au 29 juin 2000. La liste des participants
à cette réunion figure à l’appendice 3. Les fiches
internationales sur la sécurité chimique du trioxyde
(ICSC 0455) et du pentoxyde de vanadium (ICSC 0596)
établies par le Programme international sur la sécurité
chimique (IPCS, 1999a,b) sont également reproduites
dans le présent CICAD.
Le vanadium (No CAS 7440-62-2) est un métal
ductile, de couleur gris-argent, qui peut exister sous
divers degrés d’oxydation : !1, 0, +2, +3, +4 et +5. Sa
forme commerciale la plus courante est le pentoxyde
V2O5 (No CAS 1314-62-1) correspondant à la valence +5
et qui se présente sous la forme d’une poudre cristalline
qui peut être jaune, rouge ou verte.
Le vanadium est un élément abondant et très
largement répandu. 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 l’on utilise pour la production du métal.
On prépare également le pentoxyde de vanadium en
l’extrayant par solvant des minerais d’uranium ou par
grillage des sels présents dans les résidus de chaudières
ou dans ceux des usines de production de phosphore
élémentaire. La combustion des huiles lourdes dans les
chaudières et les fours conduit à la formation de résidus
solides, de suie, de tartre et de cendres volantes qui
contiennent du pentoxyde de vanadium.
48
On estime que chaque année, quelque 8,4 tonnes
de vanadium sont libérées dans l’atmosphère à partir de
sources naturelles (valeurs extrêmes : 1,5-49,2 tonnes). La
source de pollution de l’environnement par le vanadium
qui est de loin la plus importante est constituée par la
combustion du pétrole et du charbon; environ 90 % des
quelque 64 000 tonnes de vanadium libérées dans
l’atmosphère chaque année par des phénomènes
naturels ou par l’activité humaine ont en effet cette
source pour origine.
Dans l’environnement, le vanadium offre une
chimie complexe. Dans les minéraux, le degré d’oxydation
du vanadium peut être de +3, +4 ou +5. Par dissolution
dans l’eau, V3+ et V4+ sont rapidement oxydés au degré
+5, qui constitue la forme la plus commune du vanadium
dans l’environnement. En solution, cette forme
correspond aux vanadates, qui peuvent se polymériser
(pour donner principalement des dimères et des
trimères), en particulier en solution concentrée. Dans les
tissus, ce sont les formes V3+ et V4+ qui prédominent, du
fait que le milieu est largement réducteur; dans le plasma,
c’est V5+ qui prédomine.
Le vanadium est probablement essentiel pour les
systèmes enzymatiques qui fixent l’azote atmosphérique
(bactéries) et il est concentré par certains organismes
comme les tuniciers, quelques annélidés de la classe des
polychètes 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 d’autres organismes reste
posée. Rien n’indique qu’il s’accumule ou subisse une
bioamplification dans la chaîne alimentaire des
organismes marins, qui constituent le groupe le mieux
étudié.
Le lessivage du vanadium dans les différents
profils pédologiques est très limité.
On a signalé la présence de fortes concentrations
de vanadium dans l’air à proximité de sources indus-
trielles et de feux d’hydrocarbures. En ce qui concerne
les dépôts, des valeurs annuelles de 0,1 à 10 kg/ha sont
caractéristiques des zones urbaines où sont implantées
des sources importantes de vanadium; ces valeurs vont
de 0,01 à 0,1 kg/ha par an dans les zones rurales ou
urbaines où n’existent pas de sources de vanadium et
s’abaissent à <0,001-0,01 kg/ha par an dans les régions
reculées.
Dans la plupart des eaux douces de surface, la
concentration du vanadium est inférieure à 3 µg/litre; des
valeurs plus élevées, pouvant atteindre 70 µg/litre ont
été relevées dans des zones où existent d’importantes
sources géochimiques. On ne possède guère de données
sur la teneur en vanadium des eaux proches de sites
industriels; la plupart des publications font état de
 Vanadium pentoxide and other inorganic vanadium compounds
valeurs correspondant sensiblement aux concentrations
naturelles les plus fortes. Les concentrations pélagiques
vont de 1 à 3 µg/litre, dans les sédiments, la concen-
tration va de 20 à 200 µg/g, les valeurs les plus élevées
étant relevées dans la zone littorale.
Quelques organismes concentrent le vanadium, et
la concentration de ce métal peut atteindre 10 000 µg/g
chez les ascidies et 786 µg/g chez les polychètes. Chez la
plupart des êtres vivants, la concentration est, d’une
façon générale, inférieure à 50 µg/g et habituellement
beaucoup plus faible.
L’exposition par la voie alimentaire est estimée
chez l’Homme à 11-30 µg par jour. Dans l’eau de boisson,
la concentration va jusqu’à 100 µg/litre. Dans certaines
nappes souterraines qui alimentent les sources d’eau
