Chromium (EHC 61, 1988)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 61

CHROMIUM

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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.

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the United Nations Environment Programme,
the International Labour Organisation,
and the World Health Organization

World Health Orgnization
Geneva, 1988

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR CHROMIUM

1. SUMMARY AND RECOMMENDATIONS

1.1. Summary
1.1.1. Analytical methods
1.1.2. Sources of chromium, environmental levels and exposure
1.1.3. Metabolism
1.1.4. Effects on experimental animals
1.1.5. Effects on human beings
1.1.5.1 Clinical and epidemiological studies
1.1.6. Evaluation of risks for human health
1.2. Recommendations for further research
1.2.1. Analytical methods
1.2.2. Sources of chromium intake
1.2.3. Studies on health effects
1.2.4. Interaction with other environmental factors

2. PHYSICAL AND CHEMICAL PROPERTIES AND ANALYTICAL METHODS

2.1. Physical and chemical properties
2.2. Analytical methods
2.2.1. Sampling
2.2.2. Analytical methods

3. SOURCES IN THE ENVIRONMENT, ENVIRONMENTAL TRANSPORT AND DISTRIBUTION

3.1. Natural occurrence
3.1.1. Rocks
3.1.2. Soils
3.1.3. Water
3.1.4. Air
3.1.5. Plants and wildlife
3.1.6. Environmental contamination from natural sources
3.2. Production, consumption, and uses
3.3. Waste disposal
3.4. Miscellaneous sources of pollution
3.5. Environmental transport and distribution

4. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

4.1. Environmental levels
4.1.1. Air
4.1.2. Water
4.1.3. Food
4.2. General population exposure
4.2.1. Food and water
4.2.2. Other exposures
4.3. Occupational exposure
4.3.1. Inhalation exposure
4.3.2. Dermal exposure

5. KINETICS AND METABOLISM

5.1. Absorption
5.1.1. Absorption through inhalation
5.1.1.1 Animal studies
5.1.1.2 Human data
5.1.2. Absorption from the gastrointestinal tract
5.1.2.1 Animal studies
5.1.2.2 Human data
5.2. Distribution, retention, excretion
5.2.1. Animal studies
5.2.2. Human data
5.2.2.1 Concentration in tissues, blood, urine,
and hair including possible biological
indicators of exposure
5.2.2.2 Dynamic aspects of metabolism
and the influence of pathological states
5.3. Influence of chemical form

6. EFFECTS ON ORGANISMS IN THE ENVIRONMENT

6.1. Microorganisms
6.2. Plants
6.3. Aquatic organisms

7. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

7.1. Nutritional effects of chromium
7.1.1. Effects of deficiency on glucose metabolism
7.1.2. Effects of deficiency on lipid metabolism
7.1.3. Effects of deficiency on life span, growth, and reproduction
7.1.4. Other effects of deficiency
7.1.5. Mechanism of action of chromium as an essential nutrient
7.1.5.1 Enzymes, nucleic acids, and thyroid
7.1.5.2 Interaction of chromium with insulin
7.1.6. Chromium nutritional requirements of animals
7.2. Toxicity studies
7.2.1. Effects on experimental animals
7.2.1.1 Carcinogenicity
7.2.1.2 Genotoxicity
7.2.1.3 Developmental toxicity and other
reproductive effects
7.2.1.4 Cytotoxicity and micromolecular syntheses
7.2.1.5 Fibrogenicity
7.2.2. Observations in farm animals

8. EFFECTS ON MAN

8.1. Nutritional role of chromium
8.1.1. Biological measurements and their interpretation
8.1.2. Chromium deficiency
8.1.2.1 Adults
8.1.2.2 Malnourished children
8.1.2.3 Patients on total parenteral alimentation
8.1.2.4 Epidemiological studies

8.1.3. Mode of action
8.2. Acute toxic effects
8.3. Chronic toxic effects
8.3.1. Effects on skin and mucous membranes
8.3.1.1 Primary irritation of the skin
and mucous membranes
8.3.1.2 Allergic contact dermatoses
8.3.2. Effects on the lung
8.3.2.1 Bronchial irritation and sensitization
8.3.3. Effects on the kidney
8.3.4. Effects on the liver
8.3.5. Effects on the gastrointestinal tract
8.3.6. Effects on the circulatory system
8.3.7. Teratogenicity
8.3.8. Mutagenicity and other short-term tests
8.3.9. Carcinogenicity
8.3.9.1 Lung cancer
8.3.9.2 Cancer in organs other than lungs
8.3.9.3 Relative risk between cancer risk
and chromium compound

9. EVALUATION OF HEALTH RISKS FOR MAN

9.1. Occupational exposure
9.1.1. Effects other than cancer
9.1.1.1 Respiratory tract
9.1.1.2 Skin
9.1.1.3 Kidney
9.1.1.4 Other organs and systems
9.1.2. Teratogenicity
9.2. General population

REFERENCES

WHO TASK GROUP ON CHROMIUM

Members

Professor Chen Bingheng, Department of Environmental Health,
Shanghai Medical University, Shanghai, China

Dr H.N.B. Gopalan, University of Nairobi, Department of Botany,
Nairobi, Kenya

Professor C.R. Krishna Murti, Integrated Environmental
Programme on Heavy Metals, Department of Environment,
Government of India, New Delhi, India (Vice-Chairman)

Professor Aly Massoud, Department of Community, Environmental
and Occupational Medicine, Faculty of Medicine, Ain Shams
University, Cairo, Egypt

Dr W. Mertz, Human Nutrition Research Center, US Department of
Agriculture, Beltsville, Maryland, USA (Chairman)

Professor I.V. Sanotsky, Department of Toxicology, Institute
of Industrial Hygiene and Occupational Diseases, Academy
of Medical Sciences of the USSR, Moscow, USSR

Professor W. Stöber, Fraunhofer Institute for Toxicology and
Aerosol Research, Hanover, Federal Republic of Germany

Secretariat

Dr J. Parizek, International Programme on Chemical Safety,
World Health Organization, Geneva, Switzerland (Secretary)

Dr R.F. Hertel, Fraunhofer Institute for Toxicology and
Aerosol Research, Hanover, Federal Republic of Germany
(Temporary Adviser) (Rapporteur)

Dr T. Ng, Office of Occupational Health, World Health
Organization, Geneva, Switzerland

Mr J.D. Wilbourn, Unit of Carcinogen Identification and
Evaluation, International Agency for Research on Cancer,
Lyons, France

NOTE TO READERS OF THE CRITERIA DOCUMENTS

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 detailed data profile and 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).

ENVIRONMENTAL HEALTH CRITERIA FOR CHROMIUM

A WHO Task Group on Environmental Health Criteria for Chromium
met in Geneva from 24 to 27 March 1986. Dr J. Parizek opened the
meeting on behalf of the Director-General. The Task Group reviewed
and revised the draft criteria document and made an evaluation of
the health risks of exposure to chromium.

The initial draft was prepared by the INSTITUTE FOR GENERAL AND
COMMUNITY HYGIENE, MOSCOW. The second draft criteria document was
prepared by DR W. MERTZ, HUMAN NUTRITION RESEARCH CENTER, US
DEPARTMENT OF AGRICULTURE, USA, PROFESSOR ANNA BAETGER, JOHN
HOPKINS UNIVERSITY, BALTIMORE, USA (deceased), and Dr R.F. HERTEL,
FRAUNHOFER INSTITUTE OF TOXICOLOGY AND AEROSOL RESEARCH, Federal
Republic of Germany.

The efforts of all 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. The United Kingdom Department of Health and Social
Security generously supported the cost of printing.

1. SUMMARY AND RECOMMENDATIONS

1.1. Summary

1.1.1. Analytical methods

Many analytical methods are available for the determination of
chromium at trace levels, often in the 0.001 mg/kg range. Among
these are flameless atomic absorption spectrometry, atomic emission
spectrometry with various excitation sources (the inductively-
coupled plasma torch is particularly advantageous), gas
chromatography, destructive or non-destructive neutron activation
analysis, and mass spectrometry using double-isotope dilution.
Depending on the particular sample under examination as well as the
analytical technique selected for the determination, wet or dry
ashing procedures may be necessary to destroy the organic/inorganic
matrix and minimize interelemental effects.

Determination of very low chromium concentrations in
"unexposed" biological material (animal and human tissues, blood,
urine, food, as well as water and air) is extremely difficult and
many problems still have to be solved. An accurate assessment of
human exposure and nutritional chromium requirements depends on
reliable analytical results. Chromium concentrations in blood,
urine, and some low-chromium foods are close to or less than 1
µg/kg, which is near the detection limit of even the most sensitive
analytical methods. Thus, agreement as to "normal" levels of
chromium among analytical investigators has been poor, and results
of interlaboratory comparisons have differed widely, usually by one
order of magnitude. Only in recent years has agreement been reached
that "normal" chromium concentrations in unexposed blood and urine
are in the range of 0.1 - 0.5 µg/litre. In this concentration
range, it is not only the sensitivity of the final determination
step that is limiting. The preceding steps of sample collection,
preparation, and digestion are equally important. Contamination,
easily introduced through cutting instruments and dust during
collection, must be carefully controlled. Digestion procedures are
of the greatest importance. Too rigorous treatment by heat or
certain acids can cause a loss of chromium. Few biological
standard reference materials, certified for chromium, are available
and almost all of the older, and most of the recent, published data
were not checked using certified standards. For this reason,
quantitative data concerning chromium concentrations in the range
of < 1 - 100 µg/kg in biological materials must be considered
uncertain, and caution must be used in interpreting their health-
related significance.

Differential analysis for chromium species is of great
scientific and public health concern, in view of the substantial
differences in the biological availability and in the toxicity of
hexavalent chromium (Cr VI) compared with trivalent (Cr III).
Though methods based on solvent extraction, with or without prior
oxidation, differentiate between these two oxidation states, few
analytical data contain this important information.

The understanding of the chemical and physical principles of
chromium determination is increasing, and existing methods are
being improved and new methods developed. However, at present,
analysis for chromium is a sophisticated procedure requiring the
full attention of a highly trained analytical chemist.

1.1.2. Sources of chromium, environmental levels and exposure

Chromium occurs ubiquitously in nature (< 0.1 µg/m³ in air).
Natural levels in uncontaminated waters range from fractions of 1
µg to a few µg/litre.

The concentration of chromium in rocks varies from an average
of 5 mg/kg (granitic rocks) to 1800 mg/kg (ultramafic/basic and
serpentine rocks). The earth's most important deposits are either
in the elemental or the trivalent oxidation state.

In most soils, chromium occurs in low concentrations (2 - 60
mg/kg), but values of up to 4 g/kg have been reported in some
uncontaminated soils. Only a fraction of this chromium is
available to plants. It is not known whether chromium is an
essential nutrient for plants, but all plants contain the element
(up to 0.19 mg/kg on a wet weight basis).

Almost all the hexavalent chromium in the environment arises
from human activities. It is derived from the industrial oxidation
of mined chromium deposits and possibly from the combustion of
fossil fuels, wood, paper, etc. In this oxidation state, chromium
is relatively stable in air and pure water, but it is reduced to
the trivalent state, when it comes into contact with organic matter
in biota, soil, and water. There is an environmental cycle for
chromium, from rocks and soils to water, biota, air, and back to
the soil. However, a substantial amount (estimated at 6.7 x 10⁶ kg
per year) is diverted from this cycle by discharge into streams,
and by runoff and dumping into the sea. The ultimate repository is
ocean sediment.

