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 Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1988

         The International Programme on Chemical Safety (IPCS) is a
    joint venture of the United Nations Environment Programme, the
    International Labour Organisation, and the World Health
    Organization. The main objective of the IPCS is to carry out and
    disseminate evaluations of the effects of chemicals on human health
    and the quality of the environment. Supporting activities include
    the development of epidemiological, experimental laboratory, and
    risk-assessment methods that could produce internationally
    comparable results, and the development of manpower in the field of
    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

        ISBN 92 4 154281 0

         The World Health Organization welcomes requests for permission
    to reproduce or translate its publications, in part or in full.
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made
    to the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1988

         Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention. All rights reserved.

         The designations employed and the presentation of the material
    in this publication do not imply the expression of any opinion
    whatsoever on the part of the Secretariat of the World Health
    Organization concerning the legal status of any country, territory,
    city or area or of its authorities, or concerning the delimitation
    of its frontiers or boundaries.

         The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar
    nature that are not mentioned. Errors and omissions excepted, the
    names of proprietary products are distinguished by initial capital




    1.1. Identity, physical and chemical properties, analytical methods
    1.2. Sources in the environment, environmental transport and 
    1.3. Environmental levels and human exposure
    1.4. Kinetics and metabolism
    1.5. Effects on experimental animals and  in vitro test systems 
    1.6. Effects on man
         1.6.1. Local effects and dose-response relationships
         1.6.2. Systemic effects and dose-response relationships 
    1.7. Evaluation of health risks for man


    2.1. Identity
    2.2. Physical and chemical properties
    2.3. Analytical methods
         2.3.1. Atomic absorption analysis and emission spectrometry
         2.3.2. Neutron activation analysis
         2.3.3. Spark-source mass spectrometry
         2.3.4. Spectrophotometric analysis
         2.3.5. Electrochemical methods
         2.3.6. Chromatography 


    3.1. Natural occurrence 
         3.1.1. Rocks 
         3.1.2. Soils 
         3.1.3. Water 
         3.1.4. Air 
         3.1.5. Plants
         3.1.6. Animals
    3.2. Man-made sources
         3.2.1. Production levels and processes
        Extraction from ores
        Extraction from fossil fuels
        Extraction from slag 
    3.3. Consumption and use 
         3.3.1. Metallurgy 
         3.3.2. Other industries
    3.4. Environmental pollution resulting from production, use, and 
         waste disposal
         3.4.1. Metallurgy 
         3.4.2. Fossil fuel combustion
         3.4.3. Agriculture 
    3.5. Transport and transformation
         3.5.1. Geochemical processes
         3.5.2. Biogeochemical processes 
        Transport in, and removal from, water 
        Occurrence in hydrocarbons 

        Biospheric redox processes 
        Transport in air


    4.1. General population exposure
         4.1.1. Air 
         4.1.2. Water
         4.1.3. Food
        Individual foods
        Complete diets 
    4.2. Occupational exposure
         4.2.1. Metallurgy
         4.2.2. Cleaning of oil-fired boilers
         4.2.3. Occupational exposure limits


    5.1. Physiological role
         5.1.1. Microorganisms
         5.1.2. Animals
    5.2. Absorption
         5.2.1. Absorption by inhalation 
        Human studies 
        Animal studies 
         5.2.2. Absorption from the gastrointestinal tract
        Human studies 
        Animal studies 
         5.2.3. Absorption through the skin 
    5.3. Distribution and transformation
         5.3.1. Human studies 
         5.3.2. Animal studies
    5.4. Retention 
         5.4.1. Human studies 
         5.4.2. Animal studies 
    5.5. Elimination  
         5.5.1. Human studies 
         5.5.2. Animal studies 


    6.1. Aquatic organisms 
         6.1.1. Microorganisms and higher plants
         6.1.2. Invertebrates 
         6.1.3. Fish 
    6.2. Terrestrial organisms 
         6.2.1. Uptake of vanadium by plants 
         6.2.2. Effects on plants 


    7.1. General toxicity 
    7.2. Effects on metabolic processes
         7.2.1. Mechanisms of action 
    7.3. Effects on the nervous system
    7.4. Effects on the respiratory system

    7.5. Effects on the cardiovascular system 
    7.6. Effects on the kidney
    7.7. Effects on the immune system
    7.8. Reproduction, embryotoxicity, and teratogenicity
         7.8.1. Reproduction and embryotoxicity
         7.8.2. Teratogenicity
    7.9. Mutagenicity and related end-points 
    7.10. Carcinogenicity 


    8.1. Therapeutic exposure and controlled studies 
         8.1.1. Therapeutic exposure
         8.1.2. Controlled studies 
        Effects on metabolism 
        Effects on the respiratory system 
    8.2. Clinical studies
         8.2.1. Acute toxicity 
         8.2.2. Chronic toxicity 
         8.2.3. Diagnosis 
         8.2.4. Treatment of poisoning
    8.3. General population exposure  
         8.3.1. Low vanadium intake 
         8.3.2. Epidemiological studies
    8.4. Occupational exposure
         8.4.1. Metallurgy 
         8.4.2. Cleaning and related operations on oil-fired boilers 
         8.4.3. Handling of pure vanadium pentoxide or vanadate dusts
         8.4.4. Other industries


    9.1. Environmental levels and exposures
    9.2. Physiological role
    9.3. Effects and dose-response relationships
         9.3.1. Local effects and dose-response relationships
         9.3.2. Systemic effects and dose-response relationships
        Metabolic effects
        Effects on the nervous system
        Effects on the liver 
        Effects on the kidney 
        Cardiovascular effects
        Pulmonary effects 
        Effects on the immune system
         9.3.3. Reproduction, embryotoxicity, and teratogenicity 
         9.3.4. Mutagenicity 
         9.3.5. Carcinogenicity
         9.3.6. Risks from exposure of the general population





Professor A.D. Dashash, Department of Community Medicine,
    Medical  Faculty,  University  of Damascus,  Damascus, Syria
Dr R. Frentzel-Beyme, German Cancer Research Centre, Institute
    of  Epidemiology and Biometry, Heidelberg,  Federal Republic
    of Germany
Mrs Chantana Jutiteparak, Technical Division, Food and Drug
    Administration,   Ministry   of   Public  Health,   Bangkok,
Professor G.N. Krasovsky, Department of Water, Hygiene and
    Sanitary   Waterbodies   Protection,  A.N.   Sysin  Research
    Institute of General and Community Hygiene, Moscow, USSR
Dr G.D.E. Njagi, Genotoxicology Unit, Botany Department,
    Kenyatta University, Nairobi, Kenya (Rapporteur)
Dr H. Nordman, Clinical Section, Institute of Occupational
    Health, Helsinki, Finland
Professor A.V. Roshchin, Department of Occupational Hygiene,
    Central  Institute  for  Advanced Medical  Training, Moscow,
    USSR  (Vice-Chairman) 
Professor Sun Mian Ling, Department of Environmental Hygiene,
    School  of Public Health,  West China University  of Medical
    Sciences, Chengdu, China

 Representatives from Other Organizations 

Dr Z.P. Grigorevskaya, Centre for International Projects, USSR
    State Committee for Science and Technology, Moscow, USSR
Dr G.F. Shkolenok, International Register of Potentially Toxic
    Chemicals,  United  Nations  Environment Programme,  Geneva,


Professor V.Yu. Kogan, Institute for General Hygiene and Prof-
    pathology, Yerevan, Armenia, USSR
Dr S.M. Sokolov, Minsk Medical Institute, Minsk, USSR


Dr E. Smith, International Programme on Chemical Safety, World
    Health Organization, Geneva, Switzerland  (Secretary) 
Dr M. Gounar, Centre for International Projects, USSR State
    Committee for Science and Technology, Moscow, USSR


    Every  effort has been  made to present  information in  the
criteria  documents  as  accurately as  possible  without unduly
delaying their publication.  In the interest of all users of the
environmental  health  criteria  documents, readers  are  kindly
requested  to communicate any errors  that may have occurred  to
the Manager of the International Programme on  Chemical  Safety,
World  Health Organization, Geneva,  Switzerland, in order  that
they  may  be  included in  corrigenda,  which  will  appear  in
subsequent volumes.

                          *    *    *

    A legal file can be obtained from the International Register
of  Potentially Toxic Chemicals, Palais des Nations, 1211 Geneva
10, Switzerland (Telephone No.  988400 - 985850).


    A  WHO  Task  Group  on  Environmental  Health  Criteria for
Vanadium  met  in Moscow,  USSR from 30  March to 3  April 1987.
Dr M.I.  Gounar opened the  meeting and greeted  the members  on
behalf of the Centre for International Projects,  Moscow,  USSR.
Dr E.  Smith addressed the  meeting on behalf  of the three  co-
operating  organizations of the  IPCS (ILO/UNEP/WHO).  The  Task
Group  reviewed and revised the draft criteria document and made
an evaluation of the health risks of exposure to vanadium.

    The efforts of all those who helped in the  preparation  and
finalization of the document are gratefully acknowledged.

                           *   *   *

    Partial  financial  support  for  the  publication  of  this
criteria  document  was kindly  provided  by the  United  States
Department of Health and Human Services, through a contract from
the   National  Institute  of  Environmental   Health  Sciences,
Research   Triangle   Park,  North   Carolina,   USA  -   a  WHO
Collaborating   Centre   for   Environmental   Health   Effects.
Financial  support was also generously provided by the Institute
of   Occupational   Health,   Helsinki,  Finland   -   an   IPCS
Participating Institution.


1.1  Identity, Physical and Chemical Properties, Analytical Methods

    Vanadium (V) is a greyish metal that occurs in the  form  of
two  natural isotopes 50V and 51V.  It forms oxidation states of
-1, 0, +2, +3, +4, and +5, the oxidation states +3, +4,  and  +5
being the most common.  Oxidation state +4 is the  most  stable.
Vanadium  pentoxide (V2O5) is the most common commercial form of
vanadium.  It dissolves in water and acids and  forms  vanadates
with  bases.  Vanadium in the +3 oxidation state (e.g., V2O3) is
basic  and dissolves  in acid  forming a  green  hexa-aquo  ion.
Vanadium+3  salts are strong reducing agents.  Organic compounds
of vanadium are generally unstable.

    Analytical  methods have improved  during recent years,  and
extremely small amounts of vanadium can be detected  in  various
media.   Atomic absorption assays  are suitable for  the routine
determination  of vanadium in different  media.  Some refractory
oxides  do not dissociate in flame.  Sensitivity can be improved
by  the use of a high temperature oxyacetylene flame.  Flameless
atomic absorption for the determination of vanadium in air has a
detection  limit of 1 g/litre.    The same method  can also  be
used for the determination of vanadium in water  and  biological
samples,  with a detection limit  of 0.1 - 0.4  ng.  Inductively
coupled  plasma  optical  emission spectrometry  has  proved  an
accurate and scientific development of atomic absorption.

    Neutron  activation  analysis,  which  is  both  rapid   and
accurate,  has been successfully  used for the  determination of
vanadium in biological fluids, such as serum and blood,  and  in
air,   water,   and  biological   materials.   The  quantitative
separation  of the components  to be analysed  is not  necessary
with  this method.  The  detection limit of  neutron  activation
assays  is lower  than that  of atomic  absorption methods,  and
vanadium in air can be determined at a level of 10-12 g.

    Spark-source   mass   spectrometry   is  suitable   for  the
simultaneous  determination  of  several  elements  in  air  and
biological  materials  and  has a  detection  limit  of 10-11  -
10-12 g.   Neutron activation and spark-source mass spectrometry
are  sophisticated methods that, because of their high cost, are
not  always feasible.  Various electrochemical and spectrophoto-
metric  assays are being  widely used for  the determination  of
vanadium  in  a  variety  of  media.   These  methods  have  the
advantage  of being relatively cheap.  Coulometric titration and
controlled  potential  coulometry  are accurate  methods for the
determination  of  vanadium  in  solutions.   They  are  not  as
sensitive as the more sophisticated methods.

    Stripping  voltammetry  and  other modern  modifications  of
polarography,  as  well  as  electrometrical  methods  based  on
catalytic  reactions,  are  considered highly  sensitive for the
determination of vanadium in solutions and biological materials;
however,  depending on the composition of the sample, they could
involve operations to separate out interfering elements.

1.2  Sources in the Environment, Environmental Transport and Distribution

    Metallic  vanadium  does  not  occur  in  nature.   Over  70
vanadium  minerals are known, carnatite and vanadinite being the
most  important from the point of view of mining.  Production of
vanadium  is linked  with that  of other  metals such  as  iron,
uranium, titanium, and aluminium.  As rich minerals rarely occur
in large deposits, ores with a low vanadium content, which exist
in  large amounts, are  important.  Extraction of  vanadium from
fossil  fuels,  including  vanadium-rich  oil  and  coal,  tars,
bitumens, and asphaltites, is important in several countries.

    During the first half of the 1980s, the global production of
vanadium  (as vanadium  pentoxide, V2O5)  ranged from  34 to  45
million  kg, China, Finland, South Africa, the USA, and the USSR
being the biggest producers.

    Vanadium  is mainly (75 - 85%) used in ferrous metallurgy as
an  alloy additive in various  types of steel.  Its  use in non-
ferrous  metals  is important  for  the atomic  energy industry,
aircraft  construction, and space technology.   Vanadium is also
widely  used  as  a catalyst  in  the  chemical industry,  where
vanadium  pentoxide  and metavanadates  are especially important
for  the  production  of  sulfuric  acid  and  plastics.   Small
quantities   of   vanadium  are  used  in  a  variety  of  other

    From  the point of  view of environmental  pollution, power-
and  heat-producing plants using fossil  fuels (petroleum, coal,
oil)  cause the most widespread discharge of vanadium  into  the
environment.   Burning of coal wastes  or dumps of coal  dust in
mining  areas are other sources  of vanadium discharge into  the
atmosphere.   In the distillation and purification of crude oil,
most  of  the  vanadium remains  in  the  residues.  Burning  of
distilled  petroleum  fuels  contributes less  vanadium  to  the

    Emissions of vanadium may be high in the vicinity  of  large
plants producing steel alloys.  Vanadium is also  released  into
the  air:  during  the  re-smelting  of  scrap  steel  and   the
transformation  of titaniferrous and vanadic magnetite iron ores
into steel; from the roasting of vanadium slags;  from  vanadium
pentoxide smelting furnaces; and from electric furnaces in which
ferrovanadium is smelted.

    Most  of the vanadium that enters sea water is in suspension
or  adsorbed on colloids.  It does not react chemically with sea
water  and passes mechanically through it.  This is reflected in
its distribution on the sea bed in the form of silt.  Only about
10%  of the vanadium is present in a soluble form.  The very low
concentrations of vanadium in sea water indicate  that  vanadium
is  continuously  removed  from  sea  water,  but   the   actual
mechanisms  are largely unknown.   Vanadium that accumulates  in
ascidians,  holothurians, and in marine algae will end up in the

1.3  Environmental Levels and Human Exposure

    Concentrations of vanadium in ambient air vary considerably.
Elevated vanadium levels are believed to result from the burning
of  fossil fuels with  a high vanadium  content.  Thus,  heating
requirements  and seasonal differences in atmospheric inversions
are  reflected by fluctuations in  vanadium levels in air.   Air
levels  of vanadium can be reduced by using distilled instead of
residual  fuel oil.   In remote  rural areas,  levels are  below
1 ng/m3,  but burning of fossil fuels can exceptionally increase
local levels to about 75 ng/m3.  Typical concentrations in urban
air  vary over a wide  range of about 0.25  - 300 ng/m3.   Large
cities may have annual average air levels of the order of  20  -
100 ng/m3, with markedly higher concentrations during the winter
months  compared with  the summer  months.  In  the vicinity  of
metallurgical  industries, concentrations of 1 g/m3   are often
found.  Assuming an average air concentration of about 50 ng/m3,
about 1 g of vanadium may enter the respiratory tract daily.

    Vanadium concentrations in drinking-water are generally less
than  10 g/litre.   A typical range is 1 - 30 g/litre  with an
average of about 5 g/litre.

    The  main  source  of  vanadium  intake  for   the   general
population  is food.  Reported  vanadium concentrations in  food
tended to be higher in early studies compared with  more  recent
measurements,  which have shown  concentrations in the  range of
0.1 - 10 g/kg  wet weight, with typical concentrations of about
1 g/kg.   Recent estimates of daily intake suggest a  range  of
10  - 70 g  with the majority of estimates below 30 g:  higher
estimates of up to 2 mg suggested in earlier studies  were  most
likely due to analytical differences.

    Exposure to high concentrations of vanadium in the  air  may
occur  in working environments.   In the production  of vanadium
pentoxide,  dust  concentrations  containing the  pentoxide  can
range  from 0.1 to 30  mg/m3, and concentrations of  about 0.5 -
5 mg/m3 are not uncommon in the production of vanadium metal and
vanadium  catalysts.  The highest vanadium concentrations in air
occur  in boiler  cleaning where  dust concentrations  of  50  -
100 mg/m3,   but  sometimes  reaching   500  mg/m3,  have   been
encountered.  Such dusts contain 5 - 17% of  vanadium  pentoxide
and   3  -  10%   of  lower  oxides.    These  levels  are   not
representative of vanadium concentrations in the air  in  modern
plants, where levels are usually much lower.

1.4  Kinetics and Metabolism

    The  rate  of  pulmonary  absorption  of  various   vanadium
compounds  has not been  determined, but it  has been  estimated
that  about 25% of soluble  vanadium compounds may be  absorbed.
The results of experimental animal studies have  shown  complete
clearance  of the relatively soluble vanadium pentoxide from the
lung in 1 - 3 days following acute exposure.  When  48VOCl3  was
instilled  intratracheally  in the  rat  lung, 50%  was  cleared
within the first day; 3% remained after 63 days.

    Vanadium  salts are poorly  absorbed from the  human gastro-
intestinal  tract, only 0.1 - 1% of the very soluble oxytartaro-
vanadate being absorbed.  A very low level  of  gastrointestinal
absorption  has also been seen in animal studies, and, though it
has been shown that soluble vanadium compounds may  be  absorbed
through the skin of rabbits, the dermal absorption  of  vanadium
compounds is likely to be extremely small.

    Absorbed  vanadium  is  mainly transported  in  the  plasma.
Vanadium  concentrations in all  tissues are generally  low, but
are higher in the liver, kidney, and lung than in other tissues.
Levels in the liver may be in the range of 4.5 -  19 g/kg   wet
weight  and those in kidney, 3 - 7 g/kg.   Higher levels may be
found in lung tissue with mean concentrations ranging from 10 to
130 g/kg   wet weight.  Small  amounts have been  found in  the
placenta,  and vanadium passes through into the membranes rather
than  the fetus.  Vanadium is present in breast milk and saliva.
It also passes through the blood-brain barrier.  Reported levels
in  human blood differ widely,  levels in whole blood  and serum
lying  within the range  of 0.01 -  0.4 mg/litre.  Most  studies
have shown levels below 0.1 mg/litre.

    Because  of  the  low level  of  absorption  in the  gastro-
intestinal   tract,  ingested  vanadium  is   mainly  eliminated
unabsorbed with the faeces.  The principal route of excretion of
absorbed  vanadium is through the  kidneys.  Vanadium concentra-
tions  in urine are  of the order  of 0.1 -  0.2 g/litre.   The
majority  of studies on occupationally  exposed populations have
shown  a poor correlation between vanadium concentrations in air
and  the amounts  excreted in  urine.  However,  in very  highly
exposed workers, urine-vanadium levels increased 20 -  30  times
over a work-shift.

1.5  Effects on Experimental Animals and  In Vitro Test Systems

    Vanadium  is  an  essential  element  for  chicks  and rats.
Vanadium  deficiency  in  these species  causes  reduced growth,
impairment  of  reproduction,  and  disturbance  of  the   lipid
metabolism.  Vanadium has a diuretic and natriuretic  action  in
rats and inhibits the Na+-K+-ATPase (EC  in  microsomal
fractions of kidney, brain, and heart of several  species.   The
observation  of the inhibiting  effects on Na+-K+-ATPase  led to
the  discovery that a variety of enzymes are vanadium sensitive.
For  instance,  ATP  phosphohydrolase, ribonuclease,  adenylate-
kinase,   phosphofructokinase,  and  glucose-6-phosphatase   are
inhibited by vanadium compounds.

    In general, vanadium is better tolerated by  small  animals,
such   as  the rat and  mouse, than by larger  animals including
the  rabbit  and horse.   The toxicity of  vanadium is low  when
administered  orally,  moderate  when  inhaled,  and  high  when
injected.   A  1-h LC50  of 70 mg/m3  has been reported  for the
inhalation  of  vanadium  pentoxide  in  the  rat.   The minimum
concentration  of  vanadium  pentoxide  that  caused  mild signs
of  acute poisoning in  the rat was  10 mg/m3 air.   Exposure of
rabbits  to  vanadium  pentoxide  at  205  mg/m3   resulted   in

conjunctivitis     and     tracheitis,     pulmonary     oedema,
bronchopneumonia,  and death within 7  h.  The exposure of  rats
for  2 h every  other day for  3 months to  3 - 5  mg/m3  caused
pathological  changes only in  the lungs.  The  endothelium  was
swollen,  there  was capillary  congestion, perivascular oedema,
and small haemorrhages indicating altered vascular permeability.
Similarly,   respiratory  symptoms,  such  as  nasal  discharge,
sneezing,  dyspnoea,  and  asthmatic  reactions,  were  seen  in
rabbits exposed to vanadium trioxide aerosol at 40 -  75  mg/m3,
for 2 h/day over 9 - 12 months.

    The  effects of acute  and long-term inhalation  exposure on
the  respiratory  tract  may partly  be  due  to the  effect  of
vanadium on the macrophages.  A 50% reduction in  the  viability
of  cultured rabbit macrophages was seen after exposure to 13 g
vanadium/ml  (as vanadium pentoxide) for 20 h.  Exposure for 2 h
(vanadium  pentoxide) reduced the viability  of murine pulmonary
alveolar macrophages at a dose of 7 g vanadium/ml.

    Vanadium pentoxide administered in the diet at 0.05 - 0.5 mg
vanadium/kg,   per  day,  for  80  days,  caused  impairment  of
conditioned  reflexes in the rat.  Daily parenteral injection of
sodium metavanadate (3.2 g/kg  body weight per day, for 10 - 15
days)  increased the reactivity of cytochrome oxidase in guinea-
pig brain, whereas a dose of 128 g/kg  per day did  not  induce
any  effects and  5.12 mg/kg  body weight  per day  reduced  the
activity.   Cholinesterase activity in the rat brain was reduced
by  the intraperitoneal  administration of  1 -  10  mg  vanadyl

    Fatty  changes  with  partial  cell  necrosis  of  the liver
occurred in rats and rabbits exposed by inhalation  to  vanadium
pentoxide, trioxide, or trichloride (10 - 70 mg/kg, 2 h/day, for
9  -  12  months).  Fatty  changes  in  the liver  of  rats also
occurred after exposure to ammonium vanadate.

    Vanadate  has  a  diuretic  and  natriuretic  effect  on rat
kidneys,  but not on those  of the dog or  cat.  This effect  is
thought  to be due to the inhibition of Na+-K+-ATPase, which, in
turn, inhibits the tubular reabsorption.  Fatty changes  in  the
myocardium  of both the rat and rabbit were seen after long-term
inhalation of vanadium pentoxide, trioxide, or trichloride (10 -
70 mg/m3, 2 h/day, for 9 - 12 months).  Perivascular swelling of
the myocardium was also seen.

    Rats  given  metavanadate  subcutaneously (0.85  mg/kg  body
weight)     showed   shedding   of   spermatogenic   epithelium.
Gonadotoxic   effects   were   suggested  by   the   absence  of
fertilization  of female rats by male rats that had been exposed
subcutaneously  to vanadium at 0.85 mg/kg body weight.  The same
dose  administered to female rats on the fourth day of pregnancy
increased the mortality of embryos.

    Parenteral  administration  of  ammonium  vanadate   (intra-
peritoneal) to pregnant Syrian golden hamsters and  of  vanadium
pentoxide  (subcutaneous  and  intravenous)   to  pregnant  rats

resulted  in increased numbers of fetal deaths and significantly
increased  skeletal  abnormalities.   These studies  indicate  a
possible teratogenic effect of vanadium.

    There are few data on the mutagenicity  and  carcinogenicity
of  vanadium  compounds and  limited  indications of  the  muta-
genicity  of vanadium.  In  a rec assay  with  Bacillus subtilis, 
testing   DNA damaging capacity,  three compounds (VOCl2,  V2O5,
NH4VO3), gave mildly positive results, while results of tests in
 Escherichia coli and  Salmonella strains   were  mostly negative.
Bacterial  assays  have given  conflicting  results and  no firm
conclusions can be drawn.

    No information is available indicating a carcinogenic action
of vanadium.

1.6  Effects on Man

    No  data are available on the effects of vanadium deficiency
in man, and, though possible regulatory roles of  vanadium  have
been  suggested, a daily dietary requirement of vanadium for man
has not been defined.

1.6.1   Local effects and dose-response relationships

    There  are comparatively few  reports about the  effects  of
vanadium exposure on the skin.  Eczematous dermatitis  has  been
reported  in workers exposed  to vanadium pentoxide,  with  dust
levels as low as 6.5 g/m3.

    Inhalation  of vanadium pentoxide produces local irritation.
The  exposure  of  2 volunteers to 1 mg/m3 for 8 h resulted, 5 h
later,  in  coughing  that lasted  for  8  days.  Inhalation  of
0.2 mg/m3  by 5 volunteers  resulted in similar  symptoms, i.e.,
coughing that started a little later (20 h after  exposure)  and
lasted  for 7  - 10  days.  Similar  irritation was  noted in  2
volunteers  exposed  to  0.1 mg/m3  for  8  h.  A  dose-response
relationship   was observed when  11 volunteers were  exposed to
0.4 mg vanadium pentoxide/m3 condensation aerosol.  Tickling and
itching with dryness of the mucous membranes of the  mouth  were
reported  by 5 subjects at  0.16 mg/m3, whereas, at  0.08 mg/m3,
none of the subjects noted any effects.

    Workers  exposed  to  dust  containing  vanadium  at  0.01 -
0.04 mg/m3,  for about 10 months, showed irritant effects on the
mucous  membranes  of  the  upper  respiratory  tract.    Cough,
increased production of sputum and irritation of the eyes, nose,
and  throat occurred among workers exposed to a maximum of 0.9 -
5  mg  vanadium/m3.   At  high  exposures  (dust  concentrations
ranging  between 5 and  150 mg/m3), workers  developed  atrophic
rhinitis,   and   chronic  bronchitis.    Blood-stained  sputum,
haemoptysis, and bronchospasm were seen in a proportion of those
exposed.    In  workers  exhibiting  asthmatic  reactions,  when
exposed  to  vanadium  pentoxide,  there  was  no  indication of
specific  sensitization; the mechanism is thought to be a direct
chemical one.

    Among  the local effects  caused by vanadium  exposure,  the
green  tongue  occurring  in a  proportion  of  the  exposed  is
considered a sign of exposure rather than a toxic effect.

1.6.2   Systemic effects and dose-response relationships 

    The  effects of  vanadium on  dental caries  is a  debatable
issue.   It  has been  claimed that, when  added to the  diet of
hamsters, vanadium had a favourable effect on dental caries.  It
has also been shown, in one report, that the application  of  an
ammonium  salt of vanadium reduced caries in children.  However,
other studies between 1955 and 1968 failed to  demonstrate  such
beneficial effects of vanadium, and in one study, an increase in
caries  was  observed after  administration  of vanadium  in the
drinking-water at 2 mg/litre.

    The  effects of vanadium on cholesterol levels have not been
fully  elucidated.  Studies  in the  1950s and  1960s claimed  a
temporary  drop in cholesterol  levels in patients  fed ammonium
oxytartarovanadate  and  ammonium  vanadyltartrate, for  several
weeks, at 50 - 200 mg/day.  Although some data  on  experimental
animals have indicated that vanadium reduces cholesterol levels,
this has not been convincingly shown in human beings.
    The  results of studies on the effects of vanadium pentoxide
on  rats have shown a  decrease in cysteine in  hair and also  a
reduction of co-enzyme A in the liver, which could  explain  the
mechanism behind the reduction of cysteine.  Data on the effects
of vanadium on haematopoiesis are inconsistent, and it  has  not
been  possible  to  assess  the  effects  of  low-level vanadium
exposure on iron metabolism.  Vanadium has been shown to inhibit
the Na+-K+-ATPase (EC  in human red blood cells.

    Systemic  effects are rare  in workers exposed  to  vanadium
compounds.   Nonspecific signs and symptoms  including headache,
weakness,  nausea, vomiting, and ringing  in the ears have  been
reported,  and there have been reports of dizziness or giddiness
and  neuraesthenic and vegetative symptoms.  A few early reports
mention  tremor.   It is  not  possible to  derive dose-response
relationships for these effects on the nervous system.  They are
likely to be associated only with fairly high  exposure  levels.
Systemic  effects such as  anaemia,  leukopenia, and  basophilic
granulation  of  leukocytes have  been  reported, but  cannot be
expressed   in  relation  to  any   particular  exposure  level.
Although fatty changes in the liver and kidney have been seen in
experimental  animals, there  are no  data on  human  beings  to
evaluate these effects.

    In exposed workers, palpitations of the heart at rest and on
exercise  have been reported.  Transient  coronary insufficiency
and a high incidence of extrasystoles have also  been  reported.
The association between these symptoms and vanadium is doubtful.
Low-level  exposure of workers to  vanadium pentoxide at 0.01  -
0.04  mg/m3  air  for about  10 months, preceded by  exposure to
0.2  -  0.5  mg/m3  for  about  11  years,  did  not  cause  any

pathological effects on the blood picture, the cysteine level in
hair,  or the respiratory function.  Wheezing was more common in
exposed workers than in controls.

    A few attempts to relate vanadium levels in ambient  air  to
adverse  effects  on  the  general  population  have  been made.
Positive  correlations  between  mortality  from  cardiovascular
disease,  lung  carcinoma,  and  bronchitis,  and  vanadium  air
concentrations   have  been  reported,   but,  so  far,   causal
associations  have not been  reported.  Further studies  on  the
possible  effects of vanadium exposure on the general population
are  needed,  with better  control  of confounding  factors  and
various intercorrelations than that in available studies.

1.7  Evaluation of Health Risks for Man

    There   is  no  convincing  evidence  that  vanadium  is  an
essential element for man.  Vanadium interferes with a multitude
of biochemical processes, and its physiological role  should  be
carefully assessed.  Vanadium penetrates the blood-brain barrier
and is present in breast milk.  Effects on the fetuses  of  rats
and  hamsters when vanadium was administered to pregnant animals
indicate   transfer  across  the  placental   barrier;  however,
Vanadium  appears to concentrate in the membranes rather than in
the fetus.

    Current  levels of  vanadium in  the ambient  air have  been
associated  with  mortality in  the  general population  due  to
various diseases of the heart and lung.  All  studies  reporting
such  relationships  have  had  serious  flaws,  and  no  causal
relationships  between  vanadium  and  disease  in  the  general
population have been established.

    Practically  all the information on adverse effects on human
beings  has  been  derived  from  controlled,  therapeutic,   or
occupational  exposure to concentrations that do not occur under
normal  conditions.  Exposed workers may  suffer from irritation
of the eyes and the respiratory tract.  There is a dose-response
relationship  between the concentration  of vanadium in  air and
its  irritant effects.  With  short-term inhalation exposure  to
vanadium  pentoxide  at  a  concentration  of  about  0.1 mg/m3,
irritation  is manifested as coughing  with increased production
of  mucous.  Continuous exposure  to even lower  levels  (0.01 -
0.04  mg/m3) may cause some irritation, but does not impair lung
function.   A reversible decrease in forced vital capacity (FVC)
has  been  reported  with exposure  to  a  dust  containing  15%
vanadium at a level of about 0.5 mg/m3.  High exposure levels of
5 - 150 mg/m3 cause atrophic rhinitis and bronchitis with a risk
of bronchospastic effects.  Eczematous dermatitis may occur with
low-level exposure to vanadium pentoxide (6.5 g/m3).

    Non-specific  effects,  such as  headache, nausea, weakness,
ringing  in the  ears, and  palpitation, have  been reported  in
exposed  workers.  These effects  have not been  related to  any
specific  exposure level, but, on such occasions, it has been in

the  mg/m3  air  range.   Such  symptoms  may  be  taken  as  an
indication  of the need  for personal protection  in work  tasks
associated with the risk of heavy exposure to  dusts  containing

    Several  reported effects of vanadium need further research,
including  the effects on  cholesterol levels, iron  metabolism,
and  haematopoiesis.  Available data  do not imply  any risk  of
carcinogenic  effects;  however,  the data  cannot be considered
conclusive.   There  are  only  weak  indications  of   possible
mutagenic effects of vanadium compounds.  The results of studies
on  point mutations in bacteria  are conflicting, and there  are
too  few studies to  draw definite conclusions  with respect  to
mutagenicity.   The scanty evidence of spermato- and gonadotoxic
effects  needs corroboration.  The  available data suggest  that
vanadium  may  be  embryotoxic and  gonadotoxic.   However,  the
results  indicating  the  induction  of  teratogenicity  require
further confirmation.


2.1  Identity

    Vanadium  (V) is  a greyish  ductile metal  with  an  atomic
number  of 23, an atomic mass of 50.942, a melting point of 1890
 10 C, a boiling point of 3380 C at 1 atm  (1.013 x 105  Pa),
and  a specific  gravity of  6.11 at  18.7 C (Weast,  1986-87).
Vanadium  has two  natural isotopes,  50V and  51V, and  several
radioactive   isotopes  (46-49V,  52-54V)  have   been  obtained
artificially (Clark, 1975; Weast, 1987).

2.2  Physical and Chemical Properties

    Vanadium  has a maximum oxidation state of +5.  Compounds of
vanadium  may contain vanadium in oxidation states of -1, 0, +2,
+3,  +4, and +5.  Vanadium is usually found bound to oxygen as a
negatively charged polymeric oxyanion that tends to  complex  to
polarizable  ligands, such as phosphorus and sulfur (Buckingham,
1973; Cotton & Wilkinson 1980).
    Vanadium's  ability to be  either an electronegative  or  an
electropositive  metal results in  a great variety  of  chemical
compounds  (vanadium is second only  to carbon in the  number of
chemical  compounds).   Physical  properties of  some  important
compounds are shown in Table 1 (Weast, 1987).
    Vanadium   usually   occurs   in  the   pentavalent   state.
Pentavalent  vanadium is stable in aqueous solutions over a wide
range of pH.
    The  formation of isopoly  and heteropoly compounds  is most
characteristic  of  pentavalent  vanadium in  aqueous solutions.
The tendency of vanadium compounds to form V-0-V-0  linkages  is
due  to  the electronegativity  of  vanadium and  to  electronic
hybridization (Zolotavin, 1954).
    Vanadium  pentoxide (V205), the most  common commercial form
of  vanadium, dissolves  in water  (8 g/litre)  to give  a  pale
yellow  acidic  solution  containing vanadium  species  that are
moderately strong oxidizing agents (Cotton & Wilkinson, 1962).

    Vanadium5+  is  reduced  to vanadium4+  by  relatively  mild
reducing  agents.  The  4+ state  is the  most stable  oxidation
state for vanadium.  Nearly all of the complexes  of  vanadium4+
are derived from the vanadyl ion (VO2+). Most of these complexes
are  anionic and a few  are non-electrolytes.  Vanadium in  this
oxidation state forms a large number of five or  six  coordinate
complexes,   such   as   vanadyl  acetylacetonate   and  vanadyl
porphyrins found in crude petroleum.

    Vanadium3+ (e.g., V203) is completely basic and dissolves in
acid to give the green hexa-aquo ion (V(H2O)6)3+.  Vanadium3+ is
a  strong reducing  agent that  slowly attacks  water  with  the
liberation  of hydrogen and  the production of  vanadium4+.  The
hexa-aquo ion of vanadium is easily oxidized to vanadium4+.

Table 1.  Physical properties of some vanadium compounds
Compound        Melting     Boiling    Solubility in water (g/litre)
                point (C)  point (C) Cold          Hot

Vanadiuma       690         1750       0.7b          no data

Vanadiuma       1970        no data    slightly      soluble
trioxide                               soluble

Sodiuma         630         no data    211           388

Vanadium        -28  2     148.5      decomposes    no data

Vanadium        no data     127        decomposes    no data

Ammonium        200c        no data    5.2            69.5c
a   From: Weast (1987).
b   From: Cotton & Wilkinson (1980).
c   Decomposes.

2.3  Analytical Methods

    A review of analytical methods used to determine vanadium in
different    media   suggests   that   atomic   absorption   and
spectrophotometric  assays  are  the most  suitable  for routine
analysis.  Neutron  activation  analysis  has  been  widely  and
successfully used for the determination of vanadium in serum and

2.3.1   Atomic absorption analysis and emission spectrometry

    Atomic  absorption techniques have been most widely used for
the  determination of vanadium in various media.  Vanadium forms
heat-stable   refractory   oxides   that  are   not   completely
dissociated  in  a  flame.   The  use  of  a  high   temperature
oxyacetylene  flame  improves  the  sensitivity  of  the  method
(L'vov,  1970).  Other ways  of improving sensitivity  have been
suggested  (Christian  &  Feldman, 1970;  Omang,  1971; Kragten,
1981;  Wood et al., 1982).   High sensitivity has been  achieved
using  flameless  electrothermal  AAS  assays  with  a  graphite
furnace.   A flameless atomic absorption method using a graphite
furnace was recommended by NIOSH (1977) for the determination of
vanadium  in air.  A  detection limit of  1 ng/ml for a  maximum
sample injection of 100 litre  was given, corresponding  to  an
absolute sensitivity of 0.1 ng of vanadium. A detection limit of
0.4 ng  was reported by  Hwang et al.  (1972) using a  flameless
atomic  absorption method that was applicable to air, water, and
biological samples.

    A method for the determination of vanadium in work-place air
using  direct current plasma atomic  emission spectrometry (DCP-
AES)  was reported by Pyy et al.  (1983).  A detection limit for
vanadium  in air of 0.004 mg/m3 and a practical working range of
0.01  - 100 mg/litre were suggested.  The precision was given as
1%.   The results of this  assay correlated with those  obtained
with  both flame (FAAS) and electrothermal atomization (EIA-AAS)
atomic absorption spectrometry.

    Vanadium and 11 other trace elements in natural  water  were
determined  using  AAS  and the  stabilized temperature platform
furnace.  A detection limit of 0.6 g/litre  with a precision of
10 - 15% was achieved (Manning & Slavin, 1983).

    Electrothermal  AAS  methods  have been  used  to  determine
vanadium in urine.  Buchet et al. (1982) detected concentrations
in  the range  of 1  - 500 g/litre,   giving a  coefficient  of
variation  for triplicate  samples of  less than  8%  for  10 g
vanadium/litre.   A  practical  detection limit  for vanadium in
urine  of  2 g/litre  was  reported by Pyy  et al. (1984)  also
using  an  electrothermal AAS  method  with a  graphite furnace.
Extraction    of    vanadium   with    ammonium   1-pyrrolidine-
carbodithioate  into 4-methylopentan-2-one reduced the detection
limit to 0.5 g/litre.

    Atomic  absorption is widely  used for the  determination of
vanadium  in biological materials, such as tissues and serum.  A
detection  limit  of  30 pg and a sensitivity of 65 pg have been
reported  using a flameless apparatus and graphite tubes (Stroop
et al., 1982).

    AAS  methods  can  also be  used  in  the  determination  of
vanadium  in other media such  as crude petroleum (Wood  et al.,
1982)  and  sewage  sludge  (Kempton  et  al.,  1982).  Improved
techniques have been developed (Barbooti & Jasim 1982; Slavin et
al.,  1983)  including  the use  of  simultaneous  AAS and  mass
spectrometry (Styris & Kaye, 1982).

    In  general, emission spectral analysis  has been considered
less accurate than colorimetric methods (Bagget &  Huyck,  1959;
Sandell,  1959).  However, it is a universal selective method by
which  small  amounts  of vanadium  can  be  determined  in  the
presence  of numerous other elements.   The relative sensitivity
of  spectral  analysis  is 10-3  -  10-5%.   Sensitivity can  be
increased by prior separation of the element to be determined.

    Inductively coupled plasma optical emission spectrometry has
been used for the simultaneous determination of several elements
in  aerosol samples collected with  cascade impactors (Broekaert
et  al.,  1982) and  also for the  determination of vanadium  in
urine (Barnes et al., 1983).

2.3.2   Neutron activation analysis

    Neutron  activation analysis is more rapid and accurate than
other  methods.  Using  this method,  it has  been  possible  to
determine up to 70 elements in amounts of 10-12 g in  air  (Dams
et  al., 1970;  Gershkovich &  Stykan, 1972).   In carrying  out
neutron  activation analysis, a weighted sample or test solution
is  irradiated with a thermal neutron flux in an atomic reactor,
for  a certain length of time (Flaherty & Eldrige, 1970; Frolov,
1970).   During  irradiation, one  or  several isotopes  of  the
element being tested are formed.  The activity of  the  isotopes
formed  is  determined  from  the  gamma  peak  by  means  of  a
scintillation gamma spectrometer.  The sensitivity of the method
depends  on many factors including:  size of the particle  flux,
duration  of sample irradiation, efficiency of the counter, time
elapsed  since the beginning of irradiation, background response
of the counter, etc.

    The  chemical form of  vanadium in water  can be  determined
using  a  48V  tracer and  neutron  activation  (Orvini et  al.,

    Neutron  activation determination of vanadium  in biological
material  is complicated by  the high concentration  of  sodium,
even when a Ge/Li detector is used.  Because of the  short  life
of   the  isotope,  the   sodium  must  be   eliminated   before
irradiation,   normally  by  absorption  on  antimony  pentoxide
(Ralston   &   Sato,   1971).   Neutron   activation   has  been
successfully used to determine vanadium in serum (Byrne & Kosta,
1978;  Sabbioni et al., 1979;  Cornelis et al., 1980,  1981) and
body tissues (Yukawa et al., 1980).

2.3.3   Spark-source mass spectrometry

    Spark-source  mass  spectrometry is  an excellent analytical
tool  (Johnson et al., 1974).   The absolute sensitivity of  the
method  is 10-11  - 10-12  g, and  the relative  sensitivity  is
10-7 g-atom.  Up to 70 elements can be  recorded  simultaneously
on  the photographic plate and  only a few milligrams  of sample
are needed (Chupahin et al., 1972).  This method is used for the
multi-element analysis of air and biological materials.

    Evans & Morrison (1968) described the problems that occur in
analysing  ashed biological material  for vanadium using  spark-
source  mass spectrometry.  The ash  must be completely free  of
organic  mixtures,  since  vanadium  belongs  to  the  class  of
elements  in which inorganic  compounds are completely  bound to
biological  material.   The  concentration of  vanadium found by
spark-source  mass spectrometry  was 10  times as  high as  that
found by the spectral method in the same samples.

    Vanadium  levels  in  urine  and  biological  tissues   were
determined  by Pilz &  Komischke (1972) using  salicylhydroxamic
acid.   The vanadium complex was extracted with N-pentanol,  and
the vanadium was determined in the extract by spectrophotometry.

Beer's law was observed, with concentrations of vanadium ranging
from  1 to 2000 g/25  ml extract.  There was no interference by
cobalt, nickel, zinc, molybdenum, tungsten, iron, calcium, lead,
or chromium.

2.3.4   Spectrophotometric analysis

    Organic reagents are often used to improve  the  specificity
of  spectrophotometric analysis.  Over 80  organic reagents have
been  suggested  for  the direct  quantitative  determination of
vanadium  (Mustafin et al.,  1969; Muzquin et  al., 1981).   The
specificity  of  the  organic  reagents  can  be  increased when
complexing  agents are used  to bind the  interfering ions.   In
most  cases, particularly those  based on complexing  reactions,
specificity  and sensitivity are enhanced by prior separation of
vanadium,   mostly   by   extraction.    Acyl   derivatives   of
hydroxylamine  containing the OC-NOH group show high selectivity
for pentavalent vanadium, when the product of interaction  in  a
highly  acid medium is  extracted (Tandon &  Bhattacharya, 1961;
Majumdar & Das, 1965).
    Spectrophotometric  analysis  based on  catalytic reactions,
e.g.,  on acceleration of the  oxidation of aromatic amines  and
aminophenols   with   chlorates,   bromates,   periodates,   and
persulfates  in the presence of  pentavalent vanadium compounds,
is widely used to determine trace amounts of vanadium  (Bakal  &
Liseckaja,  1971; Zheljazkova et al., 1972).  The sensitivity of
kinetic  methods is theoretically  unlimited and their  use  for
analysing  biological materials is  quite promising, because  of
the considerably reduced amounts of material needed for analysis
(Jacimirskij, 1967).

    Welch  &  Allaway  (1972)  proposed  a  method  to determine
nanogram  quantities of vanadium by  means of an acid  oxidation
reaction  catalysed  by  vanadium pentoxide.   Christian  (1971)
determined vanadium in blood and urine using a method  based  on
the  catalytic effect of vanadium  on the oxidation reaction  of
phenylehydrazine-N-sulfonic     acid  with  potassium  chlorate.
Vanadium  concentrations  of  0.056  0.033 mg/litre  in  blood-
plasma,   0.061  0.019  mg/litre  in   red  blood  cells,   and
0.022  0.015  mg/litre  in  urine  were  detected  using   this

2.3.5   Electrochemical methods

    Vanadium  is commonly determined by electrochemical methods,
namely  by  volumetric  titration with  electrometric detection,
such  as  potentiometry  (Cassani, 1968),  amperometry  (Singh &
Sharma, 1970), as well as by coulometric  titrations  (Kostromin
et  al.,  1970),  polarography (Shevchenko  & Gorodynskij, 1964;
Budnikov  & Medjantseva, 1973), and coulometry (Rigdon & Harrar,
1969).   Catalytic reactions with polarographic, potentiometric,
and amperometric detection (Weisz et al., 1974) are also used.

    Stripping  voltammetry (Van den Berg & Huang Fi Qiang, 1984)
and other modifications of polarography (Veys, 1983), as well as
electrometric  methods based on  catalytic reactions are  highly
sensitive  but, depending on the composition of the sample, they
can involve operations to separate out interfering  elements  in
the  sample.  The selectivity of controlled potential coulometry
is high, making the separate determination of vanadium compounds
of   different   valencies   possible.   The   introduction   of
differential  techniques  into  both coulometric  titration  and
controlled  potential coulometry results  in very high  accuracy
(Agasyan et al., 1975; Shkolenok et al., 1977).

2.3.6   Chromatography

    The   chromatographic  method  has  found  little  practical
application  in determining trace quantities  of vanadium though
Bonig & Heigener (1971) used selective paper  chromatography  to
determine microgram quantities of vanadium.


3.1  Natural Occurrence

3.1.1 Rocks
    Vanadium is a typical rare element, present in  the  earth's
crust at concentrations of around 0.015 g/kg, which  is  roughly
in the same proportions as chromium, strontium,  and  zirconium.
It  is considerably more widespread than copper, lead, zinc, and
other minor elements.  Some 70 vanadium minerals are  known,  of
which   40  are  vanadates.   The  main  vanadium  minerals  are
vanadinite  (19%  vanadium  pentoxide), descloizite  (220 g/kg),
cuprodescloizite   (170 -  220  g/kg),  carnotite   (200  g/kg),
roscoelite  (210 - 290  g/kg), and patronite  (170 - 290  g/kg).
Admixtures  are found in  the ore minerals  titaniferromagnetite
(up  to 88 g vanadium pentoxide/kg), magnesioferrite (160 g/kg),
magnetite  (6 g/kg), rutile  (1 g/kg), and  ilimenite (4  g/kg).
Metallic  vanadium does  not occur  in nature,  and  the  richer
minerals rarely occur in large deposits.  Vanadium compounds are
present in fossil fuels (oil, coal, shale), and  some  oilfields
have a high vanadium content (NAS, 1974).

    Vanadiferrous phosphorites (1 - 10 g/kg), asphaltites (up to
500 g/kg in ash), and titaniferrous magnetite placers, mainly of
the  sea-beach type  (about 3  g/kg), are  important sources  of
vanadium.   Oolite brown iron ore  (ferrophosphorous ore), which
contains only small amounts of vanadium pentoxide (0.7 - 2 g/kg)
but  occurs  extensively, carbonaceous  cherts  (15 -  20 g/kg),
bauxites (0.2 - 0.4 g/kg), the ash of coal and combustible shale
(2  g/kg), and  ferromanganese nodules  in the  ocean,  may  all
provide  sources for vanadium extraction (Todria, 1963; Holodov,
1968,  Schumann-Vogt,  1969;  Borisenko, 1973;  Rose, 1973; NAS,
1974).  The most important deposits of vanadium ores  are  found
in  Canada, Finland, Namibia, South Africa, Sweden, the USA, the
USSR, and Zambia (Borisenko, 1973).