potable, on a relevé des concentrations de vanadium
supérieures à 50 µg/litre. L’eau minérale en bouteille peut
en contenir davantage.
On possède des données toxicocinétiques limitées
selon lesquelles chez l’Homme, le vanadium est résorbé
après inhalation puis excrété dans l’urine, l’élimination se
faisant en deux phases, une phase initiale rapide puis
une phase plus lente qui correspond vraisemblablement
à la libération progressive du vanadium retenu dans les
tissus. Après administration par voie orale, le vanadium
IV est mal résorbé dans les voies digestives. On ne
dispose pas d’études sur l’absorption percutanée.
L’expérimentation animale montre qu’après
exposition par la voie respiratoire ou orale le vanadium
absorbé sous des formes correspondant aux degrés
d’oxydation IV ou V se répartit principalement dans les
os, le foie, les reins et la rate. On en a également décelé la
présence dans les testicules. La principale voie
d’excrétion est la voie urinaire. Le mode de distribution
et d’excrétion du vanadium montre qu’une fois résorbé,
le métal peut s’accumuler et être retenu, notamment dans
les os. Il a également été montré que le vanadium
tétravalent est capable de franchir la barrière foeto-
placentaire.
Dans la seule étude de toxicité aiguë par inhalation
qui soit disponible, on a obtenu une CL67 de 1440 mg/m3
(800 mg de vanadium par m3) pour des rats exposés
pendant 1 h à de la poussière de pentoxyde de
vanadium. L’exposition de rats et de souris par la voie
orale a permis d’obtenir une DL50 qui se situait entre 10
et 160 mg/kg de poids corporel dans le cas du pentoxyde
et d’autres dérivés du vanadium V, alors qu’avec les
dérivés du vanadium IV, les valeurs étaient comprises
entre 448 et 467 mg/kg de poids corporel. On ne dispose
d’aucune donnée sur la toxicité du vanadium par la voie
percutanée.
49
Des études sur des travailleurs de l’industrie du
vanadium ont mis en évidence des cas d’irritation
oculaire. Chez 100 volontaires à qui on avait posé un
timbre cutané contenant 10 % de pentoxyde de
vanadium, on n’a pas constaté d’irritation cutanée, mais
un test analogue effectué sur des travailleurs a donné
lieu a deux réactions isolées. L’expérimentation animale
n’a permis de dégager aucun résultat clair concernant le
pouvoir irritant oculaire ou cutané des composés du
vanadium ou leur action sensibilisatrice au niveau de
l’épiderme.
Dans un groupe de volontaires exposés pendant 8
h à de la poussière contenant 0,1 mg de vanadium par m3,
on a observé des effets retardés mais prolongés sur les
bronches qui se manifestaient notamment par une
production excessive de mucus. A la concentration de
0,25 mg/m3, la réaction était analogue, avec en plus de la
toux qui s’est prolongée pendant les quelques jours
suivant l’exposition. A la concentration de 1,0 mg/m3, la
toux est devenue permanente au bout de cinq heures et
s’est maintenue longtemps. Il ne ressort de cette étude
aucune valeur de la dose maximale sans effet
bronchique.
L’inhalation répétée de vapeurs et de poussières
de pentoxyde de vanadium entraîne une irritation des
yeux, du nez et de la gorge. Chez les travailleurs exposés
à ces vapeurs et à ces poussières, on observe
couramment une respiration sifflante et de la dyspnée.
Globalement , on ne dispose pas de données suffisantes
pour établir de façon fiable une relation exposition-
réponse relative aux effets respiratoires des poussières et
des vapeurs de vanadium chez l’Homme.
Les dérivés correspondant aux valences 4 et 5 du
vanadium ont des effets aneugènes in vitro en présence
ou en l’absence d’activation métabolique. On est fondé à
penser que ces dérivés ainsi que ceux du vanadium III
sont capables de provoquer des lésions de l’ADN et des
chromosomes in vitro, mais les études existantes
donnent à cet égard des résultats qui sont tantôt
positifs, tantôt négatifs. Il semble, à la lumière des
données disponibles, que les composés du vanadium ne
soient pas mutagènes , à en juger par les tests classiques
de mutagénicité in vitro sur des cellules bactériennes ou
mammaliennes.
In vivo, une aneuploïdie des cellules somatiques
s’observe clairement après exposition à des dérivés du
vanadium IV et du vanadium V selon différentes voies.
Comme dans le cas des études in vitro, les tests destinés
à mettre en évidence des effets clastogènes donnent des
résultats mitigés et dans l’ensemble, on reste dans
l’incertitude quand au pouvoir clastogène du vanadium
vis-à-vis des cellules somatiques. Par contre, on a
obtenu un résultat positif dans le cas des cellules
germinales de souris à qui on avait injecté du pentoxyde
Concise International Chemical Assessment Document 29