Chromium compounds are used in ferrochrome production,
electroplating, pigment production, and tanning. These industries,
the burning of fossil fuels, and waste incineration are sources of
chromium in air and water. Most of the liquid effluent from the
chromium industries is trapped and disposed of in land fills and
sewage sludges, the chromium being in the form of the insoluble
trivalent hydroxide.

In chromium ore mines, the concentration of chromium in dust
ranges from 1.3 to 16.9 mg/m³. During the production of refined
ferrochromium, the air in the work-place may contain large amounts
of dust (0.03 - 3.2 mg/m³). In chromium plating factories,
concentrations of 1 µg/m³ up to 1.4 mg/m³ have been measured. In
Portland cement from 9 European countries, the contents of chromium
(VI), extractable with sodium sulfate, varied from 1 to 83 g/kg
cement.

Today, it is generally accepted that only the zero-, di-, tri-,
and hexavalent oxidation states have biological importance. The
effects of the last 2 oxidation states are so fundamentally
different that they must always be considered separately. The
trivalent form is an essential nutrient for man, in amounts of 50 -
200 µg/day.

1.1.3. Metabolism

The kinetics of chromium depend on its oxidation state and the
chemical and physical form within the oxidation state. Most of the
daily chromium intake (50 - 200 µg) is ingested with food and is in
the trivalent form. About 0.5 - 3% of the total intake of
trivalent chromium is absorbed in the body. It is possible, but it
has not yet been proved, that chromium in the form of some
complexes, such as a dinicotinic-acid-complex, glucose tolerance
factor, is better available for absorption. The gastrointestinal
absorption of 3 - 6% of the total intake of hexavalent chromium has
been reported. Once absorbed, chromium is almost entirely excreted
with the urine; the daily urinary-chromium loss of 0.5 - 1.5 µg is
approximately equal to the amount absorbed from the average diet.
However, dermal losses, losses by desquamation of intestinal cells
and by perspiration have not been quantified. Ingested or injected
chromium leaves the blood rapidly. Blood-chromium levels do not
reflect the overall chromium content of tissues, except after a
glucose load, which induces an immediate increase in the plasma-
and urine-chromium levels of chromium-sufficient subjects.
Trivalent chromium inhaled from the air is trapped in the lung
tissues, if in the form of small particles within the respirable
range. The chromium concentrations in lungs increases with age.
Larger particles (greater than 5 µm), regardless of oxidation
state, are moved to the larynx by ciliary action and become part of
the dietary intake.

The intestinal absorption of hexavalent chromium is 3 - 5 times
greater than that of trivalent forms; however, some of it is
reduced by gastric juice. Soluble chromates are rapidly absorbed
through the epithelium of the alveoli and bronchi and cleared into
the circulation, where part is preferentially accumulated by the
red cells and part is excreted by the kidneys. With the exception
of the lungs, tissue levels of chromium decline with age.

1.1.4. Effects on experimental animal

Doses of hexavalent chromium greater than 10 mg/kg diet affect
mainly the gastrointestinal tract, kidneys, and probably the
haematopoetic system. When a similar dose is introduced
parenterally, the principal effect is on the kidney, mainly in the
proximal convoluted tubules, without evidence of glomerular damage.
Toxic effects from trivalent chromium have been reported only
following parenteral administration. Dietary toxicity has not been
reported, even in studies on cats administered amounts of up to 1
g/day for 1 - 3 months. When intravenously injected in mice, the
LD₅₀ of chromium carbonyl was 30 mg/kg body weight; this represents
a 10 000-fold excess over the therapeutic dose required to cure
signs of chromium deficiency.

Many studies on experimental animals have been conducted with
chromium compounds in efforts to reproduce cancer similar to that
found in man, when exposed to chromium.

Most tests have involved subcutaneous, intramuscular, or
intrapleural injection. In addition, several hexavalent chromium
compounds have been administered to rats by intrabronchial
implantation or intratracheal instillation. Relatively insoluble
compounds, calcium chromate, strontium chromate, and certain forms
of zinc chromate produced bronchogenic carcinomas; lead chromate,
and barium chromate produced weak responses. Intratracheal
instillation of soluble sodium dichromate and dissolved calcium
chromate produced bronchogenic tumours. Injection of lead
chromate, lead chromate oxide, and cobalt-chromium alloy resulted
in the production of local sarcomas. Thus, there is sufficient
evidence that certain hexavalent chromium compounds are
carcinogenic for experimental animals. No increased tumour
incidence was observed when trivalent compounds were given orally;
however, the doses administered were low.

Hexavalent chromium has been reported to cause various forms of
genetic damage in short-term mutagenicity tests, including damage
to DNA, and misincoporation of nucleotides in DNA transcription.
It was mutagenic in bacteria in the absence of an exogenous
metabolic activation system, and in fungi. Hexavalent chromium was
also mutagenic in mammalian cells in vitro and in vivo.
Hexavalent chromium caused chromosomal abererations and sister
chromatid exchanges in mamalian cells in vitro. A few positive
results in in vitro assays for mammalian cell chromosomal
aberrations and sister chromatid exchanges were obtained only with
very high doses and could be explained by nonspecific toxic
effects. It induced formation of micronuclei in mice in vivo.
Potassium dichromate induced dominant lethal mutations in mice
treated in vivo.

Trivalent chromium is genetically active only in in vitro
tests, where it can have a direct interaction with DNA, e.g., in
experiments using purified DNA or tests to measure decreased
fidelity of DNA synthesis in vitro. Reduction of chromium (VI)
within the cell nucleus and the formation of chromium (III)
complexes suggests that chromium (III) would be the ultimate
mutagenic form of chromium. Trivalent chromium was present in RNAs
from all sources examined and probably contributes to the stability
of the structure. Injected chromium trichloride (CrCl₃)
accumulated in the cell nucleus (up to 20% of cellular chromium
content). It enhanced RNA synthesis in mice and in regenerating
rat liver, suggesting that chromium (III) is involved directly in
RNA synthesis. On the other hand, chromium (VI) inhibited RNA
synthesis and DNA replication in several systems.

1.1.5. Effects on human beings

Studies on man and experimental animals have established the
essential role of trivalent chromium for the maintenance of normal
glucose metabolism. Chromium deficiency has been demonstrated in

malnourished children, in two patients on total parenteral
nutrition, and in middle-aged subjects, the basic disturbance being
an impairment of the action of circulating insulin.

1.1.5.1. Clinical and epidemiological studies

In adult human subjects, the lethal oral dose is 50 - 70 mg
soluble chromates/kg body weight. The most important clinical
features produced following this route of entry are liver and
kidney necrosis and poisoning of blood-forming organs.

Hexavalent chromium causes marked irritation of the respiratory
tract. Ulceration and perforation of the nasal septum have
occurred frequently in workers employed in the chromate producing
and hexavalent chromium-using industries. In addition to
inhalation, direct contact of the nasal septum with contaminated
hands contributes to nasal exposure. Cancer of the septum has not
been reported. Rhinitis, bronchospasm, and pneumonia may result
from exposure to hexavalent compounds together with impairment of
pneumodynamics during respiration.

Chromate compounds, mainly sodium and potassium chromate and
dichromate, cause irritation of the skin and ulcers may develop at
the site of skin damage. Exposure to trivalent chromium does not
produce such effects. Certain persons manifest allergic skin
reactions to hexavalent and possibly trivalent chromium. Skin
reactions through dermal exposure to chromium are often described,
chromate being the most common contact allergen. However, cancer
of the skin due to chromium exposure has not been reported.

Chronic effects of exposure to chromium (excessive industrial
exposure of the skin to hexavalent chromium, when associated with
damaged skin or inhalation of airborne chromium (VI) or mixed dust)
occur in the lung, liver, kidney, gastrointestinal tract, and
ciculatory system. Teratogenic risks from chromium exposure have
not been reported for human subjects; a mutagenic potency is shown
for potassium dichromate and therefore cannot be excluded for
chromates in the chromate-using industries.

The results of epidemiological studies in various countries
have demonstrated that men working in chromate-production plants
before 1950 had a very high rate of bronchogenic carcinoma,
compared with control populations. Because of the long period
between initial exposure and the detection of cancer and the lack
of data on the extent and type of exposure, the dose-response
relationship has not been quantified. However, the few data
available indicate that, before the danger of cancer was
recognized, the exposure levels in such plants were very high.
Recent data show clearly that, though the risk of cancer in workers
in modern plants has been greatly reduced, it still remains a
problem.

Some epidemiological data suggest that an excess of lung cancer
has also occurred in the chromate-pigment industry. A few cases of
cancer involving the upper respiratory tract have been reported,
but cancer has not been convincingly demonstrated in other body

tissues. The specific compounds responsible for the cancers have
not been identified. Both hexavalent and trivalent compounds were
present in the old plants. However, on the basis of experimental
animal studies, it is currently assumed that the slowly soluble,
hexavalent chemicals, such as calcium and zinc chromate are
responsible for the cancers. This is based on the theory that
these compounds remain in contact with the tissues for long periods
of time (depot effect).

Trivalent chromium is not considered to be carcinogenic for the
following reasons: (a) there was no evidence of excess cancer in
studies in two industries where only trivalent compounds were
present; (b) results of experimental animal and mutagenicity
studies with trivalent chromium, were negative; and (c) because of
the chemical and biological characteristics of the trivalent state,
i.e., non-oxidizing, non-irritating, and probably unable to
penetrate cell membranes.

1.1.6. Evaluation of risks for human health

Chromium in the form of trivalent compounds is an essential
nutrient. The daily human intake of chromium varies considerably
between regions. Typical values range from 50 to 200 µg/day. Such
intakes do not represent a toxicity problem, and they coincide with
the calculated human requirements. Not enough data are available
for a quantitative assessment of the risk of chromium deficiency in
different populations.

Evidence from studies on experimental animals shows that
hexavalent chromium compounds, especially those of low solubility
can induce lung cancer. Mutagenicity and related studies have
shown convincingly that hexavalent chromium is genetically active.
On the other hand, trivalent chromium compounds are inactive in
most test systems, except in systems where they can directly
interact with DNA.

Both oxidation states, when injected at high levels
parenterally in animals, are teratogenic, with the hexavalent form
accumulating in the embryos to a much greater extent than the
trivalent.

A number of effects can result from occupational exposure to
airborne chromium, including irritative lesions of the skin and
upper respiratory tract, allergic reactions, and cancers of the
respiratory tract. The data on other effects in, e.g., the
gastrointestinal, cardiovascular, and urogenital systems are
insufficient for evaluation.

Epidemiological studies have shown that workers engaged in the
production of chromate salts and chromate pigments are at increased
risk of developing bronchial carcinoma. No detailed data on dose-
response relationships are available. Although a suspicion of
increased lung cancer risks in chromium-plating workers has been
raised, the available data are inconclusive and so are data for
other industrial processes where chromium compounds are used rather

than produced. There is insufficient evidence to implicate
chromium as a causative agent of cancer in any organ other than the
lung. The frequency of sister chromatid exchanges in the
lymphocytes of workers in chromium-plating factories was higher
than in control groups.

The general population living in the vicinity of ferro-alloy
plants and exposed to ambient air concentrations of up to 1 µg/m³
did not show increased lung cancer mortality.

The results of many studies suggest that exposure to chromium
through inhalation and skin contact can pose health problems for
the general population, but no data on dose-response relationships
are available. Thus, there is no reason, at present, to be
concerned that chromium in the air presents a health problem,
except under conditions of industrial exposure.