3.1.2  Soils

    The vanadium contents of soils are related to those  of  the
parent  rocks from which they are formed and range from 3 to 310
mg/kg,  the  highest concentrations  being  found in  shales and
clays  (Waters, 1977).  Vanadium  is evenly distributed  in  the
soil  horizons, but there is  sometimes a higher level  in the A
horizon, possibly connected with the vital activity  of  plants.
In  the  neighbourhood of  vanadium-bearing  rocks or  of  large
amounts  of iron  oxides, a  moderate local  increase  in  soil-
vanadium  levels may be found.  Vanadium is present in the soils
of  France,  Japan, Spain,  the United Kingdom,  and the USA  at
levels that are partly determined by the distribution of iron in
these  soils (Holodov, 1968); levels  ranged from 1 to  680 g/kg
(Vinogradov  1957). The lowest  concentration was reported  from
Japan,  and  the highest  from  Spain.  Vinogradov  (1957) found
lower vanadium concentrations in USSR podzols than in tundra and
chernozem soils.

3.1.3  Water

    The  levels of vanadium in fresh water in different parts of
the  world vary from  undetectable to 0.220  mg/litre (Table 2).
The  geographical differences in fresh water vanadium levels are
due to differences in rainwater runoff from natural  sources  or
in  industrial  effluent.  Data  on  vanadium levels  in  waters
contaminated  with industrial effluent are  presented in section
3.4.1.   Some data  on vanadium  in sea-water  are presented  in
Table 3.

3.1.4  Air

    Natural sources of airborne vanadium are marine aerosols and
continental dust.  The concentration of vanadium in the  air  at
the South Pole is very low (0.001 - 0.002 ng/m3) (Zoller et al.,
1974).   Levels in ocean air  in the middle latitudes  are about
two orders of magnitude higher (Hoffman et al., 1972; Martens et
al., 1973).
    Atmospheric concentrations of vanadium from continental dust
and sea spray can be predicted using various models (NAS, 1974).
Concentrations of 0.1 ng/m3 (range, 0.02 - 0.8  ng/m3)  measured
over the eastern Pacific Ocean and 0.72 ng/m3 (range, 0.21 - 1.9
ng/m3)   over  rural  northwestern   Canada  agree  with   these
predictions, and can be regarded as natural  background  levels.
Many  rural areas in  the USA display  similar or only  slightly
higher   levels.   However,  in  northeastern   USA,  rural  air
concentrations are higher, ranging from 2 to 64 ng/m3,  and  are
attributed  to the local  burning of fuel  oil with a  very high
vanadium content (section 4.1.1).
    Only  small amounts of airborne  vanadium are produced as  a
result of volcanic action (Zoller et al., 1973).

3.1.5  Plants

    Vanadium occurs in small amounts in all plants,  usually  at
concentrations  of  a  few mg/kg  dry  weight.   Within a  given
species,  variation is influenced by  soil-vanadium levels, soil
acidity,  and growing conditions, but the range of  variation is
not  large.  The vanadium concentrations in roots are nearly the
same as the level in the soil in which they are grown.  Vanadium
levels  are lowest in the aerial portions of most plants and are
unrelated  to soil levels.   Bertrand (1950) found  vanadium  in
each of 62 plant species analysed; mean concentrations in higher
plants  were 0.16 mg/kg  fresh weight, 1  mg/kg dry weight,  and
7 mg/kg  ash.  A mean level of 1.2 mg/kg was found in the leaves
of woody plants by Hanna & Grant (1962).

    Vanadium  accumulation  occurs  in the  fly  agaric mushroom
 (Amanita   muscaria)  , which  contains about 100 times as much as
other  mushrooms  or  plants (Bertrand,  1950).   Cowgill (1973)
determined  vanadium concentrations in fresh-water plants in the
range of 0.4 - 80 mg/kg.  The higher value of 80 mg/kg was found

in  the pickerel weed  (Pontedaris cordata)  , which  is a probable
accumulator.    Mosses  (Hypnum   cupressiforme)   also  accumulate
vanadium; concentrations of about 10 mg/kg have been measured in
rural  mosses,  whereas concentrations  may be as  high as 50  -
250 mg/kg  in  mosses from  city  areas (Tyler,  1970;  Ruhling,

Table 2.  Vanadium levels in fresh water
Source of water          Vanadium level          Reference

Rivers of Japan          0.001 mg/litre          Sugawara et al. (1956)

Waters of 5 Japanese     0.0001-0.087 mg/litre   Sugawara et al. (1956)
lakes                    (average, 0.0007


Rivers of Colorado       0.2 - 49.2 g/litre     Linstedt & Kruger (1969)

Rivers of New Mexico     up to 19 g/litre       NAS (1974)

Rivers of the USA        0.001 mg/litre          Durum & Haffty (1963)

Rivers of the Colorado   to 70 g/litre          Schroeder (197Oa)

Wyoming River            30 - 220 mg/litre       Schroeder (197Oa)


30 large rivers          traces to 0.43 mg/litre Konovalov et al. (1968)
                         average 0.037 mg/litre;
                         average in dissolved
                         form, 0.0012 mg/litre

Protva and Tarusa        0.007-0.0135 mg/litre   Tjurjukanov (1963)

Moscow River             0.0025-0.0074 mg/litre  Tjurjukanov (1963)

Rivers of the Klinsk-    0.005-0.0074 mg/litre   Tjurjukanov (1963)
Dmitrovsk ridge

Waters of the area west  0 - 34 g/litre         Petuhov et al. (1969)
of the Kama River in the
Tartar ASSR: rivers and

Uzbek SSR: surface       0.0003 - 0.003%         Mirzaeva (1965)
Table 3.  Vanadium levels in Sea-watera
Water                    Vanadium level    Reference

Sea-water                0.0005 (average)  Vinogradov (1944)

Sea-water                0.0003            Sverdrup et al.

Near the Japanese coast  0.001 - 0.002     Sugawara et al.

Sea-water                0.002             Goldberg (1961)

Western Pacific          0.003             Sugawara et al.

Sea-water                0.002 - 0.029     NAS (1974)
a   Modified from: Holodov (1968).

3.1.6  Animals

    Vanadium  appears to be present  in all animals, but  tissue
levels  in most vertebrates (especially land mammals) are so low
that  detection is difficult.   Higher concentrations have  been
found  in  marine  species, especially  invertebrates (Bertrand,
1950).  In land mammals, the highest levels occur in  the  liver
and skeletal tissues.
    Estimates  by  Vinogradov  (1959) and  Schroeder  (197Oa) of
vanadium  concentrations  in  animals  are  shown  in  Table  4.
Limited  data for several tissues  of wild animals are  shown in
Table  5, and some  concentrations in domestic  animal  tissues,
measured  by sensitive methods, are  given in Table 11  (section    On   the   whole,  these   agree   with  Bertrand's
    Using  neutron  activation  analysis, Fukai  & Meinke (1962)
reported  that concentrations of vanadium in the soft tissues of
fish  were  1000  times those  in  seaweeds  and molluscs.   The
highest concentrations of vanadium in marine organisms have been
found   in  certain  ascidians  (sea  squirts)  (e.g.,  Phallusia
mamillata , 1900  mg/kg),  certain  holothurians (sea  cucumbers)
(e.g.,  Sticopus  mobii , 1200  mg/kg), a  mollusc  (Pleurobranchus
plumula , 150 mg/kg), and marine algae.
Table 4.  Vanadium levels in animalsa
Animal                 Vanadium concentration
                       (mg/kg dry weight)

Coelenterate                   2.3
Annelid                        1.2
Mollusc                        0.7
Echinoderm                     1.9
Crustacean                     0.4
Insect                         0.15
Fish                           0.14
Mammal                         0.4
a   From: Vinogradov (1959) and Schroeder (197Oa).

Table 5.  Vanadium levels in tissues of wild animalsa
Tissueb       Number of   Vanadium concentration
              samples     (mg/kg wet weight)
                          Mean     Range

Kidney        4           0.94     0 - 2.07

Liver         4           0.25     0 - 0.94

Heart         4           1.16     0 - 3.40

Spleen        1           1.16
a   From: Schroeder (197Oa).
b   Beaver, deer, woodchuck, rabbit, muskrat, and fox.

    In  certain ascidians, trivalent  vanadium is present  as  a
chromoprotein called haemovanadin together with sulfuric acid in
green  cells  termed  vanodocytes;  in  other  forms,  the  free
haemovanadin is present in plasma (Hudson, 1964).

3.2  Man-Made Sources

3.2.1   Production levels and processes

    The  annual production of  vanadium (as vanadium  pentoxide)
ing  1980-84 was between  34 and 46  million kg (Table  6).  The
estimated world capacity up to 1990 is shown in Table 7.

Table 6.  Production of vanadium by major producersa,b,c
Country                     1981   1982   1983   1984

Australia                   0.1    0      0      0
China, Peoples Republic of  4.5    4.5    4.5    1.8
Finland                     5.2    4.8    5.0    4.5
Japan                       0.7    0.7    0.8    0.9
Norway                      0.9    0.4    0      0
USA                         13.9   10.1   3.6    5.9
South Africa                21.0   19.6   14.5   20.4
a   From: Wentzel (1985).
b   Production in millions of kg V2O5 equivalent.
c   Data on production in the USSR are lacking. It is 
    probably about 10 000-15 000 tonnes.

Table 7.  World vanadium capacitya,b
Country                       1981  1982  1983  1984  1985  1990

Australia/New Zealand          0.4   1.6   0     0     0     3.6
China, People's Republic of    5.4   5.4   5.4   5.4   5.4   5.4
Finland                        5.2   5.2   5.2   5.2   3.1   0
Japan                          1.3   1.3   1.3   1.3   1.3   1.3
Norway                         0.9   0.9   0     0     0     0
South Africa                  28.4  28.4  27.2  27.2  27.2  29.5
USA                           13.9  16.4  14.3  14.3   9.5  15.4
Venezuela                      0     0     0     0     0     2.7
a   From: Wentzel (1985).
b   Capacity in millions of kg V2O5 equivalent.

    The  major producers of  vanadium are China,  Finland, South
Africa, the USA, and the USSR.

    European countries, together with Japan and the USA, use 85%
of the total output. Extraction from ores 

    The production of vanadium is closely linked  with  that  of
other metals (particularly iron, but also uranium, titanium, and
aluminium).  It is sometimes extracted from ores directly  as  a
vanadium-rich alloy (e.g., ferrovanadium). Extraction from fossil fuels 

    Petroleum  is a source of  vanadium.  A number of  oilfields
have  a high vanadium content;  the vanadium level in  vanadium-
rich  oil  ash amounts  to as much  as 600 -  700 g/kg (Holodov,
1968;  Borisenko, 1973; Aleshin et  al., 1974; NAS, 1974).   For
this reason, vanadium is extracted from petroleum ash in some of
countries (e.g., Canada, Italy, USA).

    All   coals  contain  vanadium,  concentrations  in  various
coalfields  ranging from  extremely low  to 10  g/kg  (in  coal)
(e.g.,  Argentina, USSR)  (Holodov, 1968, 1973; Borisenko, 1973;
NAS,  1974).   Coal ash  constitutes  a supplementary  source of
vanadium (up to 300 g/kg).

    Tar  sands  (Canada), bitumens,  and asphaltites (Argentina,
Peru,  USA,  USSR)   are  potential  sources  of  vanadium.  For
instance,  burning  bitumen  from the  Sadkinskoe deposit (USSR)
yielded  an ash containing 43 - 66% vanadium pentoxide (Holodov,
1968, 1973). Extraction from slag 

    In some countries, vanadium is extracted from slag resulting
from   the  metallurgical  production   of  catalysts  (Pilz   &
Komischke,  1972;  Rose, 1973)  or  the processing  of  vanadium
catalysts.  The levels of vanadium pentoxide in  slags  obtained
from  Bessemer converters of pig  iron made from Kachkanar  ores
(USSR)   were 135 - 140 g/kg (Pastuhov & Tretjakov, 1959).  Slag
obtained  at a  factory in  South Africa  contained  a  vanadium
pentoxide concentration of about 250 g/kg (NAS, 1974).

3.3  Consumption and Use

3.3.1   Metallurgy

    Vanadium  has important industrial  uses, mainly in  ferrous
metallurgy, where 75 - 85% of all vanadium produced is  used  as
an  alloy additive in making  special steels.  Pure vanadium  is
very  seldom used as it reacts easily with oxygen, nitrogen, and
carbon at a relatively low temperature (300 C).

    To  produce various high-resistance carbon  steels, vanadium
is  combined with chromium, nickel,  manganese, boron, tungsten,
and  other elements.  The amount of vanadium in the steel ranges
from  0.3 to  51 g/kg  (Goldshtejn, 1967;  Grin et  al.,  1971).
Vanadium  may  be  a component  of  structural  steels  used  in
building,  transport, engineering, and boiler-making and in tool
steels.    It  is  added  to   steel  in  the  form   of  either
ferrovanadium  (an iron/vanadium alloy  containing 400 -  800  g
vanadium/kg)  or  vanadium carbide.  Vanadium  is also  a  major
alloying  element in high-strength titanium alloys.  The amounts
of vanadium used in recent years in the ferrous metal industries
of four major consumer countries are listed Table 8.

Table 8.  Use of vanadium in ferrous metallurgy (tonnes)a
         1964  1965  1966   1967   1968   1969   1970   1971   1972
Canada   115   113    -      -      -     187    231     -      -

France   209   239   225    340    342    539    518    402    409

United   600   600   600    500    600    800    800    600    500

USA       -    3709  4180   3425   3997   4333   3667   3346    -
a   From: US Bureau of Mines (1974).
3.3.2   Other industries

    The  consumption of vanadium  by branches of  industry other
than  metallurgy has increased, as  can be seen from  the values
given for the USA in Table 9.
Table 9.  Use of vanadium in non-ferrous 
USA industries (tonnes)a
1965  1966  1967  1968  1969  1970  1971
562   703   1325  988   1250  991   810
a   From: US Bureau of Mines (1974).

    Alloys  of  vanadium  with  non-ferrous  metals  (aluminium,
titanium,  copper, etc.) are  widely used in  the atomic  energy
industry, aircraft construction, and space technology.  Vanadium
disilicide  is  used  in  the  production  of   high-temperature
refractory  products  (Kubasky,  1957).   With  regard  to   the
production  of  chemicals,  vanadium oxides  and  vanadates have
important  applications  as  catalysts  in:  the  synthesis   of
sulfuric  acid;  the  oxidation of  organic compounds; petroleum
cracking; purifying exhaust gases; and oxidizing ethanol.  These
vanadium compounds are also used in producing glass of different
types   and   colours,   organic  ion   exchangers,  luminescent
compounds, ethylene-propylene synthetic rubber, thermistors, and
switching  elements.  The pentoxide  and various other  salts of
vanadium  are used in preparing glazes and enamels for porcelain
and   pottery,  in  producing   lacquers  and  paints,   and  as
developers, sensitizers, and colouring agents in photography and
cinematography.   Vanadium is  also used  as a  mordant  in  the
dyeing and printing of cotton, particularly for  fixing  aniline
black on silk.  Europium-activated yttrium vanadate is  used  in
colour  television tubes.   Vanadium hydride  can be  used as  a
neutron   moderator  in  atomic  reactors.    Soluble  salts  of
arsenous-vanadous   acid  have  been  used   as  fungicides  and
insecticides.   Vanadium slags are  used in casting  shops as  a
moulding  material to improve the quality of the casting surface
and to facilitate cleaning.

    In  most of these  applications, the quantities  of vanadium
used   are  small.   Some  recycling  takes  place  (e.g.,  with

3.4  Environmental Pollution Resulting from Production, Use, and Waste Disposal

    Fig.  1 shows the  cycle of the  various chemical  processes
involved  in the production and recovery of vanadium.  Expansion
of  the mining and processing of vanadiferrous materials, and of
the use of vanadium in metallurgical and other  industries,  and
the use of petroleum at power stations and in  engineering,  can
lead to increased pollution of the atmosphere  and  watercourses
with  vanadium compounds.  Pollution is mainly by the penta- and
trivalent oxides.

3.4.1   Metallurgy

    The  most  important  industry  with  respect  to   vanadium
pollution  is the metallurgical  industry, in which  vanadium is
used  to obtain  steel alloys.   Because of  the relatively  low
melting  point  of vanadium  pentoxide  (690 C), its  fumes may
enter  the air,  condense, and  form an  aerosol  with  particle
diameters  of up to  2 m  (Roshchin, 1968).   Obviously,  these
processes   may  lead not  only to contamination  of the air  in
industrial  premises, but also  to contamination of  the outdoor
atmosphere (where an aerosol of vanadium pentoxide forms part of
the smoke emission).  Vanadium pentoxide was found in 87% of all
air samples taken in the vicinity of large metallurgical plants,
in  concentrations ranging from 0.98 to 1.49 g/m3.   Concentra-
tions  in  11%  of  the  samples  exceeded  2 g/m3  (Pazhynich,

    The  process of re-smelting  steel scrap also  leads to  the
discharge  of a vanadium-containing aerosol into the atmosphere.
In  1968, in the USA, 43.5 million tonnes of steel were produced
from  the re-smelting of  scrap in basic  oxygen furnaces.   The
emission  factor  was calculated  to  be 21 kg  particulates per
tonne  of steel produced and the degree of emission control 97%.
The   aerosol  discharged  into  the  air  during  this  process
contained  a vanadium concentration  of 0.02%.  Based  on  these
figures,  an estimated  6 tonnes  of vanadium  escaped into  the
atmosphere (US EPA, 1977).

    Ferrovanadium  used for alloys in steelmaking is produced in
electric  arc  furnaces.  The  charge  consists of  scrap steel,
fused  sodium metavanadate, and carbon  with silicon, aluminium,
or  a combination of the last two elements, as a reducing agent.
An estimated 131 tonnes of vanadium were discharged into the air
as a result of ferrovanadium production in the USA in  1968  (US
EPA, 1977).

    Discharge  into  the  atmosphere is  greatest  from furnaces
roasting  vanadium slags, vanadium pentoxide  smelting furnaces,
electric  furnaces, crucibles in which  ferrovanadium is melted,
and crushing equipment (US EPA, 1977).

    Metallurgical slag may contain significant concentrations of
vanadium.   When titaniferrous and  vanadic magnetite iron  ores
are converted into steel, the resulting slag  contains  vanadium
pentoxide  concentrations of up  to 250 g/kg  (Dovgopol et  al.,
1974;  NAS,  1974).  Vanadium  is  released into  the atmosphere
during  the  loading,  transporting, unloading,  and crushing of
slag.    The  slag  formed   when  iron  is   smelted   contains
considerably  less  vanadium  than converter  slag.  However, in
view  of the considerable  and increasing use  of  blast-furnace
slags  as building-materials and in  motorway construction, they
can  be sources of environmental  pollution.  For example, in  a
plant  smelting vanadium-containing titaniferrous magnetite, the
losses  of vanadium  in slag  represented 18%  of  the  vanadium
content of the original raw material (Dovgopol et al., 1974).

    The  solid wastes formed as a result of roasting slag during
the  production of technical  vanadium pentoxide may  be another
source  of environmental pollution.  In this process, an average
of 5.16 tonnes of solid waste containing 1.2% vanadium pentoxide
are  formed  for  every  tonne  of  vanadium  pentoxide produced
(Kurmaev, 1974).


    The  liquid waste and  wash water from  metallurgical plants
often contain large amounts of vanadium, up to  several  hundred
milligrams  per litre, measured as  vanadium pentoxide.  Kurmaev
(1974)  detected  vanadium  at a  level  of  702.8  mg/litre  in
effluent   from   a  vanadium   pentoxide   plant.   In   a  new
ferrovanadium  plant,  purified  waste water  contained  340  mg
vanadium  pentoxide/litre  (Kurmaev,  1974).  Unpurified  waste-
water  discharge from a  vanadium pentoxide plant  into an  open
watercourse  produced  a vanadium  level  in the  watercourse of
2 mg/litre  (Seljankina, 1961).  Linstedt &  Kruger (1969) found
the  highest  river  concentrations of  vanadium  near  uranium-
vanadium plants and the lowest in water samples  taken  upstream
from  the  industrial  areas  (Table  2)   (section  3.1.3).  In
studies by Shilina & Malakhov (1974), water samples  taken  from
the  Moscow  River  below the  city  contained  6 times  as much
vanadium   as   samples  taken   above   the  city   (0.06   and
0.01 mg/litre, respectively).

    The  pickling of steel casts  or steel articles can  include
vanadium  in the pickling mixture.   Waste hydrochloric, nitric,
hydrofluoric,  and sulfuric acids  from a steel  smelting  plant
contained  0.02% vanadium.  The solid  residue on the bottom  of
the  acid vats contained  2.4 g vanadium/kg  (hydrochloric  acid
vat) and 1.6 g vanadium/kg (nitric and hydrofluoric  acid  vats)
(Kurmaev,  1974); vanadium in  waste acid that  is not  properly
treated may be a source of water pollution.

3.4.2   Fossil fuel combustion

    Industrial  plants producing power and heat and operating on
petroleum, coal, and heavy oils are the most  widespread  source
of  vanadium discharge  into the  environment.  In  1969,  as  a
result of the combustion of fossil fuels (coal and  oil),  about
20 000  tonnes of vanadium were  discharged into the air  in the
USA  (NAS, 1974).  The estimated levels of emission from burning
coal in the USA for 1969 are shown in Table 10.
    In a study of the vanadium discharged from coal  burning  in
six  electric  power  generating  stations,  the  total   amount
discharged  into the air in  1968 was 3760 tonnes.   Where there
were  no  ash-trapping  devices, 65%  of  the  ash  entered  the
atmosphere.   The  degree  of  atmospheric  dispersion  of   ash
particles depended on the original coalfield, the size  of  coal
used,  the type of furnace,  the combustion conditions, and  the
presence and type of ash-trapping devices (NAS, 1974).
    In  a  study  of the  metal  aerosol  content of  waste  gas
emissions  from  an oil-fired  electric  power station,  it  was
reported  that  the  concentration of  vanadium  pentoxide  (and
oxides  of  aluminium, chromium,  iron,  and manganese)  was not
affected by the type of boiler or mode of operation.  Comparison
of the metal content in the fuel oil and waste gases showed that
90%  was released into the  atmosphere (Sokolov, 1986).  In  the
USSR, there is a trend towards a reduction in the use  of  heavy
fuel oils in electric power stations.

    Other  possible sources of  vanadium discharge into  the air
are  the burning of coal  tips or dumps of  coal dust in  mining
areas, but data are not available.

    All  crude petroleum oils contain vanadium at levels ranging
from 1 to 400 g/tonne, depending on the oilfield (Holodov, 1968,
1973;  Shah et al.,  1970; Christian &  Robinson, 1971;  Nelson,
1973;  NAS, 1974).  In the distillation of crude oil, almost all
the  vanadium  remains  in  the  high  relative  molecular  mass
hydrocarbon fractions.  The vanadium contents of heavy fuel oils
range  widely from 1  to 200 g/tonne and  are almost a  thousand
times  greater  than  those of  petroleum distillates.  Assuming
that  10% of the vanadium is precipitated inside the plant (flue
and  ash trap) while 90% is discharged into the air, it has been
calculated  that atmospheric emissions in the USA as a result of
heavy fuel oil combustion were about 14 100 - 21 800  tonnes  in
1970 (Holodov, 1968, 1973; NAS, 1974).  Similar percentages were
found by Sokolov (1986).

Table 10.  Estimated emissions of vanadium resulting from coal
burning in the USA, 1969a
Type and use      Coal     Vanadium  Vanadium  Control  Vanadium
of coal          (1000     in coal   in fly    of       discharged
                 tonnes)   (tonnes)  ash       fly      into the
                                     (tonnes)  ash (%)  air
Bituminous coal

 Electric power  308 642   9254      6015      85       902

 Manufacturing   93 248    2797      1818      60       727

 Retail          12 665    380       247       50       124

 Coking          92 901    2787      -         100      0

 Subtotal        507 276   15 218    8080               1753

Anthracite coal  9275      1159      753       50       377

 Total                                                  2130
a   From: NAS (1974).

    Distilled  petroleum  fuels  produced in  the USA (gasoline,
kerosene,   diesel  fuel,  home-heating  oils)  contain  0.05 mg
vanadium/kg  (NAS, 1974).  The distillation  process used leaves
nearly  all of the vanadium  originally present in the  residual
fractions.   Analyses of the  spent gases from  petrol  engines,
sampled   directly  at  the  exhaust   outlet,  showed  vanadium

concentrations of 0.1 - 0.2 mg/kg, and exhaust gases  of  diesel
engines  contained 10 - 15 mg  vanadium/kg.  Six to 12 mg/kg  of
vanadium  was found in soot collected from the edges of flues in
a small oil-fired power station (Pilz & Komischke, 1972).

    The  amount  of  vanadium  in  natural  gas  is  less   than
0.5 g/tonne,  and  almost  no  vanadium  is  released  into  the
atmosphere on combustion (NAS, 1974).

3.4.3   Agriculture

    Vanadium  has been used as a trace fertilizer applied at the
rate of 0.75 - 1 mg/kg soil (Peterburgskij &  Tormasova,  1969).
This practice must lead to an increased level of vanadium in the
soil,  but  further  information  on  agricultural  use  is  not

3.5  Transport and Transformation

3.5.1   Geochemical processes

    Vanadium   is  involved  in  various  geochemical  processes
occurring  in  the  earth's  crust.   There  is  extremely  wide
dispersion  of vanadium during  the formation of  volcanic rocks
and  sporadic  accumulation  with  the  formation  of   vanadium
minerals  as a result of postmagmatic processes.  Like all trace
elements  that accumulate in soils, vanadium migrates within the
soil  itself and within the  system: rock-water-soil-vegetation-
    During geochemical processes in the soil and  in  weathering
and podzolization, vanadium is shifted from the A horizon to the
B horizon (Kovda et al., 1959).  However, vanadium shifting does
not  occur  during  weathering  processes  that  do  not involve
movement of sesquioxides.
    Vanadium concentrations in rocks are linked to the pH of the
rocks (Borisenko, 1973).  Neutral and acid rocks  contain  lower
vanadium concentrations than basic rocks, and acid rocks contain
lower  concentrations than neutral  rocks.  In magma  of various
types  (the main carrier of vanadium), about 92% of all vanadium
occurs  in  basic  rocks  (basalts,  gabbro,  amphibolites,  and
eclogites), and about 8% occurs in acid and neutral rocks.  Less
than 1% of the total amount of vanadium is found  in  ultrabasic
alkaline rocks.
    The main carriers of vanadium in the  sedimentation  process
are  ferric hydroxides and  solid bitumens.  The  great affinity
between the crystallochemical properties of V3+ and Fe3+  is  of
vital  importance  for  the  diffusion  of  vanadium.   There is
roughly 400 - 500 times more iron than vanadium in  the  earth's
crust.   Thus, iron is a "solvent" of trivalent vanadium, and is
responsible  for its diffusion in  magmatic rocks.  The bulk  of
the ferromagnesian rock-forming minerals (and also titaniferrous
magnetite  and  magnetite  itself)   trap  vanadium  during  the
crystallization  of  rocks,  and, during  endogenous  processes,

vanadium  is very closely  linked with trivalent  iron.  In  the
formation   of   igneous   rocks,  vanadium   is  preferentially
concentrated in those with a high iron content.

3.5.2   Biogeochemical processes

    The  accumulation of  vanadium in  soils and  in  all  other
materials  depends directly on  its concentration in  the  soil-
forming  rocks, the  atmosphere, and  the oceans  of the  world.
Migration,  diffusion,  and  concentration of  vanadium  in  the
biosphere  takes place as a  result of its extraction  by living
organisms  from water, from  food of both  vegetable and  animal
origin,   and  from  different   types  of  rock   during  their
decomposition and the formation of soils. Transport in, and removal from, water 

    In  assessing the  relative importance  of the  two ways  in
which  vanadium is transported in water, Konovalov et al. (1968)
and  Holodov (1968) concluded  that 87% is  carried away by  the
rivers  in suspended  form, and  13% in  solution.  The  average
level of dissolved vanadium in the rivers of Japan and  the  USA
(Sugawara et al., 1956; Durum & Haffty, 1963) were the  same  as
that recorded by Konovalov et al. (1968), i.e., 0.001 mg/litre.
    The bulk of vanadium enters sea-water in suspended  form  or
sorbed on colloids.  It accumulates in recent  deposits,  passes
through watercourses mechanically, and does not react chemically
with  sea-water.   This  peculiarity of  vanadium  transport  is
reflected  in  its distribution  on the sea-bed  in the form  of
    The  fate  of vanadium  that is dissolved  in water is  more
complex.   As very large amounts of dissolved vanadium have been
carried out into the oceans throughout all  geological  periods,
vanadium  levels  in sea-water  of  about 60 mg/litre  might  be
expected;   in  fact,  levels   do  not  exceed   0.003 mg/litre
(Goldschmidt,  1938;  NAS,  1974), indicating  that  vanadium is
continuously removed from sea-water.  Krauskopf (1963) concluded
that  the vanadium  content of  sea-water is  not  dependent  on
solubility  and that natural  reagents remove vanadium  from the
water.   There are two  possible pathways, namely  sorption  and
biochemical  processes.  The migratory qualities of vanadium are
poor. The content of vanadium in the earth's crust is 0.015 g/kg
(Vinogradov,  1959),  and  a mean  content  in  river  water  is
0.001 mg/litre.   Thus, very little vanadium  is transported via
water.   The bulk of vanadium  is precipitated on to  the seabed
and  becomes bound  to silts  (Petkevich et  al. 1967;  Strahov,
1968).   Levels  of vanadium  dissolved  in sea-water  amount to
0.001 - 0.003  mg/litre.   The  vanadium  comes  from  the   10%
dissolved in river water and is continuously  precipitated  from
the  water by ferric  hydroxides and organic  matter (Krauskopf,

    Biochemical   reactions  play  an  important   role  in  the
extraction  of  vanadium from  sea-water  and conversion  into a
sediment  (Vinogradov, 1937; Holodov, 1973).   This is confirmed
by the link between the concentrations of vanadium  and  organic
substances in sedimentary rocks and silt.  However, in practice,
it  is extremely difficult to determine the part of the vanadium
that  has been assimilated  by organisms and  the part that  has
been  sorbed  by  the decomposing  mass  of  organic  matter  or
introduced in dissolved form.

    An important role in the biogenic migration of  vanadium  is
played by live marine organisms and plants.  The  ascidians  and
holothurians  are  noteworthy  vanadium accumulators  (Bertrand,
1950)  (section 3.1.6).  Some marine  algae are also capable  of
accumulating  vanadium  (Krauskopf  1963). When  they die, these
organisms promote accumulation of vanadium in the silt.

    Thus,   vanadium  dissolved  in  sea-water  is  continuously
removed  either by sorption  or biochemical processes.   In  the
first case, the main precipitant is hydrated ferric trioxide; in
the second, vanadium is accumulated by marine animals, plankton,
and, less commonly, algal and plant organic material. Occurrence in hydrocarbons 

    The  accumulation  of  vanadium in  organic concentrators is
linked with its occurrence in hydrocarbons (petroleum, asphalts,
peats,  bitumens,  and  coal).   Vanadium  may  enter  petroleum
together  with  organic  matter or  accumulate in already-formed
petroleum  from  underground  waters and  petroliferous  strata.
Apparently,   both   processes   occur  in   nature.   Secondary
transformation  of petroleum into  asphalt is accompanied  by  a
proportionate  increase in the concentrations of the tar-asphalt
component and the vanadium linked to it (Vernadskij, 1940). Biospheric redox processes 

    Vanadium  takes  part  in redox  processes  not  only  of  a
geochemical  nature but  also in  plants and  animals.  Pejve  &
Ajzupiet  (1974),  studying  the intracellular  distribution  of
metals in plants, showed that a considerable  number,  including
vanadium,   were   linked   to  complex   lipid   substances  of
comparatively  high  stability  that persisted,  even  after the
cells had died.  These lipids persisted in soils and  silts  and
served  as a source of  metal in sedimentary rocks.   In various
types of plants, the proportional relationship between the level
of  iron  and  those  of  manganese,  copper,  titanium, nickel,
chromium,  cobalt,  and  vanadium  decreased  in  the  course of
evolution,  and was least significant in the leaves of flowering

    In a number of soil organisms, such  as  Microcococus  lacto-
lyticus,   Thiobacillus  terrooxidans,  and  Ferrobacillus  thio-
oxidans,  there  was a  link between  iron and  vanadium in  bio-
chemical processes (Zajic, 1969). Transport in air 

    Information on the local movement and deposition of airborne
vanadium  is presented in  section 4.1.1.  Strahov  (1947)   and
Ronov (1964) concluded that the gaseous envelope of the earth is
not  of significant importance in the transport of vanadium, but
a  study by Duce &  Hoffman (1976) documented some  transport of
man-made  airborne  vanadium  over  ocean  areas.   The  authors
estimated that about 10% of this material was deposited  in  the
ocean.   In  a  study of  trace  metals  in  European  glaciers,
Jaworowski et al. (1973) showed the presence of small amounts of
vanadium, apparently deposited from the air, which had increased
in recent decades.


4.1  General Population Exposure

4.1.1   Air

    Natural  sources of vanadium,  such as continental  dust and
marine  aerosols, cause only  low natural background  levels  of
vanadium in air.  In remote areas, such as the South  Pole,  the
concentrations range from 0.001 to 0.002 ng/m3 (Zoller  et  al.,
1974),  and in the eastern Pacific Ocean, from 0.02 to 0.8 ng/m3
(Hoffman et al., 1969).  In rural areas  in Canada,  the  United
Kingdom, and the USA, concentrations have been reported to range
from  0.2 to  about 75  ng/m3, with  annual averages  frequently
below 1 ng/m3 (Rahm, 1971; Cawse & Peirson, 1972; US EPA, 1977).
In  general, air levels  of vanadium are  higher in urban  areas
than  rural areas.  Annual averages may often be in the range of
20 - 100 ng/m3, though, exceptionally, higher averages exceeding
200  -  300 ng/m3  have been recorded  in large cities,  and the
maximum 24-h average may exceed 1000 ng/m3 (US EPA,  1977).   In
all  surveys,  there  have  been  conspicuous  geographical  and
seasonal  variations.   High  concentrations of  vanadium in air
have  been attributed to  the local burning  of fuel oil  with a
high  vanadium  content.  The  uptake  of vanadium  fall-out  by
mosses   (Hypnum   capressiforme and Bryum  argenteum)    in   the
Stockholm area indicates that heating oil is a major  source  of
vanadium  (Rhling,  1971).  In  this  regard, Faoro  & McMullen
(1977)  presented some interesting  data (Fig.  2).   The values
shown, especially for the period prior to 1971, are  typical  of
cold-climate  cities  where  high-vanadium heavy  fuel  oils are
extensively  used.  The marked  seasonal variations are  due  to
alterations  in heating requirements and seasonal differences in
atmospheric inversions.  The marked decline after 1970 is due to
the introduction of low-sulfur fuels; reduction of sulfur in oil
results  in a proportional reduction in the vanadium content.  A
similar  effect  can  be produced  by  changing  from  heavy  to
distilled  fuel oil, as noted in Boston by Barry et al.  (1975),
where  levels of airborne vanadium for comparable months in 1966
and 1972 were 1.07 and 0.114 g/m3, respectively.

    These  data  illustrate the  importance  of fossil  fuels as
sources  of vanadium  in urban  air.  The  patterns observed  in
other  areas are similar but  less extreme in concentration  and
fluctuation.     Because   of   the   variations   in   vanadium
concentrations  in oil and  coal, community levels  will  depend
mainly on the actual vanadium concentrations in the  fuels  used
and on meteorological factors.

    Pollution  of the air by  industrial facilities may be  less
than that by power stations and heating equipment.  At  a  steel
plant in the USA in 1967, concentrations of vanadium ranged from
0.04 to 0.107 g/m3  and averaged 0.072 g/m3,  corresponding to
the   mean  concentration  over  13   Pennsylvania  towns  (also
0.072 g/m3)   (NAS,  1974).   The following  levels of vanadium
pentoxide were found by Pazhynich (1967) in the USSR in areas of

extensive  metallurgical  activity  not connected  with vanadium
production:  in the years 1964-65: 1.49 g/m3  at 150 m from the
source  of  discharge;  0.47 g/m3   at  500 m;  1.35 g/m3   at
1000 m;  and  0.98 g/m3  at  1500 m.   Near a  plant  producing
technical   vanadium  pentoxide,  Kurmaev  (1974)  detected  the
following  24-h  mean  levels  of  vanadium  pentoxide:  0.004 -
0.012 mg/m3  at 500 m from  the source; 0.001 -  0.006 mg/m3  at
1000 m;  and 0.001 - 0.004 mg/m3 at  2000 m.  Seventy to 72%  of
the particles were less than 2 g in diameter.


    Boyarkina  et al. (1978)  studied vanadium precipitation  in
and  around  an  industrial  city,  in  winter,   by   measuring
concentrations in snow.  In the central area, a concentration of
24 g/litre   was  found,  decreasing  to  3.2 g/litre   at   a
distance of 40 - 50 km.

4.1.2   Water

    Natural  background levels of  vanadium in water  have  been
discussed  in section  3.1.3, and levels in industrial effluent,
in section 3.4.1.  Durfor & Becker (1963) included  vanadium  in
their  analyses for trace elements in drinking-water supplies in
large  cities in the USA.   Of the samples analysed,  91% showed
less  than 10 g  vanadium/litre; the  maximum concentration was
70 g/litre,   and the average was about 4.3 g/litre.   Many of
the samples were negative.  Twenty-six percent of 3676 tap water
samples  from  34  areas  in  the  USA  contained  vanadium   at
concentrations ranging from 1.3 to 33 g/litre  with a  mean  of
4.85 g/litre (Greathouse & Craun, 1979).

    Hoffmann  et al. (1972) published data from a regional well-
water  survey  in  Poland.  The  average vanadium concentrations
were   0.06 - 6 g/litre,   with  a  maximum   single  value  of
15 g/litre.    Bottled  waters from  mineral springs frequently
contained  higher  levels;  Schlettwein-Gzell  &  Mommsen-Straub
(1973)   reported a range of 4 - 290 g/litre  in bottled waters
from Switzerland.

    Highly-mineralized  waters  in  Argentina  contained   0.3 -
10 g   vanadium/litre (Trelles et al., 1970).  These concentra-
tions  often occur in  conjunction with high  concentrations  of
arsenic and/or fluorides.

4.1.3   Food Individual foods  

    Information  on  the  vanadium  contents  of  human  food is
sparse.   Data  from two  studies (Myron et  al., 1977; Byrne  &
Kosta, 1978) are combined in Table 11 with those from an earlier
study using a similar method (Sremark, 1967).  The  results  of
these studies agree reasonably well, but differ in some respects
from the results of earlier work, especially that  of  Schroeder
et al. (1963).  The principal difference is that Schroeder noted
high  vanadium  concentrations in  fats  and oils,  whereas  low
concentrations  were found in the  more recent studies.  Such  a
difference  may  be  accounted  for  by  the  use  of  different
analytical methods.  Similar discrepancies have been encountered
in the study of other trace elements, i.e., lower concentrations
have been found using more recently developed methods.

    The data presented in Table 11 show low levels  of  vanadium
in  most  elements  of the  human  diet.   There are  also  some
interesting  differences  among specific  foods.  Grains contain
higher levels of vanadium than fruits and vegetables.  Levels in
oils  and fats and beef and pork are low, but those in the liver
and  kidneys  of cows  and pigs are  higher.  Higher levels  are
found  in both the flesh and internal organs of the chicken, and
levels in fish flesh are also high.  Vanadium levels in milk and
eggs are low, and those in beer and wine are high.  Myron et al.
(1977)  pointed out that processing appears to raise  levels  in
food (e.g., white versus brown rice; cereal, flour,  bread,  and
gluten  versus grain; peanut  butter; bologna and  bacon  versus
pork).   No explanation was  given for the  very high levels  in
dill and parsley.

Table 11.  Vanadium concentrations in foods (g/kg)a
                   Study 1      Study 2   Study 3
  Wheat                         3.6
  Flour                                   15, 40
  Bread                         11.20     10, 13
  Gluten                        33
  Oats                                    3
  Oatmeal                       6
  Corn                                    0.7
  Cornmeal                      2
  Brown rice                    1
  White rice                    21        12, 30
  Barley                        14        1.6
  Cereal                        93

  Apple            1.1          4         0.3
  Pear             0                      0.2
  Banana                        3         0.2
  Orange                                  1
  Cherry                                  0.4
  Apricot                                 0.2
  Peach                                   0.2
  Strawberry       31.41 (dry)
  Blueberry        1.6
  Potato           0.8          1         1.2, 1.9
  Radish           52           5         0.6
  Carrot           0            1         2.3, 2.4
  Beet             0                      
  Garlic                                  0.6
  Onion                                   0.6
  Leek                                    0.3
  Navy bean                     14
  Pea              0            7         0.4
  Tomato           0.03         2         0.3
  Cucumber         2.1
  Squash                        4
  Brussels sprout                         0.5
  Cauliflower      0.08         1         0.9
  Cabbage                       2         0.3
  Lettuce          21           4         1.0, 2.7

Table 11 (contd).
                   Study 1      Study 2   Study 3
  Spinach                                 35
  Parsley          790                    1800 (dry)
  Mushroom                                50 - 2 000 (dry)
  Dill             140          431

  Beef             0            1         0.4 - 1.3
  Beef liver       2.4, 10      6         7.3
  Pork             0            1         0.6, 0.9
  Pork liver                              8.4
  Pork kidney                             8.5
  Bacon                         5
  Bolgna                        8
  Chicken, white                22        1.7
  Chicken, dark                 12
  Chicken liver                           37, 38
  Chicken kidney                          18
  Cod                           28        7.2
  Mackerel         2.6                    3.5
  Tuna                          11        10, 3
  Lobster          43           5
  Scallop                       22

Oils and fats
  Margarine                     4
  Soybean oil                   1
  Corn oil                      1         3
  Pumpkin seed oil                        0.2
  Lard                          2         0.2

  Hazel nut                               3.7
  Peanut butter                 44

Dairy products
  Milk             0 - 0.1      3         0.2, 0.2
  Powdered milk    0 - 0.2      25
  Chocolate milk                21
  Butter                        1
  Egg white                               0.3 - 1.8
  Egg yolk                                2.0 - 3.6

  Coffee           1.6
  Tea              1.3                    0.3
  Cola             0.7                    1.5
  Beer             11                     8.4
  Wine                                    3.5 - 3.2
a   Study 1: Sremark (1967) (neutron activation analysis).
    Study 2: Myron et al. (1977) (atomic absorption spectroscopy).
    Study 3: Byrne & Kosta (1978) (neutron activation analysis). Complete diets 

    Byrne  & Kosta (1978) estimated the daily intake of vanadium
to  be "a few tens  of micrograms," but added  that it may  vary
considerably.  Assuming a very low rate of intestinal absorption
of  vanadium in man  (section 5.1.2), Byrne  & Kosta  calculated
intakes   for   3  adults   in   whom  they   measured   dietary
concentrations.   The  calculated  intakes  were  36,  66,   and
11 g/day, respectively.

    Analyses of 9 selected hospital diets (Myron et  al.,  1978)
are  given  in Table  12.  Each meal  was prepared and  analysed
separately  by atomic absorption spectroscopy.  The results were
similar  to  concentrations  found in  individual  foodstuffs in
other  studies  given above.   In a later  study, Byrne &  Kosta
(1979)   reported on the determination of vanadium in total diet
samples  obtained during a nutrition  survey in 5 Italian  towns
(Table  13).  The concentrations  agree with those  reported  by
Myron et al. (1978).

Table 12.  Daily vanadium intake in dieta
Diet type                (g/day)   (g/g)   (g/1000 

General-1                13.6       0.019    4.7

Cholesterol reducing-1   25.6       0.034    8.8

Cholesterol reducing-2   16.8       0.022    5.8

Cholesterol raising      30.1       0.046    10.5

General-2                28.0       0.040    9.8

Low calorie              12.4       0.029    10.6

Low salt                 15.5       0.028    9.1

Puree                    26.0       0.050    14.1

Soft                     15.8       0.024    6.4
a   Adapted from: Myron et al. (1978).

4.2  Occupational Exposure

    In  terms  of  occupational  exposure,  the  most  important
vanadium  compounds  are vanadium  pentoxide, vanadium trioxide,
ferrovanadium,  vanadium  carbide,  and vanadium  salts, such as
sodium and ammonium vanadate.  The oxides and salts are commonly
used  in industry in powder form, giving rise to the possibility
of dust and aerosol formation, when the substances  are  crushed
or  ground.  Many metallurgical processes involve the production
of vapour containing vanadium pentoxide, which condenses to form

respirable  aerosols.  Boiler-cleaning operations generate dusts
containing  the pentoxide and trioxide compounds.  Combustion of
residual fuels with a high vanadium content is likely to produce
aerosols of the pentoxide as well as oxide complexes of vanadium
with other metals.

Table 13.  Vanadium contents of Italian freeze-dried 
total diet samplesa
Town           Dry       Vanadium          Daily
               weight    concentrationb  vanadium
               (g)       (ng/g)            intake (g)
Aosta          310       32.1   0.9 (2)    10.0

L'Aquila       173       46.0   3.4 (2)    8.0
Montfalcone    278       39.7   4.1 (2)    11.0

Mt. Amiata     377       29.7   0.8 (2)    11.2

Rome           285       42.3   4.6 (4)    12.0

Mean values              38.0   6.9        10.4   1.5
a   From: Byrne & Kosta (1979).
b   Average and standard deviation; number of aliquots 
    in parentheses.

4.2.1   Metallurgy

    The   processing  of  metals  containing  vanadium  includes
chemical  treatment  and  high-temperature operations.  However,
only  moderate  concentrations of  vanadium  were found  in  the
breathing  zone of workers engaged  in operations that would  be
expected  to  produce the  greatest  fume exposure.  During  the
addition  of  vanadium  to furnaces,  concentrations ranged from
0.006  to  0.08 mg/m3  and,  during  tapping,  from   0.004   to
0.02 mg/m3.  Concentrations found in oxyacetylene cutting ranged
from  0.008 to 0.015  mg/m3 and, in  arc-welding, from 0.002  to
0.006 mg/m3 (NAS, 1974).
    Vanadium levels in metallurgical plants have been studied in
detail (Roshchin, 1968).  Vanadium slag contains about 11 - 13%,
mainly  in  the  form of  trioxides  of  vanadium  (measured  as
vanadium  pentoxide).   Slags are  used  for the  production  of
vanadium  pentoxide  and  ferrovanadium,  and  the  process   is
accompanied by extensive formation of iron oxide  aerosol.   Air
concentrations of the dust (mainly vanadium trioxide)  found  in
the main working positions (converter operator, mixer, and crane
driver)  ranged  from  20 to  55  mg/m3.   Measured as  vanadium
pentoxide,  the contents  of the  swirling dust  did not  exceed
0.17 mg/m3.  About 75% of the dust particles had a  diameter  of
less  than  2 m  and  20% had a  diameter of between  2 m  and
4 m.

    Breaking,  loading and unloading, crushing and grinding, and
magnetic   separation  of  vanadium   slag  causes  thick   dust
formation,  with concentrations ranging  from 30 to  120  mg/m3.
The slag contains 111 - 129 g vanadium pentoxide/kg.  A diameter
of less than 2 m  was recorded for 70 - 72% of  the  particles;
86 - 96%  had a diameter of  less than 5 m.   When  the slag is
roasted,  free vanadium pentoxide  is discharged into  the work-
place  air;  atmospheric  concentrations  in  the  vicinity   of
furnaces  ranged from 0.04  to 1.56 mg/m3.  During  leaching and
precipitation,  concentrations  of vanadium  in  the air  may be
high, sometimes exceeding 0.5 mg/m3.

    The smelting and granulation of technical vanadium pentoxide
are  accompanied by the formation  of an aerosol.  This  aerosol
escapes  when the product is poured for granulation.  During the
loading   of  smelting  furnaces,  concentrations   of  vanadium
pentoxide ranged from 0.15 to 0.80 mg/m3.  During  smelting  and
granulation,  concentrations ranged from 0.7  to 11.7 mg/m3.  In
other  parts of the  work-place, concentrations may  range  from
0.03 to 0.2 mg/m3.

    In  aluminium  production,  when bauxite  is being converted
into alumina, the aluminate solutions accumulate vanadium salts,
which  crystallize  and  precipitate out.   Precipitated  sodium
polyvanadate  is smelted to  form vanadium pentoxide,  which  is
cooled  and  settles  in the  form  of  thin  plates.   Vanadium
pentoxide  dust (concentrations of up to 2.3 mg/m3) is given off
only in the terminal phase during tapping of the liquid product,
packing, and loading.

    During  the  drying,  sieving, and  calcination  of ammonium
vanadate  and during the  crushing, unloading, and  packaging of
pure  vanadium  pentoxide,  dusts  are  formed.   When  vanadium
pentoxide  is sieved after calcination, the concentration in air
may   range  from  2.2  to   26 mg/m3.   In  plants  with   less
mechanization,  incomplete sealing of equipment, and inefficient
local  exhaust ventilation, concentrations of  dust during these
operations ranged from 4.9 to 48.9 mg/m3.

    In  the production of  ferrovanadium, there is  a continuous
source  of  discharge of  vanadium  pentoxide and  lower  oxides
during the smelting process.  Data on vanadium in air at various
sites are shown in Table 14.

