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.
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.
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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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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 complete ness, 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 encour aged to characterize risk on the basis of locally measured or predicted exposure scenarios. To assist the reader, examples of exposure estimation and risk characteriza tion are provided in CICADs, whenever possible. These examples cannot be considered as representing all pos sible exposure situations, but are 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
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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 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;
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– 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.
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.
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 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 potable water show concentrations above 50 µg/litre. Levels in bottled spring water may be higher.
In humans, there is limited toxicokinetic information suggesting that vanadium is absorbed following inhalation and is subsequently excreted via the urine with an initial rapid phase of elimination, followed by a slower phase, which presumably reflects the gradual release of vanadium from body tissues. Following oral administration, tetravalent vanadium is poorly absorbed from the gastrointestinal tract. There were no dermal studies available.
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 LD50 values in the range 10–160 mg/kg body weight for vanadium pentox ide and other pentavalent vanadium compounds, while tetravalent vanadium compounds have LD50 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 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 vanadium pentoxide and other vanadium compounds is such that it is not possible to clearly identify the threshold level, for any route of exposure relevant to humans, below which there would be no concern for potential genotoxic activity.
No useful information is available on the carcinogenic potential of any form of vanadium via any route of exposure in animals2 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.
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.
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 (VO3–) and include ammonium meta vanadate (NH4VO3), sodium metavanadate (NaVO3), and sodium orthovanadate (Na3VO4). Compounds in the +4 oxidation state are derived from the vanadyl ion (VO2+) — for example, vanadyl dichloride (VOCl2) and vanadyl sulfate (VOSO4). Compounds containing vanadium in the +3 oxidation state include vanadium oxide (V2O3). Table 1 provides some physicochemical properties of vanadium compounds that are referred to in this review.
Vanadium (CAS No.
Vanadium pentoxide (CAS No.
Vapour pressures (and hence Henry’s law con stants) and octanol/water partition coefficients are not available for vanadium compounds.
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.
The measurement of vanadium in end-of-shift urine samples is appropriate for biological monitoring of vanadium exposure and has been widely used to monitor occupational exposure to vanadium compounds in a number of industrial activities (Angerer & Schaller, 1994).
Table 1: Physical/chemical properties of vanadium and selected inorganic vanadium compounds.
|
Compound |
CAS number |
Molecular / atomic mass |
Melting point |
Boiling point |
Solubility (g/litre) |
||
|
Cold water (20–25 °C) |
Hot water |
Other solvents |
|||||
|
Vanadium, V |
|
50.942 |
1890 ± 10; 1917 |
3380 |
Insoluble |
Insoluble |
Not attacked by hot or cold hydrochloric acid or cold sulfuric acid, but soluble in hydrofluoric acid, nitric acid, and aquaregia |
|
Vanadium pentoxide, V2O5 |
|
181.9 |
690 |
1750 |
8 |
No data |
Soluble in acid/alkali; insoluble in absolute alcohol |
|
Sodium meta vanadate, NaVO3 |
|
121.93 |
No data |
No data |
211 |
388 |
No data |
|
Sodium ortho-vanadate, Na3VO4 |
|
183.91 |
850–856 |
No data |
Soluble |
No data |
Soluble in alcohol |
|
Ammonium meta-vanadate, NH4VO3 |
|
116.98 |
200 (decomposes) |
No data |
58 |
Decomposes |
Soluble in ammonium carbonate |
|
Vanadium oxytri-chloride, VOCl3 |
|
|
|
|
Soluble, decomposes |
No data |
Soluble in alcohol, ether, acetic acid |
|
Vanadyl sulfate, VOSO4 |
|
|
|
|
Very soluble |
No data |
No data |
|
Vanadyl oxydi-chloride, VOCl2 |
|
|
|
|
Decomposes |
No data |
Soluble in dilute nitric acid |
|
Vanadium trioxide, V2O3 |
|
|
|
|
Slightly soluble |
Soluble |
Soluble in nitric acid, 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.
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). Instru mental neutron activation analysis gave detection limits of 0.01 µg/g in 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).
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 produc tion in 1990 was 30 700 tonnes, comprising approxi mately 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, includ ing 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 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 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).
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).
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 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).
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 polychaetes of the genus Pseudopotamilla; poly chaetes 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 con sumers from approximately 2 to 400. Although vana dium 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 inverte brates 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 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).
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).
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.
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 variation; possible causes are reviewed by Mamane & Pirrone (1998), although they can draw no firm conclu sions.