1.2. Recommendations for Further Research

1.2.1. Analytical methods

Data from the determination of chromium should not be accepted
unless proper quality assurance procedures have been used,
including the analysis of a certified reference material of similar
composition. There is a great need for the preparation and
certification of additional standards, especially of blood, serum,
or plasma, urine containing only physiological chromium
concentrations, hair, and foods.

All analyses related to the environmental role of chromium
should differentiate between hexavalent and trivalent forms and
these values should be reported separately. While the
differentiation between hexavalent and trivalent chromium can be
accomplished by established methods, the definition of the exact
chemical species of the trivalent and hexavalent forms in air,
water, food, and tissues will require much further research.

Further development of analytical instrumentation and
preanalytical processing techniques to extend the detection limit
by one order of magnitude is recommended. The need for
interlaboratory comparison persists to improve existing methods and
to validate new procedures.

1.2.2. Sources of chromium intake

More data are needed on the chemical and physical properties of
airborne chromium, such as the oxidation state, particle size, and
solubility. These are important determinants of biological and
toxic action. Existing information on the chromium contents of
foodstuffs is unreliable and incomplete and more composition data
are needed for a valid assessment of the human chromium requirement
and the supplies available in different regions of the world to
meet these requirements. Diagnostic procedures to detect marginal
deficiency and marginal overexposure in man must be developed and
the long-term effects of both these imbalances must be defined.

Finally, not enough is known about the fate of chromium in
landfills, sewage sludges, and aquatic environments. Further
studies are needed to investigate environmental factors that
influence the mobilization, migration, and bioavailability of
chromium in the biosphere.

1.2.3. Studies on health effects

Prospective studies on the health of industrial workers,
combined with the determination of the composition and
environmental levels of the chromium compounds to which they were
exposed, are needed to determine the specific chemical or chemicals
responsible for cancer, and the dose-response relationship between
hexavalent chromium and bronchogenic carcinoma. Smoking histories
should be recorded and, when possible, information on exposure to
ionizing radiation and other chemical carcinogens should be
obtained in order to evaluate possible synergistic relationships.
More studies should be carried out on the chrome-using industries.
Preventive measures include searching for more specific biochemical
indicators of chromium exposure and early effects.

Epidemiological studies are needed to assess the incidence and
severity of chromium deficiency. The relation of chromium status
to cardiovascular diseases needs further investigation,
particularly in areas with protein-energy malnutrition.

1.2.4. Interaction with other environmental factors

The interaction of other pollutants in the atmosphere with
chromium, particularly with respect to particle size, adsorption at
the particle surface, etc., require further studies.

Interactions between trivalent chromium in the diet and other
dietary constituents are poorly understood and should be
investigated.

2. PHYSICAL AND CHEMICAL PROPERTIES AND ANALYTICAL METHODS

2.1. Physical and Chemical Properties

Chromium (atomic number 24, relative atomic mass 51.996) occurs
in each of the oxidation states from -2 to +6, but only the 0
(elemental), +2, +3, and +6 states are common. Divalent chromium
is unstable in most compounds, as it is easily oxidized to the
trivalent form by air. Only the trivalent and hexavalent oxidation
states are important for human health. In the context of this
publication, it is of great importance to realize that these two
oxidation states have very different properties and biological
effects on living organisms, including man. Therefore, they must
always be examined separately: a valid generalization of the
biological effects of chromium as an element cannot be made.

This discussion will concentrate only on the aspects of
chromium chemistry that are of concern for health.

The relation between the hexavalent and trivalent states of
chromium is described by the equation:

Cr₂O₇^2- + 14H⁺ + 6e -> 2 Cr(III) + 7H₂O + 1.33v.

The difference electric potential between these 2 states reflects
the strong oxidizing properties of hexavalent chromium and the
substantial energy needed to oxidize the trivalent to the
hexavalent form. For practical purposes, it can be stated that
this oxidation never occurs in biological systems. The reduction
of hexavalent chromium occurs spontaneously in the organism, unless
present in an insoluble form. A gradual reduction of hexavalent
chromium to the trivalent state is demonstrated by the colour
change of the conventional chromate cleaning solution in the
laboratory from bright orange to green, in the presence of organic
matter. In blood, chromate is reduced to the trivalent state, once
it has penetrated the red cell membrane and becomes bound to the
haemoglobin and other constituents of the cell and therefore unable
to leave the cell again. The rapid reduction of injected
⁵¹chromium-labelled chromate in the rat has been demonstrated by
Feldman (1968). Although a compound CrF₆ is well known, the stable
forms of hexavalent chromium are almost always bound to oxygen
(e.g., CrO₄^-2, Cr₂O₇^-2). The trivalent form exists in coordination
compounds, but never as the free ion. As a rule, its coordination
number is 6, the complexes being generally octahedral.

A large number of complexes and chelates of chromium have been
investigated, ranging from simple hexa- or tetra-aquo complexes to
those with organic acids, vitamins, amino acids and others. The
rate of ligand exchange of chromium complexes is slow in comparison
with other transition elements, with the exception of the even
slower rate of cobalt complexes; most of the Cr(III)-complexes are
kinetically stable in solutions. This property adds to the relative
inertness of trivalent compounds, in addition to the
electrochemical stability of the trivalent state. However, at near
neutral or alkaline pH, the milieu of the animal organism, the

simple chromium compounds to which the organism is exposed in the
environment or through supplementation, rapidly become insoluble,
because hydroxyl ions replace the coordinated water molecules from
the metal and form bridges, linking the chromium atoms into very
large, insoluble complexes. Coordination of trivalent chromium to
biological ligands is the prerequisite for its solubility at
physiological pH and therefore for its biological function and for
its availability for intestinal absorption. The coordination
chemistry and the specific biochemical reactions have been reviewed
by Cotton & Wilkinson (1966) and Mertz (1969), respectively. The
physical and chemical properties of chromium and some chromium-
compounds are summarized in Table 1.

Common chromium compounds

Poorly soluble "sandwich complexes" of metallic chromium
(oxidation state = O) are known, e.g., Cr(C₆H₆)₂; these have little
practical application. Divalent compounds, such as chromium (II)
chloride (CrCl₂) are used as strong reducing agents in the
laboratory, but have little industrial use. Of the many hundreds
of trivalent chromium compounds known, chromic oxide (Cr₂O₃ x
nH₂O), is used as a pigment in paints and as a faecal marker in
digestive studies. It dissolves in acids and forms the hexa-aquo
or tetra-aquo complex, e.g.,

Cr₂O₃ x 9H₂O + 6HCl -> 2 [Cr(H₂O)₆] Cl₃
(colour: violet)
or
2 [Cr(H₂O)₄Cl₂] Cl + 4H₂O
(colour: dark green).

Chromium chloride ([Cr(H₂O)₆]Cl₃ or [Cr(H₂O)₄Cl₂]Cl) is used in
basic solution for leather tanning. The fluoride is used
industrially in printing and dyeing, and chromium sulfates and
nitrates are used as colouring and printing dyes.

One of the numerous organic complexes of chromium, a
dinicotinatoglutathionato-chromium complex has been isolated from
yeast. It is postulated as the physiologically active form in the
animal organism, but its exact structure is not known (Toepfer et
al., 1977).

Table 1. Physical and chemical properties of chromium and some selected chromium compounds
--------------------------------------------------------------------------------------------------------
Name Chemical Relative Specific Melting Boiling Colour Solubility CAS registry
symbol molecular gravity point point in water number
mass (g/cm³) (°C) (°C) (weight %)
--------------------------------------------------------------------------------------------------------
Chromium Cr 51.996 7.19 1857 2672 steel- insoluble 7440-47-3
grey

Chromium (III)- Cr₂O₃ 151.99 5.21 2266 4000 green insoluble 1308-38-9
oxide

Chromium (VI)- CrO₃ 99.99 2.70 196 decompo- red 62.41 1333-82-0
oxide sition

Potassium- K₂CrO₄ 194.20 2.732 968.3 decompo- yellow 39.96 7789-00-6
chromate (VI) sition

Potassium- K₂Cr₂O₇ 294.19 2.676 398 decompo- red 11.7 7778-50-9
dichromate (VI) sition

Calcium- CaCrO₄ 192.09 1025 decompo- yellow 3.5 13765-19-0
chromate (VI) x 2H₂O sition
dihydrate

Calcium- CaCr₂O₄ 208.07 4.8 2090 - olive- insoluble
chromium (III)- green
oxide
--------------------------------------------------------------------------------------------------------
For vapour pressure at 20°C, no data.
The earth's most important deposits of chromium are in either
the elemental or the trivalent oxidation state. Hexavalent
compounds of chromium in the biosphere are predominantly man-made,
and experience with hexavalent chromium is relatively short.
Chromates and dichromates are produced from chromite ore by
roasting in the presence of soda ash. From these, chromium (VI)
oxide, (CrO₃), is precipitated out by the addition of sulfuric
acid. Sodium and potassium dichromates are widely used
industrially as sources of other chromium compounds, particularly
of chromium (VI) oxide, and these processes are a major source of
hexavalent chromium pollution (US EPA, 1978).

2.2. Analytical Methods

Methods for the determination of chromium in biological and
environmental samples are developing rapidly, as shown by the fact
that chromium concentrations in the blood and urine of unexposed
subjects, reported as normal, have been revised downwards by 2
orders of magnitude, in only 15 years (Versieck et al., 1978).
This development is not only due to the increasing powers of
detection and specificity of more recent methods, but also to the
better methods of contamination control that have become available.
For these reasons, all data concerning chromium levels in blood and
urine (particularly the early results), should be interpreted with
caution following scrutiny of all experimental details. On the
other hand, analytical results concerning the much higher chromium
levels in foodstuffs and human tissue have not changed as much and
can be accepted with more confidence. However, all interpretations
of chromium data should take into account the need for caution
expressed in section 2.2.2.

2.2.1. Sampling

As chromium is present in biological materials in very low
concentrations, care must be taken to avoid contamination. The
collection of dust from air samples may introduce contamination
from the chromium in the filters; blood or tissue samples may
become highly contaminated by the chromium in needles, knives,
blenders, and other instruments (Behne & Brätter, 1979). Water
samples may extract chromium from containers. Finally, reagents
used in sample dissolution, separation, chelation, acid digestion,
and other reactions, may contribute significant amounts of
chromium. Thus, it is necessary to control for these influences by
simultaneously performing a blank analysis, i.e., by carrying out
the whole analysis, including sampling, preparation, and digestion,
using all reagents, excluding a sample (Davis & Grossman, 1971).

Conversely, chromium in low concentrations may be adsorbed on
the surface of containers during long periods of storage. This
aspect has not yet been sufficiently investigated (Shendrikar &
West, 1974). Procedures for the sampling of different materials
for chromium determination have been reviewed by Beyermann (1962),
Brown et al. (1970), Murrman et al. (1971), Versieck & Speecke
(1972), Skogerboe (1974), Johnson (1974), and US DHEW (1975). All
suggest strictest contamination control (clean rooms or laminar
flow facilities).

2.2.2. Analytical methods

The voluminous literature on analysis for chromium was reviewed
by US EPA (1978). A discussion on analytical methods must
distinguish between two categories: (a) methods for measuring
large, potentially toxic concentrations of chromium as a
contaminant, and (b) methods of analysis for chromium as an
essential nutrient. The first category requires reliable
determinations of chromium at the µg/kg level; the second requires
greater sensitivity, e.g., to determine accurately the chromium
level in urine at several hundred ng/litre.