    Using   spectrophotometric   techniques,  Roshchin   (1968),
Katayeva   &  Sapunov  (1974)  and  Kazimov  (1977)  found  high
concentrations  of  vanadium  during  smelting  and  granulation
(range,  0.16 -  1.89 mg/m3;  mean, 0.59  mg/m3;  104  samples),
production  of ferrovanadium (range,  0.58 - 4.81  mg/m3;  mean,
1.7 mg/m3;  110  samples), and  roasting  of the  charge (range,
0.44 - 3.64 mg/m3; mean, 1.52 mg/m3; 112 samples).

Table 14.  Vanadium levels in the air of a ferrovanadium planta
Work-place/operations         Vanadium pentoxide  Lower oxides of
                              (mg/m3)           vanadium (mg/m3)

Work area of smelters and     0.1 - 2.6           0.05 - 1.2

Unloading of vanadium pent-   2 - 124.6
oxide from the bin and
charging of electric furnace

Crane driver's cabin during   0.07 - 9.43         0.03 - 0.1

Cutting up ferrovanadium      0.97 - 12.6

Maintenance of the furnace    7.5 - 30
a   From: Roshchin (1968).

    Using  high-volume sampling and atomic  absorption analysis,
Usutani    et   al.    (1979)   measured    vanadium   pentoxide
concentrations  in  the  air at  several  places  in a  vanadium
refinery.  The highest concentrations (higher than 1 mg/m3) were
detected in samples collected during the removal of the vanadium
pentoxide  flake.  High-volume samples  from other locations  as
well  as  low-volume samples  obtained  over 6.5-h  work  shifts
showed lower concentrations (0.002 - 0.735 mg/m3).

    When  ductile  vanadium  is produced  by  the aluminothermic
process  (based on the reduction of pure vanadium pentoxide with
aluminium  powder), the violent exothermic reaction leads to the
release of a condensation aerosol of vanadium pentoxide.  During
preparation  of the charge mixture, work-place concentrations of
vanadium  pentoxide ranged  from 19  to 25.1  mg/m3.   When  the
burden  was placed in  crucibles inside the  smelting  chambers,
concentrations  ranged from 64  to 240 mg/m3.   During smelting,
concentrations  at the operators' workplaces ranged from 0.17 to
0.6 mg/m3.   Twenty to 30 min after smelting, levels declined to
0 -0.3 mg/m3.   Ninety-eight percent of the condensation aerosol
particles  produced had a diameter  of less than 5 m,   and 82%
had a diameter of less than 2 m (Roshchin, 1968).

    In the production of vanadium by the vacuum  carbon  thermic
method,  most  of the  pollution  occurs during  operations with
vanadium trioxide (Roshchin, 1968).  Mixing of vanadium trioxide
in  a closed mixer led to air concentrations in the workplace of
from 0.019 to 0.58 mg/m3.  Unloading of the charge  resulted  in
high  concentrations  of  14.7 -  29.4 mg/m3.   In  the  packing
department,  when the  charge was  sifted in  a  fume  cupboard,
concentrations  in  the  breathing  zone  ranged  from  0.58  to
4.7 mg/m3.   When the charge was being weighed out and packed in
a fume cupboard, concentrations ranged from 3.38 to 6.76 mg/m3.

    Levels of vanadium-containing dust and vanadium pentoxide in
the air during catalyst production are shown in Table 15.

Table 15.  Air contamination in vanadium catalyst productiona
Operation             Dust (mg/m3)              Vanadium pentoxide (mg/m3)
                  Minimum Maximum  Most      Minimum  Maximum  Most
                                   frequent                    frequent
Grinding and un-  5       45       7 - 9     1        7        1.5 - 3
loading vanadium                                               
Loading ground    12      53       14 - 17   3.2      7.5      4 - 4.2
pentoxide into                                                 
the bin                                                        
Sifting and pack- 5       17.5     5 - 7     0.1      1        0.4 - 0.5
ing granules of
bulk contact
a   From: Roshchin (1968).
4.2.2   Cleaning of oil-fired boilers

    Significant  occupational exposure to vanadium occurs during
the  cleaning of boilers in  oil-fired heating and power  plants
and  ships  (Symanski, 1939;  Roshchin,  1968; Kuzelova  et al.,
1977;  Levy et al., 1984).   Fuel oil combustion results  in the
formation of vanadium-containing dust, and large amounts of dust
result from operations connected with removing ash encrustations
in boiler cleaning and in cleaning the blades of  gas  turbines.
Most of these operations are carried out by hand, and  the  dust
in  the air inside the  boilers may range from  20 to 400 mg/m3,
the  most  common  range  being  50 - 100 mg/m3,  with  the dust
containing 5 - 17% vanadium pentoxide and from 3 to 10%  of  the
lower  vanadium oxides (Roshchin, 1968).  Kuzelova et al. (1977)
reported  dust concentrations of  136 - 36 036 ml/m3 in  the air
with  vanadium  concentrations  ranging  between  1.7  and  18.4

    Williams  (1952)  published  air sampling  data  on  boiler-
cleaning  operations in the  British power industry.   He  found
concentrations of soot dust at different points ranging from 239
to  659 mg/m3.  The vanadium concentrations  in the dust of  the
superheater  chamber  was  40.2 mg/m3, while,  in the combustion
chamber,  the concentration was 58.6 mg/m3.  Most (93.6%) of the
dust particles had a diameter of between 0.15 and 1 m.

4.2.3   Occupational exposure limits

    Some  national occupational exposure limits  for vanadium in
work-place air are shown in Table 16.

Table 16.  Examples of occupational exposure limits for vanadium in various countries
Country            Legal status            Exposure limit description             Value  Source

Australia          Recommendation          Time-weighted average (TWA) (fume)a    0.05   ILO (1980)

Belgium            Recommendation          Time-weighted average (TWA) (fume)     0.05   ILO (1980)

Czechoslovakia     Regulatory requirement  Maximum allowable concentration (MAC)         Hygienic Regula-
                                           - Time-weighted average (TWA)          0.1    tions of the
                                           - Ceiling value (fume)                 0.3    Ministry of Health
                                           - Ceiling value (dust)                 1.5    of CSR (1985) (58)
                                                                                         (Regulation No. 7;
                                                                                         section 24/ZB)

Finland            Regulatory requirement  Maximum allowable concentration (MAC)a        ILO (1980)
                                           - Time-weighted average (TWA) (fume)a  0.05

German Democratic  Regulatory requirement  Time-weighted average (TWA) (fume)a    0.1    ILO (1980)
Republic                                   Short-term exposure limit (STEL)a      0.1

Germany, Federal   Recommendation          8-h time-weighted average (TWA)a       0.5    Federal Republic
Republic of                                                                              of Germany Comm-
                                           Short-term exposure limit (STEL)a      2.5    ision for Maximum
                                           (30 min, 2x/shift)                            Work-Place Con-
                                           8-h time-weighted average (TWA)a       0.1    (1985) (xxi, 16)

                   Recommendation          Short-term exposure limit (STEL)a      0.5
                                           (30 min, 2x/shift) (fume)

Italy              Recommendation          Time-weighted average (TWA) (fume)a    0.05   ILO (1985)

Hungary            Regulatory requirement  Time-weighted average (TWA) (fume)a    0.1    ILO (1984)

Netherlands        Recommendation          Time-weighted average (TWA) (fume)a    0.05   ILO (1980)

Table 16.  (contd.)
Country            Legal status            Exposure limit description             Value  Source

Romania            Regulatory requirement  Ceiling value (fume)a                  0.1    ILO (1980)

Sweden             Regulatory requirement  Ceiling valuea                         0      ILO (1980)

Switzerland        Regulatory requirement  Time-weighted average (TWA)a           0.09   Permitted Values
                                                                                         in the Work-Place,
                                                                                         Berne (1984)

USA                Recommendation          Time-weighted average (TWA)a           0.05   ACGIH (1986)
                                           (dust and fume)

                                           Time-weighted average (TWA)a           0.5    OSHA (1977) (29
                                           (dust)                                        CFR.1910.1000)

                                           Ceiling value (15 m)a                  0.05   NIOSH (1977)
                                           (dust and fume)

                                           Time-weighted average (TWA)a           0.1    OSHA (1977) (29
                                           (fume)                                        CFR.1910.1000)

USSR               Regulatory requirement  Time-weighted average (TWA)a           0.1    ILO (1980)

Yugoslavia         Regulatory requirement  Maximum allowable concentration (MAC)a        ILO (1980)
                                           - Time-weighted average (TWA)a         0.1
a   Measured as V2O5.


5.1  Physiological Role

5.1.1   Microorganisms

    Vanadium   is  essential  for  the  mould  Aspergillus  niger 
(Bertrand,  1942) and the green alga  Scenedesmus obliguus (Arnon
&  Wessel,  1953; Arnon,  1958).  It may  play a role  in photo-
synthesis  in the latter.  A need for vanadium has been shown by
the yeast  Candida slooffii at high temperatures (Roitman et al.,
1969).   The growth effects of vanadium in  Azotobacter and other
bacteria have been related to the ability of vanadium,  in  lieu
of  molybdenum, to catalyse nitrogen  fixation reactions (Horner
et al., 1942; Takahashi & Nason, 1957).

5.1.2   Animals

    Vanadium deficiency has been reported in chicks  (Hopkins  &
Mohr 1971a; Nielsen & Ollerich, 1973) and rats (Schwarz & Milne,
1971; Strasia, 1971), and vanadium is considered  essential  for
these animals (Underwood, 1977; Vouk, 1979; Nechay, 1984).
    Hopkins  & Mohr (1974)  observed reduced feather  growth  in
chickens.   They  also  reported impaired  reproduction,  due to
decreased  fertility, and increased perinatal  mortality in rats
fed  a low  vanadium diet  (10 g/kg)  over  4  generations.   A
positive growth response in rats was observed by Schwarz & Milne
(1971)  when  vanadium  salts,  at  levels  of  between  50  and
500 g/kg   were added to a semi-purified diet (vanadium content
unspecified) fed for 26 - 28 days.
    In male Leghorn chicks fed vanadium in the diet at levels of
12.5 mg/kg and 25 mg/kg, body-weight gain was normal at 1, 2, 3,
and 4 weeks of age (Kubena et al., 1986).

    Slower  growth,  higher  haematocrits, and  higher levels of
plasma-  and bone-iron were reported  by Strasia (1971) in  rats
fed diets containing less than 100 g  vanadium/kg compared with
controls  receiving  diets  containing 500 g   vanadium/kg, but
these  results were not confirmed  in another study by  Williams
(1973).   Hopkins & Mohr  (1971a,b, 1974) reported  that a  diet
containing   less  than  10 g   vanadium/kg  decreased  plasma-
cholesterol  levels  in  chicks at  28  days  of age,  increased
plasma-cholesterol  levels  at 49  days  of age,  and  increased
plasma-triglyceride  levels  at  28  days  of  age.   Nielsen  &
Ollerich (1973) found that administration of a  diet  containing
30 - 35 g   vanadium/kg  to chicks  decreased growth, increased
haematocrits  and  plasma-cholesterol levels,  and impaired bone

    Nielsen  (1980) carried out  further studies on  chicks  and
rats,  given different types of low-vanadium experimental diets,
to  examine  the  effects  of  vanadium  deficiency.   In  rats,
vanadium   deficiency  adversely  affected   prenatal  survival,
growth,  physical  appearance,  haematocrit,  plasma-cholesterol

levels, and hepatic lipid and phospholipid levels.   In  chicks,
low   vanadium  intake  produced  adverse   effects  on  growth,
feathering,  haematocrit,  bone development,  plasma-cholesterol
levels, and hepatic lipid, phospholipid, and cholesterol levels.
However,  consistent  deficiency  effects were  not  observed in
chicks  or rats in any of the studies.  Nielsen (1980) suggested
that the inconsistency in vanadium deficiency effects  might  be
due  to the fact that different experimental diets had different
effects on the metabolism of vanadium.

    Vanadate appears to have an insulin-like action (Heyliger et
al.,   1985).   In  female   Wistar  rats  made   diabetic  with
streptozotocin  (single  iv injection  of  55 mg/kg)  and  given
sodium orthovanadate in the drinking-water at a concentration of
0.6  - 0.8 mg/ml (corresponding  to calculated daily intakes  of
between   75  3  and  100  3   mg/kg  body  weight   per  day,
respectively)  for 4 weeks, the serum-insulin level was low, but
there  was  no increase  in  blood-glucose levels  compared with
controls.   In diabetic rats  not treated with  vanadate, serum-
insulin  levels  were also  low,  but blood-glucose  levels were
increased  3-fold.  The cardiac performance  of vanadate-treated
animals did not differ significantly from that  of  non-diabetic
controls.   It  was  concluded that  vanadate  controlled blood-
glucose  levels and prevented the decline in cardiac performance
due to diabetes.

    The  results of in vitro studies  suggest that vanadium  may
play  a specific physiological role as a regulator of the sodium
pump  (Macara, 1980).  Vanadate has been shown to inhibit Na+K+-
ATPase  (EC  in intact  human red blood  cells (Rifkin,
1965;  Cantley  et  al., 1977,  1978a,b).   It  also has  potent
diuretic  and natriuretic effects in rats (Balfour et al., 1978;
Westenfelder  et al.  1981).  It  was a  powerful  inhibitor  of
Na+K+-ATPase in microsomal fractions of the kidney,  brain,  and
heart  in  several  species, including  human  beings  (kidney).
Mg2+-ATPase  was up to 10 000  times more resistant to  vanadium
inhibition than Na+K+-ATPase (Nechay & Saunders, 1978).

    Similarly,  in vivo studies  on  laying chickens  fed calcium
orthovanadate for 15 months, at levels of 0.25, 50, or 100 mg/kg
diet,  showed clear inhibition  of Na+K+-ATPase activity  in the
kidney (Phillips et al., 1982). The inhibition  of  Na+K+-ATPase
by vanadate can be reversed by catecholamines, though  these  do
not have any effects on the Na+K+-ATPase activity in the absence
of  vanadate (Hudgins  & Bond,  1979).  The  inhibition is  also
partially  prevented by the  reducing agents ascorbic  acid  and
glutathione (Grantham & Glynn, 1979).

    The  mechanism by which cells  reduce cytoplasmic vanadium5+
to  vanadium4+ was investigated using human red cells (Macara et
al., 1980).  The authors concluded that vanadate is  reduced  by
cytoplasmic glutathione and that this explains the resistance of
the Na++K+-ATPase to vanadium in intact cells.

    Since  vanadate (V5+) is a potent inhibitor of Na+K+-ATPase,
many   physiological  and  biochemical  processes  are  vanadium
sensitive (Grantham, 1980; Nechay, 1984).  For example, vanadium
compounds inhibit ATP phosphohydrolases, ribonuclease, adenylate
kinase,   phosphofructokinase,   squalene  synthetase,   glycer-
aldehyde-3-phosphate  dehydrogenase  (Macara, 1980),  glucose-6-
phosphatase  (Singh  et al.,  1981), and phosphotyrosyl-protein-
phosphatase (Swarup et al., 1982).  The membrane  neutral  (K+)-
p-nitrophenylphosphatase    in the membrane fraction of skeletal
muscle was inhibited equally by vanadium4+ and vanadium5+ at 4 x
10-8   mol/litre   (Vyskocil   et  al.,   1981).   Extracellular
application  of both  forms of  vanadium failed  to inhibit  the
electrogenic  (Na+ - K+) pump  in intact mouse diaphragm  fibres
(Vyskocil et al., 1981). In the concentration range from 10-5 to
10-3 mol/litre,   vanadium4+   even   potentiated   the   hyper-
polarization of the muscle fibres from -74 to -82 mV (Zemkova et
al.,  1982), probably by increasing  the intracellular potassium
level.   These findings have led to the hypothesis that vanadate
could  control  sodium  pump activity  in vivo ,   perhaps  via  a
vanadium5+ : vanadium4+  equilibrium connecting pump activity to
the  cellular redox state.  However, vanadate in the red cell is
reduced  to vanadium4+, which then binds to haemoglobin (Cantley
&  Aisen,  1979),  a  reaction  that  seems  to  be  essentially
quantitatively driven by glutathione (Macara et al., 1980), NADH
(Vyskocil  et al., 1980), or by other mild reducing agents, such
as ascorbate or norepinephrine (Svoboda et al., 1984).  The role
of   the   vanadium5+ : vanadium4+  redox   equilibrium  in  the
regulation  of cation flow across  cell membranes has yet  to be
unequivocally demonstrated.

    Vanadium appears to be essential for chicks and rats, but it
does  not appear to be essential in other species, as defined by
Mertz  (1970), i.e., an element  is essential if its  deficiency
reproducibly results in an impairment of a function from optimal
to suboptimal.  However, more research is needed before definite
conclusions  can be drawn  regarding the role  of vanadium as  a
nutritionally essential trace element for animals.

5.2  Absorption

    The absorption and distribution of vanadium compounds depend
on  the route of  entry and the  solubility of the  compounds in
body fluids.  The solubility of vanadium compounds in biological
media varies (Reznik, 1954).  The following compounds are listed
in  decreasing  order  of  solubility:  (a)  in  gastric juices,
vanadyl  sulfate,  sodium vanadate,  ammonium vanadate, vanadium
pentoxide;  (b)  in blood-serum  and  in 0.22%  sodium carbonate
solution,   sodium   vanadate,   ammonium   vanadate,   vanadium
pentoxide,  and vanadyl sulfate.   The higher the  solubility in
water  and  biological  media,  the  more  toxic  the  compound,
presumably because of better absorption (Roshchin, 1968).

5.2.1   Absorption by inhalation Human studies 

    There  is little information  on the deposition  of vanadium
compounds   in  the  respiratory  tract   following  inhalation.
However,  the  greatest  deposition  would  be  expected  in the
submicrometre   particle   size   fraction  and   particle  size
distribution  studies (Lee et  al., 1972) have  shown that  most
vanadium-bearing  particulate  matter  is very  small  and  well
within the respirable range for human beings.

    Soluble  vanadium  compounds  inhaled and  deposited  in the
lung,  are readily absorbed but the rates of absorption have not
been  quantified and estimates have not been made of the amounts
of  inhaled vanadium that are transported back to the pharynx by
mucociliary  clearance,  swallowed,  and are  then available for
absorption   via  the  gastrointestinal  tract.    It  has  been
estimated  that about 25% of  soluble vanadium compounds may  be
absorbed  via  the  respiratory tract  (ICRP, 1960).  Absorption
from the respiratory tract was demonstrated in  workers  exposed
to  vanadium  dust,  who  showed  increased  concentrations   of
vanadium  in the  urine (Lewis,  1959b; Gylseth  et  al.,  1979;
Maroni et al., 1983). Animal studies 

    Following acute exposure, there is complete clearance of the
relatively   soluble vanadium pentoxide from the lung within 1 -
3  days (Sjberg, 1950; Levina,  1972).  Stokinger et al  (1953)
demonstrated  that vanadium  is present  for more  than 40  days
following cessation of long-term exposure.

    Intratracheal  administration  of 48V-vanadium  nitrate (0.4
and  20 mg/kg body  weight) to albino  rats showed that  the 48V
absorption rate was maximum after 5 min and could be detected in
internal organs after 30 min.  Blood levels were initially high,
but fell to trace levels after 2 days.  48V was  not  detectable
after  4 days, but reappeared  at 8 days and  accumulated in all
internal  organs, the greatest quantity accumulating in the bone
(Ordzhonikidze, 1977).  In female Fischer rats exposed by intra-
tracheal  instillation  to  40 g  vanadium  pentoxide  in  0.9%
saline  solution,  the time  for removal of  50% of the  initial
burden  was 18 min, but traces remained for a considerable time.
At  14 days,  the vanadium  was distributed  principally in  the
carcass  (40%) and skeleton (12%)  (Rhoads & Sanders, 1985).  In
a study of the kinetics of vanadium following single or multiple
intratracheal  administration, the blood concentration  was high
initially  and  vanadium accumulated  in  the liver  and  kidney
reaching the highest level after 24 h (Roshchin & Ordzhonikidze,

    Vanadium  trioxide was cleared  from the lung  more  rapidly
than  pentoxide  or  ammonium vanadate  following  intratracheal
instillation in rats (Levina, 1972).

5.2.2   Absorption from the gastrointestinal tract Human studies 

    In  general,  vanadium salts  are  poorly absorbed  from the
human  gastrointestinal tract.   In a  study by  Curran  et  al.
(1959),  from 0.1 to  1% of 100 mg  vanadium (as highly  soluble
diammonium    oxytartratovanadate)   was   absorbed   from   the
gastrointestinal  tract and  60% of  this was  excreted via  the
kidneys  within 24 h.  The remainder  was retained in the  liver
and  bone, until  the oral  administration ceased,  when it  was
mobilized  rapidly from  the liver  and slowly  from  the  bone.
Sodium  metavanadate  (12.5 mg/day  for 12  days)  was recovered
largely  unabsorbed in the faeces  (87.6%) and the remainder  in
urine  (12.4%)  (Proescher  et al.,  1917).   The  International
Commission on Radiological Protection (ICRP, 1960)  estimate for
the  gastrointestinal  absorption of  soluble vanadium compounds
was 2%.  A low degree of absorption was also found  by  Roshchin
et al.  (1980). Animal studies 

    Mountain  (1959)a   reported an  unpublished study in  which
vanadyl  sulfate  was  fed to  adult  male  rats in  daily doses
ranging from 650 to 1250 g  (160 - 310 g  of  vanadium).   The
mean  absorption  was  about  0.5%,  but  urinary  values varied
considerably.  The duration of the study was not given.

5.2.3   Absorption through the skin

    Dermal  absorption and skin  irritation were reported  in  a
study  in which  a nearly  saturated solution  (20%)  of  sodium
metavanadate was applied to the skin of the  rabbit  (Stokinger,
    However,  according to US EPA (1977), the skin appears to be
a  minor route of  vanadium uptake for  human beings.  In  an in
vitro study using 48V radiotracer, there was no  penetration  of
human skin samples (Roshchin, 1980).

5.3  Distribution and Transformation

5.3.1   Human studies

    Vanadium  levels in man,  reported in earlier  studies, were
considerably  higher  than  those reported  more  recently.  The
difference  is  illustrated by  the  whole-body content  of 17 -
43 mg  vanadium for a 70-kg  man calculated by Schroeder  (1963)
compared  with estimates  of 100 g   derived by  Byrne &  Kosta
(1978).   The  influence  of different  sampling  procedures and
analysis (colorimetric determination, neutron activation) should
be  clarified  before  concluding  that  such  effects  are real
(Lagerkvist  et  al.,  1986)  or  that  they  reflect decreasing
environmental exposure.
a       Mountain,  J.T.  (1959)  Unpublished  results,   Toxicologic
        Services,    Occupational    Health   Field    Headquarters,
        Cincinnati, Ohio.

    Absorbed  vanadium  is  transported  mainly  in  the  plasma
(Schroeder et al.  1963; Ordhzonikidze et al., 1977; Roshchin et
al., 1980).  Some mean values obtained using  different  methods
of analysis are given in Table 17.  There is a  wide  divergence
in  the results, the  ratio between the  highest and the  lowest
mean values being about 104.  In general, levels tend to decline
chronologically  as analytical techniques become more sensitive.
There  is  also  a difference  in  results  obtained by  neutron
activation  analysis according to whether separation was carried
out before, or after, irradiation.

    In   an  extensive  investigation  on   human  tissues,  the
inadequate  sensitivity  of  the analytical  method  meant  that
quantitative   information could only  be obtained for  the lung
and intestine (Tipton & Cook, 1963).  Using  neutron  activation
analysis,  Byrne & Kosta  (1978) obtained information  on  other
organs.   Table  18  includes  autopsy  tissue  values  and some
results  from two other investigations  using neutron activation
analysis.  It is apparent that vanadium concentrations  are  low
in  all tissues, though the  liver, kidney, and lung  often show
higher  levels  than  other  tissues.   In another investigation
on  a selection of organs, using spark-source mass spectrometry,
the  vanadium levels detected   were: brain, 30 g   vanadium/kg
wet  weight  (average  from  10  specimens);  liver,   40 g/kg
(average from 11 specimens); lung, 100 g/kg  (average  from  11
specimens);  lymph node, 400 g/kg  (average  from 6 specimens);
and testis, 20 g/kg  (average from 5 specimens)   (Hamilton  et
al.,  1972/73).  The values reported are in reasonable agreement
with   those  found  in   other  animals.   However,   there  is
considerable  disagreement  between  investigators  and  between
analytical   methods,  which  has   not  been  resolved,   since
interlaboratory  and  intermethod  investigations have  not been
carried out.
    In  the general population, which  is mainly exposed to  low
levels  of  vanadium  in food  with  poor  absorption  from  the
intestine, vanadium is usually undetectable in the  urine,  even
using very sensitive methods (Byrne & Kosta, 1978).  Examination
of  urine  samples  from  50  normal  individuals  using  atomic
absorption spectrometry showed that vanadium was present in only
13;  11  samples  showed  a  level  of  0.1 g/litre   and  two,
0.2 g/litre   (Ueno  &  Ishizaki, 1980).   In  industry,  where
exposure is mainly through air and absorption from the  lung  is
high,  vanadium concentrations in the urine cover a considerable
range (section 5.4.1).

Table 17.  Vanadium levels in human blooda,b
Analytical method                 Whole blood             Serum/plasma           Reference                                 
                                  (mg/litre)              (mg/litre)                                                       
X-ray emission                                               0.01 (43)           Gofman (1962)                             
Spectrography                     0.0078 (24)                                    Lifschitz (1962)                          
Colorimetry                       0.23 (calculated)          0.42 (13)           Schroeder et al. (1963)                   
Neutron activation analy-         0.016                                          Bowen (1963)                              
sis (preseparated)                                                                                       
Neutron activation analysis                               0.67  0.32 ng/ml      Simonoff et al. (1986)                    
Spectrography                     0.126 (47)                                     Butt et al. (1964)                        
Neutron activation analy-                                    0.0046 (36)         Heydorn & Lukens (1966)                   
sis (preseparated)                                                                                       
Catalytic                                 0.01 (82)                              Allaway (1968)                            
                                   0.02 - 0.01 (7)                                                       
Spectrophotometric                                           0.057 (10)          Christian (1971)                          
Neutron activation analy-          0.0046                                        Kirzhner et al. (1974)                    
sis (preseparated)                                                                                       
Neutron activation analy-          0.022 (5)                                     Buono et al. (1977)                       
sis (preseparated)                                                                                       
Neutron activation analy-          0.0005 (5)                                    Byrne & Kosta (1978)    
sis (preseparated)                                                                                       
Neutron activation analy-                                                                                
sis (preseparated)                                         0.0066c (5)           Sabbioni et al. (1979)
Neutron activation analysis                                0.000047 (9 males)    Cornelis et al. (1979)                    
                                                           0.000024 (8 females)  Cornelis et al. (1979)                    
Neutron activation analy-                                                                                
sis                                                        0.000033 (17 females) Cornelis et al. (1980)                    
a   Adapted from: Byrne & Kosta (1978) and Versieck & Cornelis (1980).
b   Number of subjects in parentheses.
c   Recalculated values assuming an haematocrit of 0.45.

Table 18.  Vanadium levels in human organs (g/kg wet weight)a
  Tissue                         Study
          Byrne & Kosta (1978)b,c   Damsgaard (1972)c,d   Lievens (1977)b

  Kidney   3.3     3.2    2.6         nd       7

  Liver    7.5     4.5                5       19             7 - 19 (5)

  Brain    0.7    0.75

  Thyroid  3.2     3.0

  Heart    1.1

  Cardiac  0.45    0.3

  Subcut-  0.63   0.80

  Muscle   0.45   0.62   0-59         7       nd

  Spleen                              3        4

  Pancreas                            nd      14

  Lung      19 - 40 (7)               nd      13
             median 30

a   From: Byrne & Kosta (1978).
b   Parentheses enclose number of subjects.
c   Brackets embrace specimens from one autopsy.
d   nd = not detected.

    Studies  on  vanadium levels  in  human bone  have  produced
widely  varying  results.  Byrne  &  Kosta (1978)  reported  the
following  data from human  bones (lg/kg   wet  weight):  skull,
2.5,  3,  4.5, 8.3;  sternum, 3.1; rib,  0.8, 2.1; tooth  enamel
(fragmented), 2, 3.4, 4, 5.1; and tooth enamel (drill powdered),
18.   The high concentration in tooth enamel may be due to diet;
concentrations of vanadium tend to be higher in  processed  than
in  unprocessed foods  (Myron et  al., 1977),  but  vanadium  is
commonly  present in steel  alloys, especially tool  steels, and
vanadium  contamination may have occurred from the drill.  Using
atomic  absorption spectroscopy, Sumino  et al. (1975)  found  a
range  of 100 - 200 g/kg   (wet weight) in 6  specimens of rib.

Using  emission spectral analysis, Shevchenko  (1965) detected a
mean  vanadium level of 150  2 g/kg  (0.015 mg%)  (dry weight)
in  14 samples of  healthy bone tissue;  bone tumours  contained
higher levels.

    Metal  levels have been extensively studied in hair, because
of  its potential value  for exposure and  body burden  studies.
Gordus et al. (1974) and Gibson & DeWolfe (1979), using the same
method  as Byrne & Kosta  (1978), found levels of  20 - 40 g/kg
in 42 subjects and 20 - 41 g/kg  in 370 subjects, respectively.
These  results compare favourably with  those of Byrne &  Kosta,
i.e.,  12 - 87 g/kg   in 12 subjects.   Ueno & Ishizaki  (1980)
used  atomic  absorption  spectrometry to  determine vanadium in
hair  specimens  from 130  men and 132  women.  They found  mean
concentrations  of  53.6 g/kg   (range,  5  -  155 g/kg)   and
44.2 g/kg  (range, 1.8 - 118.8 g/kg),  respectively.  However,
Creason et al.  (1975), using emission spectroscopy in extensive
surveys  in  the  USA, found  levels  that  were about  10 times

    There is considerable information on vanadium levels in lung
tissue.   In studies by  Schroeder et al.  (1963), vanadium  was
found  in 97 out  of 173 lungs  examined in groups  from  7  USA
cities, group mean concentrations ranging from 10  to  130 g/kg
wet  weight.  Byrne &  Kosta (1978) found  levels of from  19 to
140 g/kg   (median,  30 g/kg)  in  7  cases; Hamilton  et  al.
(1972/73) detected a mean level of 100 g/kg  in 11  cases;  and
Sumino  et al. (1975) determined a range of 100 - 300 g/kg  for
13  observations.   Statistical  analyses of  lung  tissue trace
metal data were performed by Tipton & Shafer (1964)  using  data
taken from Tipton & Cook (1963).  One approach  was  examination
of the relationship between lung metal concentrations  and  age.
The  levels of a number of metals, including vanadium, increased
in  the  lung with  age,  indicating accumulation  of  insoluble
compounds,  and Schroeder (1970b) calculated an annual increment
rate of 1.3 g  for lung-vanadium.  However, earlier analysis of
the  same  data (Schroeder  et al., 1963)  did not show  an age-
related increase in lung-vanadium.  The later analysis by Tipton
& Shafer (1964) was performed on a subset of the  original  data
from  Tipton & Cook  (1963), which may  account for some  of the
discrepancy.   The Tipton &  Shafer (1964) data  did not show  a
graded  increase in lung-vanadium with age, and there was a high
mean level only in the oldest age group.  This could  have  been
produced  by a single  very high value  in this age  group.  The
concept  of vanadium  accumulation in  the human  lung with  age
remains  doubtful, and  the results  of animal  studies  do  not
indicate  significant accumulation in the lung (sections
and 5.3.2).

5.3.2   Animal studies

    Observations on pregnant rats, that received vanadium on the
21st -  22nd  day of  pregnancy,  revealed accumulation  in  the
placenta  but not "in perceivable  quantities" in the organs  of
the  fetus.  Vanadium was  reported to be  secreted in the  milk
(Roshchin et al., 1980).

    The  identification of cellular  components that react  with
vanadium  has  been investigated in vivo and in vitro using  48V
radiotracer (Marafante & Sabbioni, 1983).  Vanadium has  a  high
affinity  for nuclear and  mitochondrial components.  When  rats
were  treated every  day with 10 g   vanadium/rat for  up to  8
days, a dose-related increase in vanadium incorporation  in  the
subcellular fractions was observed.  There is evidence that non-
haem  Fe-containing proteins, such as  transferrin and ferritin,
have  a high affinity for  vanadium, while Fe haemoproteins  are
not able to incorporate the metal.
    In  rat serum, both  Vanadium4+ and Vanadium5+  form  metal-
protein  complexes  with  transferrins.  Specific  intracellular
vanadyl-ferritin  complexes are formed in rat liver, spleen, and
kidney (Chasteen et al., 1986).
    Ermolaev  (1969) studied the distribution of vanadium in the
organs  and tissues of  3 groups of  rabbits, i.e., animals  fed
under  ordinary conditions, animals fed a diet supplemented with
vanadium  (0.5%  solution  of vanadyl  sulfate)   at  a dose  of
0.05 mg/kg   body   weight,   and  animals   fed  the  vanadium-
supplemented  diet  and  subcutaneously injected  with  vanadium
also   at  0.05  mg/kg  body   weight.   The  results  of   this
investigation   are   given   in  Table 19.    The   method   of
administration  had little effect on the resultant blood, brain,
and stomach levels, but there were distinct differences  in  the
case of the other organs and tissues.

    The  distribution and kinetics of  vanadium, administered ip
as  80  mg  vanadocene dichloride/kg  to  strain  A  mice,  were
determined  in blood, kidney, liver, small intestine, and brain.
The  vanadium concentration decreased rapidly  and exponentially
in  the blood  (half-time =  118  43 min)  and small  intestine
(half-time a   =  18  0.14  min; half-time b   = 341  45 min).
Vanadium   accumulated   in   kidney   (maximum   concentration,
1.12  0.06  mmol  at 12  h)  and liver  (maximum concentration,
0.56  0.06  mmol at 8 h) and was then excreted (estimated half-
time, 7.9  0.7 h for kidney; 12.1  0.1 h for liver).  Vanadium
was not detected in the brain (Toney et al., 1985).

Table 19.  Vanadium levels in rabbit organs and tissues following
oral and subcutaneous administration (mg %)a
  Organ/        Control group  First group          Second group
  tissue                       (0.05 mg/kg          (0.05 mg/kg with
                                with food)           food and injected

  liver              66              88                    632

  muscle tissue      27              41                     30

  blood              29              82                     90

  spleen             68             116                    180

  kidneys            71              90                    464

  lungs              62              82                    168

  brain              20              26                     24

  heart muscle       52              68                     71

  intestine          20              22                     32

  stomach            30              70                     74

a   From: Ermolaev (1969).

    The  influence  of  the  oxidation  state  of  intravenously
injected compounds of 48V on uptake and distribution to selected
organs  and subcellular elements of the rat liver was studied by
Hopkins & Tilton (1966).  They did not observe  any  significant
differences  in  the  rate  or  amount  of  uptake  of  nanogram
quantities  of  vanadium  in three  different  oxidation  states
(VOC13, VOC12, and VC13) and concluded that either the oxidation
state  was not critical  to transport or  that the vanadium  was
converted  to a common oxidation state in vivo.  Similar results
with  respect  to  oxidation  state  and  uptake  and  also  the
distribution of vanadium in the rat were reported by Sabbioni et
al.  (1978) and Conklin et  al.  (1982).  In contrast,  Parker &
Sharma  (1978) found that levels  of vanadium in the  tissues of
male  Wistar rats given  sodium orthovanadate in  the  drinking-
water  at 50 mg/litre for 3 months were higher than those in the
tissues   of  animals  given   vanadyl  sulfate  at   the   same
concentration.  Roshchin et al.  (1964)  found evidence  of  the
partial  conversion of vanadium trioxide to the pentavalent form
in  blood-serum  and in  weakly  acidic and  basic  solutions in
vitro.   In a  later study,  Johnson et  al.   (1974)   reported
the in  vivo conversion of vanadium pentoxide to the tetravalent

    Information  on vanadium distribution  in rats after  intra-
peritoneal, intratracheal, oral, and subcutaneous administration
of  radioactive  (48V)  vanadium  nitrate  in  single  doses  of
20 mg/kg body weight (LD50) and 0.4 mg/kg body weight (non-toxic
dose)  is given in Table 20 (Roshchin et al., 1980).  The study,
which involved 1060 albino rats, showed that whatever the method
of  administration, vanadium was present in blood in significant
quantities only during the first 24 h, and that, after  2  days,
only  traces of vanadium were detectable.  No vanadium was found
in  the  blood  after 4  -  8  days.   However,  in  the  groups
administered   the   radioactive  compound   intratracheally  or
subcutaneously,  low amounts of vanadium were detected between 8
and  16 days after  administration as a  result of  reabsorption
from  the organs.  The highest level occurred 5 min after intra-
tracheal  administration,  30 min after  intraperitoneal admini-
stration,  and 15 min - 1 h  after subcutaneous or  intragastric
administration.   Vanadium  was  detected  in  all  tissues  and
organs. In 2 days, vanadium had accumulated in the bone, kidney,
liver,  and lung, which  were also the  primary targets in  rats
after   intratracheal   administration  of   vanadium  pentoxide
(48V2O5) or chloride (48VO2C1) (Conklin et al., 1982)  and after
oral  administration of vanadyl sulfate  or sodium orthovanadate
in the drinking-water (50 mg/litre) for three months  (Parker  &
Sharma, 1978).

    In  another  study, 48VOCl3,  which  is fairly  soluble, was
administered intratracheally to juvenile male Wistar rats  at  a
dose of 12.6 Ci  in 1 ml buffered solution.  Within 15 min, the
vanadium  isotope was  found in  all major  organs,  except  the
brain.   The largest fractions were  found in the blood,  heart,
spleen,  liver, and kidneys.  Peak uptake occurred between 4 and
24 h after administration and activity was maintained throughout
a 9-week period (Oberg et al., 1978).

5.4  Retention

5.4.1   Human studies

    Vanadium levels in human tissues (Table 18,  section  5.3.1)
are  low, the  highest concentrations  tending to  occur in  the
liver, kidney, and lung.
    Storage  of available vanadium in  man occurs mainly in  fat
and serum lipids (Schroeder et al., 1963).
    Shevchenko   (1965)  used  emission  spectral   analysis  to
determine  the vanadium  contents of  bone tumours  and  of  the
cortical layer of bone adjacent to the tumours.  He  found  that
vanadium  accumulated in tumours.  Healthy bone tissue contained
a  mean vanadium concentration of 0.15  0.002 mg/kg dry weight,
osteoblastomas  contained 6.38  1.17 mg/kg,  and osteosarcomas,
4.16  0.77    mg/kg.    The   cortical   layer    adjacent   to
osteoblastomas contained 2.01  0.42 mg/kg, and that adjacent to
osteosarcomas  contained  1.77  0.48 mg/kg.   In comparison  to
normal  bone,  bone  cysts, osteochondromas,  and exostoses also
showed  higher vanadium levels, but to a lesser extent than bone

    The  significant accumulation of  vanadium in the  tissue of
benign  and malignant tumours  and, to a  lesser extent, in  the
neighbouring  tissue suggests that  quantitative changes in  the
amounts  observed may indicate  disturbances in its  metabolism.
This  may be  in connection  with the  role of  vanadium in  the
phospholipid   and  cholesterol  metabolism,  which  may  become
indirect  indicators  of  the  intensity  of  the   phospholipid
turnover in tumour tissue.

5.4.2   Animal studies

    Large  amounts of vanadium  were reported in  the crude  fat
from  beef,  pork, and  lamb (Schroeder et  al., 1963), but  the
results of subsequent studies do not support this finding, which
is  probably erroneous because  of the analytical  methods  used
(NRC, 1980).
    In  rats,  after  oral  administration  of  20  mg  vanadium
nitrate/kg  body weight, levels  of vanadium in  the blood  were
detectable  only during the first 24 h, and only traces remained
after 48 h; after 4 days, no vanadium was found in  blood.   For
48 h after the administration of vanadium, concentrations in the
organs  increased by 0.4% of the administered dose in the liver,
by 0.69% in the kidneys, and by 0.16% in the spleen.   The  most
significant   increase   in   vanadium  (1.01%   of   the   dose
administered)  was found in the bones.  After 16 days, the level
in   the  bone  tissue  had  increased  by  1.72%  of  the  dose
administered,  while  in  other  organs  it  had   significantly
decreased (Roshchin et al., 1980).

    Studies  on  rats showed  that  liver, kidney,  spleen,  and
testes  continued to accumulate intravenously injected vanadium-
48 for up to 4 h and that most of the radioactivity was retained
for  up to 96 h (Hopkins & Tilton, 1966) .  After 96 h, 14 - 84%
of the 10-min uptake was retained in other organs, and  46%  and
9%  of the  vanadium-48 had  been eliminated  in the  urine  and
faeces,    respectively.    Levels   of   vanadium-48   in   the
mitochondrial   and  nuclear  fractions  of   homogenized  liver
increased  from 14 to 40%  of the total during  the first 96  h,
while  the  level of  radioactivity  in the  microsomal fraction
remained relatively constant.

    When strain A mice were given 80 mg vanadocene dichloride/kg
ip,  vanadium  accumulated in  the  liver and  kidney.   Maximum
concentrations  of  1.12  0.06 mmol  in  the kidney  and 0.56 
0.06 mmol  in  the  liver were  reached  after  12 h  and  8  h,
respectively (Toney et al., 1985).

Table 20.  Concentrations of 48vanadium in the organs and tissues of rats after intraperitoneal,
subcutaneous, intratracheal, and intragastric administration of a radioactive vanadium compound 
(expressed as % radioactivity equivalent to 10 uCi per animal)a
Organ/tissue        Intraperitoneal administration           Intratracheal administration	  
                                                         Time after administration								 
                  30 min        2 days        16 days      30 min        2 days       16 days
Liver             2.20  0.55   0.43  0.02   0.22  0     0.43  0.19   0.36  0.19  1.25  0.38
Kidney            7.20  0.85   1.60  0.02   0.66  0     1.55  0.67   1.56  0.19  4.03  0.74
Spleen            2.16  0.23   0.17  0.01   0.09  0     0.15  0.06   0.18  0.02  1.92  0.09
Lung              2.53  0.73   0.11  0           0       9.09  5.91   0.20  0.39  4.64  2.11
Stomach           2.93  0.73   0.08  0           0       2.56  0.94   0.13  0.05       0
Small intestine   2.53  0.31   0.08  0           0       0.71  0.22   0.21  0.15       0
Large intestine   3.33  0.88   0.13  0.03        0       0.19  0.08   0.17  0.05  0.47  0
Muscle            0.40  0.05   0.03  0           0       0.28  0.20   0.03  0          0
Bone              2.13  0.12   3.45  0.48   1.72  0.31  0.79  0.31   2.19  0.31  9.70  1.93
Testicle          1.30  0.15   0.09  0      0.06  0     0.09  0      0.08  0     0.54  0.08
Thyroid gland     0.60  0      0.23  0.05        0       1.21  0.69   0.54  0.40       0
Adrenals          2.53  1.01   0.11  0.02        0       0.67  0      0.06  0.02       0
Pancreas          7.88  0.26   0.31  0.06        0       0.14  0.04   0.08  0.02       0
Brain             0.16  0.04   0.01  0           0       0.02  0           0            0
Heart             1.50  0.34   0.07  0           0       0.04  0      0.08  0     0.41  0.15

Table 20 (contd.)
Organ/tissue          Intragastric administration               Subcutaneous administration	 
                                                         Time after administration								   
                  30 min        2 days        16 days      30 min        2 days       16 days
Liver             0.08  0.03   0.33  0.11   0.27  0     0.05  0.01   1.00  0.15  1.67  0.42
Kidney            0.17  0.13   0.69  0.20   0.67  0     0.13  0.03   2.30  0     4.47  1.48
Spleen            0.04  0      0.16  0.05   0.08  0     0.03  0      0.31  0.03  1.38  0.75
Lung              0.06  0.02   0.09  0.01   0.06  0     0.10  0.01   0.19  0.01  0.89  0.18
Stomach           8.08  1.49   1.55  0.05   0.05  0     0.29  0.01   0.12  0     0.39  0.06
Small intestine   4.65  9.95   0.22  0.09   0.06  0     0.77  0.66   0.11  0.01       0
Large intestine   0.12  0      0.14  0      0.01  0     0.46  0.21   0.14  0          0
Muscle            0.01  0      0.02  0      0.04  0     0.40  0.30   0.03  0     0.46  0.15
Bone              0.05  0.02   1.01  0.31   1.72  0     0.43  0.30   3.23  0.41  1.86  0.52
Testicle          0.26  0.20   0.04  0      0.06  0     0.01  0      0.12  0.01  0.64  0.07
Thyroid gland     0.08  0      0.32  0.24        0       0.15  0.05        0            0
Adrenals               -        0.09  0.03        0       0.10  0      0.16  0.04  0.39  0
Pancreas          0.32  0.29   0.04  0.04   0.08  0     0.03  0      0.09  0.01  0.83  0.04
Brain             0.02  0      0.01  0      0.02  0     0.03  0      0.02  0          0
Heart             0.06  0      0.05  0           0       0.06  0      0.12  0     0.81  0.08
a   From: Roshchin et al. (1980).
    In a study on 2 young rats (strain unspecified), the highest
uptake of vanadium-48 from V205 occurred in rapidly mineralizing
areas  of dentine and  bone (Sremark et  al., 1962).  In  mice,
high uptake occurred in the mammary glands, liver, renal cortex,
and lung (Sremark & Ullberg, 1962).
    In  studies by Belehova  (1966, 1969), vanadium  levels were
lower in carious than in normal canine teeth.  In other studies,
intramuscular injection of vanadium in dogs at a dose of 2 mg/kg
body weight resulted in vanadium levels in the hard  tissues  of
the teeth that were 1.3 times higher than those in the controls.
On  the 7th  day, the  concentration in  the enamel  had  almost
returned  to its initial  level of 8.8  mg/kg; the level  in the
dentine was still 32% higher.
    Vanadium  was reported to  decrease the incidence  of dental
caries,  when  added  to the  diet  of  hamsters (Geyer,  1953).
However,  Hein & Wisotzky (1955)  reported significant increases
in  dental  caries  in hamsters  given drinking-water containing
vanadium  pentoxide equivalent to  10 mg vanadium/litre  over an
80-day  period.  Muhler (1957)  studied the effect  of  vanadium
pentoxide on caries in Sprague-Dawley rats.  Groups of  50  rats
received  vanadium  (as  vanadium  pentoxide)  at  10  mg/litre,
20  mg/litre,  or  40  mg/litre  in  their  drinking-water.  One
control   group  received  drinking-water   containing  ammonium
fluorosilicate  (20  mg/litre),  the  other  received  untreated
water.   Vanadium did not produce any reduction in the incidence
of   dental  caries,  in  fact  there  was  a  slight,  but  not
significant  increase in dental  caries in the  groups receiving
10 mg/litre and 20 mg/litre for 140 days.  All the  rats  showed
signs of vanadium toxicity and all animals in the  highest  dose
group (40 mg/litre) died within 65 days.
    In  an in vitro study  on the  effects of  vanadate on  bone
formation  in 21-day-old fetal rat calvariae, sodium vanadate at
concentrations  of 0.1 - 10 mmol stimulated the incorporation of
3H-thymidine into DNA and increased the bone DNA content and the
mitotic index.  Sodium vanadate at a concentration of  100  mmol
produced a marked and irreversible inhibition of  DNA  labelling
and  protein synthesis.  Concentrations  of 1 mmol  (24 h)   and
10 mmol  (96 h) inhibited alkaline phosphatase activity.  Sodium
vanadate  also stimulated collagen  and non-collagen protein  at
low  concentrations,  but  again had  an irreversible inhibitory
effect at a high concentration of 100 mmol (Canalis, 1985).

5.5  Elimination

5.5.1   Human studies

    Owing  to low gastrointestinal absorption, ingested vanadium
is  predominantly  eliminated  unabsorbed  in  the  faeces.  The
principle route of excretion of absorbed vanadium is through the

    The relationship between urinary excretion and the extent of
exposure has been studied.  As part of a clinical study  on  the
effects on cholesterol level, Dimond et al. (1963) gave ammonium
vanadyl tartrate to patients (5 female, 1 male) and did not find
any  correlation  between  urinary  excretion  and  oral   dose.
Variable  absorption  was  suggested  as  the  reason  for  wide
variation  in  urinary  excretion.  In  a  50-week  study  on  2
volunteers,  Tipton et al. (1969) reported a urine/diet ratio of
0.13.  This is in agreement with the figure of  12.4%  excretion
in  urine in  a man  given sodium  metavanadate orally  (12.5 mg
daily for 12 days) (Proescher et al., 1917).