Table 2: Ranges of concentrations of vanadium in air.
|
Area |
Atmospheric concentration (ng/m3) |
Reference |
|
Urban air |
0.4–1460 |
Schroeder et al., 1987 |
|
Urban air |
0.5–1230 |
Mamane & Pirrone, 1998 |
|
Dhahran, Saudi Arabia, during Kuwait oil fires |
2.4–1170 (in the PM10 fraction) |
Sadiq & Mian, 1994 |
a
Includes the Arctic and oceanic islands in the Atlantic and Pacific.Vanadium in air from oil combustion tends to be in smaller particulate fractions. In arid areas with dust storms, high levels of vanadium have been reported; here, particle size tends to be much larger (Mamane & Pirrone, 1998).
Bulk precipitation concentration ranges have been reported at 4.1–13 µg/litre for the rural United Kingdom (Galloway et al., 1982) and 0.12–0.65 µg/litre (mean 0.45 µg/litre) in Switzerland (Atteia, 1994). Wet deposition in an area of New England remote from anthropogenic input showed concentrations of vanadium ranging from 0.2 to 1.16 µg/litre (average 0.67 µg/litre) and in Bermuda ranging from 0.049 to 0.111 µg/litre (average 0.096 µg/litre) (Church et al., 1984). Ice and snow levels in northern Norway and Alaska were 0.31 and 0.13 µg/litre, respectively (Galloway et al., 1982), and two ice core levels in Greenland were reported at 0.022 and 0.016 µg/litre. Levels in rain ranged from 1.1 to 46 µg/litre for rural and urban sites in North America and Europe (Galloway et al., 1982).
Based on these reported concentrations, Mamone & Pirrone (1998) calculated representative total depo sition rates of vanadium at 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 (Hamada, 1998). The vanadium content of water from the Colorado River basin (USA) ranged from 0.2 to 49.2 µg/litre, with the highest levels associ ated with uranium–vanadium mining (Linstedt & Kruger, 1969). A wider survey of Wyoming, Idaho, Utah, and Colorado in the USA showed vanadium concentrations of 2.0–9.0 µg/litre (Parker et al., 1978). Unfiltered water from the source area of the Yangtze River in China con tained between 0.24 and 64.5 µg/litre, whereas concen trations in filtered water ranged from 0.02 to 0.46 µg/li tre (Zhang & Zhou, 1992). The highest levels reported are in surface waters in the area of Mount Fuji in Japan. Two springs had 14.8 and 16.4 µg/litre, and five river samples showed between 17.7 and 48.8 µg/litre (Hamada, 1998).
Data on concentrations of vanadium in wastewater and local surface water are few, and studies are old; reliability for present-day operations is questionable. A single concentration of 2 mg/litre for surface water from 1961, reported in IPCS (1988), seems much higher than other more recent reports, where levels of up to 60 µg/litre in industrial areas seem more likely.
Seawater concentrations have been reviewed by Miramand & Fowler (1998). Most reported concentra tions in the open ocean have been in the range 1–3 µg/litre, with the highest reported value at 7.1 µg/litre. Sedi ment concentrations range from 20 to 200 µg/g dry weight, with higher levels in coastal sediments.
Ranges of concentrations of vanadium in marine organisms are given in Table 3, based on a review of the literature in Miramand & Fowler (1998), where the original references can be found. The ranges include values from areas of likely local contamination from industrial sources. With the exception of ascidians (tunicates), some annelids, and molluscs, concentrations of vanadium in marine organisms are low. The range for planktonic species is heavily influenced by a single study showing accumulation up to 290 mg/kg dry weight; this was mainly into shells of planktonic forms of molluscs. Generally, planktonic organisms show concentrations of vanadium around 1 mg/kg.
There are fewer data for freshwater organisms. The most comprehensive study of organisms was conducted in the Mount Fuji area of Japan, where concentrations in organisms from water with high (43.4 µg/litre) and lower (0.72 or 0.4 µg/litre) concentrations of vanadium were compared. Water plants from the high-vanadium area contained 21.8 ± 11.3 µg/g dry weight of the metal (range 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 microalga in the high-concentration area contained the highest reported concentration of the metal, at 118– 168 µg/g dry weight. The vanadium concentration in rainbow trout (Oncorhynchus mykiss) farmed in water from these areas was measured: bone concentrations were 0.87, 4.77, and 17.2 µg/g and kidney concentra tions were 0.43, 2.38, and 4.63 µg/g for water concen trations 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).
Table 3: Concentrations of vanadium in marine organisms.a
|
Organism |
Concentration of vanadium |
|
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).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).