The sensitivity of instrumental analysis for the determination
of chromium does not present any problems for concentrations in the
mg/kg range, and a number of techniques can furnish satisfactory
precision and accuracy (Table 2). On the other hand, the
sensitivity of instrumentation for the determination of chromium in
the ng or µg/kg range is severely limited, and no one method is
entirely satisfactory, at present (Seeling et al., 1979). The
biologically active concentrations are near the detection limits of
the most sensitive methods, such as neutron activation analysis or
flameless atomic absorption spectrometry. In an inter-laboratory
comparison, there was poor agreement between the analytical results
obtained by well-established, experienced analytical laboratories
in several countries (Parr, 1977). Some of the results are
presented in the Table 3. It is of paramount importance for the
interpretation of all published analytical data on chromium to
realize the great variation in reported results, even for high
concentrations. These results indicate the following conclusions:

1. No one analytical method can be expected to produce
"true" results of absolute chromium concentrations, unless
the analyses are controlled by the use of a certified
reference material with a matrix composition similar to
that of the material to be analysed.

2. No valid comparisons can be made on the basis of
analytical results obtained by different laboratories,
unless the same reference materials have been used by
both, or samples have been exchanged.

3. There is a great need for certified Standard
Reference Materials with many different matrix
compositions. Six such standards of biological materials
have been certified for chromium content (tomato leaves,
pine needles, citrus leaves, oyster tissue, unexposed
bovine serum, and brewer's yeast). In addition, seven
standard reference materials of environmental samples are
available (coal, fly ash, water, sediment, urban
particulate, etc.) and more than 180 industrial samples of
various steels and metal alloys. These are available from
the National Bureau of Standards, Washington DC, USA. New
reference specimens of blood and urine have been produced

for the quality control of heavy metals in industrial
medicine and toxicology (Müller-Wiegand et al., 1983).
The assigned values were determined by reference
laboratories of the "Deutsche Gesellschaft für
Arbeitsmedizin; the control blood and urine preparations
are offered by Behringwerke AG, D-3550 Marburg, Federal
Republic of Germany.

4. In inter-laboratory quality assurance studies, it is
preferable to use the methodology developed in the
WHO/UNEP project on biological monitoring for lead and
cadmium (Vahter, 1982).

In 1983, the German DIN-Committee AAS adopted a method for the
determination of the chromium content of water and sewage (by means
of the flame AAS) (Kempf & Sonneborn, 1976); inductively coupled
plasma emission spectrometry is recommended with regard to serial
analyses (Kempf & Sonneborn, 1981).

Two special problems in the analysis for chromium may add to,
or subtract from, the true concentrations, i.e., contamination and
possible loss through volatilization or formation of refractory
compounds during sample preparation. Contamination is a serious
problem when low concentrations in blood or urine are measured.
Dust in laboratories may contain a chromium level of 700 mg/kg
(Mertz, 1969), approximately 6 orders of magnitude higher than the
concentration in urine of 0.2 - 0.7 µg/litre (Guthrie et al.,
1979). In other words, contamination of a one-ml urine sample by
only 1 µg of dust will increase the apparent chromium concentration
two-fold. Special precautions, such as those proposed by Tölg
(1974), must be taken to control this problem. The second problem,
that of potential loss during sample preparation, has been
discussed by Wolf & Greene (1976). There is evidence from several
studies that certain methods of sample preparation, such as heating
or acid digestion in open systems, may lead to the loss of
detectable amounts of chromium (Kotz et al., 1972). A typical
example, in which identical samples were determined by the
identical method, by the same analyst, in the same laboratory is
presented in Table 4.

Table 2. Instrumental methods for the determination of chromium^a
--------------------------------------------------------------------------------------------------------
Analytical Relevant Detection Interfering substance Selectivity
method applications limit
--------------------------------------------------------------------------------------------------------
Atomic fresh and saline 2 µg/litre^b interfering substances all of the extracted
absorption water, industrial present in the original chromium is measured,
spectroscopy waste fluids, sample are usually not but only hexavalent
(flame) dust, and sediments extracted into the chromium is extracted
biological solids organic solvent from the original sample,
and liquids, alloys unless oxidative
pretreatment is used

Atomic biological solids 0.005 µg/ no interfering sub- total chromium is
absorption and fluids; tissue, litre^b substances reported determined
(electrothermal) blood, urine; for samples of urineⁿ,
industrial waste and blood^o; less than
waters 10% interference ob-
served for Na⁺, K⁺,
Ca²⁺, Mg³⁺, Cl^-,
F^-, SO₄^-3, and PO₄^-3
in certain industrial
waste waters^p

Emission a wide variety of 4 µg/litre^l no interfering total chromium is
spectroscopy biological and substances reported determined
(inductively- environmental
coupled plasma samples
source)

Emission a wide variety of 0.5 ng^c total chromium is
spectroscopy environmental determined
(arc) samples

--------------------------------------------------------------------------------------------------------

Spectrophotometry natural water and 3 µg/litre^d iron, vanadium, and after chelation, only
industrial waste mercury may interfere the hexavalent chromium
solutions having in solution is determined
5 - 400 mg hexa-
valent chromium/
litre can be
analysed; higher
concentrations
must be reduced
by dilution

X-ray fluorescence atmospheric 2 - 10 µg/g the particle size of total chromium is
particulates, (liver)^e; the sample and the determined
geological 1.5 µg/g matrix may influence
materials (coal)^f the observed measure-
ments

Neutron activation air pollution depends on interference may arise total chromium is
analysis particulates, activation from gamma ray activity measured
fresh and saline procedure; from other elements,
waters, biological typical especially Na-24, Cl-38,
liquids and solids, limit: K-42, and Mn-56; P-32
sediments, metals, 10 ng^m may also cause inter-
foods ference

Gas chromatography blood, serum, 0.03 pg^g excess chelating agent only chromium that is
(electron capture natural water or other electron- chelated and extracted
detection) samples capturing constituents is measured; other
in the sample may lead electro-negative substances
to erroneous results may elute from the column
and be detected at the
same time as the chromium
chelate

Stable isotope all biological not expected high precision and accuracy
dilution mass materials^k,q (1%) complete sample
spectrometry digestion and exchange of
endogenous chromium with
added stable isotope
--------------------------------------------------------------------------------------------------------

Table 2. (contd.)
--------------------------------------------------------------------------------------------------------
Analytical Relevant Detection Interfering substance Selectivity
method applications limit
--------------------------------------------------------------------------------------------------------
Gas chromatography blood, serum, ~1 ng^h no interference only chromium that is
(atomic biological material reported chelated and extracted is
spectroscopic detected; atomic
detection) spectroscopic methods
of detection are
inherently more selective
for chromium in complex
samples

Gas chromatography blood, plasma, 0.5 pgⁱ no interference only chromium that is
(mass serum reported chelated and extracted
spectrometric can be detected
detection)

Chemiluminescence fresh, natural 30 ng/ Co(II), Fe(II), and only trivalent chromium
waters; dissolved litre^k Fe(III) interfere but ion is measured
biological material may be compensated for
by running a blank^c
--------------------------------------------------------------------------------------------------------
^a Modified from: US EPA (1978).
^b From: Welz (1983).
^c From: Seeley & Skogerboe (1974).
^d From: American Public Health Association, American Water Works Association,
and Water Pollution Control Federation (1971).
^e From: Kemp et al. (1974).
^f From: Kuhn (1973).
^g From: Savory et al. (1969).
^h From: Wolf (1976).
ⁱ From: Wolf et al. (1972).
^k From: Seitz et al. (1972).
^l From: Welz (1980).
^m From: Keller (1980).
ⁿ From: Schaller et al. (1973).
^o From: Environmental Instrumentation Group (1973).
^p From: Morrow & McElhaney (1974).
^q From: Veillon et al. (1979).
Table 3. Results for 3 IAEA intercomparison studies^a
-----------------------------------------------------------
Laboratory Method Number of Laboratory SD (%)
code code^b determinations mean
-----------------------------------------------------------
A. Simulated air filter
(true chromium concentration: 1.85 µg/filter)

a 7 2 1.3 3
b 3 1 1.6 7
c 2 4 1.78 5
d 2 10 1.85 6
e 2 6 1.86 52
f 2 2 2.00 30
g 2 3 2.07 10
h 2 6 2.07 9
i 2 6 2.07 6
j 7 10 2.16 10
k 5 6 2.83 40
l 7 2 3.00 -^c
m 3 5 3.17 4
n 7 1 4.20 8
o 2 5 6.14 6
p 2 1 7.50 22

B. Water
(true chromium concentration: 11.1 µg/kg)

a 3 4 1.85 18
b 3 5 3.80 12
c 7 6 4.16 15
d 7 1 4.50 11
e 7 6 4.77 6
f 7 2 5.25 -
g 2 5 5.51 3
h 2 5 5.84 4
i 7 1 6.00 -
j 2 3 6.08 4
k 7 2 6.50 -
l 7 2 6.85 17
m 2 2 7.00 -
n 7 2 7.30 -
o 7 3 8.67 3
p 7 2 8.90 20
q 3 1 9.00 20
r 7 5 9.60 12
s 7 6 9.92 10
t 2 5 10.8 11
u 2 4 11.3 11
v 7 3 11.5 45
w 5 2 18.0 30
x 7 1 73.0 14
-----------------------------------------------------------

Table 3. (contd.)
-----------------------------------------------------------
Laboratory Method Number of Laboratory SD (%)
code code^b determinations mean
-----------------------------------------------------------
C. Bovine liver (SRM 1577)
(certified chromium concentration: 88 ± 12 µg/kg)

a 2 -^c 5 -^c
b 1 -^c 51 13
c 1 -^c 140 -^c
d 2 -^c 150 13
e 1 -^c 150 33
f 1 -^c 160 24
g 1 -^c 240 53
h 2 -^c 490 39
i 1 -^c 540 64
j 2 -^c 1300 -^c
k 2 -^c 1600 25
-----------------------------------------------------------
^a From: Parr (1977).
^b Method code:
1. Destructive activation analysis.
2. Nondestructive activation analysis.
3. Emission spectroscopy.
5. Spark source mass spectrometry.
7. Atomic absorption, unspecified.
^c Information not given.

At present, there is no explanation of the reason why "losses"
of almost 90% were associated with the direct graphite furnace
ashing, compared with oxygen plasma ashing in the case of molasses,
but not of refined sugar. Canfield & Doisy (1976) and Tuman et al.
(1978) suggested that the loss of chromium in biological samples,
such as urine, yeast extracts, or synthetic glucose tolerance
factor (GTF) preparations represented the biologically active GTF
fraction of the chromium. They correlated this "volatile" fraction
in yeast extracts with the antidiabetic activity of the extract in
genetically diabetic mice, and the amount of "volatile" chromium in
the urine of human subjects with the efficiency of the glucose
metabolism of these subjects. This hypothesis of "volatile"
chromium has been confirmed by some investigators (Behne et al.,
1976; Koirtyohann & Hopkins, 1976; Shapcott et al., 1977;
McClendon, 1978), and contradicted by others (Jones et al., 1975;
Rook & Wolf, 1977). While the question of the "volatility" of
chromium, under various conditions, remains unanswered, it is
obvious that chromium determination presents many problems, the
most pressing of which is the selection and control of sample
digestion (Wolf & Greene, 1976).

Table 4. Apparent chromium content depending on the method of
ashing^a
-----------------------------------------------------------------
Type of sugar Number Chromium content + SEM (µg/kg)
of Oxygen Muffle Graphite
samples plasma furnace furnace ashing
ashing ashing (1000 °C)
(150 °C) (450 °C) (direct
analysis)
-----------------------------------------------------------------
molasses 3 266 ± 50 129 ± 54 29 ± 5
sugar (unrefined) 8 162 ± 36 88 ± 20 37 ± 13
sugar (brown) 5 64 ± 5 53 ± 8 31 ± 2
sugar (refined) 7 20 ± 3 25 ± 3 < 10
-----------------------------------------------------------------
^a From: Wolf et al. (1974).