    Studies  on occupationally exposed populations  have shown a
poor  correlation  between  vanadium concentrations  in  air and
amounts  excreted  in  urine  (Williams,  1952;  Lewis,   1959b;
Jaraczewska & Jakubowski, 1964; Watanabe et al., 1966; Troppens,
1969;  Khler, 1972).  Differences  in laboratories and  methods
may  contribute  to the  wide  range of  urinary  concentrations

    In  a  study on  power-station  workers exposed  to vanadium
during  maintenance work on  an oil-fired boiler,  it was  shown
that  urinary excretion increased in those most heavily exposed,
in  spite of the use of protective masks.  For instance, urinary
levels  of vanadium in 6 welders and 4 cleaners increased over a
work shift from 2.7 to 43.8 mg vanadium/kg creatinine  and  from
1.65  to  52.8 mg/kg, respectively.   The vanadium concentration
in  air during boiler cleaning was estimated to vary between 0.1
and 5 mg/m3 (Maroni et al., 1983).  These results resemble those
reported  by Thrauf  et al.  (1979) on  54 workers  exposed  to
vanadium in a metallurgical plant. Exposed workers had a urinary
vanadium  concentration  of  33.9 mg/kg  creatinine, whereas the
level in unexposed workers was 0.6 mg/kg creatinine.

    Roshchin et al. (1980) used polarography in a study  of  the
urine  samples of 100 workers who were exposed daily to vanadium
pentoxide,  and found  vanadium in  50% of  subjects.  The  mean
concentration of vanadium in the urine was 0.18  0.03 mg/litre.
In  workers with a duration  of exposure in the  range of 1 -  2
years,  the mean concentration was 0.14  0.08 mg/litre; after 2
years,  the  mean  concentration was  0.20  0.009 mg/litre.  In
workers  employed for 2  - 6 months,  the mean concentration  of
vanadium  in the urine was 0.16  0.12 mg/litre.  There appeared
to  be  a  correlation  between  the  urinary  levels  and   the
concentration of vanadium in the air.  For example,  in  workers
exposed to mean vanadium pentoxide atmospheric concentrations of
0.28  0.06 mg/m3,  the  concentration  in the  urine was 0.20 
0.05  mg/litre;  at  an  atmospheric  concentration  of   0.17 
0.01 mg/m3,   the   urinary   concentration   was   0.19  0.007

    The  relationships between personal  exposure and blood  and
urine  levels  of  vanadium were  examined  in  16 workers  in a
ferrovanadium   plant   in   Norway  (Gylseth   et  al.,  1979).
Individual  levels did not  show any clear  relationship between
exposure  and response,  but, when  the data  were divided  into

high-  and  low-exposure  groups, significant  differences  were
found  for both blood and  urine levels in relation  to exposure
levels.   There was also  a reasonably good  correlation between
blood  and urine levels.   However, the authors  concluded  that
"the   differences  are  small  and  the  method  difficult  and
expensive,  so for a  routine control other  criteria should  be

    Kiviluoto  et  al.  (1979a,c) studied  serum-  and  urinary-
vanadium  levels in relation  to exposure levels.   Grouped  and
individual  data  were  examined at  intervals  during  vacation
periods  and compared with  those for an  unexposed group.   The
levels  of  exposure  were  low  (0.01  -  0.05 mg/m3),  and  no
correlations   between  exposure  levels  and   serum  or  urine
concentrations  were  found.   However, there  was a conspicuous
decline  in the urine  levels at the  beginning of the  vacation
period,  but  they  did not  decline  down  to the  level of the
unexposed  group.   It was  considered  that this  provided some
measure of the extent of exposure.

5.5.2   Animal studies

    Talvitie  &  Wagner (1954)  administered sodium metavanadate
monohydrate  in saline to albino Webster rats and albino rabbits
by  intraperitoneal and intravenous injection, respectively.  In
one  part  of  the study,  rats  were  given a  single  ip  dose
equivalent  to 0.5 mg vanadium/kg  body weight and, in  another,
twice   daily  ip  injections,   each  equivalent  to   0.25  mg
vanadium/kg  body  weight, for  5  days.  Rabbits  were injected
intravenously twice daily for a total of 7 or 9 days, with doses
equivalent  to 0.25  mg vanadium/kg  body weight,  except for  1
rabbit  that  received doses  of 0.4 mg/kg  body weight for  the
second 5-day period.  No histological changes were  noted.   The
ratio of vanadium eliminated in the urine and faeces was 5:1.

    Following   oral  administration  of  vanadium  sulfate  and
vanadium  pentoxide to guinea-pigs (equivalent to 2 mg vanadium/
kg body weight), Reznik (1954) found vanadium in the  urine  and
faeces for 7 - 10 days, though elimination in the  urine  ceased
before that in faeces.  The author concluded that  the  presence
of  vanadium in the  faeces, several days  after administration,
was due to its return to the intestine after internal resorption
and  excretion.   Biliary  excretion of  less  than  2%  of  the
intravenously  injected  dose  (between 0.9  and 30  g   penta-
vanadate/kg  body weight) was  demonstrated in rats  during  the
first 6 h after administration.  By comparison, 20% was excreted
with  the urine during the same period of time (Sabbioni et al.,

    Roshchin  (1968)  administered  a  dose  of  3  mg  vanadium
trichloride  to 180-g  albino rats.   Most of  the vanadium  was
excreted  via the kidneys.   Of the dose  administered, 18%  was
found in the urine after 24 h and 25%, after 48 h.   The  amount
of  vanadium excreted in the  urine fell and, after  6 days, was
low.   Elimination of vanadium via  the intestine occurred on  a
much  smaller scale and remained relatively stable; 30.9% of the

administered dose was excreted over a 6-day period.   Thus,  the
largest quantity of vanadium was eliminated during the  first  2
days,  and the  rest was  eliminated gradually.   The  ratio  of
amounts   eliminated   in  the   urine   and  faeces   was  5:1,
corroborating the findings by Talvitie & Wagner (1954).

    In  a study on mice, rats, and dogs, Mitchell & Floyd (1954)
showed  that ascorbic acid increased vanadium elimination in the
urine  during  the  first few  days  and  later in  the  faeces.
CaNa3DTPA   (salicylic  salt  of  diethylenetriamine-pentaacetic
acid)  increased  vanadium excretion  in  the urine  and reduced
elimination  via faeces.  Following the  combined administration
of both preparations, elimination in the faeces increased.


6.1  Aquatic Organisms

6.1.1   Microorganisms and higher plants

    Trace  quantities (1 - 10 g/litre)   of vanadium stimulated
the  growth  of  some algae,  including Scenedesmus or Chlorella
(Arnon   & Wessel, 1953; Hopkins  et al., 1977; Patrick,  1978).
Toxicity  studies  on  phytoplankton, mainly  using  pentavalent
vanadium,  have  revealed differences  in susceptibility between
various  species.  A concentration of 0.02 mg/litre, as ammonium
vanadate, interfered with the cell division of  the  fresh-water
algae Chlorella  pyrenoidosa, whereas  0.25 mg/litre  was lethal
(Meish & Benzschawel, 1978).  The 15-day LC50 for  an  estuarine
and  salt-water  green  alga (Dunaliella  marina) was  given  as
0.5 mg/litre  of sodium metavanadate  and that of  a  salt-water
pennote diatom (Asterionella japonica) as 2 mg/litre (Minamand &
Unsal, 1978).
    Vanadium does not appear to be essential for higher plants.

6.1.2   Invertebrates

    In a study using sea-water with a background level of 0.0017
mg  vanadium/litre,  the 9-day  LC50s  for vanadium  (as  sodium
metavanadate)    for   the  worm (Nereis   diversicolor), mussel
(Mytilus   galloprovincialis), and  crab (Carcinas  maenas) were
10,  35,  and 65  mg  vanadium/litre, respectively  (Miramand  &
Unsal, 1978).  Some marine invertebrates, such as the tunicates,
accumulate vanadium to levels that may be 10-5 to 10-6 times the
sea-water  concentrations (Table 3.).   Vanadium levels in  such
species  may exceed 3000  mg/kg dry weight  (Biggs &  Swinehart,
1976; Carlson, 1977).  It was stated that the uptake of vanadium
by the mussel (Mytilus edulis) from food (plankton) was  of  the
same  magnitude as that  from water (Unsal,  1978).  It  appears
that benthic aquatic organisms tolerate higher concentrations of
vanadium than fish (section 6.1.3).

6.1.3   Fish

    There  are some data on  the acute toxicity of  vanadium for
fish  (Van Zinderen Bakker &  Jaworski, 1980).  The 4-  to 6-day
LC50s for fresh-water species are in the range 0.5 -10 mg/litre.
Factors  influencing  toxicity  include water  hardness, and the
LC50  values are  higher in  hard water.   Giles et  al.  (1979)
studied  the  influence  of  pH  on  the  toxicity  of  vanadium
pentoxide for rainbow trout fingerlings.  The 96-h  LC50  ranged
from  6.43 to  21.75 mg/litre.   There was  some  indication  of
vanadium pentoxide being most toxic at a pH of 7.  Also, Sprague
et al. (1978) tested zebrafish  (Brachydanio rerio) with vanadium
pentoxide  and found that  a pH of  7.5 provided the  most toxic
conditions.  At this pH, death occurred between 23.5 and 45 h at
a  concentration  of 22  mg/litre, whereas at  pH 8.2, the  time
decreased to 32 h and, at pH 8.8 - 9, to 37 - 39 h.

    Studying  the  chronic  effects  of  vanadium  pentoxide  on
flagfish,  Sprague et al.  (1978) and Holdway  & Sprague  (1979)
concluded  that the sublethal  threshold concentration would  be
about 0.08 mg vanadium/litre.

    The  rainbow  trout  (Salmo  gairdneri) is the  most commonly
used  fish for toxicity studies.  Sprague et al. (1978) reported
7-day LC50 values in one series of studies ranging from  2.4  to
5.6   mg/litre.  Increasing  the   exposure  time  resulted   in
progressively  lower LC50 values, the lowest being 1.99 mg/litre
for an 11-day exposure period.  Similar results were reported by
Giles  et al.   (1979) using  experimental conditions  of pH  8,
15 C,   and  hardness  90  mg  CaCO3/litre.   The  LC50  values
decreased from 4.34 mg CaCO3/litre for 5 days exposure  to  1.95
mg CaCO3/litre for 14 days.  Neither of these groups was able to
define  a minimum lethal  level for rainbow  trout.  Studies  by
Stendahl  & Sprague (1982)   indicated that small  rainbow trout
were  more resistant than larger fish to vanadium pentoxide.  In
general, rainbow trout eggs were 10 - 15 times more resistant to
pentavalent    vanadium   than   fingerlings,   suggesting   the
possibility  of a protective function  by the chorion (Giles  et
al.,  1979).  It should be  noted that the available  studies on
vanadium  toxicity  have  been performed  on fresh-water species
only.  The effects of salinity remain to be studied.

6.2  Terrestrial Organisms

6.2.1   Uptake of vanadium by plants

    In general, the highest concentrations of vanadium in plants
growing in natural soils occur in the roots and decrease towards
the aerial portions of the plant.  The concentration of vanadium
in  soil  is, by  and large, 10  times the concentration  in the
plant  (Cannon, 1963).  Absorption appears to be passive (Welch,
    When grown in culture solution, several plant species absorb
vanadium,  which is also  translocated to the  aerial parts  and
seeds (Hopkins et al., 1977).

6.2.2   Effects on plants

    Vanadium  has  not been  demonstrated  to be  essential  for
higher land plants (Hopkins et al., 1977).  However,  traces  of
vanadate  (0.02  mmol vanadium  as VO2+ or  VO3-) were shown  to
promote  chloroplast development and oxygen production in higher
plants.  Vanadium also had a function as a redox catalyst in the
electron  flow from photosystem  II to photosystem  I (Meisch  &
Becker, 1981).

    Small  amounts of aqueous vanadium  (10 - 20 mg/litre)  have
detrimental effects on most plants (Cannon, 1963).   The  growth
of  flax, peas, soybeans,  and cabbage was  reduced in  nutrient
solutions  containing 0.5 mg  vanadium/litre (given as  VOCl2 or
VCl3)   (Warington,  1955; Hara  et  al., 1976).   Vanadium  can
induce  iron deficiency chlorosis  (Cannon, 1963) or  affect the

trace  element  nutrition  by  reducing  the  levels  of,  e.g.,
manganese,  copper,  calcium,  and phosphorus  (Warington, 1955;
Wallace et al., 1977).  Similarly, 5 mg vanadium/litre (as VO3-)
in  irrigation water reduced the  growth of sugar beets  by 30 -
50% and caused iron deficiency chlorosis (Hewitt, 1953).

    In  soils, the toxicity of vanadium may range between 10 and
1258 mg/kg, depending on plant species and type of soil (Hopkins
et  al.,  1977).   Ten mg/kg  added  to  sandy soil  as Ca(VO3)2
decreased  the growth  of sour  orange, whereas  150  mg/kg  was
lethal (Vanselow, 1950).

    Fertilizers may have a high vanadium content.  For instance,
rock  phosphate,  super phosphate,  and  basic slag  may contain
several  thousand mg vanadium/kg.  These  may cause unacceptable
levels  of  accumulation of  vanadium  in soil  (Mitchell, 1964;
Hopkins  et al., 1977).   Urban sewage sludges  usually  contain
less  than 35 mg/kg of vanadium (Bradford et al., 1975; Oliver &
Cosgrove, 1975).  On the other hand, vanadium in  sewage  sludge
may  be up to 6  times more easily available  in sludge than  in
soil (Bernow & Webber, 1972 ).


7.1  General Toxicity

    The  toxicity  of  vanadium for  experimental animals varies
with  the species and route of administration.  Smaller animals,
including the rat and mouse, tolerate the metal well; the rabbit
and  horse  are  more  sensitive  (Hudson,  1964).   In general,
toxicity  is low  when the  metal is  given by  the oral  route,
moderate  by  the  respiratory  route,  and  high  by injection.
Lethal  doses for various vanadium  salts injected intravenously
in rabbits and subcutaneously in guinea-pigs, rats, and mice are
shown in Table 21.

Table 21.  Lethal doses of vanadium (mg V2O5/kg body weight) in
experimental animalsa

Compound                 Rabbitb    Guinea-pig      Rat          Mouse

colloidal vanadium        1 - 2      20 - 28         -         87.5 - 117.5

ammonium metavanadate   1.5 - 2       1 - 2       20 - 30        25 - 30

sodium orthovanadate      2 - 3       1 - 2       50 - 60        50 - 100

sodium pyrovanadate       3 - 4       1 - 2       40 - 50        50 - 100

sodium tetravanadate      6 - 8      18 - 20      30 - 40        25 - 50

sodium hexavanadate      30 - 40     40 - 50      40 - 50       100 - 150

vanadyl sulfate          18 - 20     34 - 45      58 - 190      125 - 150

sodium vanadate             -        30 - 40      10 - 20       100 - 150

a   From: Hudson (1964).
b   Rabbits were injected intravenously; other animals subcutaneously.

    The toxicity of vanadium also varies considerably  with  the
nature  of the compound, vanadium  being toxic both as  a cation
and  as an  anion.  As  a general  rule, toxicity  increases  as
valency increases, vanadium5+ being the most toxic.   Among  the
oxides  of vanadium, vanadium pentoxide is more soluble and more
toxic than the trioxide or dioxide.

    Roshchin  (1967b,  1968)  described  the  results  of  acute
inhalation  studies on albino rats exposed to vanadium pentoxide
in the form of a condensation aerosol (fume)  at 10 -  70  mg/m3
or in the form of a dispersion aerosol (dust) at 80 - 700 mg/m3,
ammonium  vanadate  (presumably  as  a  dispersion  aerosol)  at
1000 mg/m3, and ferrovanadium, as a dispersion aerosol at 1000 -
10 000 mg/m3.   The minimum concentration of  vanadium pentoxide

(condensation  aerosol)  that gave rise  to mild signs of  acute
poisoning  was 10 mg/m3 air.  The  absolute lethal concentration
for  the condensation aerosol was 70 mg/m3.  Dispersion aerosols
(containing  large particles) were  only one-fifth as  toxic  as
condensation  aerosols.   Inhalation  of dispersion  aerosols of
ferrovanadium  did not produce any acute toxic effects, probably
because  the  particles were  too  large.  However,  acute toxic
effects  were  observed following  intratracheal instillation of
ferrovanadium.   These may have  been related to  the biological
solubility and the extent of absorption.

    The  effects of vanadium  on experimental animals  have been
investigated  in a number  of studies using  various  compounds,
species, and test protocols. Some representative acute and long-
term  studies are summarized  in Tables 22  and 23.   Subsequent
discussions  on the effects  of vanadium on  specific biological
systems are frequently based on the results of these studies.

7.2  Effects on Metabolic Processes

    Rabbits exposed to a dispersion aerosol of vanadium trioxide
(40  -  75  mg/m3, 2 h/day  for  up  to 12  months)  exhibited a
progressive weight loss amounting to an average of 4.6%  at  the
termination of the study.  Control animals gained weight  by  an
average of 12.3%.  The number of white blood cells  declined  by
the end of the test from between 7000 and 8000 down to 5000/mm3;
no change was noted in controls.  Haemoglobin levels in the test
animals  decreased from 75 to  68% of normal levelsa.     Serum-
ascorbate levels in the blood progressively decreased  to  about
20%  of controls  between 7  and 8  months.  Protein  sulfhydryl
levels in the serum of exposed animals decreased by 30% compared
with  those of the controls.  Respiration in the liver and brain
tissues  of test animals was  reduced by one-half by  the end of
the study compared with controls, but the  respiratory  quotient
was  unchanged.  Blood-cholinesterase levels in  exposed rabbits
increased by an average of 25% after the fifth  month  (Roshchin
et al., 1964; Roshchin, 1968).
    In   these  studies,  the  weight  loss  together  with  the
depression  in levels of  white cells, haemoglobin,  and protein
sulfhydryl  groups in the blood  and the decreased liver  tissue
respiration  were  taken as  indicators  of the  "general  toxic
effect" of vanadium.  Increased cholinesterase activity was held
to be indicative of sensitization.

a   Normal haemoglobin level in the rabbit is 80 -  150  g/litre
    and normal rabbit haematocrit, 30 - 50%.

Table 22.  Acute studies on experimental animals
Compound             Species      Route of         Dose       Concentration            Reference
                                  administration   index      or dose
vanadium pentoxide   mouse        intragastric     LD50       23.4 mg/kg body weight   Roshchin (1967a)
                     rat          inhalation       LC50       70 mg/m3                 Roshchin (1967a)
                     rat          inhalation       minimum    10 mg/m3                 Roshchin (1967a)
                     rat          inhalation       LC50       70 mg/m3                 Sjberg (1950)
                     cat          inhalation       LC50       500 mg/m3                Faulkner Hudson 
                     rabbit       inhalation       LC100      205 mg/m3                Sjberg (1950)
                     rat          intragastric     LD100      10 mg/kg body weight     Lewis (1959b)

ammonium vanadate    mouse        intragastric     LD50       10 mg/kg body weight     Roshchin (1968)
                     rat          intragastric     effective  20 mg/kg body weight     Kaku et al. (1971)
                     rat          subcutaneous     effective  5-30 mg/kg body weight   Kaku et al. (1971)

vanadium             mouse        intragastric     LD50       24 mg/kg body weight     Roshchin (1968)

vanadium di-iodide   mouse        intragastric     LD50       68 mg/kg body weight     Roshchin (1968)

vanadium dibromide   mouse        intragastric     LD50       88 mg/kg body weight     Roshchin (1968)

vanadium trioxide    mouse        intragastric     LD50       130 mg/kg body weight    Reznik (1954)

ammonium             rat          intragastric     LD50       10 mg/kg body weight     Gulko (1956)

vanadyl sulfate      rat          intragastric     LD100      10 mg/kg body weight     Lewis (1959b)
                     rabbit       subcutaneous     LC50       59.1 mg/kg body weight   Korkhov (1965)
                     rabbit       subcutaneous     maximum    25 mg/kg body weight     Korkhov (1965)
                     guinea-pig   subcutaneous     LD100      800 mg/kg body weight    Kopylova (1971)
                     guinea-pig   subcutaneous     LD50       560 mg/kg body weight    Kopylova (1971)
                     guinea-pig   subcutaneous     maximum    300 mg/kg body weight    Kopylova (1971)

water-soluble        mouse        intragastric     LD50       5 mg/kg body weight      Seljankina (1961)
vanadium compounds   mouse        intragastric     no effect  0.005 mg/kg body weight  Seljankina (1961)
                                                              (or 0.1 mg/litre
                                                              in water)

Table 23.  Long-term studies on experimental animals
Compound            Species   Route of         Concentration    Duration of      Reference
                              administration                    exposure

vanadium pentoxide  rabbit    inhalation       20 - 40 mg/m3    several months   Sjberg (1950)
                    rabbit    inhalation       25 mg/m3         10 months        Gulko (1956)
                    guinea-   inhalation       25 mg/m3         10 months        Gulko (1956)
                    rabbit    inhalation       8 - 18 mg/m3     9 - 12 months    Roshchin (1968)
                    rat       oral             5 - 30 mg/kg     6 months         Roshchin (1968)
                    rat       inhalation       10 - 30 mg/m3    several months   Roshchin (1967b)
                    rat       inhalation       3 - 5 mg/m3      several months   Roshchin (1967b)
                    rat       inhalation       0.027 mg/m3      70 days          Pazhynich (1966)
                    rat       inhalation       0.002 mg/m3      70 days          Pazhynich (1966)
                    rat       inhalation       0.006 mg/m3      40 days          Pazhynich (1966)

ammonium            rat       subcutaneous     1 mg/kg          30 days          Kaku et al. (1971)

sodium              guinea-   subcutaneous     3.2 - 128 ug/kg  days             Kulieva (1974)
metavanadate        pig
                    guinea-   subcutaneous     5.12 mg/kg       days             Kulieva (1974)

vanadium trioxide   rabbit    inhalation       40 - 75 mg/m3    9 - 12 months    Roshchin (1968)
                    rat       oral             5 - 30 mg/kg     6 months         Roshchin (1968)

vanadium            rabbit    oral             5 mg/kg          2 - 3 months     Roshchin (1968)

vanadium carbide    rabbit    inhalation       40 - 80 mg/m3    9 - 12 months    Roshchin (1968)
                    rat       oral             5 - 30 mg/kg     6 months         Roshchin (1968)
                    rat       intratracheal    25 mg per rat    9 - 12 months    Roshchin (1968)

ferrovanadium       rat       intratracheal    25 mg per rat    9 - 12 months    Roshchin (1968)

metallic vanadium   rat       intratracheal    25 mg per rat    9 - 12 months    Roshchin (1968)
    Chronic  poisoning,  following  the inhalation  of trivalent
vanadium  (V203)  or the  oral  administration of  vanadium tri-
chloride  (VCl3), resulted in  blood changes by  the end of  the
second   and  third  months  (Table  24).   These  changes  were
characterized  by  decreased  albumin  and  increased  globulins
(mainly y-globulins)   with  a  halving of  the albumin-globulin
ratio, and by an increase in serum concentrations of  the  amino
acids  cystine, arginine, and histidine.   There was also a  10%
increase   in  nucleic   acid  levels   in  the   blood  and   a
"considerable"  increase  in  the blood-chloride  concentration.
The  effects  of  vanadium on  the  metabolism  of proteins  and
nucleic   acids  were  considered  to  be  responsible  for  the
immunological  and allergic reactions that may occur in vanadium
poisoning (Roshchin, 1967a).
    Metabolic  changes  were observed  in  a study  by Pazhynich
(1966)  in which albino rats  were exposed by inhalation  for 70
days to condensation aerosols of vanadium pentoxide at levels of
0.027  0.002  mg/m3  and 0.002  0.00013  mg/m3.  Statistically
significant  changes  were  observed  at  the  higher  level  of
exposure, but not at the lower level.  The observations included
decreases  in:  whole blood-cholinesterase  levels, total serum-
protein  levels,  serum-globulin levels,  and the oxyhaemoglobin
content   of  venous  blood.   Elevated  serum-globulin  levels,
increased  numbers of blood  leukocytes showing yellow,  orange,
and red nuclear fluorescence with acridine orange, and increased
oxygen  consumption as indicated by  isolated liver preparations
were  also  observed  in  the  high-level  exposure  group.  The
pattern  of leukocyte nuclear fluorescence returned to normal 20
days  after cessation of  exposure.  In a  second study,  albino
rats  were continuously exposed to vanadium pentoxide at 0.006 
0.00056 mg/m3  for  40  days.   No  changes  in  blood-leukocyte
nuclear  fluorescence were observed.   During the sixth  week of
exposure, animals received water but no food.  After 3.5 days of
this  treatment,  the  number of  leukocytes  displaying altered
nuclear fluorescence increased by a factor of 4.83.
    In  an  in vitro  study,  ammonium  metavanadate was  found to
inhibit  microsomal  ketamine  N -demethylation,  lipid  peroxida-
tion,  and  hydrogen  peroxide  formation  in  rat  liver.   The
inhibiting doses of NH4VO3 ranged from 10-5 to  10-3  mol/litre.
Cytochrome c  reductase  was also  inhibited, whereas cytochrome
oxidase activity was stimulated (Beyhl, 1983).
    Parenteral injection of guinea-pigs with sodium metavanadate
in  daily doses of  3.2 g/kg,  128 g/kg,  or  5.12 mg/kg  body
weight  resulted in dose-dependent increased  succinate dehydro-
genase  activity in the liver and kidneys and cytochrome oxidase
activity in the liver (Kulieva, 1974).

Table 24.  Respiratory effects of vanadium pentoxide on experimental animalsa
Reference         Species   Form     Concentration   Exposure         Pathological findings                 
Sjberg (1950)    rabbit    dust     205             7 h              conjunctivitis, tracheitis,        
                                                                      pulmonary oedema, broncho-         
                                                                      pneumonia, enteritis, fatty        
                                                                      liver, death                       

Sjberg (1950)    rabbit    dust     20 - 40         1 h/day          chronic rhinitis, trache-          
                                                     several months   itis, emphysema, atelect-          
                                                                      asis, bronchopneumonia,            
Gulko (1956)      rabbit    dust     10 - 30         continuous,      bronchitis, pneumonia,             
                                                     acute            weight loss, bloody diarr-         
Roshchin (1963)   rat       dust,    80 - 700        continuous,      haemorrhagic inflammation in       
                            fume     10 - 70         acute            lungs, haemorrhage in inter-       
                                                                      nal organs, paralysis, res-        
                                                                      piratory failure, death            
Roshchin (1963)   rat       dust,    10 - 30         2 h/day,         haemorrhagic inflammation in          
                            fume     3 - 5           several months   lungs purulent bronchitis,         
Pazhynich (1966)  rat       fume     0.027           continuous       haemorrhagic inflammation in       
                                                     70 days          lungs, vascular congestion,        
                                                                      haemorrhage in liver, kid-         
                                                                      neys, and heart                    
a   From: Waters (1977).

    In  acute studies on  rats (Donryu strain)  weighing 200  g,
Kaku  et al. (1971) administered vanadium (as ammonium vanadate)
by  gavage at  a dose  of 20 mg/kg  body weight  or injected  it
subcutaneously  (doses of between  5 and 30 mg/kg  body weight).
There  were dose-dependent reversible  increases in the  trigly-
ceride concentrations in the liver and blood-serum,  a  decrease
in  the  serum-cholesterol  level, and  increases  in glutamate-
oxalo-acetate  transaminase and glutamate-pyruvate  transaminase
activity.   After subcutaneous injection,  there was a  fall  in
cholesterol levels.  The lowest values were reached  24 h  after
the  injection; values then returned  to normal.  Dose-dependent
increases were also observed in the concentrations  of  triglyc-
erides  in the liver  and serum.  Levels  peaked 48 h after  the
injection  and then gradually  declined.  When ammonium  vandate
solution   equivalent  to  1  mg  vanadium/kg  body  weight  was
administered  daily by subcutaneous  injection for 30  days more
marked changes in serum cholestrol were observed.

    Korkhov  (1965)  injected  0.3 mg  vanadyl  sulfate/kg  body
weight  subcutaneously  in  rabbits  with  experimental  athero-
sclerosis  and observed a lowering  of the hypercholesterolaemia
and inhibition of the rise in lecithin.  Combined administration
of vanadyl sulfate and phenylethylacetic acid lowered the aortic
cholesterol  level  3.5  times compared  with controls.  Korkhov
(1965) also showed that cholesterol biosynthesis in liver tissue
culture was inhibited by the addition of 10-4 vanadyl sulfate.

    When  30  rabbits  with  experimental  atherosclerosis  were
administered  a  mixture  of  trace  elements  (copper,  cobalt,
manganese,  and zinc) in combination with cholesterol, Babenko &
Vandzhura  (1969)  detected increases  in  the blood  lipids and
decreases  in  vanadium  concentrations, compared  with  healthy
control animals.  The same results were noted following combined
administration   of  copper  and  cobalt   plus  cholesterol  at
0.2 g/kg.   After administration of  manganese, the decrease  in
the  vanadium concentration was delayed; after administration of
zinc, vanadium remained at the same level as in healthy animals.
Vanadium concentrations in body tissues decreased as cholesterol
levels  increased, but manganese  and zinc, when  given together
with cholesterol, helped maintain vanadium concentrations in the
tissues of the body, the highest vanadium  concentrations  being
found in the liver, aorta, and muscles.

    In  the  studies  by Novakova  et  al.  (1981),  daily  oral
administration to rabbits for 4 months of vanadium pentoxide and
cholesterol  (1st group: vanadium  at 0.5 mg/kg body  weight and
cholesterol  at 0.3 mg/kg body  weight; 2nd group:  vanadium  at
1.5 mg/kg  body weight and cholesterol at 0.5 mg/kg body weight)
resulted  in  high  levels  of  cholesterol  in  the  blood  and
extensive  atherosclerosis  of  the  aorta.    In  the   animals
administered  either  cholesterol  (0.5 mg/kg body  weight)   or
vanadium (0.5 mg/kg body weight), hypercholesterolaemia was also
observed,  but the increase  was less pronounced.   Increases in
levels  of  lipids,  lipoproteins, and  triglycerides  were also
observed.  After one month of administration, cholesterol levels
in  treated  animals  were more  than  ten  times those  in  the

controls.   At the end of  the study (after the  4th month), the
cholesterol  levels  in  the treated  animals  were considerably
higher than those in the controls.

    The  effects of vanadium  on iron metabolism  have not  been
fully  elucidated.   In some  studies,  a stimulative  effect on
haemoglobin  and  erythrocyte  levels  has  been  claimed.   The
results  of  studies  by Myers  &  Beard  (1931) suggested  that
vanadium  chloride given at  0.6 mg/kg diet to  rats, previously
rendered  anaemic, had a  favourable effect on  the  haemoglobin
level, and Kopylova (1971) obtained increases in the erythrocyte
count and haemoglobin level in rabbits by  subcutaneous  admini-
stration of vanadyl sulfate (1 mg/kg body weight, daily,  for  2
months).   Trummert & Boehm (1957)  observed an increase in  the
erythrocyte  count  following intravenous  injection of vanadium
gluconate (0.3 - 1.5 mg/kg body weight, daily, for 40 days), but
the haemoglobin level was not significantly affected.

7.2.1   Mechanisms of action

    Many of the metabolic effects observed can be  explained  by
the  biochemical  effects  of vanadium  exposure in  vivo and in
    Roschin  (1967a) presented the hypothesis that the mechanism
of the initial step in the non-specific haematopoietic effect of
vanadium  and the subsequent anaemia  was the inhibition of  the
redox system of hydrogen carriers.  In response to the resulting
hypoxia,  there is increased haematopoiesis.   Possibly vanadium
interferes  with tissue respiration at the stage of dehydrogena-
tion  effected by nicotinamide  adenine dinucleotide (NAD).   By
inhibiting   this   coenzyme,   vanadium  interferes   with  the
incorporation of iron in the porphyrin complexes and haemoglobin
synthesis.   The  anti-vitamin  C  effect  of  vanadium  and the
consequent vitamin C deficiency also inhibits the utilization of
iron  for  haemoglobin  synthesis.   Iron  accumulates  in   the
reticuloendothelial tissue.
    It  is known  that vanadium  also inhibits  the activity  of
monoamine  oxidase, which catalyses the conversion of  serotonin
to  5-hydroxyindoleacetic acid.  In a study on  rabbits  exposed
to  vanadium  pentoxide dust  for 3 months,  urine levels of  5-
hydroxyindoleacetic  acid  fell  to  33%  below  control  values
(Roschin,  1967a).   It  was  suggested  by  the   author   that
inhibition  of monoamine oxidase might result in accumulation of
serotonin in the central nervous system, leading  to  functional
disturbances,  such  as  bronchospasm,  diarrhoea,  and  urinary
incontinence.    Elevated   serotonin   levels  could   also  be
responsible  for  the dystrophic  and  necrotic process  in  the
kidneys  and the  high permeability  of the  blood  vessels.   A
decrease  in sulfhydryl groups in blood-proteins and a reduction
in the cystine content of keratinized tissues might be due to an
interaction between vanadium and an unspecified enzyme.
    The  catabolism  of cystine  and  cysteine was  increased by
exposure  to vanadium (Bergel et al., 1958).  In vitro, pyridoxal

5-phosphate  induced the catabolism of sulfhydryl amino acids in
the  presence  of  VO2+ (Anbar  &  Inbar,  1962).   The  authors
suggested  that the activation of pyridoxal phosphate by vanadyl
ions  was  specific  to  elimination  and  strongly  suggested a
decrease  in -SH groups in the organism.  A reduction in cystine
levels  was observed in  keratinized tissues (hair  of rats  fed
vanadium  compounds  and  the fingernails  of  vanadium workers)
by  Mountain et al.  (1953, 1955).  It  was suggested that  this
effect  was the result  of decreased synthesis  of cysteine  and
cystine  and  that metabolic  processes  depending on  either of
these amino acids may be depressed in the presence of vanadium.

    According  to Mahler  & Cordes  (1966), coenzyme  A plays  a
central  role in many  biosynthetic and oxidative  pathways.  In
the   biosynthesis  of  coenzyme  A,  cysteine  reacts  with  4-
phosphopantothenic  acid in the  presence of adenosine  triphos-
phate  (ATP)  to  form  the  intermediate  4'-phosphopantothenyl
cystine,  and Mascitelli-Coriandoli & Citterio  (1959a,b) showed
that treatment with sodium metavanadate reduced the  content  of
coenzyme A in rat liver.

    As coenzyme A is involved in biochemical  pathways  starting
with  acetate, these processes can also be affected by vanadium;
Curran (1954) showed that the synthesis of cholesterol from 14C-
acetate  in rat liver was  reduced in the presence  of vanadium.
Later studies indicated that one site of the  inhibitory  action
of  vanadium in the synthesis of cholesterol was at the level of
the  enzyme squalene synthetase, which  catalyses the conversion
of  farnesyl pyrophosphate to squalene (Azarnoff & Curran, 1957;
Azarnoff et al., 1961).  In a study by Curran & Costello (1956),
aortic  cholesterol  was  mobilized more  rapidly  in  vanadium-
treated  atherosclerotic rabbits than in  controls.  Cholesterol
levels  appear  to  be reduced  by  vanadium  in young  animals,
including  human  beings, but  not in older  ones.  It has  been
suggested, but not demonstrated, that a regulatory enzyme in the
synthesis  of cholesterol (acetoacetyl coenzyme  A deacylase) is
activated by vanadium in the former but inhibited in the latter.

    Vanadium  might  reduce  the synthesis  of triglycerides and
phospholipids, since acetyl coenzyme A is a precursor  of  fatty
acids.  However, the results of studies by Curran and colleagues
showed  that, while the levels of triglycerides decreased in the
livers   of   rats   given  vanadium   (Curran,   1954),  serum-
triglycerides  levels  in  human beings  increased following the
ingestion of vanadium (Curran et al., 1959).  Snyder & Cornatzer
(1958)  reported  that  the incorporation  of labelled phosphate
into  rat liver phospholipids  decreased following injection  of
vanadyl  sulfate.  This could have been due to the inhibition of
phospho-lipid    biosynthesis   or   to    increased   oxidative
degradation,  as  originally  suggested by  Bernheim  & Bernheim
(1938,   1939).   Using  an  isotope   method  with  radioactive
phosphorus  as  the  indicator, Prokopenko  (1961)   observed  a
disturbance  in  the  intensity of  phosphorus  exchange between
organic  acid-soluble  compounds  and  inorganic  phosphates  in
albino rats and mice with acute ammonium vanadate poisoning.  No
changes were found in the intensity of total metabolism  and  in

liver  tissue  phosphate  levels.  After  administration  for  6
months   in  doses  of  1  mg/kg  body  weight,  phosphorylation
processes  in the  organs and  tissues were  disturbed  and  the
concentration of inorganic phosphorus in the blood and urine was

    Coenzyme A is also involved in the synthesis of  coenzyme  Q
(ubiquinone)  in  the  mitochondrial electron  transport  chain.
Ubiquinone synthesis in isolated rat mitochondria was reduced by
vanadium, but this effect was partially reversed  when  cysteine
was  given  with  vanadium.  Addition  of  ATP  and  coenzyme  A
prevented  the  inhibition  of  ubiquinone  synthesis  (Aiyar  &
Sreenivasan, 1961).

    It   has   been   suggested  that   mitochondrial  oxidative
phosphorylation  in liver homogenates  in vitro  is  uncoupled by
vanadium with a resulting depletion in ATP energy stores (Wright
et  al.,  1960).   In young  chicks,  the  addition of  ammonium
metavanadate  to the diet equivalent  to 25 mg vanadium/kg  body
weight   uncoupled   oxidative  phosphorylation   in  the  liver
mitochondria  (Hathcock et al., 1966).   These authors suggested
that  vanadate might replace the phosphate ion in ATP synthesis,
and  a  high-energy vanadyl  intermediate  (vanadium X)  or ADP-
vanadium  be formed and hydrolysed.   The results of studies  by
DeMaster & Mitchell (1973) supported the theory of the mechanism
involving    the   uncoupling   of    glyceraldehyde-3-phosphate
dehydrogenase  by  vanadium.   It  was  also  shown   that   the
vanadium5+  oxyanion  inhibited  oxidative  phosphorylation   in
intact rat liver mitochondria, but did not act as an uncoupler.

    Vanadium  salts  inhibit  the activity  of succinic dehydro-
genase, a key enzyme in the citric acid cycle and  the  electron
transport  system that is  activated by sulfhydryl  groups,  and
this  would  also reduce  ATP  synthesis (Aiyar  &  Sreenivasan,
1961).    The  inhibiting  effects   of  vanadium  on   succinic
dehydrogenase  could  involve  a  reduction  in  available   -SH

    The  oxidation  of  tryptamine  by  monoamine  oxidase  from
guinea-pig  liver and  kidney was  accelerated by  125%  in  the
presence  of vanadium (Perry et  al., 1955, 1969); however,  the
results of studies by Lewis (1959c) on dogs injected with sodium
metavanadate   indicated   that  vanadium   inhibited  monoamine
oxidase,  because  the  urinary output  of 5-hydroxyindoleacetic
acid was reduced.  The decreased output of 5-hydroxyindoleacetic
acid,  suggests  the  possibility of  accumulation of serotonin,
which was also reported by Roshchin (1967a).

    When  rats  were  administered daily  injections  of  sodium
metavanadate  (1.25 - 2.5  mg/kg body weight),  weight loss  was
correlated  with accumulation of the metal in the liver (Johnson
et  al., 1974).  The activities of the hepatic enzymes, xanthine
oxidase and sulfite oxidase, which have molybdenum  groups,  and
total  liver concentrations of  molybdenum were not  affected by
vanadium.  It was concluded that vanadium toxicity in  rats  was
not  related  to  molybdenum utilization.   Though  vanadium was

administered  in the pentavalent  state, the rat  livers had  an
electron paramagnetic resonance (EPR) spectrum characteristic of
vanadium4+.   It was suggested  that vanadium is  in a  protein-
bound  form in the livers of rats.  Vanadium4+ was also found in
the  kidneys and,  to a  limited extent,  in the  lungs of  rats
injected with sodium metavanadate, but not in the hearts; it was
considered  that the ability of  liver and kidney to  reduce the
vanadate  by  one  electron  might  be  related  to  a  specific
detoxification  mechanism present in  these organs.  Johnson  et
al.  (1974)  and Minden  & Rothe (1966)  studied the effects  of
pentavalent  vanadium  salts on  various  enzyme systems  in rat
liver   homogenates,  rabbit  blood-serum,  and  suspensions  of
erythrocytes  and concluded that  there was nothing  to  suggest
that  vanadium salts reacted  directly with coenzymes  (NAD  and
NADP, pyroxidal sulfate) or -SH groups.

    The  results of  in vitro studies, conducted by Tolman et al.
(1979), indicated that vanadium stimulated glucose oxidation and
transport  in adipocytes and glycogen synthesis in the liver and
diaphragm,  and inhibited hepatic gluconeogenesis and intestinal
glucose  transport.  There is no evidence  in vivo showing a role
of vanadium in the regulation of glucose metabolism.

    The  intimate mechanism of interaction  between vanadium and
enzymes  is not yet known.  Experimentally observed disturbances
of  the cardiovascular system,  changes in the  concentration of
-SH  groups  and  cystine,  disturbances  in  the  metabolism of
sulfur-containing,   glycogen-forming,  and  keto-forming  amino
acids, and of the functioning of the liver and kidneys,  of  RNA
and  DNA synthesis, and of cholesterol metabolism, indicate that
vanadium  possesses a broad spectrum  of action in the  body and
that  its  toxic action  is not analogous  to that of  any other
metal (Roshchin, 1968).

7.3  Effects on the Nervous System

    The  Na+K+-ATPase  in rat  brain  is inhibited  by  vanadium
pentoxide,  though not as strongly  as that in kidney  and heart
(Nechay  & Saunders, 1978).  Svoboda  et al. (1984) showed  that
the  brain microsomal N+K+-ATPase in rat is equally inhibited by
vanadate (VO3-) or the vanadyl ion (VO+2).

    In  a short-term exposure study, rats received single intra-
peritoneal injections of sodium metavanadate equal to 20% of the
LD50 (1 mg vanadium/kg body weight).  The level of noradrenaline
decreased   and  those  of  dopamine   and  5-hydroxy-tryptamine
increased.   A long-term study involved  the oral administration
of  sodium  metavanadate  (3 mg vanadium/kg  body  weight).  The
findings were similar to, but more pronounced than, those in the
short-term study (Witkowska & Brzezinski, 1979).

    When adult male CD1 mice were treated with vanadate  in  the
drinking-water for 30 days, there was a dose-related decrease in
norepinephrine levels in the hypothalamus.  Dopamine levels also
decreased significantly, but 5-hydroxytryptamine levels were not
affected.   Levels  of  dopamine  in  the  corpus  striatum were

unchanged  and there were only marginal effects on the amines in
the  other brain regions.  It  is suggested that vanadium  has a
selective effect on adrenergic pathways (Sharma et al., 1986).

    Several  inhibitors of Na+K+-ATPase,  such as ouabain,  have
been  reported  to  block DNA  and  protein  synthesis  in  cell
cultures (Kaplan, 1978).  It has also been shown  that  vanadate
inhibits  protein synthesis in  neuroblastoma cells and  in  the
brain homogenates of rats fed sodium monovanadate (125 mg/litre)
 ad libitum for 30 or 60 days (Montero et al., 1981).

    Neurophysiological  effects  have  been  reported  following
acute  exposure (oral and sc  injection) of dogs and  rabbits to
vanadium  oxides and salts (V2O3, V2O5, VCl3, NH4VO3) (Roshchin,
1967a).   These  include  disturbances of  the  central  nervous
system   (impaired   conditioned   reflexes  and   neuromuscular

    In  studies  by  Seljankina (1961),  solutions  of  vanadium
pentoxide  or ammonium vanadate were administered orally to rats
or mice in doses of 0.005 - 1 mg vanadium/kg body weight per day
for  periods ranging  from 21  days at  the higher  levels to  6
months  at the lower levels.  A dose of 0.05 mg vanadium/kg body
weight  was  found  to be  the  threshold  dose  for  functional
disturbances  in conditioned reflex  activity in both  mice  and
rats; a dose of 0.005 mg vanadium/kg body weight did not produce
any adverse effects.

    In a study by Pazhynich (1966), albino rats  underwent  con-
tinuous inhalation exposure to condensation aerosols of vanadium
pentoxide  at levels of 0.002 mg/m3 and 0.027 mg/m3.  Animals in
both  treated  and control  groups  showed normal  weight  gain.
After 30 days, the motor chronaxy of the extensor muscles of the
tibia in the group exposed to 0.027 mg/m3 decreased by an average
of  0.8 s  ( P <  0.01), and  the chronaxy of the  corresponding
flexor  muscles increased by an  average of 4 s  ( P <   0.001).
Thus, the chronaxy ratio of antagonistic muscles fell  from  1.5
at  the  beginning  of the studies to 1.0 on day 20 ( P <  0.02),
and  0.5 on day 30  ( P <  0.01). The decrease  continued until a
level  of about 0.25 was reached.  About 18 days after cessation
of  exposure  on the  70th day, the  chronaxy ratio returned  to
normal  (1.5).  Changes in motor  chronaxy were not observed  in
rats exposed at 0.002 mg/m3 or in the controls.

    In  a second study, albino rats were exposed continuously to
vanadium  pentoxide  at  0.006  0.00056 mg/m3 for  40 days.  No
changes were observed in the chronaxy of antagonistic muscles of
the tibia in exposed animals, compared with the controls, during
the  first month of exposure.  However, after 30 days, there was
a  statistically significant decrease  in chronaxy ratio.   When
animals were given only water and no food for 3.5  days,  during
the sixth week of exposure, chronaxy ratios decreased  to  0.92,
compared with 1.5 in the controls.

7.4  Effects on the Respiratory System

    Studies  on respiratory exposure  to vanadium pentoxide  are
summarized in Table 23 (section 7.1).
    Sjberg  (1950) exposed rabbits  to vanadium pentoxide  dust
particles,  nearly all  of which  were smaller  than  10 m   in
diameter  at concentrations of  77, 109, 205,  or 525 mg/m3  for
periods  of 7 h, 4 h, 7 h, or 1 h, respectively.  Death occurred
only  in the 205 mg  V205/m3 (7 h)  group (equivalent to  115 mg
vanadium/m3).    There  was  marked  tracheitis  accompanied  by
pulmonary    oedema   and   bronchopneumonia.    Conjunctivitis,
enteritis,  and  fatty  infiltration  of  the  liver  were  also
    In  further studies by the same author, rabbits were exposed
to  20 - 40 mg  V205/m3  (equivalent to  11 - 22 mg vanadium/m3)
intermittently for 1 h each day for several months.  At autopsy,
pathological  changes  observed  included chronic  rhinitis  and
tracheitis,  emphysema,  patches  of lung  atelectasis, broncho-
pneumonia  and,  in  some cases,  pyelonephritis.   Vanadium was
detected  in  ashed  lung, liver,  and  kidney,  but not  in the
intestines.  Changes of a fibrotic nature and  specific  chronic
lesions were not observed in the lungs, and there was no visible
accumulation of particles.  These findings, plus the  fact  that
vanadium  was present in the  liver and kidney, were  considered
evidence of rapid clearance and/or absorption from the lung.
    Continuous  inhalation exposure  of rabbits  to 10  - 30  mg
V205/m3   (5.6  -  16.8   mg  vanadium/m3)  caused   bronchitis,
pneumonia, loss of weight, and bloody diarrhoea (Gulko, 1956).
    In  studies by Roshchin  (1967b, 1968) described  in section
7.2,  acute inhalation toxicity in albino rats was characterized
by irritation of the respiratory mucosa and nasal discharge that
sometimes contained blood.  Animals breathed with difficulty and
there   were  crepitations.   The  animals   behaved  passively,
refusing to eat, and lost weight.  In cases of severe poisoning,
diarrhoea,  paralysis of the hind limbs, and respiratory failure
were  followed  by  death.  Pulmonary  abscesses were frequently
seen  in animals  that recovered.   Animals that  died  or  were
killed   at   various   times  after   exposure,  showed  severe
congestion,   particularly   in   the  capillaries,   and  small
haemorrhages  were observed in  all internal organs.   Signs  of
increased  intracranial pressure, and fatty  degeneration of the
liver  and kidneys  were also  seen.  In  the lungs,  there  was
capillary    congestion   together   with   tiny   haemorrhages,
perivascular   and   focal   oedema,   bronchitis,   and   focal
interstitial  pneumonia.   The  bronchitis and  bronchopneumonia
were  often purulent, and  the small bronchi  were  constricted.
There   was  a  relationship   between  the  severity   of   the
pathological  changes and the vanadium concentration in the air.
In  cases of slight  toxicity, pathological changes  were mainly
confined to the lungs.

    Pathological changes were also seen in the lungs  when  rats
were  exposed  intermittently  to  a  condensation  aerosol   of
vanadium  pentoxide at 3 - 5 mg/m3 for 2 h, every other day, for

3  months,  or  to a dispersion aerosol of V205 at 10 - 30 mg/m3
for 4 months.  Blood vessels were engorged and  the  endothelium
was   swollen;   capillary   congestion,  perivascular   oedema,
lymphostasis,  and small haemorrhages indicated altered vascular
permeability   and  disturbances  in  the   circulation  of  the
pulmonary  blood and lymph.   Occasionally, foci of  oedema  and
desquamative  bronchitis  were  observed and  small bronchi were
often  constricted.  Lymphocytes and histiocytes had infiltrated
interstitial   tissue.   Connective  tissue   proliferation  was
sometimes   seen  in  the  zone   of  lymphocytic  infiltration.
Purulent bronchitis or pneumonia occurred in some  animals,  and
occasionally lung abscesses developed.