de vanadium par voie intrapéritonéale. Le mécanisme qui
est à la base de ces effets (aneugènes et clastogènes)
n’est pas connu avec certitude. On ignore également
dans quelle mesure ces résultats peuvent être étendus à
d’autres voies d’exposition et à d’autres dérivés du
vanadium.
Etant donné la nature de la base de données sur la
génotoxicité du pentoxyde de vanadium et d’autres
dérivés de cet élément, il n’est pas possible de définir
sans ambiguité le seuil au-dessous duquel, quelle que
soit la voie d’exposition à prendre en considération chez
l’Homme, il n’y aurait pas lieu de craindre un risque
d’activité génotoxique.
On ne possède aucune information utile sur le
pouvoir cancérogène du vanadium chez l’Homme ou
l’animal, sous quelque forme et par quelque voie
d’exposition que ce soit.1
Une étude de fécondité sur des souris mâles dont
l’eau de boisson contenait du métavanadate de sodium,
incite à penser que l’exposition des animaux à ce
composé aux doses de 60 et 80 mg/kg de poids corporel
a été la cause directe d’une diminution du nombre de
spermatides et de spermatozoïdes ainsi que du nombre
de grossesses consécutives à l’accouplement de ces
mâles avec des souris femelles. Il est vrai toutefois, qu’à
la dose de 80 mg/kg p.c., la toxicité générale du composé
était également évidente (diminution du gain de poids).
de vue écotoxicologique, il serait plus judicieux de
prendre en considération l’action sur le développement
des huîtres (sensiblement réduit à 0,05 mg de vanadium
par litre) et sur la reproduction des daphnies (concen-
tration sans effet observable à 21 jours : 1,13 mg/litre).
Peu d’études ont été consacrés aux organismes
terrestres. La plupart de celles qui portent sur des
végétaux concernent des cultures hydroponiques sur
lesquelles on observe des effets à partir de 5 mg/litre.
Les résultats de ces études sont difficiles à transposer
aux plantes cultivées en pleine terre.
Dans les divers compartiments de l’environnement,
la concentration est sensiblement inférieure aux valeurs
toxiques. On ne possède que peu de données sur la
concentration au voisinage des sites industriels et il
n’est pas possible de procéder à une évaluation du
risque sur cette base. Quoi qu’il en soit, les valeurs dont
il est fait état semble correspondre aux concentrations
naturelles les plus fortes, ce qui indique que le risque
devrait être faible. Des mesures sur les lieux mêmes
s’imposent dans chaque cas particulier.