Finally, it is important in any study of the environmental
effects of chromium, to distinguish analytically between the
trivalent and hexavalent forms. This can be accomplished by
dithiocarbamate chelation and solvent extraction (for example, with
methyl isobutylketone) prior to oxidation. Only the hexavalent
chromium remains after this process, and thus it is possible to
differentiate between the oxidation states (Feldman et al., 1967;
Cresser & Hargitt, 1976; Bergmann & Hardt, 1979; Joschi & Neeb,
1980). When determining chromium in biomaterial, the samples are
usually ashed with strong acids to destroy the organic components.
The relationship between the acids used and the behaviour of
chromium were investigated by Hara (1982) who showed that the
oxidation state of chromium was apt to change (hexavalent to
trivalent), because of the reducing action of each acid and the
conditions under which they were used.

3. SOURCES IN THE ENVIRONMENT, ENVIRONMENTAL TRANSPORT AND DISTRIBUTION

3.1. Natural Occurrence

Chromium is ubiquitous in nature; it can be detected in all
matter in concentrations ranging from less than 0.1 µg/m³ in air to
4 g/kg in soils. Naturally occurring chromium is almost always
present in the trivalent state: hexavalent chromium in the
environment is almost totally derived from human activities.

Merian (1984) has compiled the global sources of chromium in
the environment. Total input (100%) consists of inputs by:
volcanic emissions (less than 1%); the biological cycle (30%)
including extraction from soil by plants (15%) and weathering of
rocks and soils (15%); and man-made emissions (70%) including those
from general ore and metal production (3%), from metal use (60%),
and from coal burning and other combustion processes (7%).

3.1.1. Rocks

Almost all the sources of chromium in the earth's crust are in
the trivalent state, the most important mineral deposit being in
the form of chromite (FeOCr₂O₃) which, however, is rarely pure.
Living matter does not produce the energy necessary to oxidize
trivalent to hexavalent chromium in the organism, therefore, it can
be stated that nearly all hexavalent chromium in the environment is
produced by human activities. The industrial use of chromium and
the oxidation to the hexavalent state on an industrial scale did
not begin until 1816. Thus, man's experience with this form is
very short.

The concentration of chromium in rocks varies from an average
of 5 mg/kg (range of 2 - 60 mg/kg) in granitic rocks, to an average
1800 mg/kg (range, 1100 - 3400 mg/kg) in ultrabasic and serpentine
rocks (US NAS, 1974b).

Chromium deposits in the hexavalent oxidation state (crocoite
PbCrO₄), were described by Lomonossow, in the year 1763 (Hintze,
1930), who found it in the Ural Mountains. Being a rare mineral,
chromium is found in the oxidized zones of lead deposits in regions
in which lead veins have traversed rocks containing chromite. It
may be associated with pyromorphite, cerussite, and wulfenite.
Notable localities are: Dundas, Tasmania; Beresovsk near
Sverdlovsk, Ural Mountains (Aleksandrov & Kainov, 1975), and
Rezbanya, Rumania. It is found in small quantities in the Vulture
district, Arizona, USA (Dana, 1971) and in the German Democratic
Republic in Callenberg, Saxony (Rohde et al., 1978).

Chromium concentrations in igneous rocks are positively
correlated with concentrations of silica, magnesium, and nickel.
Of agricultural importance, is the high chromium concentration in
sedimentary rocks, where the element is present in phosphorites.
This material is used as a phosphate fertilizer in agriculture and
is a significant source of chromium for agricultural soils.

Chromium-containing rocks and ores are found in all regions of
the world, but the major sources of the world's chromium supplies
are the ultra basic rocks of South Africa, Turkey, the USSR and
Zimbabwe (US NAS, 1974b). While underlying undisturbed rocks
contribute little chromium to the vegetation directly, the chromium
content is strongly correlated with that of the overlying soils.

Chromium can also be found in coal (5 - 10 mg/kg) (Merian,
1984).

3.1.2. Soils

The weathering of rocks produces chromium complexes that are
almost exclusively in the trivalent state. In most soils, chromium
occurs in low concentrations; an average of 863 soil samples from
the USA contained 53 mg/kg (Shacklette et al., 1970). The highest
concentrations, as high as 3.5 g/kg (Swaine & Mitchell, 1960), are
always found in serpentine soils. In a small area in Maryland,
USA, with soil infertility, the chromium concentration (as Cr₂O₃)
was as high as 27.4 g/kg (Robinson & Edington, 1935). Conversely,
low chromium concentrations (10 - 40 mg/kg) have been detected in
soils derived from granite or sandstone (Swaine & Mitchell, 1960).
Only a fraction of the chromium in soil is available to the plant;
thus, it is important to determine "available" soil-chromium. A
rough approximation of this available chromium fraction can be made
by extracting soil with acids or chelating agents and by measuring
the chromium in the extract. Though the amount of extractable
chromium is not identical with that truly available to the plant,
it is a much better measure of availability than the total
chromium. In the study of Swaine & Mitchell (1960), the amount of
chromium extracted from the soil with acetic acid varied much less
than the total soil content, and was not correlated with the latter
(Table 5).

The comparisons in this Table indicate that the amount of
chromium available to the plant is relatively independent of the
total concentration. The complex principles determining the
availability of chromium for plants are poorly understood.

Table 5. Total versus extractable chromium in different
Scottish soils^a
----------------------------------------------------------
Soil Total chromium Extractable chromium
derived from: (mg/kg) (mg/kg)
----------------------------------------------------------
Granite 20, 40, 20 0.15, 0.1, 0.11

Serpentine, 3500, 2000, 3000 0.31, 0.24, 0.63
ultrabasic
----------------------------------------------------------
^a From: Swaine & Mitchell (1960).

3.1.3. Water

It is now generally agreed that, except in areas with
substantial chromium deposits, high chromium levels in water arise
from industrial sources (US NAS, 1974b).

With the exception of areas bearing chromium deposits or in
highly industrialized areas, most surface waters contain very low
levels of chromium. The chromium content in surface water in the
Tia-ding county, Shanghai, ranged from 0 to 80 µg/litre (256
samples). According to the Yang-Pu water works, which is the
biggest water works in Shanghai, the chromium levels in well water
are below 50 µg/litre. Between 1980 and 1982, chromium was not
detectable in the Yellow River. There is no information concerning
the analytical methods used (Chen Bingheng, personal communication
to the Task Group, 1986). Kopp & Kroner (1968) detected chromium
in only 25% of surface water samples from sources in the USA, with
a range of 1 - 112 µg/litre, and a mean concentration of 9.7
µg/litre. The remaining 75% contained less than 1 µg/litre, the
detection limit. Another survey of 15 rivers in the USA revealed
levels ranging from 0.7 to 84 µg/litre, the majority of samples
containing between 1 and 10 µg/litre (Durum & Haffty, 1963). On
the other hand, chromium contents in natural water of up to 215
µg/litre were reported by Novakova et al. (1974). Although modern
methods of water treatment remove much of the naturally present
chromium, it should be noted that chlorinated drinking-water
usually contains traces of hexavalent chromium. The mean level in
the drinking-water supplies in 100 cities in the USA was only 0.43
µg/litre, with a range from barely detectable to 35 µg/litre
(Durfor & Becker, 1964).

Sea water contains less than 1 µg chromium/litre (US NAS,
1974b), but the exact chemical forms in which chromium is present
in the ocean, and surface water are not known. Theoretically,
chromium can persist in the hexavalent state in water with a low
organic matter content. In the trivalent form, chromium will form
insoluble compounds at the natural pH of water, unless protected by
complex formation. The exact distribution between the trivalent
and hexavalent state is unknown.

3.1.4. Air

Chromium occurs in the air of non-industrialized areas in
concentrations of less than 0.1 µg/m³. The natural sources of air-
chromium are forest fires and, perhaps, volcanic eruptions (section
3.5). Man-made sources include all types of combustion and
emissions by the chromium industry (section 4.1.1). The chemical
forms of chromium in the air are not known, but it should be
assumed that part of the air-chromium exists in the hexavalent
form, especially that derived from high-temperature combustion.
Chromium trioxide (CrO₃) may be the most important compound in the
air (Sullivan, 1969).

3.1.5. Plants and wildlife

It is not known whether chromium is an essential nutrient for
plants, but all plants contain the element in concentrations
detectable by modern methods.

Chromium concentrations in food plants growing on normal soils
range from not detectable to 0.19 mg/kg wet weight (Schoeder et
al., 1962). In addition, chromium of vegetable origin has a
relatively low biological activity (Toepfer et al., 1973).

Much higher concentrations have been reported in plants growing
on chromium deposits. For example, ash analysis showed a chromium
level of 0.34% in New Zealand lichen and 0.3% in Yugoslav Allysium
markgrafi (US NAS, 1974b). Growing on a serpentine soil (chromium
concentration 62 000 mg/kg in old mine tailings), the plant
chromium concentrations (on the basis of ash analysis) ranged from
700 mg/kg in Phormium colensoi and Liliacae to 5400 mg/kg in
Gentiana corymbifera (Lyon et al., 1970). Not all plants tolerate
high concentrations of available soil-chromium; chlorosis of citrus
trees has been observed in high-chromium areas and in laboratory
experiments. Plants grown in the vicinity of chromium-emitting
industries or those fertilized by sewage sludge are exposed to
substantial amounts of chromium. The chromium contents of plants
growing were determined by Taylor et al. (1975) near cooling
towers, where chromates were present as corrosion inhibitors. It
was shown that chromium levels in grasses, trees, and litter,
decreased with increasing distance from the towers. No information
was given as to whether the variations in chromium concentrations
were the result of surface contamination or of true absorption by
the roots of the plant.

The atmospheric deposition of metals and their retention in
ecosystems were studied by Mayer (1983). He measured mean annual
deposition rates in a beech and spruce forest ecosystem in the
Solling (Federal Republic of Germany) in 1974-78 and found that
chromium deposition in the forest canopy was in the range of 13.5 -
15.1 mg/m² per year; the deposition on the soil below the forest
canopy ranged from 1.6 to 2.3 mg/m² per year. Thus, up to 80% of
the metals from the atmosphere were retained in the canopy, and 30
- 50% of chromium remained in the noncycling parts of forest
biomass (bark and wood).

Sewage sludge can contain chromium levels as high as 9000
mg/kg. Application of sewage sludge to soils, which increased the
chromium levels from 36.1 to 61 mg/kg on a dry weight basis,
increased the contents of chromium in plants growing in the soil
from, e.g., 2.6 to 4.1 mg/kg in fodder rape (Andersson & Nilsson,
1972). However, most of the increased uptake in plants is retained
in the roots, and only a small fraction appears in the edible part
(Cary et al., 1977). Other elements within the sludge, e.g.,
cadmium or nickel, pose a greater problem for human health (Chaney,
1973).

Of particular importance is the chromium concentration in the
forage of meat animals. Kirchgessner et al. (1960) found strong
seasonal variations in the chromium levels in 3 different kinds of
grasses; the highest level found was 590 µg/kg dry weight in hay.

Higher levels of chromium in vegetation not used for human
consumption may account for the generally higher chromium contents
in the organs of wild animals, compared with man (Schroeder, 1966).