    Roshchin  (1967a)  observed  similar effects  with  vanadium
trioxide  and vanadium trichloride.  As vanadium trichloride was
more soluble, more marked histopathological effects were seen in
internal  organs.   Pentavalent compounds of vanadium were 3 - 5
times  more toxic (in terms of median lethal concentration) than
trivalent  compounds.  Although dispersion aerosols  of vanadium
metal,  vanadium  carbide,  and ferrovanadium  were  not  highly
toxic,  long-term  exposure  at high  concentrations resulted in
many of the signs and symptoms produced by vanadium pentoxide.

    In  studies by Pazhynich  (1966) (section 7.2),  histopatho-
logical changes observed in rats following high-level inhalation
exposure  included  marked  lung congestion,  focal lung haemor-
rhages, and extensive bronchitis.

    Effects  on the lung were observed in albino rats exposed by
inhalation  for 2 weeks  to uncoated bismuth  orthovanadate dust
(0.11  mg/litre,  1.2  mg/litre), silica-coated  bismuth  ortho-
vanadate   (0.15  mg/litre,  1.3  mg/litre),   or  silica-coated
titanium dioxide (1.19 mg/litre).  In rats sacrificed at the end
of  the  2-week exposure,  there  was a  dose-related macrophage
(dust  cell)  response to  both forms of  bismuth orthovanadate.
Three  months after exposure, the bismuth orthovanadate rats had
alveolar proteinosis, foamy macrophages with cholesterol clefts,
and hyperplastic type II pneumocytes. Six months after exposure,
these changes were more marked with cholesterol  granulomas  and
degeneration of foamy macrophages.  In rats sacrificed  after  1
year,  the pulmonary lesions were reduced, but alveolar protein-
osis  and cholesterol granulomas persisted.   Initially, similar
changes  were  observed in  rats  exposed to  the  silica-coated
titanium dioxide, but recovery was obvious at 6 months and, at 1
year,  the lungs were  almost normal with  only a few  remaining
macrophage (dust cell) aggregates (Lee & Gillies, 1986).

    The  respiratory  and  related histopathological  effects of
vanadium exposure in experimental animals were marked irritation
of   the  respiratory  mucosa;  vascular   injury  resulting  in
capillary  stasis, perivascular oedema, and  small haemorrhages;
and  an asthmatic-type bronchitis  and expiratory difficulty  on
acute exposure (Roschin, 1967b).

    In  adult male cynomolgus  monkeys exposed by  inhalation to
vanadium pentoxide dust concentrations of 0.5 mg/m3  or  5 mg/m3
at  weekly intervals, significant central and peripheral airflow
restriction  was measured one  day after each  exposure.   There
were  also  significant  increases in  respiratory  cell  counts
obtained  by bronchoalveolar lavage.   The increased cell  count
was  due  to  a marked  increase  in  the number  (absolute  and
relative    percentage)    of   polymorphonuclear    leukocytes,
indicating   pulmonary  inflammatory  changes  (Knecht  et  al.,

    In the respiratory tract of experimental animals,  the  main
differences  between the acute  and chronic effects  of vanadium
are  the  development,  after  prolonged  exposure,  of  chronic
inflammation  in the bronchi  and a greater  tendency to  septic
bronchopneumonia.   Atelectasis,  interstitial infiltration  and
proliferation, and emphysema also occur.

     Macrophages are engaged in a variety of  pulmonary  defence
mechanisms.   Theoretically, effects of vanadium  on these cells
may explain some of the observations on vanadium toxicity on the
respiratory  system.  In in vitro studies, Waters  et al. (1974)
demonstrated a 50% reduction in the viability of cultured rabbit
macrophages  after exposure to 13 mg vanadium/litre (as vanadium
pentoxide)  for  20 h.   Short-term exposure  (2 h)  to vanadium
pentoxide  at  a dose  of 7 mg  vanadium/litre also reduced  the
viability  of mouse pulmonary  alveolar macrophages to  87%.  In
another study, the phagocytic index was reduced to  71%  (Fisher
et  al., 1978).  The  incubation of bovine  alveolar macrophages
with   ammonium   metavanadate  (NH4VO3)   at   0.5  or   1   mg
vanadium/litre,  for  4 h,  reduced  viability  to  95  and 85%,
respectively.  After 8 h incubation, viability was reduced by 24
and   38%,  respectively,  and,  after  16 h,  no  viable  cells
remained.   Low levels of vanadium (0.01, 0.1 mg vanadium/litre)
stimulated  the  phagocytic  activity of  macrophages, whereas a
striking  decrease in phagocytic activity was noted with 0.5 and
1 mg/litre at 8 h, though, initially, there was  stimulation  of
activity.   Doses  of  0.01 and  0.1  mg/litre  did  not  affect
viability (Wei & Misra, 1982).
7.5  Effects on the Cardiovascular System

    Severe  exposure  of animals  to  vanadium oxides  and salts
produced  cardiovascular  changes (occurrence  of arrythmias and
extrasystole,  prolongation of the Q-RST  interval, and decrease
in  the  height  of the  P and  T waves  of the  EKG) (Roshchin,

    Intense  vasoconstriction has been  reported in the  spleen,
kidney,  and intestines following intravenous injections of sub-
lethal doses of sodium ortho- and metavanadate (Hudson, 1964).

    Intravenous injection of sodium metavanadate at 2.5 mg/kg in
dogs  provoked an increased amplitude of T-waves in the electro-
cardiogram  followed  by  depression  of  S-T  segments  (Lewis,
1959c).   Perivascular swelling, as well as fatty changes in the

myocardium, were observed by Roshchin (1968) following long-term
inhalation exposure of rats and rabbits to  vanadium  pentoxide,
trioxide, and chloride (10 - 70 mg/m3, 2 h/day, 9 - 12 months).

    Vanadium  sulfate (500 mg/kg diet, 6 weeks) mobilized excess
arterial  cholesterol  in  rabbits previously  maintained  on  a
cholesterol-rich diet (Curran & Costello, 1956).

    Feeding rats sodium orthovanadate at 100 or  200 mg/kg  body
weight (added to normal rat chow) for up to 56 weeks resulted in
a gradual increase in systolic blood pressure.  The  effect  was
unrelated  to  water  intake, urine  output,  or  urinary-sodium
excretion.   The  increased pressure  was  sustained in  a dose-
related  manner and was positively correlated with plasma levels
of vanadium that ranged from 0.04 to 0.27 mg/litre  (Steffen  et
al., 1981).  Similar increases in mean arterial  blood  pressure
have  been  reported in  both conscious (Day  et al., 1980)  and
anaesthetized rats (Hatfield & Churchill, 1981).

7.6  Effects on the Kidney

    In  earlier studies, glomerular  hyperaemia and necrosis  of
convoluted tubules were reported to be related to acute vanadium
exposure   (Hudson,   1964).    Nephrotoxicity,  manifested   as
albuminuria,  was reported after intravenous injection of sodium
metavanadate  at 2.5 - 5 mg/kg body weight in male dogs by Lewis
(1959c).  Inhalation of 10 - 70 mg vanadium chloride/m3, for 2 h
daily, for 9 - 12 months, was followed by fatty changes  in  the
kidney of the rat and rabbit (Roshchin, 1968).  In an inhalation
study  on  rats  exposed  continuously  to  vanadium   pentoxide
condensation aerosols at concentrations of 0.002 and 0.027 mg/m3
for  70 days, Pazhynich (1966) reported granular degeneration of
the  epithelial cells of the  convoluted tubules, with areas  of
necrosis. Acute tubular necrosis followed subcutaneous injection
of  NH4VO3-solutions in 0.1  mol/litre tris-HCl-NaCl buffers  in
albino mice (20 mg vanadium/kg body weight).  The mortality rate
was  higher at a pH  of 7.8 (68%) than  at pH 6.1 (20%)  (Wei et
al., 1982).

    There  are distinct species  differences with regard  to the
renal effects of vanadate (Grantham, 1980; Phillips et al. 1983;
Nechay,  1984).   Vanadate  has both  diuretic  and  natriuretic
effects  on  the rat  kidney (Balfour et  al., 1978; Day  et al.
1980; Kumar & Corder, 1980; Hatfield & Churchill, 1981; Roman et
al., 1981), but not on that of the dog (Inciarte et  al.,  1980;
Lopez  Novoa et al., 1982a,b)  or the cat (Larsen et al., 1979).
In  the  rat, the  tubular effect is  independent of changes  in
glomercular filtration rate, whereas the tubular effect  in  the
cat is either absent or masked by pronounced renal vasoconstric-
tion and anuria (Larsen et al., 1979; Larsen &  Thomsen,  1980).
Vanadate   has  also  been  reported  to  increase  the  urinary
excretion  of calcium, phosphate,  bicarbonate, and chloride  in
the rat kidney (Kumar & Corder, 1980).

7.7  Effects on the Immune System

    Exposure of mice to vanadium in drinking-water resulted in a
dose-related,  but  not  statistically-significant, decrease  in
antibody-forming  cells in the  spleens of mice  challenged with
sheep  erythrocytes;  serum  immunoglobulins were  not affected.
Splenic  lymphocytes obtained at 1, 4, 8, and 13 weeks from male
Swiss-Webster mice treated with 1, 10, or 50  mg  vanadium/litre
drinking-water  showed increased DNA  synthesis  in vitro  (Sharma
et   al.,  1981).   In   female  B6C3F1  mice   given   ammonium
metavanadate  ip at doses  of 2.5, 5,  or 10 mg/kg  body weight,
every  3 days, for 3,  6, or 9 weeks,  there was a  dose-related
increase  in resistance to  Escherichia  coli endotoxin lethality
up  to  6  weeks  and  a  dose-related  decrease  in  resistance
to Listeria lethality.   Peritoneal  macrophage  activity   also
decreased in a dose-related manner, but without any  effects  on
viability.   The rosetting capability of splenic lymphocytes was
increased.  There was enlargement of the liver and  spleen  with
enhanced formation of splenic mega-karyocytes and red blood cell
percursors.   The authors concluded that vanadium may affect the
normal functioning of the immune system (Cohen et al., 1986).

7.8  Reproduction, Embryotoxicity, and Teratogenicity

7.8.1   Reproduction and embryotoxicity

      Roshchin at al. (1980) studied the gonado- and embryotoxic
effects  of  0.85  mg metavanadate/kg  body  weight (1/20 LD50),
administered    subcutaneously   to   albino   rats.    Vanadium
administered  to pregnant  rats on  days 21  - 22  of  pregnancy
accumulated  in the placenta but  was not reported to  penetrate
the placental barrier and reach the fetus.  During the period of
lactation,  vanadium was found in  the mammary glands (0.14%  of
administered  dose/g tissue) and excreted with the milk. In new-
born  rats,  the  uptake of vanadium was in the range of 0.018 -
0.032% of the original administered dose to the  lactating  dams
per  g neonate.  Impairment of spermatogenesis was manifested as
a 10 - 33% decrease in the mobility of spermatozoa,  a  decrease
in  osmotic resistance  of 7.9 -  11.4% and  a 31%  rise in  the
number of dead spermatozoa.  There were morphological changes in
spermatozoa  and desquamation of the spermatogenic epithelium in
the  seminal tubuli.  The impairment of spermatogenesis affected
the  reproduction  of  animals,  resulting  in  pre-implantation
deaths  of embryos.  Gonadotoxic  effects were suggested  by the
absence  of fertilization of  female rats by  male rats  exposed
daily to vanadium at 0.85 mg/kg body weight.  In  other  studies
(Hackett  & Kelman, 1983)  in pregnant rats  vanadium tended  to
localize  initially in the  placenta and then  to preferentially
concentrate in the membranes rather than in the fetus.

    The  administration of similar  doses of vanadium  to female
rats  on  the 4th  day of pregnancy  increased the mortality  of
embryos  as a result of  pre-implantation deaths; the number  of
fetuses in each female rat was only half that in  the  untreated
animals.   These effects were observed in the absence of general
toxicity in the experimental animals.

     In    vitro,     orthovanadate   (0.2 - 2 mmol)    inhibited
luteinizing   hormone-induced  cyclic  adenosine   monophosphate
(cAMP)   in  isolated corpora  lutea from  pseudopregnant  rats.
When  added simultaneously with luteinizing  hormone, inhibition
occurred  within 25 min, but not when the  corpora lutea had been
pretreated  with luteinizing hormone for 60 min.  A decrease was
also observed when  corpora lutea were exposed to vanadate in the
presence  of 3-isobutyl-1-methylxanthene (0.5 mmol),  a phospho-
diesterase  inhibitor.  Cyclic adenosine monophosphate  was also
inhibited  by vanadate in  copora lutea incubated in a  calcium-
depleted medium.  Vanadyl sulfate (0.4, 2 mmol) was as effective
as  vanadate  in  inhibiting luteinizing  hormone-induced cyclic
adenosine monophosphate accumulation (Lahav et al., 1986).

7.8.2   Teratogenicity

    Carlton  et  al. (1982)  injected  80 mature  Syrian  golden
hamsters  ip  with  ammonium  vanadate  at  0,  0.47,  1.88,  or
3.75 mg/kg body weight.  Injections were carried out on days 5 -
10 of gestation.  A significant increase in  skeletal  anomalies
was  observed in all  groups exposed to  vanadate compared  with
control animals. A significant increase in deaths was registered
in the 1.88 mg/kg group. There was no dose-response relationship
as regards anomalies.

    Pregnant  NMRI albino mice were  injected intravenously with
1 mmol  vanadium pentoxide dissolved in distilled water on day 3
or day 8 of pregnancy (day 1 = finding of vaginal plug). Control
groups  were given 0.1 ml physiological saline on the same days.
Mice  were killed  on day  17, the  uterine horns  examined  for
resorbed  embryos,  and the  fetuses  were removed  for detailed
examination.   Vanadium pentoxide did not produce any effects in
implantation,  and fetuses from  the day 3-treated  and  control
groups  did  not  show any  differences  in  litter size,  fetal
weight, or external and internal morphology.  The  fetuses  from
the  day 8-treated group showed a statistically significant high
frequency  (71%)  of delayed  ossification (supraoccipital bone,
sternum,  metatarsals, and caudal vertebrae),  and broken spinal
cord occurred in a few fetuses (Wide, 1984).

    Vanadium   pentoxide  was  administered   subcutaneously  to
pregnant  rats  (strain unspecified)  at doses of  0.5, 1, or  4
mg/kg  body  weight  for 10  days,  from  day 7  to  day  16  of
gestation.  The incidences of resorbed and dead fetuses in the 1
and 4 mg/kg groups were 17% and 27.2%, respectively.  These were
significantly higher than those found in the controls (3.5%). In
the  4 mg/kg group,  52.38% of fetuses  showed wavy ribs.   In a
separate  study, pregnant rats were given an aqueous solution of
V2O5  by ip injection  at concentrations of  0.3, 1, or  3 mg/kg
body weight.  This induced a higher level of resorbed  and  dead
fetuses  than  oral administration.   Both  ip injection  of 0.3
mg/kg  and oral administration  of 9 mg/kg  induced an array  of
skeletal  anomalies, namely wavy  ribs, supernumerary ribs,  and
fused  sternebrae  and  vertebrae  (Sun,  ed.,  1987).    Though
tentative,  these  results suggest  that  vanadium may  have the
potential to induce teratogenicity in a mammalian system.

7.9  Mutagenicity and Related End-Points

    There  are  few studies  on  the mutagenicity  and  carcino-
genicity  of vanadium  compounds.  Mutagens  in the  air can  be
divided  into two groups: a non-polar extract rich in polycyclic
aromatic  hydrocarbons (PAHs) and other promutagens, and a polar
extract  containing direct acting mutagens,  i.e., not requiring
microsomal  activation  (Madsen  et al.,  1982).   The non-polar
fraction was strongly influenced by automobile exhaust products,
whereas the polar was more attributable to  secondary  emissions
transformed  by atmospheric reactions, and  to primary emissions
from  stationary  sources.   The role  of  PAHs  in the  overall
mutagenicity was estimated to be modest; thus, the importance of
other  substances increases.  Vanadium  was found at  all sample
sites and is a well-known constituent of, for instance, coal fly
ash (section 3.4.2).

    Vanadium5+  has been shown  both to inhibit  or enhance  DNA
synthesis   in vitro , depending on the concentration in the media
(Hori  & Oka, 1980; Carpenter,  1981; Jackson & Linskens,  1982;
Smith, 1983).

    In a DNA synthesis inhibition assay in male  mice,  vanadium
pentoxide  suspended  in  3% starch  solution  was  administered
orally at doses of 14.6, 29.2, or 58.4 mg/kg body  weight.   The
animals  were killed 24  h after dosing;  3 h before  sacrifice,
1 Ci    3H-thymidine/g   body   weight  was   administered  ip.
Incorporation  of 3H-thymidine in the testes, spleen, liver, and
blood  was  measured  in a  liquid  scintillation  spectrometer.
There  were no significant differences  between the experimental
groups and the solvent control group (Sun, ed., 1987).

    In   a  study  using  FADU  (Fluorescence  Analysis  of  DNA
Unwinding),  vanadyl chloride at a concentration of 5 x 10-5 mol
failed  to induce DNA damage (strand breaks) in human peripheral
white blood cells (McLean et al., 1982).

    Kanematsu  et al. (1980) carried out rec assays on 127 metal
compounds   with Bacillus subtilis to  test  their  DNA-damaging
capacity.  Mild positive results were noted for  three  vanadium
compounds (VOCl2, V2O5, NH4VO3).

    A  lack of induction  of spot mutations  in  Escherichia coli 
and  in  Salmonella typhimurium was demonstrated by  Kanematsu &
Kada  (1978)  and  Kada et  al.  (1980).   Similar results  were
obtained  by Si Rongshan  et al. (1982)  with  E.  coli . However,
ammonium   metavanadate   was   found  to   be  mutagenic  in  S. 
 typhimurium TA1535  in a modified plate  incorporation assay and
in the fluctuation test with TA100 (Arlauskas et al., 1985).  In
a  recent study, Sun, ed.  (1987) demonstrated the induction  of
reverse   mutations  by  vanadium  pentoxide  with E.  coli WP2,
WP2uvrA,  and Cm-981, but  no frameshift mutations  with strains
ND-160  and MR102.  Vanadium  pentoxide showed negative  results
with  S.  typhimurium strains  TA1535,  TA1537, TA98,  and TA100.
Thus,  the  results of  mutagenicity  studies of  vanadium  with
bacterial assays are conflicting, and no firm conclusions can be

    In  a micronucleus test, vanadium pentoxide was administered
to  two strains of mice (615 and Kunming albino) by ip injection
at  doses of 6.4, 2.13, or 0.17 mg/kg body weight for 5 consecu-
tive days; cyclophosphamide was used as a positive control (Sun,
ed., 1987).  Significant levels of induced micronuclei  in  both
strains  were observed.  Both subcutaneous injection of vanadium
pentoxide  solution (0.25,  1, or  4 mg/kg)  and  inhalation  of
vanadium pentoxide dust (0.5, 2, or 8 mg/m3) also induced micro-
nuclei  in  mice strain  615.   However, negative  results  were
obtained following oral administration of a 3% starch suspension
of  vanadium  pentoxide  at  doses  of  1.44,  2.83,  5.65,   or
11.3 mg/kg  body weight, daily, for  6 weeks, to Kunming  albino
mice (Sun, ed., 1987).

    In an  in vitro  study on human peripheral lymphocyte cultures
with  vanadium  pentoxide  concentrations  of  0.047,  0.47,  or
4.7 moles  (mitomycin  c  was  used  as  positive  control),  no
increases  in the frequency  of sister chromatid  exchange  were
observed (Sun, ed., 1987).

    In  a  dominant-lethal  mutation assay,  vanadium  pentoxide
(0.2,  1, or  4 mg/kg  body weight)  was administered  daily  by
subcutaneous  injection  to 5  groups of male  mice, aged 5  - 6
weeks at the start of the study, for 3 months,  following  which
they   were  mated  with  females.    Ethylmethanesulfonate  and
distilled  water were used  as positive and  negative  controls,
respectively.   The females were killed 17 days after conception
and  the  numbers  of  fetuses  and  resorptions  recorded.  The
results  were considered negative for the induction of dominant-
lethal mutations (Sun, ed., 1987).

7.10  Carcinogenicity

    In  a  study  on  13  metallic  compounds,   intraperitoneal
injections of vanadium3+ 2.4-pentanedione at doses of 24, 60, or
120  mg/kg  body  weight  did  not  significantly  increase  the
incidence of lung adenomas in mice (Stoner et al., 1976).
    In life-span  studies, the  incidence of  tumours in  mice
given  vanadyl ions (as  the sulfate) at  5 g/litre   drinking-
water  was  similar  to that  in  control  animals  (Kanisawa  &
Schroeder,  1967; Schroeder et al., 1970; Schroeder & Mitchener,
    In  rats,  the induction  of  mammary carcinogenesis  by  1-
methyl-1-nitrosurea  was  blocked  by feeding  a  purified  diet
supplemented  with 25 mg  vanadyl4+ sulfate/kg during  the post-
initiation  stages  of  the  neoplastic  process.   Both  cancer
incidence and the average number of cancers per rat were reduced
by  the vanadium4+ diet without inhibiting the overall growth of
the  animals (Thompson et  al., 1984).  It  has also been  shown
that  metallocene dichlorides, (C2H5)2MCl2 (where  M = titanium,
vanadium,   molybdenum,   or  niobium),   exhibit  cancerostatic
activity against the Erlich ascites tumour system in  mice,  and
that treatment with such substances cured the tumour (Kpf-Maier
et  al., 1980).  Vanadocene  dichloride was reported  to have  a

chemotherapeutic  activity similar to that of cis-dichlordiamine
platinum  (II) when used  against liver tumours  in mice  (Kpf-
Maier & Kpf, 1979). The mechanism of the preventive  effect  of
vanadium is not clear.  Modulation of one or more aspects of the
DNA metabolism could account for these results.

    The effects of ammonium vanadate on the development of large
bowel neoplasms in mice treated with 1,2-dimethylhydrazine (DMH)
were  studied by Kingsnorth  et al. (1986).   Mice were  treated
with DMH (20 mg/kg body weight per week) for 20 weeks.  Ammonium
vanadate  was given in the drinking-water (10 or 20 mg/litre) to
groups  of mice during  the study.  At  30 weeks, the  colons of
DMH-treated   mice  (not  receiving  ammonium  vanadate)  showed
increases  in RNA  content (+14%)  and DNA  content  (+18%)  and
deeper crypts (+33%). In the mice treated with DMH and receiving
ammonium  vanadate  at 10  or 20 mg/litre,  the RNA content  was
decreased   by   11%.   Although   thymidine  incorporation  was
increased,  ammonium vanadate did  not have any  effects on  the
incidence or type of tumour induced by DMH (Kingsnorth  et  al.,

    In a long-term study in which the carcinogenic  activity  of
various   materials  was  studied  using  intrabronchial  pellet
implantation in the lower left bronchus of rats, vanadium solids
produced  chronic inflammatory changes in 44/100 rats, bronchial
inflammation in 50/100, squamous metaplasia in 10/100,  and  one
bronchial carcinoma in a male rat after 645 days.  These results
were not significant for carcinogenicity (Levy et al., 1986).


8.1  Therapeutic Exposure and Controlled Studies

8.1.1   Therapeutic exposure

    In  the past, vanadium compounds were prescribed  as  thera-
peutic   agents   for  anaemia,   chlorosis,  tuberculosis,  and
diabetes.   They  were  also used  as  an  antiseptic, a  spiro-
chetocide,  and a tonic.   For example, sodium  metavanadate was
given  therapeutically by mouth in doses of 1 - 8 mg, and sodium
tartrate  was  injected intramuscularly  at  levels as  high  as
150 mg.  Due to poor absorption from the gastrointestinal tract,
the metal is not very toxic for human beings when ingested, but,
if introduced directly into the circulation in a  soluble  form,
Hudson  (1964) estimated that the lethal dose for a 70-kg person
would be only 30 mg V205 (0.42 mg V205/kg body weight).

8.1.2   Controlled studies Effects on metabolism 

    Vanadium  has been administered under  controlled conditions
to study its effects on blood-cholesterol levels.  Curran et al.
(1959)  conducted a clinical study in which 5 healthy adult male
volunteers  were  fed  soluble diammonium  oxytartarovanadate at
150 -  200 mg/day (21 - 30 mg vanadium/day) for 6 weeks.  At the
end   of   the  period,   plasma-cholesterol  was  significantly

    Lewis  (1959a)  compared  age-matched groups  of 32 vanadium
workers  with 45 controls, all  over 45 years of  age.  Vanadium
workers exposed for at least 6 months excreted  greater  amounts
of  vanadium  and  exhibited  slightly  lower  serum-cholesterol
levels  than the controls.   Mean cholesterol values  for the  2
reference  groups (representing 2 geographical  areas) were 2309
and  2267  mg/litre.   Mean  levels  for  vanadium  workers from
corresponding areas were lower at 2049 and 2067  mg/litre  (P <
0.05), respectively.

    A  clinical  study  by Somerville  &  Davies  (1962)  on  12
patients (9 of whom were hypercholesterolaemic) given diammonium
vanadotartrate  orally for 6 months  (25 mg 3 times daily  for 2
weeks, increased to 125 mg daily in 10 patients)  did  not  show
any  significant  changes  in serum-cholesterol  levels over 5.5
months. The mean pretreatment control level of serum-cholesterol
was  4110 mg/litre, and the  mean age was 49.2 years.  The study
is  not  comparable with  that of Curran  et al. (1959),  as the
patients  were hypercholesterolaemic and  older.  Dimond et  al.
(1963)  observed temporary drops (not statistically significant)
in  cholesterol  levels in  2 out of  6 patients given  ammonium
vanadyl tartrate for several weeks at levels of between  50  and
100 mg/day.  No statistically significant changes  were observed
in  blood-lipids, phospholipids, triglycerides, 17-ketosteroids,
or 17-hydroxycorticosteroids. Two patients complained of fatigue
and lethargy while they were taking vanadium.  All complained of

cramps  and  loosened stools,  and  all developed  green tongue.
Schroeder et al. (1963) reporting findings similar to  those  of
Dimond  et al.  (1963) considered  that the  slight  effects  of
vanadium  on serum-cholesterol were pharmacological  rather than
caused  by  correction  of  a  physiological  deficiency.   They
further  pointed out that dietary regimens based on the consump-
tion  of  unsaturated  fats, which  reduce plasma-cholesterol in
human  beings,  are  associated with  the  intake  of 1  -  4 mg
vanadium/day  and  that  the feeding  of vanadium-poor saturated
fats raises cholesterol.

    Studies have been undertaken on the effects of  vanadium  on
human  dental  caries.   Belehova  (1969)  studied  583   school
children ranging in age from 7 to 11 years.  The  subjects  were
divided  into 4 groups.  Children  in Group I received  fluoride
twice  a year, those in Group II received a local application of
a  50% paste of an ammonium salt of vanadium and glycerol, Group
III received both fluoride and vanadium, and Group IV  acted  as
the  control.   The incidence  of caries was  11% in Group  III,
15.4%  in  Group II,  29.7% in Group  I, and 43%  in the control
group.  Belehova concluded that the lower incidence of caries in
subjects  receiving  vanadium suggested  a possible prophylactic
action.   However, other studies (Hein & Wisotzky, 1955; Muhler,
1957;  Hadjimarkos, 1966, 1968; McLundie et al., 1968) failed to
demonstrate  a clearly beneficial  effect with regard  to dental
caries in human beings.

    Data  on the effects of  vanadium on the haematopoiesis  are
inconsistent.   Lewis  (1959a) did  not  observe any  effects of
exposure  to  vanadium  on  haematocrit  levels  in  32 vanadium
workers compared with 45 controls matched for age.  A beneficial
effect  of  low-level  vanadium  administration  on  nutritional
anaemia  has been suggested (Beard  et al., 1931; Myers  & Beard
1931;  Hadjimarkos, 1966; Kopylova, 1971).  However, the effects
of  vanadium on  iron metabolism  have not  been fully  assessed
(Vouk, 1979).

    The    administration   of  w -methylpantothenic   acid,   an
antimetabolite  of pantothenic acid, to human beings resulted in
a   syndrome  consisting  of  postural  hypotension,  dizziness,
tachycardia, fatigue, drowsiness, epigastric distress, anorexia,
numbness  and tingling of  the hands and  feet, and  hyperactive
deep reflexes.  It is not known whether these symptoms  are  the
result of an induced deficiency of pantothenic acid or are toxic
effects  of the anti-metabolite.  However, the symptoms resemble
those   resulting  from  exposure  to   high  concentrations  of
vanadium.   The  common  denominator in  both  cases  may  be  a
reduction in hepatic coenzyme A levels (Waters, 1977). Effects on the respiratory system 

    Zenz  &  Berg  (1967)  studied  the  effects   of   vanadium
inhalation  in 9 healthy volunteers aged 27 - 44 years, for whom
baseline  lung  function  data were  available.  Two volunteers,
exposed   to   vanadium  pentoxide  dust  at  1 mg/m3  for  8 h,
developed sporadic coughing after 5 h and a frequent cough after

nearly  7 h.  Coughing lasted 8  days, but lung sounds  remained
clear  and  there  were no  other  signs  of  irritation.   Lung
function  tests,  complete  blood counts,  urinalyses, and nasal
smears were normal up to 3 weeks.  Three weeks later, the same 2
volunteers  were accidently exposed for 5 min to a "heavy cloud"
of vanadium pentoxide dust.  A productive cough developed within
16 h, and, within 24 h, rales and expiratory  rhonchi  developed
throughout  the  lung,  but pulmonary  function remained normal.
Isoproterenol  (1:2000) relieved the symptoms for about 1 h, but
coughing then resumed and continued for 7 days.  There  were  no
other  symptoms.   Eosinophils were  not  present in  the  nasal

    Exposure   of   5   volunteers  to   a  lower  concentration
(0.2 mg/m3,  98% of particle  size 5 m)  had  similar  effects,
though  the symptoms took longer  to develop, i.e., after  20 h.
Coughing, without other systemic effects, persisted for 7  -  10
days.   Pulmonary  function  tests and  differential white blood
counts remained normal.  The vanadium concentration in the urine
was   highest  (0.13 mg/litre)  on  the  third  day,  with  none
detectable  after 7 days.  The maximal faecal-vanadium level was
3 mg/kg,  with  none detectable  after 14 days.   Exposure to  a
concentration  of 0.1 mg/m3 for 8 h did not produce any coughing
in 2 subjects not previously exposed.  However, an  increase  in
the production of mucous, 24 h later, indicated some respiratory
irritation.  Then there was slight coughing, which  became  more
severe  after 48 h, subsided  after 72 h, and  disappeared after
96 h.   Pulmonary  function  tests and  differential white blood
counts remained normal.

    Pazhynich  (1967) studied the  irritant effects of  vanadium
pentoxide   condensation  aerosol  on   11  volunteers.   At   a
concentration of 0.4 mg/m3, all reported a tickling  or  itching
sensation  and a feeling of dryness in the region of the root of
the tongue, the posterior wall of the pharynx, and  the  fauces,
as  well  as  a  slight  prickling  sensation  in the  nose  and
posterior pharyngeal wall. These symptoms were easily tolerated.
A concentration of 0.16 mg/m3 caused mild signs of irritation in
only  5 volunteers, and  a concentration of  0.08 mg/m3 was  not
noticed  by  any  volunteer.  It  was  concluded  that the  mean
perceptible  concentration  for  human beings  is 0.27 mg/m3 and
that 0.16 mg/m3 is imperceptible.

8.2  Clinical Studies

    The clinical picture of poisoning shows the  broad  spectrum
of toxic effects of vanadium.  The lesions observed  affect  the
respiratory  system, circulatory system, central nervous system,
digestive organs, kidneys, and skin.  Poisoning can  be  divided
into acute and chronic forms.

8.2.1   Acute toxicity

    Acute  toxicity is characterized  by a latent  period, which
depends  on  the  concentration  of  vanadium,  the   individual
sensitivity of the subject, and the properties of  the  specific

vanadium compound.  The more soluble salts of vanadium pentoxide
have  a more rapid action than the vanadium oxides.  Chemically-
pure  vanadium pentoxide acts  more rapidly than  the  technical
grade.   A condensation aerosol  of vanadium pentoxide  is  more
toxic  than a disintegration aerosol (Roshchin, 1964).  Vanadium
chloride is toxic more rapidly than other compounds.
    Roshchin  (1968)  subdivided  acute  vanadium  effects  into
"mild",  "moderate", and "severe" forms.   The clinical features
of  mild toxicity  include rhinitis  with a  profuse  and  often
bloody discharge, sneezing, and an itching and burning sensation
in  the throat.  The rhinitis may be followed by the development
of  a dry cough  with expectoration of  small amounts of  viscid
sputum,   general   weakness,  and   exhaustion.   A  sub-normal
temperature  may be present; in other cases, the temperature may
be  high or normal.  The  patient is afebrile in  the absence of
pneumonic disease (Sjberg, 1950).  Conjunctivitis is frequently
observed.   The symptoms and course of mild toxicity resemble an
upper  respiratory  tract  infection.   Other  symptoms  include
diarrhoea   due  to  intensified  intestinal  peristalsis.   The
symptoms  disappear from 2 - 5  days after cessation  of contact
with the dust.
    In  moderate  toxicity,  in addition  to  conjunctivitis and
irritation of the upper respiratory tract, there  is  bronchitis
with  expiratory dyspnoea and bronchospasm.   There are frequent
disturbances  in  the  activity of  the  gastrointestinal tract,
including  vomiting  and  diarrhoea.  Taken  together  with  the
bronchospasm,  this points to a response of the smooth muscle to
vanadium   exposure.   Some  affected  persons   have  cutaneous
manifestations of toxicity in the form of rashes and eczema with
itching  papules and  dry patches  (Browne, 1955;  Zenz et  al.,

    Bronchitis and bronchopneumonia are features of severe toxic
effects.   Other symptoms may  also be more  prominent, such  as
headache,  vomiting,  diarrhoea,  palpitations,  sweating,   and
general  weakness.   Disorders  of the  nervous  system  include
severe  neurotic states  and tremor  of the  fingers  and  hands
(Wyers,  1946; Sjberg, 1955).   Functional disturbances of  the
respiratory system can be expected, and X-ray  examination  will
reveal intensification of the lung pattern.

    Kidney  damage, highlighted by  grave dystrophic changes  in
the epithelium of the convoluted tubules and  disturbed  tubular
secretion, occurs immediately after the start of exposure to low
vanadium  doses in both  acute and chronic  intoxication.   Once
triggered off, the changes are irreversible, even if exposure is
discontinued.  Therefore, the kidneys are a critical  organ  for
vanadium poisoning (Korkhov, 1965).

8.2.2   Chronic toxicity

    Chronic  vanadium intoxication produces profound  changes in
the  respiratory  organs,  because  of  the  irritant  action of
vanadium   and  the  biochemical  and   functional  disturbances

connected   with   its   general  resorptive   action.   Chronic
respiratory  illness takes the form  of diffuse pneumosclerosis,
chronic bronchitis, chronic rhinitis, and pharyngitis (Roshchin,
1968).   However,  Parkes  (1982)  claimed  that  the  available
evidence (Sjberg, 1950; Williams, 1952; Zenz & Berg, 1967)  did
not support the contention that prolonged exposure  to  vanadium
compounds   leads  to  chronic   bronchitis,  with  or   without
emphysema.   Although  wheezing  is more  common  among vanadium
pentoxide  workers than among  unexposed workers, lung  function
tests  and chest radiography  have not revealed  persistent lung
damage  (Kiviluoto,  1980).   The cardiovascular  system (Wyers,
1946; Sjberg, 1950; Izycki et al., 1971) is  commonly  affected
in  chronic respiratory disorders  by a diagnosable  accentuated
second cardiac sound on the pulmonary artery and  an  attenuated
first sound on the apex cordis.  Most of these  workers  exhibit
heavy sinus arrhythmia and a shift of the EGG-axis to the right.
After  extensive exposure, workers may develop bradycardia and a
change  of the P  wave in the  second and third  standard leads;
coronary  spasm is also usually recognizable in such workers.  A
statistically  significant increase in the incidence of enlarged
liver  and  a  decrease  in  functional  tests   together   with
bilirubinaemia and a direct reaction to bilirubin have been seen
in the blood of exposed workers (Roshchin,  1968).   Biochemical
alterations have also been found, such as reduction in albumins,
and expansion of the globulin fractions at the expense of gamma-
globulins,  even  though  the  total  protein  content  remained
normal.  Furthermore, a marked reduction in sulfhydryl groups in
blood-serum  and in vitamin  C levels in  the blood, and  a less
marked  drop in cholesterol levels have been observed.  Systemic
effects, such as a tendency towards anaemia and leukopaenia, and
basophilic   granulation   of  leukocytes   have  been  reported
(Watanabe et al., 1966).

    Vanadium levels in whole blood and serum have  been  studied
to  investigate  the possible  role  of vanadium  in  depressive
states.   In a study  involving neutron activation  analysis  of
vanadium  levels in the whole blood, serum, and hair of patients
suffering  from mania  or depression,  and of  patients who  had
recovered  from these conditions,  as well as  normal  controls,
manic  patients were  reported to  have normal  levels in  whole
blood  and  serum,  but  significantly  raised  levels  in hair.
Depressed patients had raised levels in whole blood  and  serum.
In  both  conditions, raised  levels  fell with  recovery.   The
levels  of vanadium in serum were correlated with those in whole
blood but not with hair levels (Naylor et al., 1984). In another
study,  serum-vanadium  levels,  measured by  neutron activation
analysis, were reported to be 3.10  1.38 mg/litre  in  patients
suffering  from depressive illness and  0.67  0.32 g/litre  in
normal subjects (Simonoff et al., 1986).  However, in  a  series
of  25  depressive, 13  recovered  depressive patients,  and  24
controls,   the  whole-blood  concentrations  of  vanadium  were
similar  to normal levels, and vanadium levels did not change in
depressive patients after recovery (Ali et al., 1985).

8.2.3   Diagnosis

    Information  on likely exposure,  the clinical picture,  and
certain  biochemical  indications  of probable  exposure can aid
diagnosis,  but no specific test can be recommended.  Determina-
tion of the vanadium contents of the blood and especially of the
urine provides documentation of exposure, though the correlation
between  vanadium levels in the  urine or serum and  air is poor
(Kiviluoto et al., 1979a,c).  In view of the work  of  Schroeder
et al. (1963), it would seem desirable to measure  the  vanadium
contents  of the  serum separately  from that  of  the  cellular
elements,  since the concentration of vanadium in the latter may
be  more indicative of exposure levels.  As reported by Watanabe
et al. (1966), a decreased urinary output of ascorbic  acid  may
be one characteristic of vanadium exposure, but differences from
controls  do not appear sufficient  to make the test  clinically

    Green  colouration of the  tongue is also  an indication  of
vanadium exposure (Wyers 1946; Williams, 1952; Lewis 1959b). The
green  hexaquo ion (V(H2O))63+  is probably responsible  for the
green-coloured  tongue.   However,  several other  bright  green
complexes of vanadium+4 are known and may also account  for  the
sign (Cotton & Wilkinson, 1962; Durrant & Durrant,  1970).   The
"green  tongue"  may  be  absent,  even  in  prolonged  exposure
(Sjberg, 1950).

    During  continuous  exposure,  measurement  of  the  cystine
content  of fingernails was reported to be a sensitive indicator
of  exposure.  This  parameter was  negatively  correlated  with
vanadium exposure in workers.  A decrease in cystine  levels  in
fingernails  was demonstrated when urinary-vanadium  levels were
only  0.02 - 0.03 mg/litre  (Mountain et al., 1955).   A similar
reduction  in  the cystine  content of rat  hair was noted  when
vanadium  in the diet  ranged from 25 -1000  mg/kg (Mountain  et
al., 1953).  Some evidence suggesting that vanadium may directly
inhibit  the synthesis  of cystine  or cysteine  has  also  been
reported (Mountain et al., 1953, 1955).

    In  a  recent  study on  workers  exposed  to low  levels of
vanadium  pentoxide  (0.1  - 0.6  mg/m3)  for  about  14  years,
Kiviluoto et al. (198O) could not corroborate  the  observations
by  Mountain and  co-workers as  no differences  were  found  in
fingernail cystine contents between the 22 exposed  workers  and
22 unexposed controls.  A small reduction in the cystine content
of  fingernails  (89 mg  cystine/kg fingernail  for  exposed and
99 mg/kg  for controls) was found by Thrauf et al. (1979) in 54
exposed  workers with an increased  urine-vanadium concentration
of 37.8 g/litre (controls 0.8 g/litre).

8.2.4   Treatment of poisoning

    There  are few  published data  on the  treatment  of  human
poisoning  by vanadium.  BAL has  been used successfully in  two
cases of overexposure (Sjberg, 1955).  Experimentally, ascorbic
acid  in doses of 125 mg/kg body weight given 20 min prior to an

LD70  dose of NaVO3H2O  had a strong  protective effect in  mice
(Mitchell & Floyd 1956).  CaNa2-EDTA was also antidotal in dogs,
when given intraperitoneally in doses of 100 mg/kg  body  weight
after the first sign of poisoning became evident and again 2 and
4 h  later.  Jones &  Basinger (1983)  tested  various chelating
agents  and their  protective effects  in mice  and  found  that
efficient  antidotes for both vanadate (VO33- and vanadyl (VO2+)
were   ascorbic  acid,  deferoxamine   D-penicillamine,  sodium,
calcium,  Na3CaDTPA, Na2CaEDTa, and glutathione.   Ascorbic acid
appeared best suited for human use as an antidote.

    Intraperitoneal  doses  of NaVO3  (0.3  - 1.2  mmol/kg  body
weight) were injected in mice followed by chelating and reducing
agents  at one-quarter of  their respective LD50s.   Significant
increases  in the survival  rate, 14 days  after the  treatment,
were  noted with ascorbic  acid, deferoxamine, and  tiron  (4,5-
dihydroxy-1,3-benzene-disulfonic  acid).  Other chelators tested
included EOTA, DTPA (Na3Ca-diethylene triaminepenta-acetate) and
L-cysteine.  Ascorbic acid was the most effective  substance  in
preventing  vanadium  intoxication  (Domingo et  al., 1986).  In
another  report,  sodium  salicylate and  D-L-penicillamine were
found useless as antidotes for acute toxicity caused by NaVO3.

8.3  General Population Exposure

8.3.1   Low vanadium intake

    Because conditions required to achieve reproducible vanadium
deficiency  in animals have  not been defined  precisely, it  is
difficult  to  predict the consequences of a low vanadium intake
on human health.
    Statistical studies have shown negative correlations between
environmental  levels  of  vanadium  and  certain  other   trace
elements  and the incidence of cardiovascular disease.  Consump-
tion  of hard water  containing vanadium was  associated with  a
lower  incidence  of  cardiovascular disease  (Strain, 1961)a.
Schroeder  (1966)  reported  a significant  negative correlation
between the vanadium content of municipal waters and death rates
due  to arteriosclerotic  heart disease.   In a  study by  Voors
(1971) on the correlation between 7 metals  (calcium,  chromium,
lithium, zinc, manganese, nickel, vanadium) and arteriosclerotic
heart  disease, a low  vanadium intake was  associated  signifi-
cantly with a higher incidence of arteriosclerotic heart disease
in   non-white  populations,  but  no   direct  correlation  was
demonstrated for white populations.

a       Strain,  W.H.  (1961)  Effects  of  some  minor  elements  in
         animals and people.  Paper presented at the meeting  of  the
        American Association for the Advancement of Science, Denver,
        29 December 1961 (unpublished).

    In  a joint WHO and IAEA study on the role of trace elements
in  the etiology of cardiovascular  diseases in 20 countries,  a
significant role was shown for environmental lack of vanadium as
well  as  chromium,  zinc,  manganese,  calcium,  and  magnesium
(Masironi,  1969).   Conversely, Hickey  et  al. (1967)  noted a
positive  correlation between airborne  vanadium levels and  the
incidence of cardiovascular disease (section 8.3.2).
    The  evidence  implicating  vanadium as  an  essential trace
element  for human beings is not satisfactory.  Although certain
statistical  studies have indicated that low vanadium intake may
be   associated   with   human  cardiovascular   disease,  these
relationships  do not furnish any direct proof for a nutritional
role of vanadium in human health. However, they do suggest leads
for further laboratory and epidemiological investigations.

8.3.2   Epidemiological studies

    Descriptive  epidemiological  work has  been published using
a  correlational  approach,  which has  well-known  limitations,
though it imitates a population-based cohort study.
Despite their limitations, such studies can give indications for
more  intensive and detailed  controlled studies into  suspected
health  hazards,  comparing  incidences of  diseases  in defined
exposure groups (such as production workers) with those obtained
from reference populations.

    Stocks  (1960) reported  the results  of a  study  in  which
airborne  concentrations  of  13 trace  elements were correlated
with mortality from lung cancer, pneumonia, and bronchitis in 23
localities  in  the  United Kingdom.   At concentrations ranging
from 1.1 to 42 g/1000  m3, vanadium showed a  weak  association
with  mortality  from  lung cancer  (taking  into  consideration
population   density,   sex,   and  age),   with  a  correlation
coefficient  of  0.347.   Airborne  vanadium  levels  were  also
correlated  with  mortality  from  pneumonia  in  males,  with a
correlation  coefficient for mortality from  pneumonia of 0.443.
For  mortality involving bronchitis, vanadium gave a correlation
coefficient  of 0.563.  Vanadium also showed an association with
mortality  from cancers other than lung cancer in males, but not
in females.  However, in this study, as is usual in  studies  of
this  kind,  it  is not  certain  that  cases of  interest (lung
cancer,  pneumonia) had been exposed at all.  There are also the
uncertainties   of  mortality  data  and   failure  to  consider
confounding factors.

    In  another study, Hickey et al. (1967) considered 10 metals
in  the air, including vanadium,  in 25 communities in  the USA.
Various  techniques, including canonical analysis,  were used to
correlate  airborne metal concentrations  with mortality indices
for  1962 and  1963 involving  8 disease  categories.  The  mean
atmospheric concentrations for vanadium at the various locations
ranged  from 0.001 to  0.672 g/m3.   The incidence  of  several
diseases,  including  "diseases  of the  heart",  nephritis, and
"arteriosclerotic  heart",  could be  correlated reasonably well

with  air levels of  vanadium and other  metals.  A high  inter-
correlation  between vanadium  and nickel was unexplained.  This
study  was of a very preliminary nature, with no adjustments for
the  basic pertinent variables normally employed.  Other studies
have  demonstrated significant negative correlations between the
incidence  of cardiovascular disease and environmental levels of
vanadium (section 8.3.1).

    An  additional multivariate analysis of  air-vanadium levels
in relation to selected white male mortality levels was included
in an unpublished US Environmental Protection Agency staff study
by  Pinkerton et al.  (1972)a.    Several categories  of cardio-
vascular   disease  were  used,  and  also  influenza-pneumonia.
Vanadium  was not correlated with the latter, but was correlated
with  the  cardiovascular  categories.  However,  adjustment for
population  density produced a considerable reduction in some of
these  relationships.   It  was  concluded  that  the   observed
statistical  associations  of  air-manganese  and   air-vanadium
levels  were not causal  associations, and represented  either a
reflection   of  other  more   directly  associated  causes   or
statistical artifacts.

    Barannik  et al. (1969)  studied the role  of certain  trace
elements and the natural radioactivity of food products  in  the
etiology  of endemic  goitre in  the USSR.   More  chromium  and
vanadium  and less  lead were  found in  most of  the  vegetable
products  from a region where  goitre was endemic compared  with
those  from a goitre-free region.   The differences in the  mean
concentrations   of  these  trace  elements  were  statistically

    The  differences  between  these  general   population-based
observations and the occupational studies on health  effects  in
vanadium  workers  (section  8.3)  are  connected  to  different
approaches.   The  correlational epidemiological  studies, based
exclusively  on  long-term  effects  and  causes  of  death, are
considered at the expense of lack of individual  exposure  data,
while  the  medical  studies, cross-sectional  in nature, cannot
consider  the selection effects  and lack long-term  information
(such  as cause of death).  Their strength, however, lies in the
fact  that they permit analysis according to different levels of
exposure,  though further occupational and population studies on
chronic illness in unambiguous relationship to vanadium exposure
are  needed to verify  previous work and  determine if there  is
evidence  of  a  dose-response relationship.   In  such studies,
morbidity as well as mortality should be considered.

a   Pinkerton,  C., Hammer, D.I.,  McClain, K., Williams,  M.E.,
    Bridbord,  K.,  &  Riggins, W.B.   (1972)    Relationship  of
    manganese and vanadium in the ambient air to  heart  disease
    and  influenza-pneumonia mortality rates, Research  Triangle
    Park,  North  Carolina,  US Environmental  Protection Agency
    (unpublished data).

8.4  Occupational Exposure

    Occupational  poisoning occurs mainly during  the industrial
production   and  use  of   vanadium  and  in   boiler  cleaning
operations.   Under  these  conditions, vanadium  may  enter the
human  body through the  respiratory tract; an  unknown quantity
will  be  transported to  the  alimentary tract  when swallowed.
Vanadium can also enter through the skin (Roshchin, 1968).
    Both  acute  and  chronic poisoning  can  occur.   Vanadium-
containing industrial aerosols differ in chemical and structural
composition  and  thus evoke  different  responses in  the human
    In sections 8.3.1 - 8.3.4, a survey is made of the available
clinical  and  epidemiological data  on  the health  effects  of
vanadium   in   workers   occupationally  exposed   to  vanadium
compounds.   Most  of  the reported  clinical  symptoms  reflect
irritant effects of vanadium on the respiratory tract and eyes.