Un certain nombre d’études ont été consacrées à

l’action des composés du vanadium IV et V sur le
développement. Elles révèlent systématiquement la
présence d’anomalies du squelette. Les résultats de ces
études sont difficiles à interpréter car les voies
d’exposition étaient inhabituelles et la toxicité manifeste
des composés pour les mères a pu influer sur les effets
constatés dans la progéniture.

Chez l’Homme les points d’aboutissement de

l’action toxique à prendre en considération sont la
génotoxicité et l’irritation des voies respiratoires. Comme
il n’est pas possible de définir le seuil de concentration à
partir duquel il n’y a plus d’effets toxiques, il est
recommandé de réduire le plus possible le niveau
d’exposition.

Pour les organismes aquatiques, les valeurs de la

CL50 vont de 0,2 à environ 120 mg/litre, la majorité des
valeurs se situant entre 1 et 12 mg par litre. D’une point

1
Les auteurs de ce document ont connaissance d’une
étude au cours de laquelle on a fait inhaler pendant 2 ans
des dérivés du vanadium à des rongeurs. Cette étude
vient de s’achever aux Etats-Unis dans le cadre du
National Toxicology Program et les résultats n’en sont
pas encore disponibles.

50
 Vanadium pentoxide and other inorganic vanadium compounds
RESUMEN DE ORIENTACIÓN
Este CICAD sobre el pentóxido de vanadio y otros
compuestos inorgánicos de vanadio se basó en un
examen de los problemas relativos a la salud humana
(fundamentalmente profesionales) preparado por la
Dirección de Salud y Seguridad del Reino Unido (HSE,
en prensa). Este examen se concentra en las vías de
exposición de interés para el entorno ocupacional, pero
contiene también información sobre el medio ambiente.
Figuran los datos identificados hasta noviembre de 1998.
Se realizó una ulterior búsqueda bibliográfica hasta mayo
de 1999 para localizar cualquier información nueva que
se hubiera publicado desde la terminación del examen. Se
utilizó una monografía de los Criterios de Salud
Ambiental (IPCS, 1988) como documento original para la
información ambiental. Puesto que no se disponía de
documentos originales más recientes sobre el destino y
los efectos en el medio ambiente, se realizó una
búsqueda bibliográfica para obtener más información. La
información acerca del carácter del examen colegiado y la
disponibilidad de los documentos originales figura en el
apéndice 1. La información sobre el examen colegiado de
este CICAD aparece en el apéndice 2. Este CICAD se
aprobó como evaluación internacional en una reunión de
la Junta de Evaluación Final celebrada en Helsinki
(Finlandia) del 26 al 29 de junio de 2000. La lista de
participantes en esta reunión figura en el apéndice 3. Las
Fichas internacionales de seguridad química sobre el
trióxido de vanadio (ICSC 0455) y el pentóxido de
vanadio (ICSC 0596), preparadas por el Programa
Internacional de Seguridad de las Sustancias Químicas
(IPCS, 1999a,b), también se reproducen en el presente
documento.
El vanadio (CAS Nº 7440-62-2) es un metal gris
plateado suave que puede existir en varios estados de
oxidación diferentes: !1, 0, +2, +3, +4 y +5. La forma
comercial más común es el pentóxido de vanadio (V2O5;
CAS Nº 1314-62-1) y en este estado pentavalente es un
polvo cristalino rojo-amarillento o verde.
El vanadio es un elemento abundante, con una
distribución muy amplia; se extrae en Sudáfrica, Rusia y
China. Durante la fusión de la mena de hierro se forma
escoria de vanadio con pentóxido de vanadio, que se
utiliza para la producción de vanadio metálico. El
pentóxido de vanadio se obtiene también por extracción
con disolventes a partir de menas de uranio y mediante
un proceso de calcinación de las sales de los residuos de
las calderas o de los residuos de las instalaciones de
fosfato elemental. Durante la combustión de fueloil en
calderas y hornos, hay pentóxido de vanadio en los
residuos sólidos, el hollín, las incrustaciones de las
calderas y las cenizas volátiles.
51
Las emisiones atmosféricas a partir de fuentes
naturales en todo el mundo se han estimado en 8,4 tone-
ladas al año (gama de 1,5-49,2 toneladas). La fuente más
importante de contaminación ambiental por vanadio es
con diferencia la combustión de petróleo y de carbón;
alrededor del 90% de las aproximadamente 64 000 tone-
ladas de vanadio que se liberan en la atmósfera cada año
a partir de fuentes tanto naturales como antropogénicas
procede de la combustión del petróleo.
La química del vanadio en el medio ambiente es
compleja. En los minerales, el estado de oxidación del
vanadio puede ser +3, +4 ó +5. La disolución en agua
oxida rápidamente el V3+ y el V4+ al estado pentavalente,
que es la forma más común del metal en el medio
ambiente. El vanadato, compuesto pentavalente en
solución, se puede polimerizar (principalmente a las
formas diméricas o triméricas), en particular a concen-
traciones más altas de las sales. En los tejidos de los
organismos predominan el V3+ y el V4+, debido en gran
parte a las condiciones de reducción; en el plasma
predomina el V5+.
El vanadio es probablemente esencial para los
sistemas enzimáticos que fijan el nitrógeno de la atmós-
fera (bacterias) y lo concentran algunos organismos
(tunicados, algunos anélidos poliquetos, algunas micro-
algas), pero no se conoce bien su función en estos
organismos. Sigue siendo una cuestión abierta si el
vanadio es o no esencial para otros organismos. No hay
pruebas de acumulación o bioamplificación en las
cadenas alimentarias de los organismos marinos, que
forman el grupo mejor estudiado.
Hay una lixiviación muy limitada del vanadio a
través de los perfiles del suelo.
Se han notificado niveles más altos de vanadio en
el aire próximo a fuentes industriales e incendios de
hidrocarburos. Las tasas de deposición representativas
son de 0,1-10 kg/ha al año para zonas urbanas afectadas
por fuentes locales importantes, de 0,01-0,1 kg/ha al año
para las zonas rurales y urbanas que no tienen una