Schroeder (1970) determined the chromium concentrations in
different organs and muscles of wild animals and found that they
ranged from 0.04 to 0.48 mg/kg on a wet weight basis. Chromium
concentrations in the hair of several wild-animal species,
collected by Huckabee et al. (1972), ranged from 640 mg/kg in a
pronghorn antelope living in Lemhi Range, Idaho, USA, to about 0.6
mg/kg in a coyote, sampled in Jackson Hole, Wyoming, USA.

3.1.6. Environmental contamination from natural sources

No data have been found that indicate any significant
contamination of the environment from natural sources, though major
catastrophic events, such as large forest fires or volcanic
eruptions, could conceivably contribute to the concentration of
chromium in air. Water supplies originating in areas with chromium
deposits may contain elevated chromium concentrations (section
4.1.2). However, none of these natural sources contributes enough
chromium to pose a hazard for human or animal health.

3.2. Production, Consumption, and Uses

The world's mining production of chromium ore was approximately
9.73 million tonnes (gross weight) in 1980; it fell to 9 million
during 1981 (Thomson, 1982), but rose again to 11 million tonnes in
1985. Exact data on the yield of elemental chromium are not
available, but may range around half of the gross weight of the
mined ore.

The major uses and amounts of chromium used in the USA in 1968
in thousands of tonnes were: transportation, 77; construction
products, 105; machinery and equipment, 72; home appliances and
equipment, 25; refractory products, 68; plating of metals, 20;
pigment and paints, 15; leather goods, 10; and other uses, 66;
giving a total of 458 thousand tonnes.

The principal uses of chromium are in the metallurgical
processing of ferrochromium and other metallurgical products,
chiefly stainless steel, and, to a much lesser extent, in the
refractory processing of chrome bricks and chemical processing to
make chromic acid and chromates.

Chromates are used for the oxidation of various organic
materials, in the purification of chemicals, in inorganic
oxidation, and in the production of pigments. A large percentage
of chromic acid is used for plating. Dichromate is converted to
chromic sulfate for tanning. Fungicides and wood preservatives
consume an estimated 1.3 million kg of chromium annually.
Chromates are used as rust and corrosion inhibitors, for example,
in diesel engines. Because chromite has a high melting point and
is chemically inert, it is used in the manufacture of bricks for
lining metallurgical furnaces.

In 1981, the demand for chromium was at its lowest level since
1975. However, on the basis of 1978 figures, the demand for
chromium is expected to increase at an annual rate of about 3.2%,
up to 1990. While the level of stainless steel production will
continue to be the principal influence affecting markets for
chromite and ferrochrome, other factors could have a significant
impact on future trends, e.g., purchases for government stockpiles
(in 1981, the USA had a stockpile of 1.48 million tonnes, and
France and Japan announced the build up of stockpiles) or the
development of new alloys and steels (Thomson, 1982).

3.3. Waste Disposal

Substantial amounts of chromium enter sewage-treatment plants
in major cities. Klein et al. (1974) estimated a total daily
chromium burden for New York city treatment plants of 676 kg, of
which 43% came from electroplating, 9% from other industries, 9%
from runoff, 11% from unknown sources, and 28% from residential
homes. This waste from one city alone (amounting to 2.4 x 10⁵
kg/year), if untreated, would add a significant burden to the
ocean, in comparison with the estimated global natural chromium
mobilization by weathering of 3.6 x 10⁷ kg/year (Bertine &
Goldberg, 1971). The high chromium discharge from homes is
difficult to explain; it has been suggested that this could arise
from the corrosion of stainless steel or the use of waste disposal
units in domestic sinks. The contribution from excreta, estimated
at 100 µg chromium/day per person, should not exceed 1 kg/day for
the 10 million people in the New York area.

The concentration of chromium in the waste-water received at
the New York treatment plants varied between 40 and 500 µg/litre;
this range is probably representative of the chromium discharge in
major cities. The removal of chromium from the waste-water was
studied by Brown et al. (1973). Primary sewage treatment removed
only 27%, secondary treatment using a trickling-filter method
removed 38%; the most effective secondary treatment method
(activated sludge) removed 78%. In another study of a treatment

plant (Chen et al., 1974), the primary effluent contained 300
µg/litre and the secondary effluent, after the activated sewage
sludge and sedimentation process, 60 µg/litre (80% removal). The
final discharge from the plant, a mixture of primary and secondary
effluent and digested sludge had quite a high chromium content of
200 µg/litre. This level is substantially higher than the natural
chromium content of surface water and represents a significant
source of contamination.

Waste-waters from chromium industries contain very high levels
of chromium, ranging from 40 mg/litre (leather industry) to 50 000
mg/litre (chromium plating) (Cheremisinoff & Habib, 1972). These
levels must be reduced by precipitation before the waste-water can
be discharged. The steps include reduction of hexavalent to
trivalent chromium at an acidic pH, followed by precipitation of
the hydroxides at pH 9.5 (Ottinger et al., 1973). The precipitates
containing chromium and other metals are then collected in settling
ponds and disposed of by landfill, incineration, or dumping in the
ocean (US EPA, 1980). If the last procedure is used, the waste-
water treatment itself will contribute to the contamination of the
oceans.

Landfill and sewage sludge operations are, in turn, potential
sources of contamination of soil and groundwater by chromium.
However, at alkaline pH values, chromium hydroxides are insoluble
and leaching by any but very acidic water should be minimal.
Pohland (1975) did not detect any measurable concentrations of
chromium in the leachate from a simulated landfill.

Similary, the chromium in sewage sludge is very poorly soluble.
Berrow & Webber (1972) found a mean concentration of only 22
mg/litre (range, < 0.9 - 170 mg/litre) in samples of 42 sludges
extracted with 2.5% acetic acid. This represented 0.7 - 8.5% of
the chromium concentration in the original sludge. As acetic acid
is a good complexing and extracting agent for chromium, the
reported levels of extractable chromium are probably much greater
than those resulting from extraction with water at near neutral pH.
However, sludge application to land does increase the chromium
content of the soil (LeRiche, 1968). The application of 66
tonnes/hectare each year, for 19 years, resulted in an increase in
the acetic acid-soluble chromium in the soil from 0.9 to 2.6 mg/kg,
7 years after sludge application was discontinued. This
extractable chromium is presumably available to the plant. The
final link in the cycle of the soil-chromium derived from sewage
sludge is not well known. Undoubtedly, some will be removed by the
growth of vegetation (section 3.1.5). The rate of migration into
ground water depends on the properties of the soil and climatic
conditions. Thus, it is not surprising that, in one study
(LeRiche, 1968), a very slow rate of disappearance was reported
(reduction of extractable chromium from 2.8 to 2.6 mg/kg in 8
years), whereas in another, there was a very rapid rate of
disappearance (reduction of total chromium from 118 to 30 mg/kg, in
3 years) (Page, 1974).

3.4. Miscellaneous Sources of Pollution

As discussed earlier, waste-waters from residential areas in
New York carried approximately 200 kg of chromium daily to the
treatment plants. Of this amount, only 1 kg can be accounted for
by the human excreta of 10 million persons. If a water use of 200
litres per person and a (high) chromium content of 10 µg/litre is
assumed, this concentration would account only for an additional 20
kg. The origin of the rest is unknown (section 3.3). It should be
pointed out that analytical accuracy is difficult to achieve in
chromium analysis (section 2.2.2) and will affect the results of
all "balance" calculations.

It is evident that the chief source of air pollution with
chromium is ferrochromium refining. Appreciable, but far smaller
emissions, come from refractory operations and inadvertent sources.
The lowest emissions come from the chemical processes in the
production of dichromate and other chrome chemicals. Combustion of
coal and oil, and cement production, large-scale, spray-painting
operations (e.g., ships and planes) and glass plants constitute
other major sources of chromium emissions.

3.5. Environmental Transport and Distribution

Industrial effluents containing chromium, some of which is in
the hexavalent form, are emitted into streams and the air. Whether
the chromium remains hexavalent until it reaches the ocean depends
on the amount of organic matter present in the water. If it is
present in large quantities, the hexavalent chromium may be reduced
by, and the trivalent chromium adsorbed on, the particulate matter.
If it is not adsorbed, the trivalent chromium will form large,
polynucleate complexes that are no longer soluble. These may
remain in colloidal suspension and be transported to the ocean as
such, or they may precipitate and become part of the stream
sediment. Similar processes occur in the oceans: hexavalent
chromium is reduced and settles on the ocean bed. It is replaced
by an estimated 6.7 x 10⁶ kg of chromium from rivers (Bowen, 1966).
In a study of the oxidation state of chromium in ocean water, Fukai
(1967) detected an increased proportion of the trivalent form with
increasing depth.

Chromium is emitted into the air, not only by the chromium
industries, but also by every combustion process, including forest
fires. The oxidation state of chromium emissions is not well
defined quantitatively, but it can be assumed that the heat of
combustion may oxidize an unknown proportion of the element to the
hexavalent state. While suspended in the air, this state is
probably stable, until it settles down and comes into contact with
organic matter, which will eventually reduce it to the trivalent
form. Living plants and animals absorb the hexavalent form in
preference to the trivalent, but once absorbed, it is reduced to
the stable, trivalent state.

The transport of chromium in the environment is summarized in
Fig. 1. It should be noted that there is a complete cycle from
rocks or soil to plants, animals, and man, and back to soil. Only
part of the chromium is diverted to a second pathway leading to the
repository, the ocean floor. This part consists of chromium from
rocks and soil carried by water (concentrations, a few µg/litre)
and animal and human excreta, a small part of which may find their
way into water (e.g., runoff from sewage sludge). Another cycle
consists of airborne chromium from natural sources, such as fires,
and from the chromate industry. This cycle also contains some
hexavalent chromium, with byproducts going into the water and air.
Part of the air-chromium completes the cycle by settling on the
land, but a very significant portion goes into the repository, the
ocean, where it ends up as sediment on the ocean floor.

4. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

4.1. Environmental Levels

4.1.1. Air

Chromium concentrations in air vary with location. Background
levels determined at the South Pole ranged from 2.5 to 10 pg/m³ and
are believed to be due to the weathering of crustal material (US
NAS, 1974a). Data collected by the US National Air Sampling
Network in 1964 gave the national average concentration for
chromium in the ambient air as 0.015 µg/m³, varying from non-
measurable levels to a maximum of 0.35 µg/m³. Chromium
concentrations in most non-urban areas and even in many urban areas
were below detection levels. Yearly average concentrations for
cities in the USA varied from 0.009 to 0.102 µg/m³. Concentrations
ranging from 0.017 to 0.087 µg/m³ have been reported for Osaka,
Japan (US EPA, 1978). The chromium content of the air in the
vicinity of industrial plants may be higher. In 1973, the reported
chromium concentrations ranged from 1 to 100 mg/m³ for coal-fired
power plants, from 100 to 1000 mg/m³ for cement plants, from 10 to
100 mg/m³ for iron and steel industries, and from 100 to 1000 mg/m³
for municipal incinerators (US EPA, 1978). Ferrochromium plants
have the highest emission rates (Radian Corporation, 1983).
However, modern chromium chemical plants contribute very little to
pollution today, because of the installation of collecting
equipment that returns the material for reuse. Drift from cooling-
towers contributes to atmospheric pollution, when chromium is used
as a corrosion inhibitor (section 3.1.5). Little information
exists on the particle size distribution of chromium in the air.
The mass median diameter in a study in the United Kingdom was
1.5 µm (Cawse, 1974).