8.4.1   Metallurgy

    Dutton  (1911)  first  described the  effects  of industrial
exposure to vanadium-bearing ores. He reported a dry, paroxysmal
cough  with haemoptysis and  irritation of the  eyes, nose,  and
throat.  Temporary increases in haemoglobin levels and red blood
cells  were followed  by reductions  in both  and the  onset  of
anaemia.   Vanadium  was  recovered in  all  bodily  secretions.
Postmortem  examination  revealed  highly congested  lungs  with
destruction  of  the  alveolar epithelium  and congested kidneys
with  evidence  of  haemorrhagic nephritis.   Unfortunately, the
workers  frequently suffered from pulmonary  tuberculosis, which
undoubtedly  produced  many  symptoms that  were  aggravated  by
vanadium  exposure,  and  no  details  regarding  the  number of
workers examined or the incidence of the signs and symptoms were
    A later study by Symanski (1939) on relatively healthy metal
workers exposed to vanadium pentoxide dust for  periods  ranging
from  a few months up to several years reported severe conjunct-
ivitis,  rhinitis,  pharyngitis,  chronic productive  cough, and
tightness of the chest; severe chronic bronchitis  and  bronchi-
ectasis sometimes occurred with longer exposure.  There  was  no
evidence of a generalized systemic action of vanadium.
    Rundberg  (1939)  observed bronchitis  with purulent sputum,
general weakness, and skin irritation of the face and  hands  in
20  men handling vanadium  pentoxide in a  metallurgical  works.
Productive  cough,  bronchitis,  and shortness  of  breath  were
reported by Balestra & Molfino (1942) in 25 workers  exposed  to
vanadium  pentoxide dust from  petroleum ash.  Other  substances
were  involved, and chest  X-rays showed definite  lung markings
suggesting  pneumonoconiosis.  Bronchiectasis was suspected in 2
    Studies  were reported  by Wyers  (1946, 1948)  on  50 -  90
workers  exposed  to vanadium  pentoxide  as an  oil  combustion
residue  and  to  slag  from  the  production  of ferrovanadium.
Findings   included  bronchospasm,  often  with  elevated  blood
pressure  and accentuated pulmonary  second sound, a  paroxsymal
cough,  dyspnoea, skin pallor,  tremor of fingers,  palpitation,
chest  pains, and reticulation  of the lungs.   Wyers emphasized
the  irritant effects of  vanadium pentoxide on  the respiratory
tract, but also found evidence of systemic toxicity.

    An extensive report including data on the dust  contents  of
the  air in a  metallurgical plant producing  vanadium pentoxide
was  published  by  Sjberg  (1950).   The  dust  particles were
relatively large in size  (39% less than 12 m,  22%  less  than
8 m).    It  was  estimated  that  a  concentration  of  6.5 g
V205/m3  represented the worst exposure  conditions.  Thirty-six
men  between  20 and  50 years of  age had been  employed in the
plant since 1946: 22 had a dry cough; wheezing sounds  could  be
detected  in 31; and 27 were short of breath.  One man developed
acute  pneumonitis,  and  4 others  developed  bronchopneumonia.
There was no evidence of systemic toxicity.

    A  dry eczematous dermatitis developed in 9 men in Sjberg's
(1950)  study, but  only 1  man showed  a positive  patch  test.
Sjberg (1951) and Sjberg & Rigner (1956) believed that allergy
might play a role in the development of eczema  and  pneumonitis
following vanadium exposure.  Zenz et al. (1962) also considered
this  an explanation for the  more severe symptoms found  on re-
exposure  in  their study.   In a follow-up  to the 1950  study,
Sjberg & Rigner (1956) reported that the 16 men  most  severely
affected  still  complained  of  shortness  of  breath,   cough,
fatigue,  and  wheezing.   Bronchitis  was  present  in  2  men.
However,  spirometric  measurements,  cardiac  function   tests,
electrocardiograms,  haematological tests, and urinanalyses were
essentially normal.

    Lewis (1959b) studied 24 male workers in an  environment  in
which  the  maximum  exposure  was  only  0.925 mg  vanadium (as
V205)/m3  of  air.  In  most cases, the  exposure was to  0.3 mg
vanadium/m3.  More than 92% of the dust particles  were  smaller
than 0.5 g  in every process area sampled.  Symptoms  of  cough
with  sputum production, eye,  nose, and throat  irritation, and
wheezing were related to physical findings of wheezes, rales, or
rhonchi,  injected  pharynx, and  green  tongue.  All  of  these
symptoms and physical findings were statistically significant in
comparison to those in 45 referents (Tables 25 and 26).

    A  report  by  Rajner (1960)  on  30  vanadium workers  in a
metallurgical  plant  described  particularly severe  signs  and
symptoms, but did not give any estimates of exposure  except  in
conjunction  with urinary-vanadium levels.  In  acutely poisoned
workers,  vanadium values were about  4000 g/litre  urine.  The
average  value   among  permanent   employees  was  45 g/litre;
vanadium pentoxide smelter workers had maximum values  of  about
400 g/litre.    When a new  production process was  introduced,
symptoms of acute vanadium poisoning occurred in 3 workers after

16 h  of work including  severe respiratory difficulties,  head-
ache,  dejection,  and  loss of  appetite.   Acute  inflammatory
changes  of  the upper  respiratory  tract with  copious  mucous
production,  oedema of the  vocal cords, and  profuse  epistaxes
were reported.  All workers who had been exposed for a long time
(up  to  22 years  in 27 subjects,  mostly in ferrovanadium  and
vanadium  pentoxide smelting operations) complained  of coughing
and  eye,  nose,  and throat  irritation, breathing difficulties
during   physical  exertion  ("more   than  two-thirds  of   the
workers"),  and headache (12 cases).  Clinical findings included
intense  hyperaemia of  the mucosa  of the  nasal septum  in  20
workers;   perforation of the nasal septum was seen in 4 workers
exposed for an average of 18 years.  Intense hyperaemia  of  the
mucosa  of the throat and  larynx with dilated fine  capillaries
was  found in 50%  of the workers.   Bronchoscopy indicated  the
presence  of chronic bronchitis,  and bronchial smears  revealed
sloughed epithelium.

    Matantseva  (1960)  studied  77  workers  in  contact   with
vanadium  pentoxide in the form  of dust and fume  in concentra-
tions  exceeding  the  MAC value  (dust  =  0.5 mg/m3;  fumes  =
0.1 mg/m3) for periods ranging from 1 to 12 years.   Nearly  all
the  subjects  had  various  complaints  relating  to  the upper
respiratory tract including unpleasant sensations in the nose, a
liquid   mucous  discharge  from  the   nose,  obstructed  nasal
breathing,  a sensation  of burning  and dryness  in  the  naso-
pharynx,  scratching,  dryness,  and  tickling  in  the  throat,
hoarseness of the voice, and cough.  Physical examination showed
rhinitis,  which  was  of a  simple  catarrhal  form in  workers
exposed  for less than 3  years, a hypertrophic and  subatrophic
form  if the exposure was for more than 3 years, and an atrophic
form if the exposure was for between 7 and 12  years.   Examina-
tion of the lungs revealed acute and chronic lesions in the form
of  bronchitis,  peribronchitis,  and  pneumosclerosis.   Hyper-
ventilation and an elevated basal metabolic rate were noted.

Table 25.  Symptoms in 24 vanadium workers and 45 unexposed referentsa
Symptom                    Incidence (%)        X2 value
                       Referents    Exposed

Cough                  33.3         83.4        13.71b

Sputum                 13.3         41.5        5.55c

Exertional dyspnoea    24.4         12.5        0.592

Eyes, nose, throat     6.6          62.5        23.17b

Headache               20           12.5        0.124

Palpitations           11.1         20.8        0.538

Epistaxis              0            4.2         0.148

Wheezing               0            16.6        5.20c
a    From: Lewis (1959b).
b    Significant beyond P = 0.01.
c    Significant at  P = 0.02.

Table 26.  Physical findings in 24 vanadium workers and 45 unexposed
Physical finding            Incidence (%)       X2 value
                        Referents   Exposed
Tremors of hands        4.5         4.2         0.0320

Hypertension            13.3        16.6        0.0002

Wheezes, rales,         0           20.8        6.93b
or rhonchi

Hepatomegaly            8.9         12.5        0.003

Eye irritation          2.2         16.6        2.94

Injected pharynx        4.4         41.5        12.62b

Green tongue            0           37.5        14.53b
a    From: Lewis (1959b).
b    Significant beyond  P = 0.01.

    Roshchin  (1963b)  published an  account  of the  effects of
vanadium-containing  Bessemer  slag  dust on  45  workers.  Dust
concentrations in the air during various phases of  this  opera-
tion ranged from 5 to 150 mg/m3, with the highest concentrations

occurring  during  loading/unloading  of  broken  slag  as   the
trivalent oxide, mostly within spinellide. Repeated examinations
of  the 45 workers showed the slag dust to have an effect on the
respiratory  mucosa.   Subatrophic  rhinitis,  bronchitis,   and
pneumosclerosis  were  seen  in subjects  with long occupational
exposure  (11 workers).  Chronic  bronchitis was found  in every
worker  employed  for  5 years  or  more.   Clinical  and  X-ray
examination of all 45 subjects showed radiological changes in 24
employed for 10 years or more; in 11 subjects, pneumoconiosis of
stage  I-II  was  diagnosed.  X-ray  examination  showed diffuse
sclerotic  changes over  the whole  extent of  the  lung  fields
(except  for the supraclavicular zones),  small focal opacities,
intensified and enlarged shadows at the root of the  lungs,  and
marked  signs of bullous emphysema.   Predominant involvement of
the lower regions of the lungs (characteristic of silicosis) was
not present.  This pneumosclerosis was accompanied by changes in
the cardiovascular and nervous systems, biochemical disturbances
(hyper-vitaminosis  with dysproteinaemia and an  increase in the
serum concentration of sulfhydryl groups), a tendency to anaemia
and leukopaenia, and changes in the liver.

    In  another study, Roshchin (1964) described chronic effects
of vanadium in 193 workers who had been exposed to  aerosols  of
free vanadium pentoxide: 127 worked in vanadium  metallurgy  and
66   were  boiler  cleaners  (section  8.3.2).   The  length  of
occupational  contact with vanadium was  over 10 years for  60%,
from  5 to 10 years for 30%, and under 5 years for the remaining
10%.   Practically all complained of irritation of the nasal and
pharyngeal  mucosa including itching,  a profusely running  nose
(especially  during  work),  and unpleasant  sensations  in  the
throat  and  nose.  Epistaxis  was  frequent  in  20%.  Physical
examination  revealed a high incidence  of changes in the  nasal
mucosa:  dryness (40%), erosion  (23%), scars (8%),  perforation
(4%), hyperaemia (10%), and hypertrophy (7%).  Also  noted  were
dryness  of the pharynx  (5%),  hyperaemia of the pharynx  (5%),
hyperaemia of the larynx (4%), and tonsillitis (5%).   The  most
common  pathological changes in the upper respiratory tract were
subatrophic  rhinitis  (40%)  and destructive  changes  in nasal
mucosa  (35%), while hypertrophic  rhinitis was less  frequently
seen  (7%).  The overwhelming  majority had a  dry cough;  cough
with  viscid  sputum  was  less  common.   Workers  with  longer
occupational  exposure complained of shortness  of breath, which
appeared  sometimes after 5 but mostly after 10 years of work in
the industry.  Nearly all complained of aching or shooting pains
in the chest and of lassitude and weakness. The main respiratory
diseases  diagnosed  were  chronic bronchitis  (40%) and diffuse
pneumosclerosis  (13%).   Haematological tests  showed the total
serum-protein  concentration  to  be normal, y-globulins   to be
raised (19.4% compared with 12.2% in controls), and the albumin-
globulin ratio to be 1:1 - 1:2 (1:9 in controls).  Determination
of  total, residual, and protein sulfhydryl groups in the blood-
serum  revealed a marked decrease  of 7 - 13% compared  with the
controls.  Regular observations over a period of 14 years showed
that the chronic bronchitis tended to get worse,  with  develop-
ment of bronchospasm. After a long period of time, some subjects
developed  pneumosclerosis;  in  others, the  disease progressed

slowly  from chronic bronchitis  to diffuse pneumosclerosis  and
pulmonary emphysema.

    Eisler  et  al.  (1968)  studied  48  metallurgical  workers
occupationally  exposed to vanadium for  between 17.6  9 years.
Definite  clinical evidence of chronic bronchitis was present in
90%  of the subjects, and 50% had severe obstructive bronchitis.
In  control  groups,  which  included  basic-slag  crushers  and
furnace  operators (99 and 50, respectively), chronic bronchitis
was observed in 33% and 26%, respectively.

    A study on 13 workers engaged in the extraction and refining
of vanadium pentoxide from soot generated by the  combustion  of
heavy  fuel  oil  was  reported  by  Nishiyama  et  al.  (1977).
Concentrations  of vanadium in the  air at various locations  in
the work environment were all less than 0.5 mg/m3 (mean,  1.2  -
12 g/m3).   There was a significant incidence of  injection  of
the  pharynx (58.3%) compared with controls.  Elevated levels of
vanadium  in the urine and hair were detected both in currently-
exposed as well as in previously-exposed subjects.  Apart from a
slight  depression  in serum-cholesterol  levels, haematological
results were normal.

    Roshchin  (1968)  analysed  the incidence  of  influenza and
upper  respiratory catarrh as  a cause of  lost working time  in
workers  in vanadium metallurgical plants  compared with ferrous
metallurgical workers in adjacent plants.  The results are given
in  Table  27.   The  morbidity  was  consistently  higher among
workers   producing  vanadium  than   among  workers  in   other
departments in all years.

Table 27.  Morbidity from influenza and upper respiratory catarrha
Department                      Cases                   Days off work
                          (per 100 workers)           (per 100 workers)
                     1958   1959   1960  1962    1958   1959   1960   1962

Vanadium plant       40.6   68.4   58.8  59.8    180.6  376.7  271.9  336.5

Open hearth furnace  22.2   53.2   45.6  62.1     76.9  331.1  176    213.3

Blast furnace        21.9   46.7   37.8  47.6     36.3  262.8  166.6  215.5

Engineering shop     19.6   39.1   33.9  44.9     86.8  224.8  154.3  223.6

a    From: Roshchin (1968).

    Asthma  was  reported  in  4  workers  exposed  to  vanadium
pentoxide  dust  in  a  newly  established  vanadium   pentoxide
refinery (Musk & Tees, 1982).  One of the workers  had  positive
skin  tests  to environmental  allergens;  the others  were non-
atopic.  Three were smokers; one was an ex-smoker.  One  of  the
subjects  experienced irritation of the  upper respiratory tract
after a single exposure; dyspnoea and wheezing developed 2 weeks

later.   All  workers had  similar  irritant symptoms  and green
tongue.   Two  showed bronchial  hyperreactivity when challenged
with  histamine; these  were the  workers with  the most  recent
exposure.  In one worker, the asthmatic symptoms continued for 8
weeks after cessation of exposure.  There was no  indication  of
an immunological aetiology, and the authors concluded  that  the
effect was likely to be a direct chemical one.

    Kiviluoto  et  al.  (1979a,b, 1980,  1981a,b)  and Kiviluoto
(1980)  reported the results  of a cross-sectional  study on  63
males exposed to vanadium-containing dust in a vanadium factory;
a  reference group matched for age and smoking was selected from
a  magnetite ore mine.  The workers had been exposed to vanadium
dust for an average of 11 years at concentrations  ranging  from
0.1  to 3.9 mg/m3  (estimated average exposure  levels of 0.2  -
0.5 mg/m3); the respirable fraction (< 5 m)   was  20%.   Nasal
biopsies  and lung function tests  were taken at the  end of the
summer  holidays (duration,  2 -  4 weeks).   Nasal  smears  and
biopsies were repeated in 31 workers, 7 - 11 months later, after
hygienic  improvements had reduced the exposure levels to 0.01 -
0.04  mg/m3.  Microscopic examination of nasal smears revealed a
significant increase in neutrophils and biopsies of nasal mucosa
showed  significantly elevated numbers of plasma and round cells
in  the exposed workers.  There  was no further increase  in the
cell findings after 10 months of exposure to 0.01 -  0.04  mg/m3
vanadium  dust; eosinophils did not show any differences between
the  exposed and the  referents.  The authors  attributed  these
findings to "an irritating effect of vanadium dust on the mucous
membranes  of  the  upper  respiratory  tract".   Biopsies  from
workers  with the longest exposures (170 - 241 months) showed "a
zone-like  sub-epithelial infiltration of mononuclear  cells and
frequent  papillarity in the  mucous membrane surface  with  its
hyperaemic  capillaries".   The similarity  between this pattern
and  that seen in  vanadium-exposed rabbits (Sjberg,  1950) was
noted  (Kiviluoto et al., 1979b).   A random sample of  12 nasal
biopsies  was further investigated for the amount and classes of
immunoglobulins (IgE, IgG, IgM, and IgD).  IgG  subclasses  were
not studied.  There were no differences between the  12  workers
and their referents, which was construed as a further indication
of non-specific inflammation (Kiviluoto et al., 1981b).

    Pulmonary condition was assessed by means of questionnaires,
X-ray,  and  pulmonary function  testing.   There was  only  one
significant  difference  between  the  workers  exposed  for  an
average of 11 years to 0.1 - 3.9 mg/m3 (estimated average, 0.2 -
0.5   mg/m3)  and  at  the  time  of  investigation  to  0.01  -
0.04 mg/m3,  and their matched  referents; complaints of  wheeze
were  more common in the exposed worker group (Kiviluoto, 1980).
The  importance  of  this  finding  remained  doubtful.   It may
reflect  the respiratory findings  mentioned above, since  upper
respiratory  irritation may be  accompanied by transient  reflex
bronchospasm.   A series of  laboratory tests were  designed  to
evaluate  electrolyte,  protein  fractions,  carbohydrate,   and
lipids,  liver,  renal,  muscle,  pancreatic,  and  bone  marrow
functions, and immunological status.  There were no decreases in
serum-cholesterol  or triglycerides, and no clinical differences
between worker and control groups (Kiviluoto et al., 1981a).

    The  effects of vanadium compounds on health is not confined
to  the  development  of  local  respiratory  or  other lesions.
Various  studies, most of them  rather old, on patterns  of lost
working time due to morbidity have shown that the  incidence  of
disease  among workers in plants producing vanadium compounds is
considerably  higher than among  other workers (Symanski,  1939;
Syers,  1946; Sjberg, 1950,  1956; Reznik, 1954;  Reinl,  1958;
Matantseva, 1961; Watanabe et al., 1966; Roshchin,  1968,  1969;
Athanassiadis, 1969; Schumann-Vogt, 1969; Chiriatti, 1971).  The
most  significant  differences are  found  in the  incidences of
influenza,  upper respiratory catarrh,  and inflammation of  the
lungs.   The  difference  in  the  incidence  of  bronchitis  is
particularly marked.

8.4.2   Cleaning and related operations on oil-fired boilers

    Bronchitis  and  conjunctivitis  resulting from  exposure to
soot  (containing 6 - 11% vanadium)  during the cleaning of  the
stacks  of  oil-fired boilers  were  first recognized  by  Frost
(1951).   Frost did  not report  any other  effects, but,  in  a
subsequent  report  of  a boiler-cleaning  operation by Williams
(1952),  sneezing,  nasal discharge,  lachrymation, sore throat,
and  substernal  pain occurred  within  0.5 - 12 h  of exposure.
Within  6 - 24 h, secondary symptoms  developed; these consisted
of  dry  cough,  wheezing, laboured  breathing,  lassitude,  and
depression.   In  some cases,  the  cough became  paroxysmal and
productive.   Symptoms  lessened  only after  removal  from  the
working environment for 3 days.  Air sampling showed most of the
dust  particles to be smaller  than 1 g.  The vanadium  concen-
tration  ranged  from 17.2 mg/m3  in  a superheater  chamber  to
58.6 mg/m3 in a combustion chamber.  Roshchin (1962)  observed 8
cases  of acute vanadium poisoning in workers who cleaned boiler
flues  at power stations  burning high-sulfur oil.   Analysis of
soot  deposits showed that  the soot in  the region of  greatest
dust  formation (the pipes  of the steam  superheater and  water
economizer)  contained from 24  to 40% vanadium  pentoxide.  The
workers  carried out cleaning operations  without respirators or
with  respirators that did not provide the necessary protection.
After cleaning the boilers, the workers developed acute vanadium
poisoning: itching in the throat, sneezing, cough with difficult
expectoration,  and smarting eyes.   On the following  days, the
symptoms  became more severe.  Tightness in the chest, sweating,
general  weakness, conjunctivitis, and noticeable loss of weight
developed.  On examination one week later, hyperaemia and oedema
of  the  fauces and  posterior  pharyngeal wall  were  observed.
Harsh  breathing sounds and dry  crepitations were heard in  the
lungs.   X-ray examination showed  intensified lung markings  in
the middle zones of the right and left lungs and  thickening  of
the  fissure  on the  right.  One month  later, only one  worker
still  had cough, weakness,  perspiration, loss of  energy,  and
dyspnoea.   The other workers  recovered quickly, with  complete
disappearance of cough and shortness of breath.

    In  another  study  on workers  engaged  in  boiler-cleaning
operations  (Troppens,  1969),  the symptoms  were  described as
similar  to mild coryza or influenza with bronchitis.  Following

recovery,  workers  were tired,  debilitated, irritable, without
any appetite, and complained of watery eyes.  The first symptoms
were swelling of face and eyes as early as 20 min after entering
the boiler area.  Removal from exposure for 2 - 3 weeks resulted
in the disappearance of symptoms.  Skin blemishes  described  as
allergic  dermatoses were attributed  to absorption of  vanadium
through  sensitive  skin.  Troppens  claimed  that there  was an
increased  susceptibility  of  the vanadium  worker to asthmatic
bronchitis and emphysema.

    An  investigation  is  reported  on  53  workers  performing
emergency repair work on oil-fired power station boilers (Izycki
et  al., 1971).   They were  exposed to  vanadium  pentoxide  in
average  concentrations of  from 1.2  to 11 mg/m3  and  also  to
manganese,  calcium,  and  nickel oxides,  and sulfur compounds.
Characteristic  features  of  both acute  and  chronic  vanadium
poisoning  included upper respiratory catarrh  in 45%, increased
lung  markings  in  24.5%, and  bradycardia  in  22%  of  cases.
Persistent  chronic changes in the  respiratory tract (rhinitis,
pharyngeal  catarrh,  laryngitis,  and changes  in the paranasal
sinuses) were present in 45%.

    Milby  (1974)  reported 21  cases  of vanadium  poisoning in
boilermakers  installing  new  catalytic-converter tubes.   This
work  involved marble-sized pellets of vanadium containing 11.7%
V2O5.  The dust formed during the shaking of these pellets had a
particle  size of 1.1  - 1.5 m.   After  working for 72 h,  the
workers  began  to  complain  of  nasal,  eye,   and   bronchial
irritation.  By the 4th day, most felt very ill, with  signs  of
irritation  of the upper respiratory tract and eyes and pains in
the chest.

    In  a  study  by Garlej  (1974)  50  workers engaged  in the
cleaning of oil-fired boilers were compared with a control group
of  60 other workers.   Boiler deposits contained  44 -65% V2O5;
the  maximum exposure was estimated to be 10 mg/m3.  Although no
clinical  evidence of vanadium poisoning  was seen, a number  of
exposure-dependent  positive biochemical reactions were found in
the  boiler-cleaning  group.  Urinary  excretion of delta-amino-
levulinic  acid  (ALA),  porphobilinogen  (PBG),  and  porphyrin
increased  beyond the physiological limit, and the positive Nadi
reaction  (with  associated  green fluorescence)  occurred.  The
increased  excretion  of cytochrome  (as  indicated by  the Nadi
reaction)  suggested oxidation through V2O5 of the  thiol  group
-SH  cysteine  in the  protein  carrier, resulting  in decreased
binding of cytochrome in the mitochondria.

    A study on 17 men who were engaged in cleaning boilers at an
electric  generating station was  reported by Lees  (1980).   In
addition  to  clinical findings,  which  were similar  to  those
described  above,  urine-vanadium  levels were  determined,  and
pulmonary function measurements were made for a  week  following
exposure.   Sixteen  of the  men  wore protective  clothing, and
respirators  that were  found to  have about  9%  leakage.   One
workman  volunteered to wear only  a simple oro-nasal dust  mask

for 1 h of exposure.  The dust exposure level was  estimated  to
be  26 mg/m3;  respirable dust  (under  10 m)  was  measured at
523 g/m3   with a vanadium  content of 15.3%.   All of the  men
developed reduced pulmonary function that had not fully returned
to  normal  in one  week, but did  so after one  month.  Reduced
function outlasted the clinical symptoms by several days. Fig. 3
shows  the  contrast  in  pulmonary  reaction  between  the more
heavily  exposed individual and one  of the other workmen.   The
urine-vanadium level of the volunteer was 280 g/litre,  whereas
those of the remainder of the workers were below 40 g/litre.


    Other  observations of boiler-cleaning operations  have been
made  by Fallentin  & Frost  (1954), Sjberg  (1955),  Thomas  &
Stiebris  (1956), Hickling (1958),  and Kuzelova et  al. (1975).
In terms of respiratory symptoms relating to boiler-cleaning, it
should be noted that sulfates and sulfuric acid may  be  present
in  boiler soot  and may  be partly  responsible for  irritative
effects.   Hudson  (1964)  suggested  that  the quick  onset  of
symptoms  (lachrymation  with  nose and  throat irritation) with
rapid  recovery  following  removal from  exposure is character-
istic  of exposure to acid sulfates.  Response to vanadium expo-
sure is characterized by some delay in the onset  of  irritative
symptoms  (a  few  hours to  several  days)  and persistence  of
symptoms following removal from exposure (Hudson, 1964).

    A   recent   report  by  Levy  et  al.  (1984)  concerned  a
comparatively   high  incidence  of  severe   respiratory  tract
irritation  in boilermakers (74/100),  many of them  welders  in
areas   without   adequate  ventilation,   exposed  to  vanadium
pentoxide fumes in a power plant where conversion  from  oil- to
coal-burning occurred.  The severe illness of 70 men  caused  an
average of 5 days of absence, some objective tests  (e.g.,  FVC)
being  markedly  affected.   The vanadium  pentoxide content was
above  the permissible  exposure limit  in 8  samples, and  this
resulted   in  litigation  for  inadequate   protection  of  the

    Kuzelova  et al. (1977)  drew attention to  the occupational
risk   of   chimney   sweeps  cleaning   large-capacity  heating
facilities  in large housing settlements.  This coincided with a
report  of a detailed cross-sectional examination of 121 chimney
sweeps by Holzhauer & Schaller (1977) in the Federal Republic of
Germany  with an  average exposure  duration of  19 years  (  5
years).   Vanadium exposure was determined  by personal samples,
and measurements between 0.73 and 13.7 mg vanadium pentoxide/day
were  determined  compared with  4 g   in the  normal (average)
population.  Urinary excretion was determined to be between 0.15
and 13 g/litre,  which was significantly higher than the values
in 31 referents.  The main complaints of the chimney sweeps were
wheezing,  rhinitis,  conjunctival  irritation,  cough,   sputum
dyspnoea,  and  hoarseness;  there  were  no  skin  symptoms.  A
prospective  follow-up  of the  cohort  was emphasized,  but the
results are not yet available.

8.4.3   Handling of pure vanadium pentoxide or vanadate dusts

    Health effects due to occupational handling of pure vanadium
pentoxide  or vanadate dusts  have been reported.   Tara et  al.
(1953)  described the  effects of  vanadium exposure  in 4  dock
workers who unloaded and bagged spilled calcium  vanadate.   The
symptoms  (bronchitic  wheezing  sounds,  dyspnoea,   productive
cough,  haemoptysis  in  one case,  and  headache)  necessitated
interruption  of the work  after 1  days.   Zenz et al.  (1962)
described an acute illness that occurred in 18  workers  pellet-
izing pure vanadium pentoxide; it was characterized by a rapidly
developing  mild conjunctivitis, severe pharyngeal irritation, a
non-productive  persistent  cough,  diffuse rales,  and broncho-
spasm.  With severe exposure, 4 men complained of  itching  skin
and  a sensation of heat in the face and forearms.  The symptoms
became more severe after each exposure, suggesting a sensitivity
reaction,  but  their duration  was  not prolonged  by  repeated

8.4.4   Other industries

    Browne  (1955)  studied  vanadium poisoning  in  12 patients
exposed to exhaust fumes from gas turbines using heavy fuel oil.
Evidence of poisoning appeared between the first and 14th day of
exposure  and  consisted  of  conjunctivitis,  rhinitis,  cough,
crepitations,   and  dyspnoea.   Bleeding  appeared  before  the

    Other  occupations in which respiratory  effects of vanadium
exposure  have been reported  include operations connected  with
the  gasification  of  fuel oil  (Fear  &  Tyrer, 1958)  and the
manufacture  of phosphor for television picture tubes (Tebrock &
Machle, 1968).  In the latter study, elevated blood pressure was
noted in men exposed to vanadium pentoxide.


9.1  Environmental Levels and Exposures

    While  vanadium concentrations in  the air of  remote  rural
areas are less than 1 ng/m3, other rural areas  show  concentra-
tions  in excess of 50  ng/m3.  This is generally  considered to
reflect  the local  burning of  fuel oil  with a  high  vanadium
content.   Typical concentrations in  urban air may  range  from
below  1 ng/m3 to over 300 ng/m3, with annual averages for large
cities  of  about  20 -  100  ng/m3.   At an  annual  average of
50 ng/m3  and a respiration rate  of 20 m3, the  total amount of
vanadium  reaching the respiratory  tract would be  only  1 g.
Assuming  a rate of  absorption of about  25%, the direct  daily
contribution of vanadium from air would be about 250 ng.

    Drinking-water supplies without excessive vanadium pollution
contain  from  less  than  1 g/litre   to  occasional   maximum
concentrations  of 15 - 30 g/litre.   Two comprehensive surveys
have  shown  average  concentrations of  4.3 and 4.85 g/litre,
respectively.   At a  daily intake  of 2  litres of  water,  the
average  daily intake  of vanadium  with water  would  be  about
10 g,   ranging from  about 1 g   to 30  -  60 g.    Although
levels  in  ordinary  water supplies  would  vary  considerably,
intake  should rarely exceed  100 g/day.   Intake with  bottled
waters from mineral springs may exceed these values.

    As  a rule, the  concentration of vanadium  in food is  low.
High  levels reported in early  studies have been attributed  to
analytical   differences.   Recent  studies  on  complete  diets
suggest  a daily intake of  vanadium of about 10 -  70 g,  with
the majority of estimates remaining below 30 g.    Assuming  an
absorption rate from the gastrointestinal tract of 1 -  2%,  the
contribution  from food  and water  is unlikely  to exceed  4  -
5 g/day.

    Vanadium  concentrations in air  in the vicinity  of  metal-
lurgical industries are often about 1 g/m3.   In the production
of vanadium metal or compounds, concentrations may reach  a  few
mg/m3.   In  boiler-cleaning operations,  dust concentrations in
air  are frequently around 50 - 100 mg/m3, and concentrations as
high  as 500 mg/m3 have  been reported; the vanadium  content of
the  dust is about 5 - 17% as vanadium pentoxide and 3 - 10 % as
lower vanadium oxides.  The need for personal protection devices
in such operations is obvious.

9.2  Physiological Role

    While  present  knowledge  indicates  that  vanadium  is  an
essential  element for chicks and rats, conclusive evidence that
vanadium  is  essential for  other  species, including  man,  is
lacking.   A variety of physiological  and biochemical processes
have  been found  to be  vanadium sensitive.   However, so  far,
there  is no evidence of  adverse effects arising from  vanadium
deficiency  in man, and the daily requirement of vanadium in the
diet is not known.

9.3  Effects and Dose-Response Relationships

    The toxicity of vanadium varies in experimental animals with
both  the species and  route of administration.   Small animals,
such  as the rat and  mouse, tolerate the metal  better than the
rabbit  and horse.  The toxicity  of vanadium is low  when given
orally,  moderate when inhaled,  and high when  injected.  As  a
rule,   the  toxicity  of  vanadium  increases  as  the  valency
increases, pentavalent vanadium being the most toxic.

9.3.1   Local effects and dose-response relationships

    Exposure  of  2 volunteers  to  vanadium pentoxide  dust  at
1 mg/m3  for 8 h resulted in irritation of the respiratory tract
with  cough starting 5  h later.  The  cough lasted for  8 days.
Exposure  of 5 volunteers to a concentration of 0.2 mg/m3 caused
the  same symptoms, i.e., coughing,  but with an onset  at 20 h.
The  cough lasted for 7  - 10 days.  Respiratory  irritation was
noted  in 2 subjects exposed to 0.1 mg/m3 for 8 h.  The irritant
effect  was manifested as an increase in mucous production, 24 h
after  exposure, and total recovery within 4 days.  Tickling and
itching,  together with dryness of  the mucous membranes of  the
mouth,  was reported by  11 volunteers exposed  to 0.4 mg/m3  of
vanadium  pentoxide  condensation  aerosol;  0.16  mg/m3  caused
irritation  in only 5  subjects, and 0.08  mg/m3 did not  induce
symptoms in any of the subjects.
    Exposure to high concentrations of vanadium is  possible  in
the industrial production and use of vanadium, especially in the
cleaning  of  oil-fired  boilers.  Frequently  reported irritant
symptoms  include sneezing, nasal  discharge, irritation of  the
eyes  with lachrymation, sore  throat, dry or  productive cough,
and chest pain.  Normally, such symptoms disappear in a few days
when   exposure  has  ceased.   Cough,   increased  sputum,  and
particularly irritation of the eyes, nose, and  throat  occurred
among  24 male  workers exposed  to a  maximum of  0.9  -  5  mg
vanadium/m3 (measured as vanadium pentoxide V2O5).  Most workers
had  been  exposed  to 0.3  mg/m3  (section  8.4.1).   A  cross-
sectional  study of 63 male workers exposed for an average of 11
years  to vanadium-containing dust at  0.2 - 0.5 mg  vanadium/m3
(range,  0.1 - 3.9 mg/m3) showed chronic irritant effects in the
mucous  membranes  of the  nose.   The nasal  changes  persisted
unchanged  during  subsequent  exposure  to  much  lower  levels
(0.01 - 0.04 mg/m3).

    Heavily   exposed  workers  (dust  concentrations   of  5  -
150 mg/m3)   developed atrophic rhinitis and chronic bronchitis.
Bronchospasm is also a feature in heavily exposed workers.

    The  effects on 63 workers of long-term exposure to vanadium
at  0.2 -  0.5 mg/m3  were studied  using matched  referents,  a
questionnaire  on  respiratory symptoms,  chest radiography, and
lung  function testing (section  8.4).  There was  no change  in
ventilatory  function compared with the matched reference group;
only complaints of wheezing were significantly more common among
exposed workers than among referents.  However, in another study

the  forced vital capacity (FVC)   was reversibly reduced in  17
boiler  cleaners who had been exposed to a time-weighted average
respirable dust of 523 g/3  containing 15% of vanadium (section

    Vanadium  poses  weak  sensitizing properties  when skin and
mucous membranes of the upper respiratory tract are  exposed  to
high  concentrations, manifested by the  development of allergic
dermatitis  and rhinitis in  workers in contact  with  vanadium.
The  allergic  nature  of  these  manifestations  is  proved  by
positive reactions of epicutaneous tests with a 2%  solution  of
sodium vanadate.  There is information on the sensitizing effect
of vanadium in tests on animals.

    In  one study (section 8.4.1), 9 workers out of 36 developed
a  dry eczematous dermatitis.  These workers had been exposed to
vanadium pentoxide at about 6.5 g/m3.

    Green tongue is seen in a proportion of workers  exposed  to
vanadium-containing dust, and is an indication of exposure.

9.3.2   Systemic effects and dose-response relationships Metabolic effects 

    The  effect of vanadium on dental caries remains a debatable
issue  (section 5.4.2).  The  application of a  50% paste of  an
ammonium  salt of vanadium and  glycerol was reported to  reduce
caries  in children aged  7 - 11 years.   Other studies  between
1955  and 1968 have failed  to demonstrate a clearly  beneficial
effect (section
    Soluble  diammonium oxytartarovanadate (150 - 200 mg/day for
6  weeks) was administered to  5 healthy adult male  volunteers.
There  was a significant reduction  of plasma-cholesterol levels
at the end of the period.  A temporary drop in  the  cholesterol
level  was also observed in  2 out of 6  patients given ammonium
vanadyl tartrate for 7 weeks at 50 or 100 mg/day.   The  results
were not convincing and the temporary drops in cholesterol
levels  were  not  statistically  significant.   No  significant
changes in serum-cholesterol levels were noted in 12 patients (9
of  whom  were  hypercholesterolaemic) given  diammonium vanado-
tartrate  orally for 6  months, (25 mg  three times daily  for 2
weeks, increased to 125 mg daily in 10 patients).  Although some
studies   on   rats   and  rabbits   have  indicated  decreasing
cholesterol levels following administration of vanadium and have
corroborated the reduced levels of cholesterol observed by other
authors,  this  effect of  vanadium  has not  been  convincingly
demonstrated in human beings so far (section

    Vanadium  pentoxide in the diet  (25 - 1000 mg  vanadium/kg)
resulted in lower levels of cystine in the hair of rats compared
with  those in controls,  indicating the inhibition  of  cystine
synthesis  (section  7.2.1).  Rats  administered sodium vanadate
intraperitoneally  (5  -  10  mg/kg  body  weight  as  a  single

injection  or  a  dietary  concentration  of  500  mg/kg) showed
reduction of co-enzyme A in the liver; this has  been  construed
as an explanation of the reduction of cystine  (section  7.2.1).
When  workers  were  exposed to  vanadium-containing dust (0.2 -
0.5 mg  vanadium/m3,  at the  time of the  study), there was  no
correlation  between  exposure  level  and  cystine  levels   in
fingernails, and no decrease in levels of  serum-cholesterol  or
triglycerides (section 8.4.1).

    The  data on the effects  of vanadium on haematopoiesis  are
inconsistent.   A favourable effect of vanadium chloride (0.6 mg
vanadium/kg diet) on haemoglobin levels in rats, previously made
anaemic,  had already been suggested  in 1931 (section 7.2).   A
small  increase  in  erythrocytes  and  haemoglobin  levels  was
observed  in  rabbits  given vanadyl  sulfate subcutaneously, at
1 mg/kg  body weight  daily, for  2 months).   When 32  vanadium
workers  who  had  been exposed  for  more  than 6  months  were
compared with 45 referents, matched for age, no differences were
seen  in haematocrit levels  (  It is  not possible  to
assess  the  effects  of  low-level  vanadium  exposure  on iron
metabolism. Effects on the nervous system 

    Systemic  effects are rare  in workers exposed  to  vanadium
compounds.   Non-specific signs and symptoms including headache,
weakness,  nausea,  vomiting,  and tinnitus  have been reported.
Such  signs and symptoms have mostly occurred in workers exposed
to  extremely high dust concentrations,  when cleaning oil-fired
boilers,  but it has not  been possible to derive  dose-response
relationships for them.

    Elevated  vanadium levels in whole blood and serum have been
reported  in patients suffering from depressive illness.  In one
report,  the vanadium levels fell to normal with recovery of the
patients.   The role  of vanadium  in depressive  states is  not
known (section 8.2.2).

    In mice and rats, repeated oral administration  of  vanadium
pentoxide  or  ammonium  vanadate  at  doses  of  0.05 - 0.5  mg
vanadium/kg  body  weight,  daily, for  6  months  and 21  days,
respectively,  resulted in impaired conditioned reflexes.  Daily
oral  doses of sodium  metavanadate (3.2 g/kg  body  weight per
day  for 10  - 15  days)  caused  increases in  the activity  of
cytochrome  oxidase  in  the brain  of  guinea-pigs;  a dose  of
128 g/kg  per day did not have any effect, whereas  5.12  mg/kg
per   day   reduced   the   activity   (section   7.2).    Total
cholinesterase activity in the brain of rats  was  significantly
reduced by the intraperitoneal administration  of 1  mg  vanadyl
sulfate/kg body weight (section 7.3). Effects on the liver 

    There are insufficient human data to make an  assessment  of
the  effects of vanadium on the liver.  Rats and rabbits exposed

through  inhalation  to  vanadium pentoxide,  trioxide,  or tri-
chloride  (10  - 70  mg/kg, 2 h/day,  for 9 -  12 months) showed
fatty  changes with partial cell necrosis in the liver.  A clear
reduction  in the liver tissue respiration and a decrease in the
albumin/globulin  ratio in the serum were also observed.  Subcu-
taneous  injection of ammonium  vanadate (1 mg  vanadium/kg body
weight per day, for 30 days) caused similar fatty changes in the
liver  of  rats.   Intraperitoneal injections  of  sodium  meta-
vanadate  (1.25 - 2.5 mg vanadium/kg body weight) in rats caused
loss of weight.  The toxic effects observed were correlated with
the concentration of vanadium in the liver (section 7.2). Effects on the kidney 

    Data  on  the effects  of vanadium on  the human kidney  are
lacking.   Intravenous injection of  sodium metavanadate (2.5  -
5 mg/kg body weight) in male dogs resulted in  albuminuria.   In
mice,  acute tubular necrosis followed subcutaneous injection of
ammonium vanadate at a dose equivalent to 20 mg vanadium/kg body
weight.  Rats and rabbits inhaling vanadium chloride  (70  mg/m3
2 h/day,  for 9 - 12 months) caused fatty changes in the kidney.
Vanadate has diuretic and natriuretic effects on the  kidney  in
the  rat but not  in the dog  or cat.  Vanadate  has  also  been
reported   to  increase  the   urinary  excretion  of   calcium,
phosphate, bicarbonate, and chloride by the rat  kidney.   These
diuretic  and natriuretic effects are  thought to be due  to the
inhibition  of Na+-K+-ATPase causing  inhibition of the  tubular
reabsorption. Cardiovascular effects 

    Palpitation  of the heart at  rest and on exercise  has been
reported   in   workers  occupationally   exposed  to  vanadium.
Transient  coronary  insufficiency,  a high  incidence of extra-
systoles  and bradycardia were reported (section 8.3).  Exposure
of workers to low levels of vanadium pentoxide (0.2 - 0.5 mg/m3)
did  not cause  any pathological  changes in  the blood  picture
(section 8.4.1).

    Electrocardiographic    changes    (ST-segment   depression,
increased   T-wave  amplitudes)  were  seen   after  intravenous
injection  of sodium metavanadate  in dogs (2.5  - 5 mg/kg  body
weight).  Long-term inhalation exposure of rats and  rabbits  to
vanadium  pentoxide,  trioxide,  or  chloride  (10  -  70 mg/m3,
2 h/day,  for 9 -  12 months) caused  fatty changes in  the myo-
cardium as well as perivascular swelling. Pulmonary effects 

    Asthmatic   reactions   in  conjunction   with  non-specific
bronchial  hyperreactivity  have  occasionally been  reported in
refinery  workers exposed to vanadium pentoxide dust.  There has
not  been any evidence of an immunological mechanism behind such
cases.   A dose-dependent decline in forced expiratory volume in
one  second (FEV1)  and forced  vital capacity  (FVC)  has  been
demonstrated  in boiler cleaners.   The functional increase  did

not return to normal during the first week  following  exposure,
but  fully recovered within one month.  The mechanism leading to
the obstructive pulmonary impairment has not been clarified. Effects on the immune system 

    In  mice, vanadium and  ammonium vanadate affect  the normal
function of the immune system.  Vanadium had  slight  depressant
effects on antibody-forming cells and increased DNA synthesis in
splenic  leukocytes.   Ammonium  vanadate  increased  resistance
to E.  coli endotoxin,  but  decreased  resistance   to Listeria
lethality.  In the spleen, it increased the rosetting capability
of  leukocytes, the formation  of megakaryocytes, and  red blood
cell precursors (section 7.7).

9.3.3   Reproduction, embryotoxicity, and teratogenicity

    Human  data on the effects  of vanadium on reproduction  and
embryotoxicity  are lacking.  Vanadium administered  to pregnant
rats by subcutaneous administration of metavanadate (0.85 mg/kg,
equal to 1/20 LD50) accumulated in the placenta.   However,  the
extent  to  which  it reaches  the  fetus  has not  been clearly
established.  During the lactation period, vanadium was found in
the  mammary glands and  was excreted with  milk.  Morphological
changes  in spermatozoa as well as desquamation of spermatogenic
epithelium  in  the  seminal tubuli  were observed.  Gonadotoxic
effects were suggested by the absence of fertilization of female
rats by male rats that had been exposed to 0.85  mg  vanadium/kg
body weight.  The same doses of vanadium given to female rats on
the fourth day of pregnancy significantly decreased  the  number
of fetuses (section 7.8.1).

    Weanling  pigs receiving vanadate  (200 mg vanadium/kg  body
weight) showed a suppressed growth rate and increased mortality.
Vanadium  was  not  markedly toxic  when  fed  to growing  lambs
(200 mg/kg, 84 days) (section 7.8.1).

    Tentative  results suggest that vanadium  is teratogenic for
rats  and hamsters causing skeletal  anomalies and death of  the
fetuses.  Dose-response relationships have not been demonstrated
(section  7.8.2).  There are  no human data  concerning possible
teratogenic effects of vanadium.

9.3.4   Mutagenicity

    The data on the mutagenic potential of vanadium in bacterial
systems  are  inconclusive.   There are  positive  and  negative
results  with E.  coli and  Salmonella tests (section  7.9).  Data
suggest the induction of micronuclei, but not  sister  chromatid
exchange  or  dominant-lethal mutations.   Chromosome effects in
vivo and  in vitro  have not been studied.

9.3.5   Carcinogenicity

    Life-time studies on mice given 5 g  vanadyl ions/ml as the
sulfate  in  drinking-water did  not  increase the  incidence of

spontaneous    tumours   and   intraperitoneal   injections   of
vanadium(III)2.4pentanedione  (24, 60, or 120 mg/kg body weight)
did  not increase the incidence  of lung adenomas in  mice.  The
results  of  a long-term  study  on rats  with  intrabronchiolar
implants  of  vanadium solids  were  negative.  The  few studies
available do not provide any indications of carcinogenic effects
of vanadium (section 7.10).

9.3.6   Risks from exposure of the general population

    There  are  only a  few studies on  the possible effects  of
vanadium  in  ambient air  on  the general  population  (section
8.3.2).  In one study, air concentrations of  vanadium  together
with  12 other trace elements  were found to be  correlated with
mortality  from  pneumonia  and  lung  cancer  (coefficients  of
correlation  of  0.443 and  0.347,  respectively) and  also with
mortality from bronchitis (coefficient of correlation of 0.563).
In  another study, a correlation between the levels of vanadium,
cadmium,  zinc, tin,  and nickel  and the  incidence of  several
diseases  including  "diseases  of the  heart", "nephritis", and
"arteriosclerotic heart" was claimed, but the results  of  these
studies do not establish any causal relationships.


    There  is a conspicuous lack  of data on several  aspects of
the health effects of vanadium compounds.  The overwhelming bulk
of  recent  research  focuses on  the  effects  of  vanadium  on
biochemical systems, especially specific effects on enzymes, and
there  are major gaps in  knowledge with respect to  analytical,
metabolic, and exposure data.

    There   are  indications  of  a  weak  mutagenic  effect  of
vanadium,    but   the   data   are   partly   conflicting   and
uncorroborated.    Further  confirmative  mutagenicity  studies,
including studies on chromosomal effects, should be  given  high
priority.   Data on the  carcinogenicity of vanadium  in various
species  are practically non-existent.  Such  studies are urgent
and should be conducted as long-term exposure studies.

    Vanadium  induces  toxic  effects on  the  fetus.   However,
whether these are direct effects or indirect  effects  resulting
from effects of vanadium on the mother is not known.  Studies to
assess the nature of the teratogenic effects and  the  mechanism
behind them should be encouraged.

    Effects   resulting  from  high  occupational   exposure  to
vanadium  dusts  have  been  reasonably  well  described.   Such
exposure  levels may cause a variety of clinical manifestations.
However,  they  should be  remedied  by hygienic  and  technical
improvements.   Dose-effect and dose-response relationships have
not  been well defined  at low exposure  levels in the  range of
approximately 0.01 - 0.5 mg/m3.  It is considered  important  to
develop specific indicators for the detection of  early  adverse
effects of vanadium on man.

    Epidemiological  studies  on  occupational  cohorts,  paying
particular  attention  to  exposure  levels  and  using   proper
referent  groups,  should  be  encouraged.   The  literature  is
inconsistent   regarding   the   documentation  of   sensitizing
properties of vanadium compounds.  This is an  important  aspect
with regard to worker protection.
    An area of great importance is the exposure of  the  general
population.   There are considerable geographical  variations in
vanadium  concentrations  in  air  and  water.   Epidemiological
studies  on  populations  living  in  areas  with  high vanadium
exposure  should  be  carried  out,  relating  possible  adverse
effects  to  exposure levels.   Such  studies should  take  into
account possible interactions with other pollutants.