fuente local importante y <0,001-0,01 kg/ha al año para
las zonas remotas.
La mayor parte de las aguas superficiales dulces
contienen menos de 3 µg de vanadio/litro; se han
notificado niveles más altos, de hasta unos 70 µg/litro,
en zonas con fuentes geoquímicas grandes. Los datos
sobre los niveles de vanadio en aguas superficiales
próximas a actividades industriales son escasos; la
mayoría de los informes parecen indicar niveles
aproximadamente iguales a los naturales más elevados.
Las concentraciones en el agua marina en mar abierta
oscilan entre 1 y 3 µg/litro y en los sedimentos van de 20
a 200 µg/g; los niveles más altos se observan en los
sedimentos costeros.
Concise International Chemical Assessment Document 29
Algunos organismos concentran vanadio en can-
tidades que ascienden hasta 10 000 µg/g en las ascidias
y 786 µg/g en los anélidos poliquetos. La mayoría de los
organismos suelen contener menos de 50 µg/g y normal-
mente concentraciones mucho más bajas.
Las estimaciones de la exposición total de las
personas en los alimentos oscilan entre 11 y 30 µg/día.
Los niveles en el agua de bebida ascienden hasta
100 µg/litro. Algunas fuentes de agua freática que
abastecen de agua potable muestran concentraciones
superiores a 50 µg/litro. Los niveles en el agua de
manantial embotellada pueden ser más altos.
En las personas, la limitada información tóxico-
cinetica disponible parece indicar que se absorbe
vanadio tras la inhalación y luego se excreta en la orina
con una fase inicial de eliminación rápida, seguida de
una fase más lenta, que posiblemente se debe a la
eliminación gradual de vanadio de los tejidos del
organismo. Tras la administración oral, la absorción de
vanadio tetravalente a partir del sistema gastrointestinal
es escasa. No se disponía de estudios cutáneos.
En estudios de inhalación y de administración oral
en animales de laboratorio, el vanadio absorbido en los
estados pentavalente o tetravalente se distribuye funda-
mentalmente en los huesos, el hígado, el riñón y el bazo,
y también se detecta en los testículos. La vía principal de
excreción del vanadio es a través de la orina. Su pauta de
distribución y excreción indica que es posible la
acumulación y retención del vanadio absorbido, sobre
todo en los huesos. Hay pruebas de que el vanadio
tetravalente puede atravesar la barrera placentaría y
llegar al feto.
En el único estudio de inhalación aguda disponible
se notificó una CL67 de 1440 mg/m3 (800 mg de vanadio/
m3) tras la exposición de ratas a polvo de pentóxido de
vanadio durante una hora. En estudios de administración
oral en ratas y ratones se obtuvieron valores de la DL50
del orden de 10-160 mg/kg de peso corporal para el
pentóxido 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 información
relativa a la toxicidad cutánea.
En estudios realizados con trabajadores del vana-
dio se ha notificado irritación ocular. No se informó de
irritación cutánea en 100 voluntarios humanos tras la
prueba del parche cutáneo con un 10% de pentóxido de
vanadio, aunque la prueba del parche realizada en los
trabajadores produjo dos reacciones aisladas. No hay
información clara disponible de estudios en animales con
respecto al potencial de los compuestos de vanadio para
producir irritación cutánea u ocular o bien sensibilización
cutánea.
52
En un grupo de voluntarios humanos, una expo-
sición aislada de ocho horas a 0,1 mg de polvo de
pentóxido de vanadio/m3 produjo efectos bronquiales
retardados, pero prolongados, con una producción
excesiva de moco. Con 0,25 mg/m3 se observó una pauta
de respuesta semejante, con la adición de tos durante
algunos días después de la exposición. La exposición a
1,0 mg/m3 produjo una tos persistente y prolongada
después de cinco horas. En este estudio no se identificó
un nivel sin efectos para los trastornos bronquiales.
La exposición por inhalación repetida al polvo y el
humo de pentóxido de vanadio está asociada con la
irritación de los ojos, la nariz y la garganta. En los
trabajadores expuestos al polvo y el humo de pentóxido
de vanadio se suelen notificar jadeo y disnea. En con-
junto, no hay datos suficientes que permitan describir de
manera fidedigna la relación exposición-respuesta para
los efectos respiratorios del polvo y el humo de pen-
tóxido de vanadio en las personas.
Las formas pentavalentes y tetravelentes del
vanadio han provocado efectos aneugénicos in vitro
con activación metabólica y sin ella. Hay pruebas de que
estas formas de vanadio, así como el vanadio trivalente,
también pueden producir in vitro daños en el ADN/
cromosomas, habiéndose 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 genéticas en pruebas normalizadas in vitro
en células de bacterias o de mamíferos.
In vivo, tanto los compuestos de vanadio penta-
valentes como los tetravalentes han dado pruebas
manifiestas de aneuploidía de las células somáticas tras
la exposición mediante varias vías diferentes. Las
pruebas de que los compuestos de vanadio también
pueden producir efectos clastogénicos son desiguales,
al igual que en los estudios in vitro, y la posición global
sobre la clastogenicidad en las células somáticas es
incierta. Se obtuvo un resultado positivo en células
germinales de ratones a los que se administró pentóxido
de vanadio por inyección intraperitoneal. Sin embargo,
hay dudas acerca del mecanismo en el que se basa este
efecto (aneugenicidad; clastogenicidad). Tampoco está
claro cómo se pueden generalizar estos resultados a vías
de exposición más realistas o a otros compuestos de
vanadio.
Las características de la base de datos sobre la
genotoxicidad del pentóxido de vanadio y otros com-
puestos de vanadio son tales que no es posible identi-
ficar claramente el nivel umbral para ninguna vía de
exposición de interés para el ser humano por debajo del
cual no habría que preocuparse por la posible actividad
genotóxica.
 Vanadium pentoxide and other inorganic vanadium compounds