The chemical form of chromium in air depends on the source.
Chromium from metallurgical production is usually in the trivalent
or zero state. During chromate production, chromate dusts can be
emitted. Aerosols containing chromic acid can be produced during
the chrome-plating process; chromate is also the form found in air
contaminated by cooling-tower drift.

4.1.2. Water

Except for regions with substantial chromium deposits, the
natural content of chromium in surface waters and drinking-water is
very low, most of the samples containing between 1 and 10 µg/litre
(US NAS, 1974a). Substantially higher concentrations are almost
always the result of human activities, reflecting pollution from
industrial activities or sewage waste (Perlmutter & Lieber, 1970).
Thus, the chromium concentration in untreated surface water
supplies reflects the extent of the industrial activity in an area
(Table 6).

Table 6. Chromium in water supplies
-----------------------------------------------------------------------
Country Chromium Range Reference
concentration (µg/litre)
(µg/litre)
-----------------------------------------------------------------------
Bulgaria
flat district -^a 7 - 8 Novakova et al.
hilly district - 60 - 215 (1974)

Canada
Great Lakes 1 0.2 - 19 Weiler & Chawla
(1969)
Ottawa River 0.01 - Durum & Haffty
(1963);
Merrit (1971)

China
Yellow River undetectable - Chen Bingheng
Tia-Ding country - 0 - 80 (personal
surface water communication, 1986)

Germany, Federal
Republic of
Rhine River 18 DeGroot & Allersma
(1973)
Poland
Wisla - 31 - 112 Pasternak (1973)

USA
Illinois River 21 5 - 38 Mathis & Cummings
(1973)
Lake Tahoe < 0.07 - Bond et al. (1973)
Mississipi River 3 - 20 Bond et al. (1973)
New York area, 1250 - Lieber et al. (1964)
contaminated stream
-----------------------------------------------------------------------
^a No data available.
Drinking-water from 100 public water supplies in the USA had a
median chromium content of 0.43 µg/litre, ranging from non-
detectable concentrations to 35 µg/litre. In the Federal Republic
of Germany, levels in about 90% of drinking-water samples from 1062
public water supplies were below 0.5 µg/litre; in 1.4% of the water
samples, levels exceeded the prescribed limit value of 50 µg/litre
(Kempf & Sonneborn, 1981).

Both trivalent and hexavalent forms of chromium occur in water.
National and international drinking-water standards reject
drinking-water containing hexavalent chromium concentrations of
more than 50 µg/litre. Such high concentrations occur naturally,
only in areas with substantial chromium deposits (Novakova et al.,
1974); in all other regions they would be caused by industrial
wastes.

4.1.3. Food

The available food data (Schroeder et al., 1962; Schlettwein-
Gsell & Mommsen-Straub, 1971; Toepfer et al., 1973; Kumpulainen et
al., 1979) indicate a range of the chromium concentrations in
different foodstuffs of 5 -250 mg/kg (Table 7). Highly refined
foods, such as sugar and flour of low extraction, contain the
lowest levels. Very high concentrations have been reported in
pepper (Schroeder et al., 1962) and brewer's yeast.

Table 7. Ranges of chromium concentrations in some
food groups^a
---------------------------------------------------
Food Chromium content
(µg/kg of wet weight)
Mean Range
---------------------------------------------------
Flour, refined < 20

Bran 50

Meat (beef, pork, chicken) 10 - 60

Fish, fresh < 10 - 10

Vegetables 5 - 30

Nuts 140

Whole Milk 10

Cheeses 10 - 130

Sugar, refined < 20

Egg yolk 200
---------------------------------------------------
^a From: Koivistoinen (1980).

4.2. General Population Exposure

4.2.1. Food and water

The chromium intake from diet and water varies considerably
between regions (Table 8). However, these variations should be
interpreted with caution because not all the analyses have been
controlled by the use of standard reference material or proper
quality assurance procedures, and discrepancies in methods cannot
be completely discounted.

Table 8. Chromium intake from diet and water
--------------------------------------------------------------------
Region Chromium Remarks Reference
intake
(µg/day)
(range)
--------------------------------------------------------------------
Canada 189 - Canada, National
(136 - Health and Welfare
282) (1980)

Germany, Federal 62 DA^a; 4 subjects, Schelenz (1977)
Republic of (11 - 1 week
195)

Japan 723 urban adults Murakami et al.
(202 - (1965)
1710)

943 rural adults^b Murakami et al.
(> 180 - (1965)
1190)

New Zealand 81 ± 32 DA^a; 11 women, Guthrie (1973)
(39 - 190) self-selected
diets

United Kingdom (80 - 100) Facer, J.L.
(1983)^c

USA 52 DA^a Levine et al.
(5 - 115) (1968)

USA 78 ± 42 DA; 28 diets, Kumpulainen
(25 - 224) complete et al.
(controlled (1979)
by SRM)

USSR
Tatar (88 - 126) children^d Goncharov (1968)
--------------------------------------------------------------------
^a DA = Direct analysis of composite diets as consumed.
^b Analysis of composite of cooked servings for one complete day
collected from 10 families in different localities.
^c Personal communication to Dr M. Mercier, IPCS (United Kingdom
Ministry of Agriculture, Fisheries and Food, London).
^d Analysis of diets in kindergartens.

Most reported chromium intakes range from 50 to 200 µg/day.
However, a comparison of the chromium levels reported by different
investigators reveals substantial differences, some of which may be
due to the influence of the location where the foods were grown.
Only one study (Kumpulainen et al., 1979) was controlled by the use
of standard reference materials. The data should therefore be
treated as preliminary. Furthermore, data concerning total
chromium concentrations do not include information on the species

of chromium in the food and their biological availability. In an
attempt to estimate the biologically available chromium in food,
Toepfer et al. (1973) measured the effects of extracts from foods
on the potentiation of insulin action in epididymal fat tissue in
vitro. No correlation was found between the insulin potentiation
and the total chromium extracted from the foods by acid hydrolysis,
but a significant correlation ( P = 0.01) appeared between the
ethanol-extractable amount of chromium and biological activity.
The highest concentrations of ethanol-extractable chromium were
found in brewer's yeast, black pepper, calf liver, cheese, and
wheatgerm.

4.2.2. Other exposures

Since chromium compounds are increasingly present in products
used in daily life, chromium eczemas are often observed in the
general population. Polak et al. (1973) surveyed the most
important chromium-containing materials or objects: chromium ore,
baths, colours, lubricating oils, anti-corrosive agents, wood
preservation salts, cement, cleaning materials, textiles, and
leather tanned with chromium. According to Polak et al. (1973),
people who work with material containing mere traces of chromium
salts are more at risk than workers who come into contact with high
concentrations of chromium salts. Some less frequently occurring
cases include sensitization by tattooing (especially green and
light-blue)( Tazelaar, 1970), artificial dentures made of chromium-
containing steel, metal pins used for internal fixation of broken
bones, and bullets retained in the body (Langard & Hensten-
Pettersen, 1981).

4.3. Occupational Exposure

4.3.1. Inhalation exposure

In chromium ore mines, the concentration of dust in the air in
different work-places ranged from 1.3 to 16.9 mg/m³. In the
crushing and sorting factory, it varied from 6.1 to 148 mg/m³. The
chromium content in settled dust (calculated as Cr₂O₃) varied from
3.6 to 48%. During the period 1955-69, levels of trivalent
chromium in the dust in different work-places in ferro-alloy
factories ranged from 16 to 42%, while the concentrations of dust
in the air varied from 14 to 38 mg/m³ (Pokrovskaja & Shabynina,
1974).

In the past, the production of refined ferrochromium led to
high concentrations of dust in the air of the work-place (10 - 30
mg/m³) (Velichkovsky & Pokrovskaja, 1973). The concentrations of
hexavalent chromium after implementation of a number of sanitation
and hygienic measures were 0.03 - 0.06 mg/m³ (Velichkovsky &
Pokrovskaja, 1973).

In the manufacture of chromates, the oxidation state,
solubility, and composition of air-borne material varied in
different areas of the plant. Exposure in the ore-crushing area
was to trivalent, insoluble particulates; in the leaching area,

exposure was to tri- and hexavalent, soluble and insoluble
particulates and droplets; at the dry end of the process, the
workers were exposed to the very soluble hexavalent chromates in
particulate form, and to the insoluble residue after leaching
(Velichkovsky & Pokrovskaja, 1973). In plants using calcium in the
roasting process, the residue that is recycled contains, among
other products, calcium chromate, currently believed, on the basis
of animal studies, to be at least partly responsible for the
carcinogenicity of chromium.

Chromium plating of metal surfaces was accompanied by the
release of hexavalent chromium into the air in work premises, in
concentrations ranging from 0.04 to 0.4 mg/m³ (Yunisova &
Pavlovskaja, 1975). In one electroplating factory, the
concentration of chromic acid vapours in the air varied from 0.1 to
1.4 mg/m³ (Gomes, 1972). In the vicinity of 3 different baths in a
Swedish chromium plating factory, chromium concentrations ranged
from 20 to 46 µg chromium (VI)/m³, while, at another factory, the
exposure levels near all baths were below 1 µg/m³ (Lindberg et al.,
1985).

Occupational exposure to chromium during welding has been
analysed and the results published by several authors (Stern,
1981). Welding of metals using chromium and nickel electrodes
require high temperatures that melt both the material welded and
the electrode, producing a complex mixture of gases, oxides, and
other compounds, the chemistry of which is determined by the
technology, materials, and welding parameters used in each case
(Lautner et al., 1978). Hexavalent chromium compounds were found in
the respiratory zone of the welder at concentrations ranging from
3.8 to 6.6 µg/m³ (Migai, 1975). For the welding industry as a
whole, the average exposure arising from welding is not homogeneous
but depends on the type and conditions of the welding process
(Stern, 1982).

In a cement-producing factory, the concentration of hexavalent
chromium in the air in the work-place varied from 0.0047 to 0.008
mg/m³. The presence of chromium was explained by the fact that the
lining of the kilns was composed of chrome-magnesium bricks
containing 17 - 28% chromium compounds (Retnev, 1960). Forty-two
types of American cement were analysed for total chromium content
and particularly for hexavalent chromium. It was found that
hexavalent chromium was present in 18 out of 42 samples in
concentrations varying from 0.1 to 5.4 g/kg cement, while the total
chromium content ranged from 5 to 124 g/kg (Perone et al., 1974).
Analysis of 59 samples of Portland cement from 9 European countries
showed that the contents of hexavalent chromium extractable with
sodium sulfate varied from 1 to 83 g/kg of cement, while the total
chromium contents ranged from 35 to 173 g/kg (Fregert & Gruvberger,
1972).

4.3.2. Dermal exposure

Occupational dermal exposure can result in percutaneous
absorption and in harmful effects on the skin (section 8.3.1),
though the percutaneous absorption of chromium (III) sulfate has
been questioned by Aitio et al. (1984).

Chromium, especially chromate, is the most common contact
allergen and of great importance in occupational contact dermatitis
(Thormann et al., 1979).

Chromium eczema occurred most frequently in building labourers
followed by painters, galvanizers, machine drillers, metal-workers,
graphic artists, and workers in the timber, chemical, leather, and
textile industries (Polak et al., 1973). This is likely to reflect
the exposure to chromium compounds from a large number of every-day
products (section 4.2.2). The skin exposure to cement may be of
particular importance as building labourers belong to the most
affected group.