ACGIH   (1986)   Threshold  limit values  for chemical substances
and  physical agents in the  work environment , Cincinnati, Ohio,
American Conference of Governmental Industrial Hygienists.

M.Z.,  SHKOLENOK, G.F., & KHREPINYUK,  T.E.  (1975)  [Determina-
tion  of  the  bulk  substances  in  preparations  of  potassium
dichromate  and  ammonium  vanadate  by  means  of  differential
coulometry.]  Zavod. Lab ., 41(4): 385-387 (in Russian).

AIYAR,  A.S.  &  SREENIVASAN,  A.   (1961)   Effect  of vanadium
administration  on  coenzyme  Q metabolism  in  rats.  Proc. Soc. 
 Exp. Biol. Med ., 107: 914-916.

G.G.    (1974)   [The  chemistry  and   technology  of  vanadium
compounds.] In: Ivakin, A.A. & Voronova, E.M., ed. [ Proceedings
of  the International Conference on the Chemistry and Technology
of  Vanadium  Compounds ,]   Perm, Scientific  Institute of Black
Metals (in Russian).

ALI,  S.A., PEET,  M., &  WARD, N.I.   (1985)  Blood  levels  of
vanadium, caesium, and other elements in depressive patients.  J.
affective Disord ., 9(2): 187-191.

ALLAWAY,  W.H.   (l968)   Selenium, molybdenum,  and vanadium in
human blood.  Arch. environ. Health , 16: 342-348.

ANBAR,  M. & INBAR, M.  (1962)  Effect of pyrodoxial 5-phosphate
in  the  presence  of  vanadyl  ions  of  the  de-iodination  of
thyroxine.  Nature (Lond.) , 196: 1213.

ARNON,  D.I.   (1958)   The  role  of  micronutrients  in  plant
nutrition  with special reference to photosynthesis and nitrogen
assimilation.  In: Lamb, C.A.,  Bentley, 0.G., &  Beattie, J.M.,
ed.  Trace elements , New York, Academic Press, pp. 1-32.

ARNON,  D.I. &  WESSEL, G.   (1953)  Vanadium  as  an  essential
element for green plants.  Nature (Lond.) , 172: 1039-1040.

ATHANASSIADIS,  Y.C.   (1969)   Preliminary  air pollution survey
of  vanadium  and  its compounds:  A literature review , Raleigh,
North  Carolina,  National Air  Pollution Control Administration
(Publication No. APTD 69-48).

AZARNOFF,   D.L.  &  CURRAN,  G.L.   (1957)   Site  of  vanadium
inhibition  of cholesterol biosynthesis (letter  to the editor).
 J. Am. Chem. Soc ., 79: 2968.

AZARNOFF,  D.L., BROCK, F.E., & CURRAN, G.L.  (1961)  A specific
site   of  vanadium  inhibition  of   cholesterol  biosynthesis.
 Biochem. Biophys. Acta , 51: 379-398.

BABENKO,  G.A. & VANDZHURA,  I.N.  (1969)  [Vanadium  metabolism
after  supplementary administration of certain  microelements in
experimental  atherosclerosis.]  Bull.  exp.  Biol.  Med ., 67(6):
72-73 (in Russian).

BAGGETT,  W.L. & HUYCK, H.P.  (1959)  Spectrochemical determina-
tion  of  vanadium  in alkali  brines.  Anal. Chem ., 31(8): 1320-

BAKAL,  G.F.  &  LISECKAJA,  G.S.   (1971)   [Determination   of
vanadium  in  mercury  using  the  reaction  of   oxidation   of
pyrocatechin  by  ammonium  persulfate.]  Ukr. khim  Zh .,  37(6):
594-597 (in Russian).

BALESTRA,  G. & MOLFINO,  F.  (1942)  [Lung  impairments due  to
dusts  in operations to  extract vanadium from  petroleum  ash.]
 Rass. Med. Ind. Ig.  Lav ., 13: 5-12 (in Italian).

BALFOUR, W.E., GRANTHAM, J.J., & GLYNN, I.M.  (1978)  Vanadate -
stimulated natriuresis.  Nature (Lond.) , 275: 768.

BARANNIK,  P.I., MIKHALYUK, I.A., & MOTUZKOV, I.N.  (1969)  Data
on the role of chromium, lead, vanadium and the  natural  radio-
activity of foodstuffs in the etiology of  endemic  goiter.  Hyg.
Sanit ., 35(2): 289-291.

BARBOOTI,  M.M.  &  JASIM, F.   (1982)   Electrothermal  atomic-
absorption determination of vanadium.  Talanta , 29: 107-111.

BARNES,  R.M.,  FODOR,  P., INAGAKI,  K.,  &  FODOR, M.   (1983)
Determination  of  trace  elements in  urine  using  inductively
coupled   plasma   spectroscopy  with   a  poly(dithiocarbamate)
chelating resin.  Spectrochim. Acta , 38B: 245-257.

BARRY,  E.F., REI, M.T., REYNOLDS,  H.H., & O'BRIEN, J.   (1975)
Determination  of  nickel  and  vanadium  in  the  atmosphere of
eastern Massachusetts.  Environ. Lett ., 8(4): 381-385.

BEARD,  H.H., BAKER, R.W., & MYERS, V.C.  (1931)  Studies in the
nutritional anemia of the rat.  J. biol. Chem ., 94: 123.

BELEHOVA,  V.A.  (1966)  [Spectral analysis  of vanadium content
in  intact teeth and in teeth damaged by caries.]  Stomatologija ,
4: 85-86 (in Russian).

BELEHOVA,  V.A.  (1969)  [Vanadization  of teeth as  a means  of
preventing  dental caries.]  Nauchn. Tr. Irkutsk. Med. Inst ., 95:
20-33 (in Russian).

BERGEL, F., BRAY, R.C., & HARRAP, Y.R.  (1958)  A  model  system
for   cysteine   desulphydrase   action:  pyridoxal   phosphate-
vanadium.  Nature (Lond.) , 181: 1654-1655.

BERNHEIM, F. & BERNHEIM, M.L.C.  (1938)  Action of  vanadium  on
tissue oxidation. Science, 88: 481.

BERNHEIM,  F. & BERNHEIM, M.L.C.  (1939)  The action of vanadium
on the oxidation of phospholipids by certain  tissues.  J.  biol.
Chem ., 127: 353.

BERROW,  M.L. &  WEBBER, J.   (1972)  Trace  elements in  sewage
sludges.  J. Sci. Food Agric ., 23: 93-100.

BERTRAND,  D.  (1942)  Le vanadium comme lment oligosynergique
pour  l'Aspergillus niger. Ann. Inst. Pasteur , 68: 226-244.

BERTRAND,  D.   (1950)   Survey  of  contemporary  knowledge  of
biochemistry.  II.  The  biogeochemistry of  vanadium.  Bull. Am.
Mus. Natl Hist ., 94(7): 407-455.

BEYHL,  F.E.  (1983)  Action of ammonium metavanadate on hepatic
 enzymes in vitro . Arch. Toxicol ., Suppl. 6: 250-253.

BIGGS,  W.R.  & SWINEHART,  J.H.   (1976)  Vanadium  in selected
biological  systems. In: Sigel, H., ed.  Metal ions in biological
systems , New York, Marcel Dekker, Vol. 6 , pp. 141-196.

BONIG,  G.  &  HEIGENER,  H.   (l971)   [Micro-determination  of
vanadium   in   biological   substances   by   selective   paper
chromatography.]  Landwirtsch. Forsch ., 25: 139-143 (in German).

BORISENKO,  L.F.  (1973)  [ Vanadium ,]   Moscow, Nedra Publishing
House (in Russian).

BOWEN,  H.J.M.  (1963)   The elementary  composition of mammalian
blood , Berkshire,  Wantage Research Laboratory, Isotope Research
Division (AERE-R 4196).

A.V., & TIUKIUPO, E.B.  (1978)  [On the accumulation  of  nickel
and  vanadium  in the  vicinity  of industrial  centres.]  Gig. i
Sanit ., 43(2): 92-95 (in Russian).

BRODERICK,  G.N.   (1977)    Vanadium -  1977 , Washington  DC, US
Department of the Interior, Bureau of Mines  (Mineral  Commodity
Profiles, MCP-8).

BROEKAERT, J.A.C., WOPENKA, B., & PUXBAUM, H. (1982) Inductively
coupled plasma optical emission spectrometry for the analysis of
aerosol samples collected by cascade impactors.  Anal. Chem ., 54:

BROWNE,  R.C.  (1955)  Vanadium poisoning from gas turbines.  Br.
J. ind. Med ., 12: 57-59.

BROWNE,  R.  & STEEL,  J.  (1963)  The  control of the  vanadium
hazard in catalytic oil-gas plants.  Ann. occup. Hyg ., 6: 75-79.

BROWNING,  E.   (1969)   Vanadium.  In:  Toxicity  of  industrial
metals , 2nd ed., London, Butterworths, pp. 340-347.

BUCHET, J.P., KNEPPER, E., & LAUWERYS, R.  (1982)  Determination
of  vanadium  in  urine  by  electrothermal  atomic   absorption
spectrometry.  Anal. Chim. Acta , 136: 243-248.

BUCKINGHAM,  D.A.   (1973)   Structure  and  stereochemistry  of
coordination  compounds.  Part  1. Coordination  chemistry.  In:
Eichhorn, G.L., ed.  Inorganic biochemistry , Amsterdam, New York,
Oxford, Elsevier Science Publishers,  Vol. 1 , p. 18.

BUDNIKOV,  G.K.  &  MEDJANCEVA, E.P.   (1973)  [Determination of
vanadium  and nickel in  bitumen by oscillographic  polarography
with  linear change of potential.]  Zh.  anal. Khim ., 28(2): 301-
305 (in Russian).

BUONO, J.A., BUONO, J.C., & FASCHING, J.L.  (1977)  Simultaneous
determination of Al, V. Mn and Cu from  neutronactivated  saline
matrices  by precipitation with poly-5-vinyl-8-hydroxyquinoline.
 J. radioanal. Chem ., 36: 353.

BUTT,  E.M., NUSBAUM, R.E., GILMOUR, T.C., DIDIO, S.L., & Sister
MARIANO   (1964)  Trace metal levels  in human serum and  blood.
 Arch. environ. Health , 8: 60.

BYRNE,  A.R. & KOSTA, L.  (1978)  Vanadium in foods and in human
body fluids and tissues. Sci. total Environ ., 10: 17-30.

BYRNE,  A.R.  &  KOSTA, L.   (1979)   On  the vanadium  and  tin
contents of diet and human blood.  Sci. total  Environ ., 11:  87-

CANALIS,  E.  (1985)  Effect  of sodium vanadate  on  deoxyribo-
nucleic  acid and protein  synthesis in cultured  rat calvariae.
 Endocrinology , 116(3): 855-862.

CANNON,  H.L.   (1963)   The biogeochemistry  of  vanadium.  Soil
Sci., 96(3): 196-204.

CANTLEY, L.C., Jr & AISEN, P.  (1979)  The fate  of  cytoplasmic
vanadium.  Implications  on (Na,  K)-ATPase inhibition.  J. biol.
Chem ., 254: 1781-1784.

LECHENE,  C.,  &  GUIDOTTI, G.   (1977)   Vanadate  is a  potent
(Na++,K)-ATPase  inhibitor  found  in ATP  derived from muscle.  J.
biol. Chem ., 252(21): 7421-7423.

CANTLEY,  L.C., Jr, CANTLEY, L.G.,  & JOSEPHSON, L.  (1978a)   A
characterization  of  vanadate  interactions  with  the  (Na,K)-
ATPase.  J. biol. Chem ., 253: 7361-7368.

CANTLEY, L.C., Jr, RESH, M.D., & GUIDOTTI, G.  (1978b)  Vanadate
inhibits  red cell, (Na+, K+) ATPase from the cytoplasmic side.
 Nature (Lond.) , 272: 552-554.

CARLSON,  R.M.K.  (1977)   The  structure of the  native vanadium
chromagen   in  tunicate  blood  cells , Palo  Alto,  California,
Stanford  University, 252 pp  (Ph.D. Thesis) (University  Micro-
films No. 78-2142).

CARLTON,  B.D., BENEKE, M.B., & FISHER, G.L.  (1982)  Assessment
of the teratogenicity of ammonium vanadate using  Syrian  golden
hamsters.  Environ. Res ., 29(2): 256-262.

CARPENTER, G.  (1981)  Vanadate, epidermal growth factor and the
stimulation  of  DNA synthesis.  Biochem.  biophys. Res. Commun., 
102: 1115-1121.

CASSANI,  F.  (1969)  [Potentiometric determination  of titanium
and vanadium.]  Chim. Ind. (Milan) , 51: 1248-1251 (in Italian).

CAWSE,  P.A. & PEIRSON, D.H.,  ed.  (1972)   Analytical study  of
trace  elements in the atmospheric  environment , Harwell, Atomic
Energy Research Establishment (No. AERE-R 7134).

(1986)   Vandium complexes of  transferrin and ferritin  in  the
rat.  Biochim. Biophys. Acta , 884(1): 84-92.

CHIRIATTI,  G.N.   (1971)  [Prevention  of occupational vanadium
poisoning.]  Folia med ., 54: 57-76 (in Italian).

CHRISTIAN,  G.D.  (1971)  Catalytic determination of vanadium in
blood and urine.  Anal. Lett ., 4(4): 187-196.

CHRISTIAN,  G.D.  &  FELDMAN, F.I.   (1970)   Atomic  absorption
spectroscopy.  In:  Applications  in  agriculture,  biology,  and
medicine , New York, John Wiley and Sons, pp. 276-281.

CHRISTIAN, H.C.M. & ROBINSON, J.W.  (1971)  The determination of
vanadium and nickel in mineral oils by flameless  graphite  tube
atomization.  Anal. Chim . Acta, 56: 470-473.

CHUPAHIN,  S.M.,  KRIUCHKOV,  O.M.,  &  RAMENDI,  G.I.    (1972)
[ Analytical   capabilities of spark-source  mass spectrometry ,]
Moscow, Atom Publishers (in Russian).

CLARK, R.J.H.  (1975)   The chemistry of vanadium,  niobium,  and
tantalum , Oxford, Pergamon Press, pp. 491-535.

COHEN,  M.D., WEI, C.I., TAN, H., & KAO, K.J.  (1986)  Effect of
ammonium metavanadate on the murine immune response.  J. Toxicol.
environ. Health , 19(2): 279-298.

(1982)   Clearance and distribution of intratracheally instilled
48vanadium compounds in the rat.  Toxicol. Lett ., 11: 199-203.

& BARBIER, F.  (1979)  Neutron activation analysis  of  vanadium
in  human liver and  serum. In:  Proceedings of  an International
Symposium on Nuclear Activation Techniques in the Life Sciences,
Vienna,  22-26  May,  1978 , Vienna, International  Atomic Energy
Agency, pp. 165-177.

(1980)   Determination  of vanadium  in  human serum  by neutron
activation analysis.  J. radioanal. Chem ., 55(1): 35-43.

(1981)   The ultratrace element  vanadium in human  serum.  Biol.
Trace Elem. Res ., 3: 257-263.

COTTON,  F.A.  &  WILKINSON,  G.   (1962)    Advanced   inorganic
chemistry , New York, Interscience.

COTTON,  F.A.  &  WILKINSON,  G.   (1980)    Advanced   inorganic
chemistry , 4th ed., New York, John Wiley and Sons, pp. 708-719.

COWGILL,  U.M.   (1973)   The determination  of  all  detectable
elements  in the aquatic plants  of Linsley Pond and  Cedar Lake
(North  Branford,  Connecticut)  by X-ray  emission  and optical
emission spectroscopy.  Appl. Spectrosci ., 27: 5-9.

(l975)   Trace  elements  in hair,  as  related  to exposure  in
Metropolitan New York.  Clin. Chem ., 21: 603-612.

CURRAN,  G.L.   (1954)   Effect  of  certain  transition   group
elements  on  hepatic synthesis  of  cholesterol in  the rat.  J.
biol. Chem., 210: 765-770.

CURRAN,  G.L.  &  BURCH,  R.E.   (1967)   Biological  and health
effects  of  vanadium.  In:  Proceedings  of  the  First   Annual
Conference   on   Trace  Substances   in  Environmental  Health,
Columbia,  10-11  July, 1967 , Columbia,  University of Missouri,
pp. 96-104.

CURRAN,  G.L.  & COSTELLO,  R.L.   (1956)  Reduction  of  excess
cholesterol  in  the rabbit  aorta  by inhibition  of endogenous
cholesterol synthesis.  J. exp. Med ., 103: 49-56.

CURRAN, G.L., AZARNOFF, D.L., & BOLINGER, R.E.   (1959)   Effect
of  cholesterol synthesis inhibition in normocholesteremic young
men. J. clin. Invest ., 38: 1251-1261.

DAMS,  R., ROBBINS, J.A., RAHN, K.A., & WINCHESTER, J.W.  (1970)
Nondestructive  neutron  activation  analyses of  air  pollution
particulates.  Anal. Chem ., 42: 861-867.

(1980)  The renal response to intravenous vanadate  in  rats.  J.
lab. clin. Med., 96: 382-395.

DEMASTER,  E.G.  &  MITCHELL,  R.A.   (1973)   A  comparison  of
arsenate   and   vanadate   as  inhibitors   or   uncouplers  of
mitochondria  and  glycolytic  energy  metabolism.  Biochemistry, 
12(19): 3616-3621.

DHEW    (1968)    Air  quality   data  from  the   National   Air
Surveillance Networks and contributing state and local networks ,
1966   ed.,  Durham, North  Carolina,  US Department  of Health,
Education,   and   Welfare,   National  Air   Pollution  Control

DIMOND, E.G., CARAVACA, J., & BENCHIMOL, A.   (1963)   Vanadium:
Excretion,  toxicity, lipid effect  in man.  Am. J.  clin. Nutr .,
12: 49-53.

DOMINGO,  J.L., LLOBET, J.M., & CORBELLA, J.  (1985)  Protection
of  mice against the  lethal effects of  sodium metavanadate:  a
quantitative  comparison  of  a  number  of  chelating   agents.
 Toxicol. Lett ., 26(2-3): 95-99.

Influence of chelating agents on the toxicity, distribution, and
excretion  of  vanadium  in mice.  J.  appl. Toxicol ., 6(5): 337-

J.P.,  & MEDVEDEVA, L.A.  (1974)  [The chemistry and engineering
technology  of vanadium compounds.] In: Ivakin, A.A. & Voronova,
E.M., ed. [ Proceedings  of the International Conference  on  the
Chemistry   and   Technology  of   Vanadium  Compounds ,]   Perm,
Scientific Institute of Black Metals, pp. 477-480 (in Russian).

DUCE,  R.A.  &  HOFFMAN,  G.L.   (1976)   Atmospheric   vanadium
transport to the ocean.  Atmos. Environ ., 10: 989-996.

DURFOR,  C.N. &  BECKER, E.   (1963)   Public  water supplies  of
the  100 largest cities  in the United  States, 1962 , Washington
DC, US Geological Survey (Water-Supply Paper No. 1812).

DURRANT,  P.J. & DURRANT,  B.  (1970)   Introduction  to advanced
inorganic chemistry , 2nd ed., New York, John Wiley and Sons.

DURUM,  W.H. &  HAFFTY, J.   (1963)  Implications  of the  minor
element  content of some  major streams of  the  world.  Geochim.
Cosmochim. Acta , 23: 1-11.

DUTTON,  W.F.  (1911)  Vanadiumism.  J. Am.  Med. Assoc ., 56(22):

EISLER, L., SIMECEK, R., & USTUPSKY, J.  (1968)  [Effect of work
in vanadium workshop on respiratory ways.]  Prac. Lek., 20(2/3):
52-57 (in Czech).

ELINDER,  C.G.   (1984)    Metabolism  and  toxicity  of  metals ,
Stockholm,   Department  of  Environmental  Hygiene,  Karolinska
Institute  and the National Institute of Environmental Medicine,
pp. 265-274 (Life Sciences Research Report No. 28).

ELVES,  M.V., WILSON, J.N., SCALES, J.T., & KEMP, H.B.S.  (1975)
Incidence  of  metal sensitivity  in  patients with  total joint
replacements.  Br. med. J ., 4: 376-378.

ERMOLAEV,   G.F.   (1969)   [Effect   of  vanadium  on   certain
biochemical processes in rabbit organs.] In: [ Trace  elements in
medicine ,] Moscow, Ivano-Frankovsk, pp. 190-192 (in Russian).

EVANS,  C.A.  & MORRISON,  G.H.   (1968)  Trace  element  survey
analysis   of   biological   materials  by   spark  source  mass
spectrometry.  Anal. Chem ., 40: 869-875.

FALLENTIN, B. & FROST, J.  (1954)  [Health hazards from cleaning
oil-fired  boilers caused by vanadium  and sulfuric acid in  the
soot.]  Nord. Hyg. Tidskr ., 3: 58-65 (in Danish).

FAORO, R.B. & MCMULLEN, T.B.  (1977)   National trends  in  trace
metals  in ambient air 1965-1974 , Research  Triangle Park, North
Carolina,  US  Environmental  Protection  Agency  (EPA-450/1-77-

FAULKNER   HUDSON,   T.G.   (1964)     Vanadium:  toxicology  and
biological  significance , Amsterdam, New York,  Oxford, Elsevier
Science Publishers, 135 pp.

FEAR,  E.C. & TYRER, F.H.  (1958)  A study of vanadium poisoning
in gas workers.  Trans. Assoc. Ind. Med. Off ., 8: 153-155.

FENNELLY,  P.F.  (1976)  The  origin and influence  of  airborne
particulates.  Am. Sci ., 64(1): 46-56.

FISHER,  G.L., MCNEILL, K.L., WHALEY,  C.B., & FONG, J.   (1978)
Attachment   and  phagocytosis  studies  with  murine  pulmonary
alveolar macrophages.  J. Reticuloendothel. Soc ., 24: 243-252.

FISHER,  G.L.,  MCNEILL, K.L.,  &  DEMOCKO, C.J.   (1986)  Trace
element   interactions  affecting  pulmonary   macrophage  cyto-
toxicity.  Environ. Res ., 39(1): 164-171.

FLAHERTY,  J.P.  &  ELDRIDGE, H.B.   (1970)   Neutron activation
analysis of residual oil for vanadium.  Appl. Spectrosci ., 24(5):

FROLOV,  V.V.  (1970) [Determination of chlorine and vanadium in
graphite  by the activation method.]  Zavod. Lab ., 36(7): 807-809
(in Russian).

FROST,  J  (1951)  [Vanadium  poisoning from cleaning  the smoke
stacks  of boilers burning fuel oil.]  Ugeskr. Laeger , 113: 1309-
1312 (in Danish).

FUKAI,  R.  &  MEINKE,  W.W.   (1962)   Activation  analyses  of
vanadium,  arsenic, molybdenum, tungsten,  rhenium, and gold  in
marine organisms.  Limnol. Oceanogr ., 7: 186.

GARLEJ, T.  (1974)  [The influence of vanadium-bearing  dust  on
the workers' health in the Plock thermal-electric power station:
New  exposure  tests.]  Pol.  Tyg.  Lek ., 29(49):  2143-2144  (in

GERSHKOVICH, E.E. & STYKAN, T.P.  (1972)  [A catalytic method of
measuring  hydrogen  sulfide  levels  in  air.]  Gig.  Tr.  prof.
Zabol .,  2: 60-61 (in Russian).

GEYER, C.F.  (1953)  Vanadium, a caries-inhibiting trace element
in the Syrian hamster.  J. dent. Res ., 35: 590-595.

GIBSON, R.S. & DEWOLFE, M.S.  (1979)  Copper,  zinc,  manganese,
vanadium,  and iodine concentrations in the hair of Canadian low
birth  wight neonates.  Am. J. clin. Nutr ., 32: 1728-1733.

GILES,  M.A., KLAVERKAMP, J.F.,  & LAWRENCE, S.G.   (1979)    The
acute toxicity of saline groundwater and of vanadium to fish and
aquatic  invertebrates , Edmonton,  Environment  Alberta, 172  pp
(Prepared  for  the  Alberta Oil  Sands  Environmental  Research
Program) (Project No. AF 3.2.1).

GOFMAN  J.W.  (1962)  Chemical elements  of the blood of  man in
health.  Adv. biol. med. Phys ., 8: 1.

GOLDBERG,  E.D.   (1961)   Marine geochemistry.  In: Eyring, H.,
Christensen,  C.J.,  &  Johnston,  H.S.,  ed.  Annual  review  of
physical  chemistry , Vol.  12,  Palo  Alto,  California,  Annual
Reviews, Inc., pp. 29-48.

GOLDSCHMIDT,   V.M.    (1938)    Collected   articles   on   the
geochemistry of rare elements. In: [ Collection  of papers on the
geochemistry   of  rare   metals ,]   Moscow,  Amalgamated  State
Technical and Scientific Publishing Houses (in Russian).

GOLDSHTEJN, M.I. (1967)  [ Vanadium-containing  steels ,]  Moscow,
Chermetinformacija (in Russian).

GORDUS, A.A., MAHER, C.C., III, & BIRD, G.C.  (1974)  Human hair
as  an  indicator of  trace  metal environmental  exposure.  In:
 Proceedings    of  the  First  Annual   NSF  Trace  Contaminants
Conference , Springfield,     Virginia,     National    Technical
Information Service, pp. 463-487 (Conf. 730802).

GOYER, R.A. & MEHLMANN, M.A., ed.  (1977)  Toxicology  of  trace
elements.  In:  Advances  in  modern  toxicology, Washington  DC,
Hemisphere, Vol. 2 , 303 pp.

GRANTHAM,  J.J.  (1980)  The renal sodium pump and vanadate.  Am.
J. Physiol ., 239: F97-F106.

GRANTHAM,  J.J.  &  GLYNN,  I.M.   (1979)   Renal  Na,  K-ATPase:
determinants of inhibition by vanadium.  Am. J. Physiol ., 236(6):

NAIMUCHINA,  L.F.  (1971)  [Low-alloyed welded steels containing
vanadium  for  construction.]  In:  [ Problems   of  Kachkanar ,]
Sverdlovsk, Central Bureau of Technical Information, pp. 186-196
(in Russian).

GULKO, A.G.  (1956)  [On the characteristics of vanadium  as  an
industrial poison.]  Gig. i Sanit ., 21(11): 24-28 (in Russian).

Vanadium in the blood and urine of workers in a feraalloy plant.
 Scand. J. Work environ. Health , 5: 188-194.

HACKETT,  P.L. & KELMAN, B.J. (1983) Availability of toxic trace
metals to the conceptus.   Sci. total environ .,28: 433-442.

HADJIMARKOS,  D.M.   (1966)  Vanadium  and dental caries.  Nature
(Lond.) , 209: 1137.

HADJIMARKOS,  D.M.  (1968) Effect  of trace elements  on  dental
caries.  Adv. oral Biol ., 3: 282-285.

HAMILTON,  E.I., MINSKI, M.J.,  & CLEARY, J.J.   (1972-73)   The
concentration  and  distribution  of  some  stable  elements  in
healthy  human  tissues  from  the  United  Kingdom.  Sci.  total
Environ ., 1: 341-374.

HAMMOND, P.B. & FOULKES, E.C.  (1986)  Metal ion toxicity in man
and  animals. In:  Metal ions in  biological systems , Cincinatti,
Ohio, Kettering Laboratory, Vol. 20 , pp. 157-200.

HANNA, W.J. & GRANT, C.L.  (1962)  Spectrochemical  analyses  of
certain trees and ornamentals for 23 elements.  Bull. Torrey Bot.
Club , 89: 293-302.

HARA,  T., SONODA, Y.,  & IWAI, I.   (1976)  Growth response  of
cabbage  plants  to  transition  elements  under  water  culture
conditions.  I.  Titanium,  vanadium, chromium,  manganese,  and
iron.  Soil Sci. plant Nutr ., 22(3): 307-315.

HARRIS,  W.R., FRIEDMAN, S.B., & SILBERMAN, D.  (1984)  Behavior
of vanadate and vanadyl ion in canine blood.  J. inorg. Biochem .,
20(2): 157-169.

HATFIELD, M. & CHURCHILL, P.  (1981)  Renal vascular and tubular
effects of vanadate in the anaesthetized rat.  J. Pharmacol. exp.
Ther ., 217: 406-410.

HATHCOCK,  J.N., HILL, C.H., & TOVE, S.B.  (1966)  Uncoupling of
oxidative  phosphorylation  by  vanadate.  Can. J.  Biochem ., 44:

HEIN,  J.W.  &  WISOTZKY, J.   (1955)   The  effect of  a 10 ppm
vanadium drinking solution on dental caries in male  and  female
Syrian hamsters.  J. dent. Res ., 34: 756.

HEWITT,   E.J.    (1953)   Metal   interrelationships  in  plant
nutrition.  I. Effects of some  metal toxicities on sugar  beet,
tomato,  oat, potato, and marrowstem kale grown in sand culture.
 J. exp. Bot ., 4(10): 59-64.

HEYDORN,  K. & LUKENS, H.R.   (1966)   Pre-irradiation separation
for  the determination  of vanadium  in blood  serum by  reactor
neutron  activation  analysis , Roskilde,  Danish  Atomic  Energy
Commission, Research Establishment Ris (Ris Report No. 138).

HEYLIGER, C.E., TAHILIANI, A.G., & MCNEILL, J.H.  (1985)  Effect
of  vanadate  on  elevated blood-glucose  and  depressed cardiac
performance of diabetic rats.  Science , 227(4693): 1474-1477.

HICKEY,   R.J.,   SCHOFF,   E.0.,  &   CLELLAND,   R.C.   (1967)
Relationship  between air pollution and  certain chronic disease
death rates.  Arch. environ. Health , 15: 728-738.

HICKLING, S.  (1958)  Vanadium poisoning.  N.Z. med. J ., 57: 607-

[The occurence of vanadium in the drinking-water in  the  region
of  Bialystock Province.]  Rocz. Panstw. Zakl.  Hig ., 23(2): 155-
159 (in Polish).

HOFFMAN,  G.L., DUCE, R.A.,  & ZOLLER, W.H.   (1969)   Vanadium,
copper,  and aluminum in the lower atmosphere between California
and Hawaii.  Environ. Sci. Technol ., 3: 1207-1210.

HOFFMAN, G.L., DUCE, R.A., & HOFFMAN, E.J.  (1972)  Trace metals
in  the Hawaiian marine atmosphere.  J.  geophys. Res ., 77: 5322-

HOLDWAY,  D.A.  & SPRAGUE,  J.B.   (1979)  Chronic  toxicity  of
vanadium to flagfish.  Water Res ., 13: 905-910.

HOLODOV,  V.N.   (1968)  [ Vanadium ,]    Moscow, Nauka Publishing
House (in Russian).

HOLODOV,   V.N.    (1973)    [ Sedimentary   ore   formation  and
metallogeny  on vanadium ,]  Moscow,  Nauka Publishing House  (in

HOLZHAUER,   K.P.  &  SCHALLER,  K.-H.   (1977)   [ Occupational
medicine studies in chimney sweeps. Hazards at the workplace and
occupation-linked  health  damage ,]   Stuttgart, G.  Thieme  (in

HOPKINS,   L.L.,  Jr  &  MOHR,  H.E.   (197la)   The  biological
essentiality of vanadium. In: Mertz, W. & Cornatzer,  W.E.,  ed.
 Newer   trace  elements  in nutrition , New  York, Marcel Dekker,
pp. 195-213.

HOPKINS,  L.L., Jr  & MOHR,  H.E.  (197lb)   Effect of  vanadium
deficiency  on  plasma  cholesterol of  chicks.  Fed.  Proc ., 30:

HOPKINS, L.L., Jr & MOHR, H.E.  (1974)  Vanadium as an essential
nutrient.  Fed. Proc ., 33(6): 1173-1175.

HOPKINS,  L.L., Jr & TILTON,  B.E.  (1966)  Metabolism of  trace
amounts  of vanadium  48 in  rat organs  and  liver  subcellular
particles.  Am. J. Physiol ., 211: 169-172.

HOPKINS,  L.L.,  CANNON,  H.L.,  MUSCH,  A.T.,  WELCH,  R.M.,  &
NIELSEN, F.H.  (1977)  Vanadium.  Geochem. Environ ., 2: 93-107.

HORI,  C. & OKA, T.   (1980)  Vanadate enhances the  stimulatory
action  of insulin on  DNA synthesis in  cultured mouse  mammary
glands.  Biochim. Biophys. Acta , 610: 235-240.

HORNER,  C.K., BURCK, D., ALLISON,  F., & SHERMAN, M.S.   (1942)
Nitrogen fixation by azotobacter as influenced by molybdenum and
vanadium.  J. agric. Res ., 65: 173-193.

HUDGINS,  P.M.  &  BOND,  G.H.   (1979)   Reversal  of  vanadate
inhibition  of Na++K-ATPase by catecholamines.  Res.  Commun. chem.
Pathol. Pharmacol ., 23(2): 313-326.

HUDSON,  T.G.F.   (1964)    Vanadium: toxicology  and  biological
significance , Amsterdam,  New  York,  Oxford,  Elsevier  Science

HWANG,  I.Y.,  ULLICCI, P.A.,  & SMITH, S.B.   (1972)  A  simple
flameless atomizer.  Am. Lab ., 3: 41-43.

ICRP   (1960)   Report of  Committee II on  Permissible Dose  for
Internal  Radiation (1959). Recommendations of the International
Commission  on  Radiological Protection , Oxford,  Pergamon Press
(ICRP Publication No. 2).

ILO   (1980)    Occupational  Exposure Limits  for Airborne Toxic
Substances; Occupational Safety and Health Series, No.  37,  2nd
revised ed ., Geneva, International Labour Office.

JOHNSTON, J., & HADDY, F.J.  (1980)  Cardiovascular  effects  of
vanadate in the dog.  Am. J. Physiol ., 239: 47-56.

(1971)    [Evaluation  of  professional  exposure   to  vanadium
compounds and other environmental factors of workers employed in
cleaning of oil-fired boilers with special regard to  the  state
of respiratory tract.]  Med. Pr ., 22(4): 421-431 (in Polish).

JACIMIRSKIJ,  K.B.   (1967)   [ Kinetic  methods  of  analysis ,]
Moscow, Himija (in Russian).

JACKSON,  J.F.  &  LINSKENS,  H.F.   (1982)   Metal  ion induced
unscheduled  DNA synthesis in Petunia  pollen.  Mol. gen. Genet .,
187: 112.

JANDHYALA, B.S. & HOM, G.J.  (1983)  Physiological and pharmaco-
logical properties of vanadium.  Life Sci ., 33: 1325-1340.

JARACZEWSKA,  W.  &  JAKUBOWSKI,  M.   (1964)   [The  attempt of
evaluation  of vanadium exposure in the chemical industry.]  Med.
Pr ., 15(6): 375-383 (in Polish).

KOWNACKA,  L.,  &  WRONSKI,  Z.   (1973)   Radiation  hazards to
population  from conventional and nuclear  power production. In:
 Symposium    on   environmental   surveillance  around   nuclear
installations, Warsaw, 5-9 November, 1973, Vienna, International
Atomic Energy Agency (IAEA-SM-180/20).

JOHNSON, J.L., COHEN, H.L., & RAJAGOPALAN, K.V.  (1974)  Studies
of  vanadium  toxicity  in the  rat;  lack  of correlation  with
molybdenum  utilization.  Biochem. biophys. Res.  Commun ., 56(4):

JONES,  M.M.  & BASINGER,  M.A.   (1983)  Chelate  antidotes for
sodium  vanadate  and  vanadyl sulfate  intoxication in mice.  J.
Toxicol. environ. Health , 12(4-6): 749-756.

KADA,  T.,  HIRANO,  K., &  SHIRASU,  Y.   (1980)  Screening  of
environmental  chemical  mutagens  by the  rec-assay system with
 Bacillus   subtilis. In: de Serres,  F.J. & Hollaender,  A., ed.
Chemical   mutagens: principles and methods for their detection ,
New York, Plenum Press, pp. 149-173.

KOGA,  S., & KOGA, M.  (1971)  [Experimental studies on vanadium
poisoning.  I. Vanadium-induced hepatic injuries  in rats.]  Jap.
J. ind. Health , 13: 263-267 (in Japanese).

KANEMATSU,   K.  &  KADA,  T.   (1978)   Mutagenicity  of  metal
compounds.  Mutat. Res ., 53(2): 207-208.

KANEMATSU,  N., HARA,  M., &  KADA, T.   (1980)   Rec-assay  and
mutagenicity  studies on metal compounds.  Mutat.  Res ., 77: 109-

KANISAWA, M. & SCHROEDER, H.A.  (1967)  Life-term studies on the
effects  of arsenic, germanium, tin, and vanadium on spontaneous
tumours in mice.  Cancer Res ., 27: 1192-1195.

KATAYEVA,  I.G.  &  SAPUNOV,  S.F.   (1974)   [Sanitary-hygienic
characteristics   of  vanadium  ferroalloy  production   at  the
Chusovoy  Metallurgical  Plant.]  Gig.  Tr. prof.  Zabol ., 18(1):
37-39 (in Russian).

KAZIMOV, M.A.  (1977)  [Occupational hygiene with new methods of
the  ferrovanadium  production.]  Gig. Tr.  prof. Zabol ., 6: 8-12
(in Russian).

KEJT,  M. & DEGENS,  E.  (1961)  [Geometrical  indicators.]  In:
[ Geometrical   research  at  low temperatures  and  pressures ,]
Moscow, Foreign Language Publishers, pp. 56-84 (in Russian).

KEMPTON,  S., STERRITT, R.M.,  & LESTER, J.N.   (1982)   Atomic-
absorption   spectrophotometric   determination   of   antimony,
arsenic,  bismuth,  tellurium,  thallium and  vanadium in sewage
sludge.  Talanta , 29: 675-681.

(1986)   Vanadate supplements and  1,2-dimethylhydrazine induced
colon  cancer in mice: increased thymidine incorporation without
enhanced carcinogenesis.  Br. J.  Cancer, 53(5): 683-686.

KIRZHNER,  M.A., KRYZHENKOVA, N.A., & KIST, A.A.  (1974)  [Scope
for   the  preliminary  concentration  in  the  use  of  neutron
activation  in matrix analysis for  aluminium and vanadium.]  At.
Energ ., 37: 498 (in Russian).

KIVILUOTO,  M.  (1980)  Observations  on the lungs  of  vanadium
workers.  Br. J. ind. Med ., 37: 363-366.

KIVILUOTO,  M., PYY,  L., &  PAKARINEN, A.   (1979a)  Serum  and
urinary  vanadium pentoxide.  Int. Arch. occup.  Health , 48: 251-

KIVILUOTO, M., RASANEN, 0., RINNE, A., & RISSANEN,  M.   (1979b)
Effects of vanadium on the upper respiratory tract of workers in
a vanadium factory.  Scand. J. Work environ. Health , 5: 50-58.

KIVILUOTO,  M., RASANEN, 0., RINNE, A., & RISSANEN, M.,  (1979c)
Serum  and urinary vanadium of  vanadium exposed workers.  Scand.
J. Work environ. Health , 5: 362-367.

KIVILUOTO,  M.,  PYY, L.,  &  PAKARINEN, A.   (1980)  Fingernail
cystine  of vanadium workers.  Int. Arch. occup. environ. Health, 
46: 179-182.

KIVILUOTO,  M.,  PYY, L.,  &  PAKARINEN, A.   (1981a)   Clinical
laboratory  results of vanadium-exposed  workers.  Arch. environ.
Health , 36(3): 109-113.

Intracellular  immunoglobulins in plasma cells of nasal biopsies
taken  from vanadium-exposed workers.  Anat. Anz. Jena , 149: 446-

T.R.   (1985)   Pulmonary  effects of  acute  vanadium pentoxide
inhalation  in  monkeys.  Am.  Rev. respir.  Dis ., 132(6):  1181-

KOHLER,  R.  (1972)  [Rebuttal:  problems of vanadium  pentoxide
intoxication.]  Dtsch. Gesundheitswes ., 27: 815-816 (in German).

LLOKAZOV,   E.D.,  AZFALOVA,  R.U.,  &   SANDLER,  V.I.   (1971)
[Improvement  of technology of utilisation of vanadium contained
in  waste  water.]  In: [ Problems   of  Kachkanar ,]  Sverdlovsk,
Central   Bureau  of  Technical  Information,   pp. 229-231  (in

[Scattered  rare  elements  dissolved  in  water  contained   in
colloidal   substances  of  the  major  USSR  rivers.]  In:  [ A
collection  of papers on  the geochemistry of  sedimentary rocks
and ores. Documentation of the Seventh All-Union  Conference  on
Lithology  of the  Academy of  Sciences of  the USSR],   Moscow,
Nauka Publishing House, pp. 72-87 (in Russian).

KPF-MAIER,  P.  &  KPF, H.   (1979)   [Vanadocene  dichloride:
another  anti-tumour  agent  from  the  metallocene  series.]  Z.
Naturforsch ., 34B: 805-807 (in German).

KPF-MAIER, P., HESSE, B., & KPF, H.  (1980)  Tumour inhibition
by  metallocenes: effect of titanocene and hafnocene dichlorides
on  Ehrlich ascites tumour in mice.  J. Cancer Res. clin. Oncol .,
96(1): 43-51.

KOPYLOVA,  L.M.   (1971)   [A  study  of  some  blood indicators
following  prolonged  administration  of vanadium  sulfate.]  Tr.
Voronezh. Med. Inst ., 85: 62-65 (in Russian).

KORKHOV, V.V.  (1965)  [Vanadium in prophylaxis and treatment of
experimental  atheroslerosis.]  Farmakol. i Toksikol ., 28(1): 83-
87 (in Russian).

KOSTROMIN,   A.I.,  AKHMETOV,  A.A.,  &   ORLOVA,  L.N.   (1970)
[Coulometric  determination of manganese (II), cesium (III), and
vanadium (IV).]  Zh. anal. Khim ., 25: 195-196 (in Russian).

[ Trace   elements in the  soils of the  Soviet Union ,]   Moscow,
Moscow University Publishing House (in Russian).

KRAGTEN, J.  (1981)  Improved determination of vanadium by flame
AAS  by preventing polynuclear hydroxide  complex formation.  At.
Spectrosci ., 2(4): 135-136.

KRAUSKOPF,  F.K.  (1963)  Factors governing the concentration of
thirteen  rare  metals in  seawater.  Collected articles  on the
geochemistry  of  rock  formation.  In:  [ The   geochemistry  of
lithogenesis ,]   Moscow, Foreign Languages Publishing House, pp.
294-338 (in Russian).

KUBASKY,  A.  (1957)   Waste from  a vanadium  work as  moulding
material.  Slevarenstvi , 5(1): 4-7.

(1986)   Influence  of  ochratoxin  A  and  vanadium  on various
parameters in growing chicks.  Poult. Sci ., 65(9): 1671-1678.

KULIEVA,  T.K.  (1974)  [Effect of  vanadium on the activity  of
some  tissue-respiration enzymes.]  Zdravookhr. Turkm .,  3:  7-17
(in Russian).

KUMAR, A. & CORDER, C.N.  (1980)  Diuretic  and  vasoconstrictor
effects  of sodium orthovanadate  on the isolated  perfused  rat
kidney.  J. Pharmacol. exp. Ther ., 213: 85-90.

KURMAEV, R.H.  (1974)  [Solid, liquid and aerosol waste  in  the
production  of technical vanadium pentoxide.] In: Ivakin, A.A. &
Voronova,   E.M.,   ed.   [ Proceedings   of   the  International
Conference   on  the  Chemistry   and  Technology  of   Vanadium
Compounds ,] Perm,  Scientific Institute of Black Metals, pp. 43-
46 (in Russian).

KUZELOVA,  M.,  SIRL, J.,  &  POPLER, A.   (1975)  [Occupational
poisonings  by  vanadium compounds  in  workers at  mazut boiler
houses.]  Prac. Lek ., 27(5): 170-173 (in Czech).

KUZELOVA,  M., HAVEL,  V., POPLER,  A., &  STEPANEK, O.   (1977)
[The  problems of occupational medicine  in the work of  chimney
sweeps.]  Prac. Lek ., 29: 225-228 (in Czech).

LAGERKVIST,  B., NORDBERG, G.F.,  & VOUK, V.   (1986)  Vanadium.
In: Friberg, G.F., Nordberg, G.F., & Vouk, V.B., ed.  Handbook on
the  toxicology of metals.  II. Specific metals , Amsterdam,  New
York, Oxford, Elsevier Science Publishers, pp. 638-663.

LAHAV,  M., RENNERT, H., &  BARZILAI, D.  (1986)  Inhibition  by
vanadate of cyclic AMP production in rat  corpora lutea incubated
 in vitro . Life Sci ., 39(26): 2557-2564.

(1971)   Spectrographic  determination  of elments  in  airborne
dirt.  Appl. Spectrosci ., 25: 270-275.

LARSEN,  J.A. & THOMSEN,  O.  (1980)  Vanadate-induced  oliguria
and  vasoconstriction  in  the cat.  Acta  physiol.  Scand ., 110:

LARSEN,  J.A.,  THOMSEN, O.,  &  HANSEN, O.   (1979)   Vanadate-
induced oliguria in the anaesthetized cat.  Acta physiol. Scand .,
106: 495-496.

LEE,  K.P.  &  GILLIES,  P.J.   (1986)   Pulmonary  response and
intrapulmonary  lipids in rats exposed  to bismuth orthovanadate
dust by inhalation.  Environ. Res ., 40(1): 115-135.

LEE, R.E., GORANSON, S.S., ENROINE, R.E., & MORGAN, G.B.  (1972)
National  air  surveillance  Cascade Impactor  Network. II. Size
distribution  measurements  of trace  metal components.  Environ.
Sci. Technol ., 6: 1025-1030.

LEE,  K.,  NALEWAJKO,  C., &  JACK,  T.R.   (1978)   Effects  of
vanadium  on freshwater algae.  In:  Abstracts of the  5th Annual
Aquatic  Toxicity  Workshop,  Hamilton, Ontario,  7-9  November ,
Burlington, Ontario, Canada Centre for Inland Waters.

LEES, R.E.M.  (1980)  Changes in lung function after exposure to
vanadium compounds in fuel oil ash.  Br. J. ind.  Med ., 37:  253-

LEVlNA, E.N.  (1972)  [Relationships between solubility of metal
compounds and their toxicity, distribution, and elimination from
the body.]  Gig. Tr. prof. Zabol ., 16: 40-43 (in Russian).

LEVY,  B.S., HOFFMAN, L., & GOTTSEGEN, S.  (1984)  Boilermakers'
bronchitis:   respiratory   tract  irritation   associated  with
vanadium  pentoxide exposure during oil-to-coal  conversion of a
power plant.  J. occup. Med ., 26(8): 567-570.

LEVY, L.S., MARTIN, P.A., & BIDSTRUP, P.L. (1986)  Investigation
of   the  potential  carcinogenicity  of  a  range  of  chromium
containing  materials on rat lung.  Br. J. ind. Med ., 43(4): 243-

LEWIS,  C.E.  (1959a)  The  biological actions of  vanadium.  Am.
Med. Assoc. Arch. Ind. Health , 19: 419-424.

LEWIS,  C.E.  (1959b)  The  biological effects of  vanadium. II.
The  signs and symptoms  of occupational vanadium  exposure.  Am.
Med. Assoc. Arch. Ind. Health , 19: 497-503.

LEWIS,  C.E.  (1959c)  The  biological actions of  vanadium.  Am.
Med. Assoc. Arch. Ind. Health , 20(5): 455-466.

LIFSCHITZ,   V.M.   (1962)   [Spectral  determination  of  trace
elements  in human blood (group determination of Ni, Ag, Zn, Cu,
Cd, V, Pb, Mn, Fe, and Co).]  Tr. Voronezh. Med.  Inst ., 49:  110
(in Russian).

LINSTEDT,  K.D. & KRUGER, P.  (1969)  Vanadium concentrations in
Colorado  River Basin waters.  J. Am.  Water Works Assoc ., 61(2):

LINTER,   C.M.    (1985)   Neuropsychiatric   aspects  of  trace
elements.  Br. J. hosp. Med ., 34(6): 361-365.

&  MARTINEZ-MALDONADO,  M.   (1982a)  Effect  of  sodium  ortho-
vanadate on renal renin secretion   in vivo. J.  Pharmacol.  exp.
Ther ., 222: 447-451.

Renal actions of orthovanadate in the dog.  Proc. Soc. Exp. Biol.
Med ., 170: 418-426.

L'VOV, B.V.  (1970)   Atomic absorption spectrochemical analysis,
2nd ed., London, Adam Hilger.

MACARA, I.G.  (1980)  Vanadium - an element in search of a role.
 Trends biochem. Sci ., April: 92-94.

MACARA,  I.G., KUSTIN, K., &  CANTLEY, L.C., Jr  (1980)   Gluta-
thione  reduces cytoplasmic vanadate mechanism and physiological
implications.  Biochim. Biophys. Acta , 629: 95-106.