No se dispone de información útil sobre el pocos datos sobre las concentraciones en lugares
potencial carcinogénico de ninguna de las formas de industriales específicos y no es posible realizar una
vanadio por ninguna de las vías de exposición para los evaluación del riesgo sobre esta base. Sin embargo, las
animales 1 o las personas. concentraciones notificadas parecen ser semejantes a las
naturales más altas, lo que parece indicar que el riesgo
Un estudio de la fecundidad en ratones machos, sería bajo. Se deben realizar mediciones locales para
con exposición al metavanadato de sodio en el agua de evaluar el riesgo en cualquier circunstancia determinada.
bebida, parece indicar la posibilidad de que la exposición
oral de los ratones machos a este compuesto a
concentraciones de 60 y 80 mg/kg de peso corporal
causara directamente una disminución del recuento de
espermátidas/espermatozoides y del número de gesta-
ciones tras el apareamiento. Sin embargo, también se
pudo observar una toxicidad general significativa
(disminución 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 observación sistemática de anoma-
lías esqueléticas. La interpretación de estos estudios es
difícil, debido a las vías de exposición no tradicionales
utilizadas y a que hay pruebas de toxicidad materna, la
cual podría contribuir por sí misma a los efectos detec-
tados en las crías.

Los efectos toxicológicos finales motivo de pre-

ocupación para las personas son la genotoxicidad y la
irritación de las vías respiratorias. Puesto que no es
posible determinar un nivel de exposición 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 acuáticos oscila entre 0,2 y unos 120 mg/li-
tro, aunque para la mayoría están entre 1 y 12 mg/litro.
Otros efectos finales importantes desde el punto de vista
ecotoxicológico se observaron en el desarrollo de las
larvas de ostras (reducción significativa con 0,05 mg de
vanadio/litro) y en la reproducción de Daphnia (con-
centración sin efectos observados en 21 días con
1,13 mg/litro). Son pocos los estudios terrestres. La
mayoría de los estudios en plantas se han realizado en
cultivos hidropónicos, donde se detectaron efectos a
concentraciones de 5 mg/litro y superiores; estos
estudios son difíciles de interpretar en relación con las
plantas cultivadas en el suelo.

Las concentraciones en los compartimentos del

medio ambiente son notablemente inferiores a las
concentraciones tóxicas notificadas. Se dispone de

1
Los autores de este documento tienen conocimiento de
que recientemente se ha completado en el Programa
Nacional de Toxicología de los Estados Unidos una
biovaloración por inhalación de dos años en roedores.
Sin embargo, en este momento no están disponibles
todavía 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)

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