5. KINETICS AND METABOLISM

5.1. Absorption

5.1.1. Absorption through inhalation

5.1.1.1. Animal studies

Few animal studies have been performed to determine the
absorption of chromium compounds via inhalation. In one early
study, mice and rats were exposed to chromium particulates in an
inhalation chamber for various periods of time. The concentrations
of soluble chromium (CrO₃) in air were between 1 and 2 mg/m³ for
the mice and 2 and 3 mg/m³ for the rats. The concentrations of
soluble versus insoluble chromium in the lung tissue of the mice
varied greatly. The soluble chromium concentrations ranged from
4.3 to 10.7 µg/kg dry tissue, after 100 weeks of exposure (Baetjer
et al., 1959a).

The amount of chromium that is absorbed through inhalation
depends on the size of the particles and droplets, on their
solubility in body fluids, and on their reaction with the
respiratory mucosa. Particles greater than 5 µm in diameter
(aerodynamic size) are deposited on the mucosal surface of the
nasal membrane, trachea, and bronchi and are carried by the action
of the cilia to the pharynx, where they are swallowed. Smaller
particles and droplets, especially those below 2 mm in size,
penetrate to the alveoli. Particles and droplets of soluble
compounds, such as hexavalent chromium compounds, are rapidly
absorbed in the blood. Insoluble particles, such as chromite, are
taken up by macrophages and slowly cleared. Soluble materials that
react with the constituents of the lung tissue, such as soluble
trivalent compounds, are also cleared slowly. Baetjer et al.
(1959b) were the first to describe the differences in the clearance
rates of soluble chromates and chromic chloride, when injected
intratracheally into the lungs of animals. The hexavalent chromate
was more rapidly transported from the lungs to other tissues than
the trivalent chromic chloride. Ten minutes after injection, only
15% chromium (IV) remained in the lung compared with 70% chromium
(III). After 60 days, the corresponding figures were 1.7% and 13%
(Baetjer et al., 1959b). Hexavalent chromium is taken up by the
red blood cells in much larger quantities than trivalent chromium.
This finding has been confirmed by Wiegand et al. (1984b)
performing intratracheal instillation (Na₂⁵¹CrO₄) studies on
anaesthetized rabbits, as shown in Fig. 2. Confirmation of the
macrophage uptake of insoluble chromate was obtained by exposing
hamsters to 0.5 - 1 mg chromic oxide dust/m³ for 4 h. The median
diameter of the particles was 0.17 µm. Over 90% of the oxide was
found in the macrophages (Sanders et al., 1971).

5.1.1.2. Human data

A mean chromium concentration of 0.22 mg/kg wet weight was
found in the lung tissue of subjects from various locations in the
USA, but there was no correlation between chromium levels in the
lungs and those in the air (Schroeder et al., 1962).

A Committee of the National Research Council (US NAS, 1974a)
concluded: "It is unlikely that the intake from air under ordinary
conditions contributes significantly to the total intake of
available chromium; the intake from the air is calculated to be
less than 1 µg/day; but excessive exposure to airborne chromium
does result in some increased intake".

5.1.2. Absorption from the gastrointestinal tract

The absorption of ingested chromium compounds can be estimated
by measuring the amount of chromium excreted in the urine, as
almost all of intravenously injected chromium is excreted via the
urine and only 2% is found in the faeces. Although a potential loss
of endogenous chromium via the skin and its annexa has not yet been
measured and quantified, it can be stated that this organ, as well
as the gastrointestinal tract are of minor importance in the
excretion of endogenous chromium. The gastrointestinal tract is,
of course, the major organ for the excretion of exogenous chromium.

When considering the gastrointestinal absorption of chromium,
it is essential to recognize the substantial differences in the
efficiency of absorption of trivalent and hexavalent compounds.
These differences exist in both man and animals. Many trivalent
chromium compounds are so poorly absorbed that they have been used
as faecal markers in man and animals. The absorption of hexavalent
chromium, administered orally, was higher in all species examined,
but did not exceed 5% of the dose (Donaldson & Barreras, 1966). No
physiological regulation has yet been established for chromium
absorption.

5.1.2.1. Animal studies

The gastrointestinal absorption of chromate in rats has been
reported to be between 3 and 6% of a tracer dose (MacKenzie et al.,
1958; Byerrum, 1961). As in man, trivalent chromium compounds are
less well absorbed in the rat, with reported efficiencies ranging
from less than 0.5% (Visek et al., 1953) to 3% (Mertz et al.,
1965a). Within the category of trivalent compounds, there are
moderate differences in absorption, depending on the chemical form.
Binding of the chromium ion to suitable ligands, such as certain
organic acids, stabilizes the metal against precipitation in the
alkaline milieu of the intestines and increases absorption
efficiency by a factor of 3 - 5 times, compared with that for
chromium chloride. This has been shown for certain chelating
agents (Chen et al., 1973), a yet unidentified small peptide
complex isolated from yeast (Votava et al., 1973), and synthetic
glucose tolerance factor (GTF), a dinicotinic-acid-glutathione-
chromium complex (Mertz et al., 1974). Nothing is known about the
interaction of chromium with the flora of the gastrointestinal
tract. Absorption of chromium chloride by ruminant species is
similar to that in rats, with a mean efficiency of 0.76% (Anke et
al., 1971); laying hens have been found to absorb almost 15% of a
tracer dose of the element (Hennig et al., 1971).

5.1.2.2. Human studies

Donaldson & Barreras (1966) studied the gastrointestinal
absorption of hexavalent chromium by administering trace doses of
Na₂⁵¹CrO₄ orally to 6 volunteer patients, who were hospitalized,
and by measuring the amount of radioactivity in the faeces and
urine. The mean urinary excretion, expressing the absorption
efficiency, was 2.1 ± 1.5% of the dose given. Administration by
jejunal infusion in 4 volunteers increased these values, suggesting
reduction of the chromate to trivalent compounds by the acid
content of the gastric juice. The same authors reported a mean
absorption efficiency of only 0.5 ± 0.3% for trivalent chromium,
administered as CrCl₃ x 6H₂O, with a range of 0.1 - 1.2%.

On the basis of the chromium content in diets (60 µg) and
chromium excretion (0.22 µg) in healthy subjects, Anderson et al.
(1983) calculated a minimum chromium absorption of about 0.4%.
Increasing intake by supplementation with chromium (chromic
chloride tablets, furnishing 200 µg chromium/day) led to an
excretion of 0.99 µg, equivalent to 0.4% of the intake.

Aitio et al. (1984) investigated the intake and urinary
excretion of chromium (III) in leather tanning workers. The
environmental concentrations were recorded as low, but chromium was
present in air in the form of large droplets that were not
collected by the standard air measurement technique. It was assumed
that the large droplets were cleared by the upper respiratory tract
and swallowed, and that the chromium in the droplets was absorbed
from the gastrointestinal tract. A calculation showed that this
would explain the urinary excretion levels. No absorption of
chromium through the skin was detected.

In a recent study, the minimum chromium absorption calculated
on the basis of urinary-chromium excretion was about 0.4%.
Increasing intake 5-fold, by chromium supplementation, led to a
nearly 5-fold increase in chromium excretion, suggesting that the
extent of absorption of supplemental inorganic chromium was similar
to that from normal dietary sources (Anderson et al., 1983a).

A similar absorption for trivalent chromium of 0.69% was
reported by Doisy et al. (1968) in healthy human subjects,
regardless of age. However, a group of 14 insulin-requiring
diabetic patients absorbed 4 times as much of the chromium dose as
the non-diabetic or maturity-onset diabetic subjects, as shown by
elevated levels of ⁵¹chromium in blood plasma and urine (Doisy et
al., 1971).

5.2. Distribution, Retention, Excretion

5.2.1. Animal studies

Most animal studies on chromium metabolism have been performed
on rats. From the site of intestinal absorption, chromium is taken
up by plasma-protein fractions. Small, physiological doses of
⁵¹chromium have been shown to bind almost entirely to the iron-
binding protein, transferrin (Hopkins & Schwarz, 1964). On the
other hand, inhaled chromium (Glaser et al., 1984) was bound to
albumin rather than to transferrin. With larger quantities of
trivalent chromium, non-specific binding to other proteins also
occurred, but not to the red blood cells. Visek et al. (1953)
measured the effects of the different chemical forms of chromium on
tissue distribution and found that soluble, chelated forms, such as
acetate or citrate complexes, were cleared quite rapidly, in
contrast with colloidal or protein-binding forms (chromite, chromic
chloride), which have a great affinity for the reticulo-endothelial
system (bone marrow, liver, spleen), and clear more slowly. The
blood clearance of hexavalent chromium, such as chromate, was slow,
because of irreversible binding within the red blood cells. Tissue
distribution of ⁵¹chromium, administered in nanogram doses to rats
was studied by Hopkins (1965). As in the preceeding studies, the
element accumulated in bone, spleen, testes, and epididymis; much
less was retained in the lungs, brain, heart, and pancreas. This
obvious difference in chromium distribution between man and rats is
unexplained.

As in man, trivalent ⁵¹chromium in the rat was rapidly cleared
from the blood, after absorption, and was retained by the tissues
(Mertz et al., 1965a). These tissue stores, labelled with
⁵¹chromium chloride, administered orally or intravenously, were not
immediately available for specific physiological functions. For
example, ⁵¹chromium, administered as CrCl₃ x 6H₂O to pregnant rats,
was not transported into the embryos (Mertz et al., 1969), nor did
any ⁵¹chromium appear in the blood in response to glucose or
insulin injections (Mertz & Roginski, 1971). The fact that fetal
chromium concentrations are low, when the pregnant rats are fed a
low-chromium Torula yeast diet, and increase when a high-chromium
natural stock ration is fed, indicates that placental transport and
possibly, the acute chromium response depend on a special form of
chromium, which is different from chromium chloride. It is
possible, but has not yet been proved, that this form is the
dinicotinic acid-glutathione-chromium complex, known as glucose
tolerance factor. Yeast extracts containing this factor labelled
with ⁵¹chromium have been shown to cross the placenta (Mertz et
al., 1969) and, in preliminary studies, to furnish chromium for the
acute chromium response (Mertz & Roginski, 1971).

With reference to interactions between chromium and other trace
elements, competition with iron by way of their common carrier
(transferrin) has been suggested in rats (Hopkins & Schwarz, 1964)
and in human beings (Sargent et al., 1979). Goncharov (1968)
reported a close interaction between chromium and dietary iodine.
In iodine-deficient white rats, addition of chromium to the diets
in amounts supplying from 0.6 to 600 µg/animal per day stimulated
thyroid function, as indicated by morphological and functional
changes. Conversely, chromium, in all but the lowest dose,
decreased thyroid function in animals receiving adequate iodine
levels. This relation is in agreement with epidemiological data
from the USSR (Goncharov, 1968).

5.2.2. Human data

5.2.2.1. Concentration in tissues, blood, urine, and hair
including possible biological indicators of exposure

(a) Tissues

The most comprehensive survey of tissue-chromium concentrations
is that of Schroeder et al. (1962), who carried out a
spectrographic analyses on 20 - 39 samples for each autopsy tissue,
all of which had been carefully collected to avoid extraneous
contamination. The following results were obtained (mean values in
mg/kg ash) for a group of subjects who had died between the ages of
30 and 40 years: lung, 15.6; aorta, 9.1; pancreas, 6.5; heart, 3.8;
testes, 3.1; kidney, 2.1; liver, 1.8; spleen, 1.7. In all tissues,
except for the lungs there was a rapid decline in chromium
concentrations from time of birth to the age of 10 years, followed
by a more gradual decrease to the age of 80 years. It cannot be
stated with certainty whether the decline is an expression of a
physiological mechanism or of a dietary deficiency. The lungs lost
their initially high chromium levels (85.