(1982)  Rapid detection of DNA strand breaks in human peripheral
blood  cells and animal organs following treatment with physical
and  chemical agents. In: Bora, K.C., Douglas, G.R., & Nestmann,
E.R., ed.  Chemical mutagenesis, human population monitoring, and
genetic  risk assessment , Amsterdam, Oxford, New  York, Elsevier
Science  Publishers,  p.  137 (Progress  in  Mutation  Research,
Vol. 3).

MCLUNDIE, A.C., SHEPHERD, J.B., & MOBBS, D.R.A.  (1968)  Studies
on  the effects of various ions on enamel solubility.  Arch. oral
Biol ., 13: 1321-1330.

MADSEN,  E.S.,  NIELSEN, P.A.,  &  PEDERSEN, J.C.   (1982)   The
distribution  and origin of  mutagens in airborne  particulates,
detected  by  the  Salmonella /microsome   assay  in  relation  to
levels  of lead, vanadium, and  PAH.  Sci. total Environ ., 24(1):

MAHLER,  H.R. & CORDES, E.H.   (1966)   Biological chemistry , New
York, Harper & Row.

MAJUMDAR,  A.K. & DAS, G.   (1965)  Spectrophotometric determin-
ation  of  vanadium  with  N -benzoyl- N -p-chlorophenylhydroxyl-
amine.  J. Indian Chem. Soc ., 42(3): 189.

MANNING, D.C. & SLAVIN, W.  (1983)  The determination  of  trace
elements  in  natural  waters using  the  stabilized temperature
platform furnace.  Appl. Spectrosci ., 37(1): 1-10.

MARAFANTE,  E.  & SABBIONI,  E.   (1983)  Metabolic  studies  on
vanadium:  in  vivo and  in  vitro association   with   cellular
components.  In:  Proceedings  of an  International Conference on
Heavy  Metals  in  the  Environment,  London,  18-21  September,
1979 , Edinburgh, CEC Consultants, pp.  171-174.

SABBIONI,  E.,  & PIETRA,  R.   (1983)  Urinary  elimination  of
vanadium in boiler cleaners. In:  Proceedings of an International
Conference  on Heavy Metals  in the Environment,  London,  18-21
September, 1979 , Edinburgh, CEC Consultants, pp. 66-69.

Sources of vanadium in Puerto Rican and San Francisco  bay  area
aerosols.  Environ. Sci. Technol ., 7: 817-819.

MASCITELLI-CORIANDOLI,  E.  &  CITTERIO, C.   (1959a)  Effect of
vanadium  upon  liver  coenzyme A  in rats.  Nature (Lond.) , 183:

MASCITELLI-CORIANDOLI, E. & CITTERIO, C.  (1959b)  Intracellular
thioctic  acid  and  coenzyme A  following  vanadium  treatment.
 Nature (Lond.) , 184: 1641.

MASIRONl,   R.    (1969)   Trace   elements  and  cardiovascular
diseases.  Bull. World Health Organ ., 40: 305-312.

MATANTSEVA, E.I.  (1960)  [The state of the  respiratory  organs
in  workers coming into  contact with vanadium  pentoxide.]  Gig.
Tr. prof. Zabol ., 7: 41-44 (in Russian).

MEISCH,  H.U. & BECKER, L.J.  (1981)  Vanadium in photosynthesis
of  Chlorellafusca  and  higher plants.  Biochim.  Biophys. Acta ,
636: 119-125.

MEISCH,  H.U. &  BENZSCHAWEL, H.   (1978)  Role  of vanadium  in
green  plants.  III. Influence  on  cell division  of chlorella.
 Arch. Microbiol ., 116(1): 91-95.

MERTZ,  W.  (1970)  Some  aspects of nutritional  trace  element
research.  Fed. Proc ., 29: 1482-1488.

MINDEN, H. & ROTHE, R.  (1966)  [Biochemical mechanism of action
of vanadium.]  Z. gesamte Hyg ., 12(5): 315-321 (in German).

MIRAMAND,  P. & UNSAL, M.  (1978)  Acute toxicity of vanadium to
some  marine  benthic and  phytoplanktonic species.  Chemosphere ,
10: 827-832.

MIRZAEVA,  K.H.  (1965)  [Trace  elements in natural  waters  in
some  districts of Uzbekistan.]  In: [ Trace  elements  in  agri-
culture ,]   Tashkent, Science Publishers of Uzbekistan, pp. 122-
126 (in Russian).

MISIEWICZ,  A.   (1980)   [Effect of  air  containing  gasoline,
tungsten,  titanium,  cobalt,  and vanadium  on  the  phagocytic
activity  of leucocytes.]  Pol. Tyg. Lek ., 35(50):  1965-1967 (in

MISIEWICZ,  A.   (1983)   [Effect  of  air  containing  benzine,
wolfram,  titanium, cobalt, and  vanadium on peripheral  blood.]
 Med. Pr ., 34(3): 251-257 (in Polish).

MITCHELL,  R.L.  (1964)  Trace elements in soil. In: Bear, F.E.,
ed.  Chemistry   of  the  soil , New  York,  Reinhold  Publishing,
pp. 320-368.

MITCHELL,   W.G.  &  FLOYD,  E.P.   (1954)   Ascorbic  acid  and
ethylenediaminetetracetate  (EDTA) as antidotes  in experimental
vanadium poisoning.  Proc. Soc. Exp. Biol. Med ., 85: 206-208.

Inhibition of protein synthesis in cell cultures by vanadate and
in  brain  homogenates  of  rats  fed  vanadate.  Physiol.  Chem.
Physics , 13: 281-287.

MORGAN, W.K.C. & SEATON, A.  (1984)   Occupational lung diseases ,
2nd ed., Philadelphia, W.B. Saunders & Co.

MOUNTAIN,  J.T.  (1963)  Detecting hypersusceptibility  to toxic
substances.  Arch. environ. Health , 6: 357-365.

MOUNTAIN, J.T., DELKER, L.L., & STOKINGER, H.E.  (1953)  Studies
in vanadium toxicology. I. Reduction in the cystine  content  of
rat hair.  Am. Med. Assoc. Arch. Ind. Hyg. Occup. Med ., 8: 406.

MOUNTAIN,  J.T., STOCKELL, F.R.,  Jr, & STOKINGER,  H.E.  (1955)
Studies  in  vanadium  toxicology.  Am. Med.  Assoc.  Arch.  Ind.
Health , 12: 494.

MUHLER,   J.C.   (1957)   The  effect   of  vanadium  pentoxide,
fluorides,  and tin compounds on the dental caries experience in
rats.  J. dent. Res ., 36: 787-794.

MUSK, A.W. & TEES, J.G.  (1982)  Asthma caused  by  occupational
exposure to vanadium compounds.  Med. J. Aust ., 1: 183-184.

MUSTAFIN,  I.S., NECHAENKO, T.M., & FRUMINA, N.S.  (1969)  [ The
range of reagents available for vanadium ,]  Moscow, Moscow State
University (in Russian).

I.YA.   (1981)   [ Analytical   chemistry of  vanadium ,]  Moscow,
Nauka Publishing House, 216 pp (in Russian).

MYERS,  V.C. & BEARD, H.H.   (1931)  Studies in the  nutritional
anaemia  of the rat. II.  Influence of iron plus  supplements of
other  inorganic  elements  upon  blood  regeneration.  J.  biol.
Chem ., 94: 89.

MYRON,  D.R., GIVAND, S.H.,  & NIELSEN, F.H.   (1977)   Vanadium
content  of  selected foods  as  determined by  flameless atomic
absorption spectroscopy.  J. agric. food Chem ., 25(2): 297-299.

D.E.,  & NIELSEN, F.H.  (1978)  Intake of nickel and vanadium by
humans. A survey of selected diets.  Am. J.  clin.  Nutr ., 31(3):

NAS    (1974)    Vanadium , Washington  DC,  National  Academy  of

NAS   (1978)   Vanadium supply and demand outlook , Washington DC,
National  Academy of Sciences, National Materials Advisory Board
(Publication NMAB-346).

NASON, A.  (1958)  The metabolic role of vanadium and molybdenum
in plants and animals. In: Lamb, C.A., Bentley, 0.G., & Beattie,
J.M.,  ed.  Trace  elements , New  York, Academic  Press, pp. 269-

NAYLOR,  G.J.  (1984)  Vanadium and  manic depressive psychosis.
 Nutr. Health , 3(1-2): 79-85.

NAYLOR, G.J., SMITH, A.H., BRYCE-SMITH, D., & WARD, N.I.  (1984)
Tissue  vanadium levels in  manic-depressive psychosis.  Psychol.
Med ., 14(4): 767-772.

NECHAY,  R.  (1984)  Mechanisms of action of vanadate.  Ann. Rev.
Pharmacol. Toxicol ., 24: 501-524.

NECHAY, R. & SAUNDERS, J.P.  (1978)  Inhibition by  vanadium  of
sodium  and potassium dependent  adenosinetriphosphatase derived
from  animal and human tissues.  J. environ. Pathol. Toxicol ., 2:

NELSON,  W.L.  (1973)  Direct desulfurization handles low-metals
topped crudes.  Oil Gas J ., 19 November: 54-56.

NIELSEN,  F.H. & OLLERICH, D.A.   (1973)  Studies on a  vanadium
deficiency in chicks.  Fed. Proc ., 32: 929.

NIOSH  (1977)   Occupational exposure to vanadium , Washington DC,
National  Institute for Occupational Safety and Health (Document
No. 77-222), 142 pp.

TOJYO,  Y.  (1977)  [A survey of workers on vanadium pentoxide.]
 Shikoku igaku zasshi , 31(6): 389-393 (in Japanese).

MAUTNER,  G.   (1981)   [Effect  of  vanadium  on   experimental
atherosclerosis.]  Gig. i Sanit ., 11: 58-59 (in Russian).

NRC   (1980)   Drinking-water and health , Washington DC, National
Academy   Press,  Vol.  3,  pp.   350-354  (Safe  Drinking-Water

OBERG,   S.G.,   PARKER,   R.D.R.,  &   SHARMA,   R.P.    (1978)
Distribution  and elimination of an intratracheally administered
vanadium compound in the rat.  Toxicology , 11: 315-323.

OLEFFE,  J. & WILMET, J.  (1980)  Generalized dermatitis from an
osteosynthesis screw.  Contact Dermat ., 6: 365.

OLIVER, B.G. & COSGROVE, E.G.  (1975)  Metal  concentrations  in
the  sewage,  effluents and  sludges  of some  Southern  Ontario
wastewater treatment plants.  Environ. Lett ., 9(1): 75-90.

OMANG, S.H.  (1971)  The determination of vanadium and nickel in
mineral oils by flameless graphite tube atomization.  Anal. Chim.
Acta , 56: 470-473.

M.YA.,  &  KAZIMOV,  M.A.   (1977)   [On  the  distribution  and
elimination  of  vanadium  from the  organisms.]  Gig.  Tr. prof.
Zabol ., 6: 29-34 (in Russian).

(1979)   Determination  of  the  chemical  forms  of   dissolved
vanadium  in freshwater as determined by 48V radiotracer experi-
ments  and neutron activation analysis.  Sci. total Environ ., 13:

PARKER,   R.D.R.  &  SHARMA,  R.P.    (1978)   Accumulation  and
depletion of vanadium in selected tissues of rats  treated  with
vanadyl  sulfate  and sodium  orthovanadate.  J. environ. Pathol.
Toxicol ., 2: 235-245.

PARKES,  W.R.   (1982)    Occupational lung  disorders , 2nd  ed.,
London, Butterworths & Co.

PASTUHOV,   A.I.   &  TRETJAKOV,   M.A.   (1959)   Metallurgical
processing  of cast iron from titanomagnetites from the Kackanar
district  into steel. In: [ Problems  of Kachkanar ,]  Sverdlovsk,
Central   Bureau  of  Technical  Information,   pp.  95-104  (in

PATRICK,  R.  (1978)   Effects of  trace metals  in the  aquatic
ecosystem.  Am. Sci ., 66: 185-191.

PAZHYNICH,  V.M.   (1966)  Maximum  permissible concentration of
vanadium pentoxide in the atmosphere.  Hyg. Sanit ., 31: 6-11.

PAZHYNICH,  V.M.  (1967)  [Experimental basis for the determina-
tion of maximum allowable concentration of vanadium pentoxide in
atmospheric  air.]  In:  Rjazanov, V.A.,  ed.  [ The   biological
effect  and  hygienic  importance of  atmospheric  pollutants ,]
Moscow, Medicina Publishing House, pp. 201-217 (in Russian).

PAZHYNICH, V.M.  (1980)  [Effect of aerosols of rare  metals  on
the  functional state of  the body of  workers in conditions  of
powder wire production.]  Vrach. Delo , 3: 102-104 (in Russian).

PEJVE,  J.V. & AJZUPIET,  I.P.  (1974)  [A  short review of  the
results  of research  on the  problem "Trace  elements in  plant
cultivation  and  livestock  rearing  in  1972".]  In:   [ Trace
elements  in  the  USSR. XV.  Methodological  material ,]   Riga,
Knowledge Publishers (in Russian).

PERRY, H.M., TEITLEBAUM, S., & SCHWARTZ, P.L.   (1955)   Effects
of  antihypertensive  agents  on amino  acid decarboxylation and
amine oxidation.  Fed. Proc ., 14: 113-114.

PERRY,  H.M.,  Jr,  SCHWARTZ,  P.L.,  &  SAHAGIAN,  B.M.  (1969)
Effects  of  transition  metals and  of metal-binding antihyper-
tensive  agents on tryptamine  oxidase sand dopa  decarboxylase.
 Proc. Soc. Exp. Biol. Med ., 130: 273-277.

PETERBURGSKIJ,  A.V. & TORMASOVA,  E.E.  (1969)  [The  effect of
vanadium  on certain physiologycal  processes in the  pea.]  Dok.
Timiryazevsk. Akad ., 149: (in Russian).

PETKEVICH,  A.N.,  VILLER,  G.E.,  &  VOROTNIKOV,  B.A.   (1967)
[Some  trace elements in natural waters of Kama's district.] In:
[ Trace   elements  in the  biosphere  and their  application  in
agriculture  and medicine in Siberia  and the Far East ,]   Ulan-
Ude, Ulan-Ude Book Publishers, pp. 223-227 (in Russian).

Some  microelements in  natural waters  near the  source of  the
Kama.  Tr. Kazanskogo Med. Inst ., 29: 100-103.

(1982)    Vanadium-induced   inhibition   of   renal   Na+   K+-
adenosinetriphosphatase  in  the  chicken after  chronic dietary
exposure.  J. Toxicol. environ. Health , 9: 651-661.

PHILLIPS,  T.D.,  NECHAY,  B.R.,  &  HEIDELBAUGH,  N.D.   (1983)
Vanadium:  chemistry  and the  kidney.  Fed. Proc ., 42(13): 2969-

PIELSTICKER,  F.   (1954)   [Health  effects  due  to   vanadium
compounds.   Symptoms   and   prognosis.]  Arch.   Gewerbepathol.
Gewerbehyg ., 13: 73-96 (in German).

PILZ,  W. & KOMISCHKE, S.  (1972)  [Determination of vanadium in
biological material and air. II. The decomposition of biological
material:  air  analyses.]  Int.  J. environ.  anal. Chem ., 1(4):
275-282 (in German).

POERSEL,   B.    (1977)   [ The    biological  and  toxicological
significance  of vanadium ,]  Dusseldorf,  Med. Diss., 86  pp (in

PROESCHER,   F.,  SEIL,  H.H.,  &  STILLIANS,  A.W.   (1917)   A
contribution to the action of vanadium with particular reference
to syphilis.  Am. J. Syph ., 1: 347-405.

PROKOPENKO,   T.A.   (1961)   [Effect  of   industrial  poisons,
fluorine,   vanadium,  manganese,  and  some   drugs  tested  in
treatment  on  the  tissue metabolism  of  compounds  containing
phosphorus.]  In: [ Proceedings  of  the 9th All-Union  Pharmaco-
logical Conference, Sverdlovsk ,]   Sverdlovsk, Central Bureau of
Technical Information, pp.  210-211 (in Russian).

PYY,  L.,  KIVILUOTO, M.,  &  PAKARINEN, A.   (1980)  Fingernail
cystine  of vanadium workers.  Int. Arch. occup. environ. Health ,
46(2): 179-182.

PYY, L., LAJUNEN, L.H.J., & HAKALA, E.  (1983)  Determination of
vanadium  in  work-place  air by  DCP emission spectrometry.  Am.
Ind. Hyg. Assoc. J ., 44(8): 609-614.

PYY,  L., HAKALA, E., &  LAJUNEN, L.H.J.  (1984)  Screening  for
vanadium  in  urine-  and blood-serum  by  electrothermal atomic
absorption   spectrometry   and   dc  plasma   atomic   emission
spectrometry.  Anal. Chim. Acta , 158: 297-303.

Effects of vanadium on the upper respiratory tract of workers in
a  vanadium factory: a macroscopic and microscopic study.  Scand.
J. Work environ. Health , 5(1): 50-58.

RAJNER,  V.   (1960)  [Effect  of  vanadium in  the  respiratory
tract.]  Cesk. Otolaryngol ., 9: 202-204 (in Czech).

RALSTON,  H.R. & SATO, E.S.  (1971)  Sodium removal as an aid to
neutron activation analysis.  Anal. Chem ., 43: 129-131.

REINL,  W.  (1958)  [Illnesses  caused by basic  slag,  vanadium
slag,   and   vanadium  compounds.]  Staub , 18(5):   143-148  (in

REZNIK, J.B.  (1954)  [The importance of vanadium compounds from
the  point  of  view of  industrial toxicology.]  Vrach. Delo , 7:
627-632 (in Russian).

RHAN, K.A.  (1971)    Sources of trace elements in  aerosols:  an
approach  to  clean  air , Ann  Arbor,  Michigan,  University  of
Michigan,  Department of Meteorology,  309 pp (US  Atomic Energy
Commission Contract No. COO-1705-9).

RHOADS,  K.  & SANDERS,  C.L.   (1985)  Lung  clearance,  trans-
location,  and  acute  toxicity of  arsenic, beryllium, cadmium,
cobalt, lead, selenium, vanadium, and ytterbium oxides following
deposition in rat lung.  Environ. Res ., 36(2): 359-378.

RIFKIN,  R.J.  (1965)  In vitro inhibition  of Na+ -K+ and  Mg2+
ATPases  by mono-, di-,  and trivalent cations.  Proc.  Soc. Exp.
Biol. Med ., 120: 802-804.

RIGDON, L.P. & HARRAR, J.E.  (1969)  Determination  of  vanadium
by controlled-potential coulometry.  Anal. Chem ., 41: 1673-1675.

Choline, trace elements, and amino acids as factors  for  growth
of  an enteric yeast,  Candida slooffii. Sabouraudia J. Int. Soc.
Hum. Anim. Mycol ., 7: 15-19.

ROMAN, R.J., BONVENTRE, J.V., SILVA, P., & LECHENE,  C.   (1981)
Sodium orthovanadate diuresis in rats.  J. Pharmacol. exp. Ther .,
218: 168-174.

RONOV, A.B.  (1964)  [General tendencies in the evolution of the
composition   of  the  Earth's   crust,  the  oceans   and   the
atmosphere.]  Geohimija , 8: 715-743 (in Russian).

ROSE,  E.R.   (1973)    Geology  of  vanadium  and   vanadiferous
occurrences  in  Canada , Ottawa,  Geological Survey  of  Canada,
Department of Energy, Mines and Resources, pp.  7-101  (Economic
Geology Report No. 27).

ROSHCHIN,  A.V.  (1962)  [The  hazards of occupational  vanadium
intoxication  in  boiler  cleaning operations  at electric power
stations  operating on fuel oil,  and prevention problems.]  Gig.
Tr. prof. Zabol ., 6: 17-22 (in Russian).

ROSHCHIN, A.V.  (1963a)  [Biological effects of rare, dispersed,
and  other  metals  and  their  compounds  used   in   industry:
vanadium.] In: [ Toxicology  of the less common metals ,]  Moscow,
Meditsina, pp. 83-95 (in Russian).

ROSHCHIN,  A.V.   (1963b)   [Hygienic evaluation  of  dust  from
vanadium-containing   slag.]  Gig.   i   Sanit ., 12:  23-29   (in

ROSHCHIN,  A.V.  (1964)  [Vanadium  metallurgy in the  light  of
industrial  hygiene and questions concerned  with the prevention
of  occupational  diseases  and  intoxication.]  Gig.  Tr.  prof.
Zabol ., 8: 3-10 (in Russian).

ROSHCHIN,  A.V.  (1967a)  Toxicology of  vanadium compounds used
in modern industry.  Hyg. Sanit ., 32: 345-352.

ROSHCHIN,  A.V.   (1967b)   Vanadium. In:  Izraelson,  Z.I., ed.
 Toxicology   of the rare  metals , Jerusalem, Israel Program  for
Scientific Translations Ltd., pp. 52-59 (AEC-tr-6710).

ROSHCHIN,  A.V.  (1968)  [ Vanadium  and its compounds ,]  Moscow,
Medicina Publishing House (in Russian).

ROSHCHIN,  A.V.  &  ORDZHONIKIDZE, E.K.   (1986)  [Metal toxico-
kinetics  and  its  significance for  prevention of occupational
poisoning.]  Gig. Tr. prof. Zabol ., 3: 1-6 (in Russian).

L.A.  (1964)  [Research into effects of vanadium  trioxide  dust
on organisms.]  Gig. Tr. prof. Zabol ., 8: 25-30 (in Russian).

Vanadium   -   toxicity,  metabolism,   carrier  state.  J.  Hyg.
Epidemiol. Microbiol. Immunol ., 24(4): 377-383.

RUHLING, A.  (1971)  [Pollution with heavy metals in the greater
Stockholm area.] In: [ Report  No. 12 on ecological  heavy  metal
research ,]   Lund,  University  of  Lund,  Department  of  Plant
Ecology (in Swedish).

RUNDBERG,  G.  (1939)  Modern problems  of occupational diseases
in Sweden.  Nord. Med ., 2: 1845-1856.

(1978)   Similarity in metabolic patterns  of different chemical
species of vanadium in the rat.  Bioinorg. Chem ., 8: 503-515.

&  ORVINI, E.  (1979)  The association of vanadium with the iron
transport  system in human blood as determined by gel filtration
and  neutron activation analysis. In:  Proceedings of a Symposium
on Nuclear Activation Techniques in the Life  Sciences,  Vienna,
22-26 May, 1978 , Vienna, International Atomic Energy Agency, pp.

A.,  & MANZO, L.  (1981)  Biliary excretion of vanadium in rats.
 Toxicol. Eur. Res ., 3(2): 93-98.

SANDELL,  E., ed.  (1959)  Vanadium. In:  Colorimetric determina-
tion  of  traces  of  metals , 3rd  ed.,  New  York, Interscience
Publishers, Vol. 3, pp. 923-940 (Chemical Analysis Series).

SCHLETTWEIN-GZELL,  D.  &  MOMMSEN-STRAUB,  S.   (1973)   [Trace
elements   in   foodstuffs.   XI.  Vanadium.]  Int.   Z.  Vitam.-
Ernhrungsforsch ., 43(2): 242-250 (in German).

SCHROEDER,  H.A.   (1966)  Municipal  drinking-water and cardio-
vascular death rates.  J. Am. Med. Assoc ., 195: 81-85.

SCHROEDER,  H.A.   (197Oa)    Vanadium , Washington  DC,  American
Petroleum Institute (Air Quality Monograph No. 70-13).

SCHROEDER,  H.A.  (197Ob)  A sensible  look at air pollution  by
metals.  Arch. environ. Health , 21: 798-806.

SCHROEDER,  H.A.  & MITCHENER,  M.  (1975) Life-term  effects of
mercury,  methylmercury, and nine other trace metals on mice.  J.
Nutr ., 105(4): 452-458.

SCHROEDER, H.A., BALASSA, J.J., & TIPTON, I.H.  (1963)  Abnormal
trace metals in man: vanadium.  J. chron. Dis ., 16: 1047-1071.

SCHROEDER, H.A., MITCHENER, M., & NASON, A.P. (1970)  Zirconium,
niobium,  antimony,  vanadium,  and  lead  in  rats:   life-term
studies.  J. Nutr ., 100(1): 59-68.

SCHUMANN-VOGT, B.  (1969)  [Health hazards in industry caused by
vanadium.]  Zentralbl.  Arbeitsmed.  Arbeitsschutz , 19(2):  33-39
(in German).

SCHWARZ, K. & MILNE, D.B.  (1971)  Growth effects of vanadium in
the rat.  Science , 174: 426-428.

SELJANKINA,  K.P.   (1961)   [Data for  determining  the maximum
permissible content of vanadium in water basins.]  Gig. i Sanit .,
26(10): 6-12 (in Russian).

SHAH, K.R., FILBY, R.H., & HALLER, W.A.   (1970)   Determination
of trace elements in petroleum by neutron  activation  analysis.
1.  Determination of Na, S,  Li, La, V, Mn,  Cu, Ga, and  Br.  J.
radioanal. Chem ., 6: 185-192.

S.A.   (1981)  Effects of vanadium on immunologic functions.  Am.
J. ind. Med ., 2(2): 91-99.

SHARMA,  R.P.,  COULOMBE, R.A.,  Jr,  & SRISUCHART,  B.   (1986)
Effects of dietary vanadium exposure on levels of regional brain
neurotransmitters  and  their metabolites.  Biochem.  Pharmacol .,
35(3): 461-465.

SHEVCHENKO,  I.T. & GORODYNSKYJ, V.I.  (1964)  [ Polarography  in
medicine  and biology ,]  Kiev,  State Medical Publishers  of the
Ukraine (in Russian).

SHEVCHENKO, S.D.  (1965)  [Content of vanadium in bone tumours.]
 Ortop. Travmatol. Protez ., 8: 83 (in Russian).

SHILINA,  A.I.  & MALAKHOV,  S.G.   (1974)  [Trace  elements  in
natural waters and the atmosphere.] In: [ A  collection of papers
on   experimental  meteorology ,]   Moscow,   Gidrometeozdat  (in

SHKOLENOK,  G.F.,  NIKOLAEVA,  E.R.,  &  AGASYAN,  P.K.   (1977)
[Differential  controlled-potential coulometry. Determination of
vanadium(V) and vanadium(IV).]  Zavod. Lab ., 43(9): 1048-1050 (in

SIMONOFF,  M., CONRI, C.,  & SIMONOFF, G.   (1986)  Vanadium  in
depressive   states.  Acta   pharmacol.  toxicol .   (Copenhagen) ,
59(Suppl. 7): 463-466.

SINGH,  D. & SHARMA,  S.  (1970)  Amperometric  permanganometric
estimations  at low concentrations in  stirred solutions.  Indian
J. Chem ., 8(2): 192.

SINGH, J., NORDLIE, R.C., & JORGENSON, R.A.   (1981)   Vanadate:
a  potent  inhibitor  of multifunctional  glucose-6-phosphatase.
 Biochim. Biophys . Acta , 678: 477-482.

SJBERG,  S.-G.  (1950)  Vanadium pentoxide dust: A clinical and
experimental  investigation on its effect after inhalation.  Acta
med. Scand ., 138(Suppl. 238): 1-188.

SJBERG,  S.-G.   (1951)   Possible  importance  of  allergy  in
diseases caused by inhalation of inorganic dust.  Acta allergol .,
4(4): 357-361.

SJBERG,  S.-G.  (1955)  Vanadium bronchitis  from cleaning oil-
fired boilers.  Arch. ind. Health , 11(6): 505-512.

SJBERG,  S.-G.  (1956)  Vanadium  dust, chronic bronchitis  and
possible risk of emphysema. A follow-up investigation of workers
at a vanadium factory.  Acta med. Scand ., 44(5):  381-386.

SJBERG,   S.-G.  &  RIGNER,  K.-G.   (1956)   [Skin,  eye,  and
respiratory  tract symptoms associated with the cleaning of oil-
fired boilers.]  Nord. Hyg. Tidskr ., 37: 217-228 (in Swedish).

(1983)   Recent  experiences  with  the  stabilized  temperature
platform   furnace   and   zeeman   background   correction.  At.
Spectrosci ., 4(3): 69-86.

SMITH,  J.B.  (1983)  Vanadium  ions stimulate DNA  synthesis in
Swiss  mouse 3T3  and 3T6  cells.  Proc. Natl  Acad. Sci.  (USA) ,
80(20): 6162-6166.

SNYDER,  F. & CORNATZER,  W.E.  (1958)  Vanadium  inhibition  of
phospholipid  sulphydryl activity in rat  liver.  Nature (Lond.) ,
182: 462.

SOKOLOV,  S.M.   (1986)   Metholodological aspects  of assessing
atmospheric contamination with metal aerosols in the vicinity of
thermal   power   complexes.  J.   Hyg.   Epidemiol.   Microbiol.
Immunol ., 30(3): 249-254.

SOMERVILLE, J. & DAVIES, B.  (1962)  Effect of vanadium on serum
cholesterol.  Am. Heart J ., 64: 54-56.

SREMARK,  R.  (1967)  Vanadium in some biological specimens.  J.
Nutr ., 92: 183-190.

SREMARK, R. & ULLBERG, S.  (1962)  Distribution and kinetics of
48V2O5 in mice. In: Friend, N., ed.  Proceedings of  a  Symposium
on  the Use of Radioisotopes  in Animal Biology and  the Medical
Sciences,  Mexico City, 21 November-1  December, 1961 , New York,
Academic Press, Vol. 2, pp. 103-114.

SREMARK,  R.,  ULLBERG, S.,  &  APPELGREN, L.E.   (1962)  Auto-
radiographic  localization  of  vanadium pentoxide  (V24805)  in
developing  teeth and bones  of rats.  Acta odontol.  Scand ., 20:

SPRAGUE,  J.B., HOLDWAY, D.A.,  & STENDAHL, D.H.   (1978)   Acute
and  chronic toxicity of vanadium to fish , Edmonton, Environment
Alberta,  92 pp  (Prepared for  the Alberta  Oil Sands  Research
Program (Project No. AF 3.5.1).

S.M.,  &  HADDY,  F.J.   (1981)   Effect  of  prolonged  dietary
administration  of  vanadate  on  blood  pressure  in  the  rat.
 Hypertension , 3: I/173-I/178.

STENDAHL,  D.H.  &  SPRAGUE,  J.B.   (1982)   Effects  of  water
hardness  and pH on  vanadium lethality to  rainbow trout.  Water
Res ., 16: 1479-1488.

STOCKS,  P.   (1960)   On  the  relations  between   atmospheric
pollution  in  urban and  rural  localitites and  mortality from
cancer,  bronchitis and pneumonia, with  particular reference to
3:4  benzopyrene, beryllium, molybdenum, vanadium,  and arsenic.
 Br. J. Cancer , 14: 397-418.

DOBROGORSKI,  O.J., & KEENAN, R.G.   (1967)  In Vanadium V.  In:
Clayton,  G.D. & Clayton, F.E., eds.  Patty's  Industrial hygiene
and  toxicology , 3rd revised ed. (1981), New York, Interscience,
Vol. 2A, pp.  2013-2033.

TERRY,  L.S.   (1976)   Test  for  carcinogenicity  of  metallic
compounds  by the  pulmonary tumor  response in  strain a  mice.
 Cancer Res ., 36: 1744-1747.

STRAHOV, N.F.  (1947)  [Iron-ore facies and their  analogues  in
the  history of the earth.]  Tr. Inst. Geol. AN SSSR, geol. Ser .,
73: 22 (in Russian).

STRAHOV,  N.M.  (1968)  [On the theory of geochemical process in
humid zones.] In: [ A  collection of papers on  the  geochemistry
of sedimentary rocks and ores ,]  Moscow, Na++uka Publishing House,
pp.  102-134 (Documentation of the  Seventh All-Union Conference
on  Lithology  of  the Academy  of  Sciences  of the  USSR)  (in

STRASIA,  C.A.  (1971)   Vanadium:  essentiality and toxicity  in
the laboratory rat , Ann Arbor, Michigan Purdue University (Ph.D.

STROOP,   S.D.,  HELINEK,  G.,  &  GREENE,  H.L.   (1982)   More
sensitive  flameless atomic absorption  analysis of vanadium  in
tissue and serum.  Clin. Chem ., 28(1): 79-82.

STYRIS, D.L. & KAYE, J.H.  (1982)  Mechanisms of vaporization of
vanadium  pentaoxide from vitreous carbon  and tantalum furnaces
by  combined  atomic absorption/mass  spectrometry.  Anal. Chem .,
54: 864-869.

SUGAWARA, K., NAITO, H., & YAMADA, S.  (1956)   Geochemistry  of
vanadium  in natural waters.  J.  earth Sci. Nagoya  Univ ., 4(1):

Heavy  metals in normal Japanese tissues.  Arch. environ. Health ,
30: 487-494.

SUN,  MIANLING,  ed.   (1987)    Toxicity  of  vanadium  and  its
environmental health standard , Chengdu, West China University of
Medical Sciences, 20 pp.

SVERDRUP,  H.U.,  JOHNSON, M.W.,  &  FLEMING, R.H.   (1950)   The
oceans,  their physics, chemistry and general biology , Englewood
Cliffs, New Jersey, Prentice-Hall Inc., pp. 175-177.

Vanadyl  (VO2+)  and  vanadate  (VO3-)  ions  inhibit  the brain
microsomal  Na,  K-AtPase with similar affinities.  Protection by
transferrin  and  noradrenaline.  Biochem. Pharmacol ., 33:  2485-

SWARUP,  G., COHEN, S., &  GARBERS, D.L.  (1982)  Inhibition  of
membrane    phosphotyrosyl-protein   phosphatase   activity   by
vanadate.  Biochem. biophys. Res. Commun ., 107: 1104-1109.

SYMANSKI,  J.   (1939)   [Occupational vanadium  poisoning,  its
occurrence     and     symptomatology.]  Arch.     Gewerbepathol.
Gewerbehyg ., 9: 295-313 (in German).

TAKAHASHI,  H. & NASON, A.   (1957)  Tungstate as a  competitive
inhibitor of molybdate in nitrate assimilation and  N2  fixation
by azotobacter.  Biochim. Biophys. Acta , 23: 433-435.

TALVITIE,  N.A.   & WAGNER,  W.D.   (1954)  Studies  in vanadium
toxicology.  II.  Distribution  and  excretion  of  vanadium  in
animals.  Arch. ind. Hyg ., 9: 414-422.

TANDON,  A.G.  &  BHATTACHARYA, S.C.   (1961)  Use of  N-2-thio-
phenecarbonyl- N-p-tolylhydroxylamine     and   N-2-thiophene-
carbonyl- N-phenylhydroxylamine   as reagents for vanadium.  Anal.
Chem ., 33(9): 1267.

TARA,  S., CAVIGNEAUX, A.,  & DEPLACE, Y.   (1953)  Intoxication
par  le vanadate de  calcium.  Arch. Mal. prof.  Md. Trav.  Sc.
soc ., 14: 378-380.

TEBROCK,  H.E.  &  MACHLE,  W.   (1968)   Exposure  to europium-
activated  yttrium orthovanadate: a cathodoluminescent phosphor.
 J. occup. Med ., 10(12): 692-696.

THOMAS,  D.L.G. & STIEBRIS,  K.  (1956)  Vanadium  poisoning  in
industry.  Med. J. Aust ., 1: 607-609.

THOMPSON,  H.J., CHASTEEN, N.D., & MEEKER, L.D.  (1984)  Dietary
vanadyl   (IV)   sulfate  inhibits   chemically-induced  mammary
carcinogenesis.  Carcinogenicity , 5: 849-851.

THURAUF,  J., SYGA, G.,  & SCHALLER, K.H.   (1979)  Field  tests
carried  out to determine the occupational exposure to vanadium.
 Zbl. Bakteriol. Hyg., I. Abt. Orig. B , 168: 273-290.

TIPTON,  I.H. &  COOK, M.J.   (1963)  Trace  elements  in  human
tissue. II. Adult subjects from the United States.  Health Phys .,
9: 103-145.

TIPTON,  I.H. & SHAFER,  J.J.  (1964)  Statistical  analysis  of
lung trace element levels.  Arch. environ. Health , 8: 58-67.

TIPTON,  I.H., STEWART, P.L., & DICKSON, J.  (1969)  Patterns of
elemental  excretion in long-term balance studies.  Health Phys .,
16: 455-462.

TJURJUKANOV,  A.N.   (1963)   Vanadium.  In:  Trace  elements  in
agriculture , Kiev, Gosselhozizdat, pp. 472-475.

TODRIA,  F.F.  (1963)  [Identification  of vanadium in  ashes of
Tkibul coals.] In: [ Abstracts  of scientific papers  of  Tbilisi
Medical  Institute ,]  Tbilisi, Tbilisi State  Medical Institute,
p. 144 (in Russian).

R.   (1979)  Effects of vanadium on glucose metabolism  in vitro .
 Life Sci ., 25: 1159-1164.

TONEY, J.H., MURTHY, M.S., & MARKS, T.J.   (1985)   Biodistribu-
tion  and pharmacokinetics of vanadium following intraperitoneal
administration  of  vanadocene  dichloride to  mice.  Chem.-biol.
Interact ., 56(1): 45-54.

TRELLES, R.A., LARGHI, L.A., & PAEZ, L.J.P.  (1970)  [The health
problem of human drinking-water with high contents  of  arsenic,
vanadium,   and   fluorine.]  Saneamiento , 34(217):   31-80   (in

TROPPENS,  H.  (1969)  [The uncertainties  of vanadium pentoxide
intoxication.]  Dtsch. Gesundheitswes ., 24:     1089-1092     (in

TRUMMERT,  W. & BOEHM, G.   (1957)  [The trace element  vanadium
and its haemopoietic action.]  Blut , 3: 210-216 (in German).

TYLER,  G.   (1970)   [Pollution  with  heavy  metals   in   the
Norrkkoping area. II. Molybdenum and vanadium.] In: [ Report  No.
12  on ecological heavy  metal research ,]  Lund,  University  of
Lund, Department of Plant Ecology (in Swedish).

UENO, S. & ISHIZAKI, M.  (1980)  Concentrations of  vanadium  in
human urine and hair.  Jpn. J. ind. Health , 22: 318-379.

UNDERWOOD,  E.J.  (1977)  Vanadium. In:  Trace  elements in human
and  animal  nutrition , 4th  ed.,  New  York,  Academic   Press,
pp. 388-397.

UNSAL,  M.   (1978)   Study of  the  transfer  pathways and  the
accumulation  phenomena of vanadium in  mollusca  Mytilus edulis.
Rev. int. oceanogr. Med ., 51/52: 71-81.

US BUREAU OF MINES  (1974) Metals Information Bulletin. Washing-
ton DC, US Department of the Interior, Bureau of  Mines,  Branch
of Ferrous Metals.

US  EPA  (1977)   Scientific  and technical assessment  report on
vanadium , Washington  DC,  US  Environmental  Protection  Agency
(STAR series, EPA-600/6-77-002).

USMONOV,  S.M.   (1973)   [Vanadium content  in  constituents of
bone,  urine,  and  faeces in  sufferers  of  acute and  chronic
dysentery.] In: [ Epidemiological,  microbiological, and clinical
problems  in the infectious pathology of Uzbekistan ,]  Tashkent,
Institute  of  Hygiene,  Sanitation, and  Occupational Diseases,
pp. 125-128 (in Russian).

HOSOKAWA,  Y., &  IZUMI, S.   (1979)  [An  investigation of  the
environment  in  a  certain  vanadium  refinery.]  Jpn.  J.  ind.
Health , 21: 11-20 (in Japanese).

VAN DEN BERG, C.M.G. & HUANG ZI QIANG  (1984)   Direct  electro-
chemical  determination  of  dissolved vanadium  in  seawater by
cathodic  stripping  voltammetry  with the  hanging mercury drop
electrode.  Anal. Chem ., 56(13): 2383-2386.

VANSELOW,  A.P.  (1950)  Unpublished  data cited by  Pratt, P.F.
In: Diagnostic  criteria  for  plants and  soils,   University of
California,  Division  of  Agricultural Sciences , University  of
California, pp. 480-482.

VAN ZINDEREN BAKKER, E.M. & JAWORSKI, J.F.  (1980)    Effects  of
vanadium  in the Canadian environment , Ottawa, National Research
Council of Canada (Publication No. 18132).

VERSIECK,  J. &  CORNELIS, R.   (1980)  Normal  levels of  trace
elements in human blood-plasma or -serum.  Anal. Chim. Acta , 116:

VEYS,  C.   (1983)   Possibilits  offertes  par  les   mthodes
modernes  de  polarographie  au dosage    lments tracs.  Ind.
Sci ., 59(3): 1-6.

VIGLIANI,  E.C.  (1969)   WHO  Technical Report Series  No.  415:
Permissible  levels of occupational  exposure to airborne  toxic
substances  (Sixth  Report of  the  Joint ILO/WHO  Committee  on
Occupational  Health) , Geneva, World Health Organization, pp. 5-

VlNOGRADOV,  A.P.  (1937)  [The chemical  elements entering into
the  composition of marine organisms.  Part II.]  Tr. biogeokhim.
Lab ., 4: 217 (in Russian).

VINOGRADOV  A.P.  (1944)  [The geochemistry of trace elements in
seawater.]  Uspehi Himii , 13(1): 123-129 (in Russian).

VINOGRADOV,  A.P.  (1957)  [ Geochemistry  of  rare and dispersed
chemical  elements in soils ,]   2nd ed (revised),  Moscow,  USSR
Academy of Sciences, pp. 122-129, 216-217 (in Russian).

VINOGRADOV,  A.P.   (1959)   [ The   geochemistry  of  rare   and
dispersed  elements in soil ,]   2nd ed., New  York,  Consultants
Bureau Inc., 209 pp (in Russian).

C., & OCHOA, R.  (1955)  Study of the health of workers employed
in  mining and processing  of vanadium ore.  Arch.  ind.  Health ,
12: 635.

VOORS,  A.W.   (1971)   Minerals  in  the  municipal  water  and
atherosclerotic heart death.  Am. J. Epidemiol ., 93: 259-266.

VOUK, V.  (1979)  Vanadium. In: Friberg, L., Nordberg,  G.F.,  &
Vouk,  V., ed.  Handbook on the  toxicology of metals , Amsterdam,
New York, Oxford, Elsevier Science Publishers, pp. 659-674.

VYSKOCIL,  F., TEISINGER, J., &  DLOUHA, H.  (1980)  A  specific
enzyme  is not necessary for vanadate-induced oxidation of NADH.
 Nature (Lond.) , 286(5772): 516-517.

VYSKOCIL, F., TEISINGER, J., & DLOUHA, H.  (1981)  The disparity
between  effects of vanadate (V) and vanadyl (IV) ions on (Na+ -
K+)  AtPase  and  K+-phosphatase  in  skeletal  muscle.  Biochem.
biophys. Res. Commun ., 100: 982-987.

WALDRON, H.A.  (1979)  Metal poisoning: the three common causes.
 Mod. Med ., 24(9): 45-47.

WALLACE, A., ALEXANDER, G.V., & CHADHURY, F.M.   (1977)   Phyto-
toxicity  of cobalt, vanadium,  titanium, silver, and  chromium.
 Commun. soil. Sci. plant Anal ., 8(9): 751-756.

WARINGTON,  K.  (1955)  The  influence of iron  supply on  toxic
effects of manganese, molybdenum and vanadium in soybeans, peas,
and flax.  Ann. appl. Biol ., 41: 1-22.

WATANABE,  H.,  MURAYAMA,  H.,  &  YAMAOKA,  S.   (1966)   [Some
clinical  findings  in  vanadium workers.]  Jpn.  J. ind. Health ,
8(7): 23-27 (in Japanese).

WATERS,   M.D.    (1977)   Toxicology   of  vanadium.  Adv.  mod.
Toxicol ., 2: 147-189.

WATERS, M.D., GARDNER, D.E., & COFFIN. D.L.   (1974)   Cytotoxic
effects  of  vanadium  on rabbit  alvolar  macrophages  in vitro .
 Toxicol. appl. Pharmacol ., 28: 253-263.

WATERS,  M.D., GARDNER, D.E., ARANYI, C., & COFFIN, D.L.  (1975)
Metal   toxicity  for  rabbit  alveolar   macrophages  in  vitro.
Environ. Res ., 9: 32-47.

WEAST, R.C.  (1987)   CRC handbook of chemistry and physics , 67th
ed., Boca Raton, Florida, CRC Press.

WEI,  C.I. & MISRA, H.P.  (1982)  Cytotoxicity of ammonium meta-
vanadate  to  cultured  bovine alveolar  macrophage.  J. Toxicol.
environ. Health , 9(5-6): 995-1006.

&  HANSEN, L.D.  (1982)  Acute toxicity of ammonium metavanadate
in mice.  J. Toxicol. environ. Health , 10(4/5): 673-687.

WEISZ,   H.,  ROTHMAIER,  K.,  &  LUDWIG,  H.   (1974)   Kinetic
determination of thorium, vanadium, and iodide with the use of a
potentiometer.  Anal. Chim. Acta , 73(1): 224-228.

WELCH,  R.M.   (1973)   Vanadium uptake  by  plants.  Absorption
kinetics  and the effects of pH, metabolic inhibitors, and other
anions and cations.  Plant Physiol ., 51: 828-832.

WELCH, R.M. & ALLAWAY, W.H.  (1972)  Vanadium  determination  in
biological materials at nanogram levels by a  catalytic  method.
 Anal. Chem ., 44(9): 1644-1647.

WENTZEL,  C.T.  (1985)  Vanadium:  a moderate recovery  in 1984.
 Eng. mining J ., March: 87-88.

WESTENFELDER,  C.,  HAMBURGER,  R.K.,  &  GARCIA,  M.E.   (1981)
Effect  of vanadate on  renal tubular function  in rats.  Am.  J.
Physiol ., 240: F522-F529.

WIDE,   M.   (1984)   Effect  of  short-term  exposure  to  five
industrial  metals on the embryonic and fetal development of the
mouse.  Environ. Res ., 33: 47-53.

WILLIAMS, D.L.  (1973)   Biological value of vanadium  for  rats,
chickens,  and  sheep , Ann  Arbor, Michigan,  Purdue  University
(Ph.D. Thesis).

WILLIAMS, N.  (1952)  Vanadium poisoning from cleaning oil-fired
boilers.  Br. J. ind. Med ., 9: 50-55.

WITKOWSKA,  D.  & BRZEZINSKI,  J.   (1979)  Alteration  of brain
noradrenaline,  dopamine, and 5-hydroxytryptamine  levels during
vanadium poisoning.  Pol. J. Pharmacol. Pharm ., 31: 393-398.

WOOD,  B.J., GALOBARDES, J.F., & ROGERS, L.B.  (1982)  Effect of
the  organic ligand on the response for vanadium in flame atomic
emission spectrometry.  Anal. Chim. Acta , 135: 145-152.

WRIGHT,  L.D.,  LI,  L.F., &  TRAGER,  R.   (1960)  The  site of
vanadyl   inhibition   of  chloesterol   biosynthesis  in  liver
homogenates.  Biochem. biophys. Res. Commun ., 3: 264-267.

WYERS,  H.  (1946)  Some  toxic effects of  vanadium  pentoxide.
 Br. J. ind. Med ., 3: 177-182.

WYERS,  H.  (1948)  Some recent  observations on hazards in  the
chemical  industry.  In:  Proceedings  of the  9th  International
Congress   of  Industrial  Medicine,  London,  13-17  September ,
Bristol, John Wright, pp. 900-903.

Distribution of trace elements in the human body  determined  by
neutron  activation analysis.  Arch. environ.  Health , 35(1): 36-

ZAJIC,   J.E.   (1969)   Microbial  biochemistry.  12.   Vanadium
biogeochemistry , New York, Academic Press, pp. 126-202.

ZEMKOVA,   H.,  TEISINGER,  J.,  &  VYSKOCIL,  F.   (1982)   The
comparison of vanadyl (IV) and insulin-induced hyperpolarization
of  the mammalian muscle cell.  Biochim. Biophys. Acta , 720: 405-

ZENZ,  C. & BERG,  B.A.  (1967)  Human  responses to  controlled
vanadium  pentoxide  exposure.  Arch.  environ. Health , 14:  709-

ZENZ, C., BARTLETT, J.P., & THIEDE, W.H.  (1962)  Acute vanadium
pentoxide intoxication.  Arch. environ. Health , 5(6):  542-546.

[A  catalytic  method  for determining  nanogram  quantities  of
vanadium.]  Zh. anal. Khim ., 27(4): 795-798 (in Russian).

ZOLLER, W.H., GLADNEY, E.S., & DUCE, R.A.   (1974)   Atmospheric
concentration  and sources of  trace metals at  the South  Pole.
 Science , 183: 198-200.

ZOLLER, W.H., GORDON, G.E., GLADNEY, E.S., & JONES, A.G.  (1973)
The  sources and distribution of vanadium in the atmosphere. In:
Kothy,  E.L., ed.  Trace elements in  the environment , Washington
DC,  American Chemical Society, pp. 31-47 (Advances in Chemistry
Series 123).

ZOLOTAVIN,  V.L.  (1954)  [Achieving  a pure solution  of chlor-
vanadyl.]  Zh. obshch. Khim ., 24: 433 (in Russian).

    See Also:
       Toxicological Abbreviations