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).
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 vana dium 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 per son over a 2-month period. The mean respirable fraction (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).
Table 4: Biological monitoring studies of occupational vanadium exposure.
|
Industry |
Sample matrix |
No. of subjects |
Measured air V (mg/m3) (TWA) |
Urine V (µg/litre) |
Reference |
|
V2O5 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 |
|
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 |
|
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 manufacture |
Urine |
8 |
Not known |
2.3 (0.8–6.3) |
Arbouine, 1990 |
|
V2O5 staining |
Urine |
2 |
(<0.04–0.13) |
<4–124 |
Kawai et al., 1989 |
|
Unexposed (general population) |
Urine |
213 012 |
|
0.22 (0.07–0.5) |
Kucera et al., 1992 |
a
RPE = respiratory protective equipment.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 radiochemi cal and instrumental neutron activation analyses in all instances.
Estimates given in IPCS (1988) for total dietary intake of the general population in food range from 11 to 30 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 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/ litre (Giammanco et al., 1996). Older studies summar ized in IPCS (1988) report drinking-water concentrations up to 70 µg/litre, although the majority of samples con tained 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).
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).
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).
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 vana dium 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.
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 (approx imately 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 vana dium 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 accumu lation and retention of absorbed vanadium, particularly in the bone. One oral study in which groups of 22 preg nant 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.
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.
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.
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 irri tation" (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 LD50 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 LD50 values of around 10 mg/kg body weight for rats and 23 mg/kg body weight for mice (MAK, 1992). No fur ther details are available.
For mice, oral LD50 values for vanadium pentoxide were in the range 64–117 mg/kg body weight (Yao et al., 1986b). Similarly, an oral LD50 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.
Groups of 10 male rats received aqueous sodium metavanadate by gavage (Llobet & Domingo, 1984). The LD50 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, 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 LD50 values in the range 18–160 mg/kg body weight for ammonium metavanadate. No further details are available.
An oral LD50 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.
An oral LD50 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 LD50 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 LD50 for vanadyl sulfate pentahydrate of 450 mg/kg body weight.
The MAK (1992) review cites a rat oral LD50 value of 350 mg/kg body weight and a mouse LD50 value of around 23 mg/kg body weight for vanadium trichloride and a mouse oral LD50 of 130 mg/kg body weight for vanadium trioxide. No further details are available.
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.
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 experi ence 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 vana dium 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 base line values), forced expiratory volume (FEV0.5; 95% of baseline values), and forced expiratory flow (FEF50; 92% of baseline values), these changes giving an indication of airflow limitation in the large central airways; a statis tically significant decrease in FEF25 (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 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 (concen tration × 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 occurred only on peak exposure days during the first few weeks of exposure. Pre-subchronic exposure provocation challenges with vanadium pentoxide produced statis tically 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 FEF50/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 FEF50/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 immuno globulins 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.
Oral studies are described below; no dermal studies are available.
Short-term immunotoxicity studies are described briefly in section 8.9.1.
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, plate let count, reticulocyte count, and erythrocyte osmotic fragility) of the peripheral blood were investigated in all animals. There were no other investigations. No differ ence in food intake or body weight was apparent 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 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 metavana date/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 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.
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.
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 experi ment, 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 nitro gen, protein, or sodium. Urinary potassium decreased with dose, whereas urinary calcium was reduced at 10 µg/ml only. Again, this study did not reveal any clearly toxicologically significant changes attributable to vanadium exposure.
There are no data available.
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.
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).
Only very limited data are available (see section 8.7.7).
There are no data available.
There are no data available.
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).
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 lympho cytes (Roldan & Altamirano, 1990). Cells were incu bated in the absence of metabolic activation with vana dium 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 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, respec tively).
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.
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).
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/li tre, 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 between 80 and 210 mmol/litre in both the presence and absence of metabolic activation (Bronzetti et al., 1990).
Cell transformation and gap junctional intercellu lar 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 trans formation 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.
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 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).
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.
Vanadium pentoxide did not increase incidences of sister chromatid exchange, while studies with other pentavalent, tetravalent, and trivalent compounds did, in a number of different cell systems, over a range of concentrations (0.3–19.2 µg/ml) (Owusu-Yaw et al., 1990; Roldan & Altamirano, 1990; Migliore et al., 1993; Zhong et al., 1994).
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.
Chinese hamster V79 cells and human leukaemic T-lymphocyte (MOLT4) cells were exposed to ammo nium 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).
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.
Only very limited data are available (see section 8.7.7).
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 hypo