IPCS INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
ENVIRONMENTAL HEALTH CRITERIA 18
ARSENIC
This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organization, or the World Health Organization.
Published under the joint sponsorship of
the United Nations Environment Programme,
the International Labour Organisation,
and the World Health Organization
World Health Organization Geneva, 1981
ISBN 92 4 154078 8
(c) World Health Organization 1981
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CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR ARSENIC
1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH
1.1. Summary
1.1.1. Properties, uses, and analytical procedures
1.1.1.1 Properties and uses
1.1.1.2 Analytical procedures
1.1.2. Environmental transport and distribution
1.1.3. Exposure
1.1.4. Metabolism
1.1.5. Normal levels in man and biological indicators of
exposure
1.1.6. Effects and evaluation of health risks
1.1.6.1 Inorganic arsenic compounds
1.1.6.2 Organic arsenic compounds
1.2. Recommendations for further research
1.2.1. Sampling and determination
1.2.2. Exposure
1.2.3. Metabolism and indicators of exposure
1.2.4. Effects
2. PROPERTIES AND ANALYTICAL PROCEDURES
2.1. Chemical and physical properties of arsenic compounds
2.1.1. Inorganic arsenic compounds
2.1.2. Organic arsenic compounds
2.2. Analytical procedures
2.2.1. Sampling and sample treatment
2.2.1.1 Natural waters
2.2.1.2 Air
2.2.1.3 Biological materials
2.2.2. Analytical methods
2.2.2.1 Methods for total arsenic
2.2.2.2 Analyses for specific arsenic compounds
3. SOURCES AND OCCURRENCE OF ARSENIC IN THE ENVIRONMENT
3.1. Natural occurrence
3.1.1. Rocks, soils, and sediments
3.1.2. Air
3.1.3. Water
3.1.4. Biota
3.2. Industrial production and uses of arsenic
3.2.1. Industrial production
3.2.2. Uses of arsenic compounds
3.2.3. Sources of environmental pollution
4. ENVIRONMENTAL TRANSPORT AND DISTRIBUTION
4.1. General
4.2. Aquatic systems
4.3. Air-soil systems
5. LEVELS OF EXPOSURE TO ARSENIC AND ITS COMPOUNDS
5.1. General population exposure through air, drinking water,
food, and beverages
5.1.1. Air
5.1.2. Drinking water
5.1.3. Food and beverages
5.1.4. Tobacco
5.1.5. Drugs
5.1.6. Total daily intake in the general population
5.2. Occupational exposure
6. METABOLISM OF ARSENIC
6.1. Inorganic arsenic
6.1.1. Absorption
6.1.1.1 Respiratory deposition and absorption
6.1.1.1.1 Animals
6.1.1.1.2 Man
6.1.1.2 Gastrointestinal absorption
6.1.1.2.1 Animals
6.1.1.2.2 Man
6.1.1.3 Skin absorption
6.1.1.3.1 Animals
6.1.1.3.2 Man
6.1.1.4 Placental transfer
6.1.1.4.1 Animals
6.1.1.4.2 Man
6.1.2. Distribution in organisms
6.1.2.1 Fate of arsenic in blood
6.1.2.1.1 Animals
6.1.2.1.2 Man
6.1.2.2 Tissue distribution
6.1.2.2.1 Animals
6.1.2.2.2 Man
6.1.3. Elimination
6.1.3.1 Animals
6.1.3.2 Man
6.1.4. Biotransformation
6.1.4.1 Animals
6.1.4.2 Man
6.2. Organic arsenic compounds
6.2.1. Absorption
6.2.1.1 Respiratory absorption
6.2.1.1.1 Animals
6.2.1.1.2 Man
6.2.1.2 Gastrointestinal absorption
6.2.1.2.1 Animals
6.2.1.2.2 Man
6.2.1.3 Skin absorption
6.2.1.4 Placental transfer
6.2.1.4.1 Animals
6.2.1.4.2 Man
6.2.2. Distribution in organisms
6.2.2.1 Fate of organic arsenic in blood
6.2.2.1.1 Animals
6.2.2.1.2 Man
6.2.2.2 Tissue distribution of organic arsenic
6.2.2.2.1 Animals
6.2.2.2.2 Man
6.2.3. Elimination
6.2.3.1 Animals
6.2.3.2 Man
6.2.4. Biotransformation
6.2.4.1 Animals
6.2.4.2 Man
7. NORMAL LEVELS IN MAN AND BIOLOGICAL INDICATORS OF EXPOSURE
7.1. Blood
7.2. Urine
7.3. Hair
7.4. Other tissues
8. EFFECTS AND DOSE-RESPONSE RELATIONSHIPS OF INORGANIC ARSENIC
8.1. Acute and subacute effects after short-term exposure
8.1.1. Man
8.1.2. Animals
8.2. Effects on reproduction and teratogenicity
8.2.1. Man
8.2.2. Animals
8.3. Noncarcinogenic effects after long-term exposure and
sequelae of short-term exposure to inorganic arsenic
8.3.1. Effects on the respiratory system
8.3.1.1 Man
8.3.1.2 Animals
8.3.2. Effects on skin
8.3.2.1 Man
8.3.2.2 Animals
8.3.3. Effects on the liver
8.3.3.1 Man
8.3.3.2 Animals
8.3.4. Effects on the cardiovascular system
8.3.4.1 Man
8.3.4.2 Animals
8.3.5. Effects on the nervous system
8.3.5.1 Man
8.3.5.2 Animals
8.3.6. Effects on other organs
8.3.6.1 Man
8.3.6.2 Animals
8.4. Carcinogenicity
8.4.1. Man
8.4.1.1 Cancer of the respiratory system
8.4.1.2 Cancer of the skin
8.4.1.3 Cancer of the liver
8.4.1.4 Leukaemia and tumours of the
haematopoietic system
8.4.1.5 Cancer of other organs
8.4.2. Experimental animal studies
8.4.2.1 Cancer of the respiratory system
8.4.2.2 Skin application
8.4.2.3 Oral administration
8.4.2.4 Other experimental systems
8.5. Mutagenicity
8.6. Mechanisms of toxicity
9. EFFECTS AND DOSE-RESPONSE RELATIONSHIPS OF ORGANIC ARSENIC
COMPOUNDS
9.1. Acute and chronic toxicity
9.1.1. Man
9.1.2. Animals
9.2. Teratogenicity
9.3. Carcinogenicity
9.3.1. Animals
9.4. Mutagenicity
9.5. Mechanisms of toxicity
10. INTERACTIONS WITH OTHER CHEMICALS
10.1. Thiol-compounds
10.2. Selenium
10.3. Cadmium and lead
11. EVALUATION OF HEALTH RISKS TO MAN FROM EXPOSURE TO ARSENIC
11.1. Introduction
11.2. Exposure
11.3. Inorganic arsenic compounds
11.3.1. Acute and subacute effects after short-term
exposure
11.3.2. Noncarcinogenic effects after long-term exposure
and sequelae of short-term exposure
11.3.2.1 Skin effects
11.3.2.2 Cardiovascular effects
11.3.2.3 Neurological effects
11.3.3. Carcinogenicity
11.3.3.1 Cancer of the respiratory system
11.3.3.2 Skin cancer
11.4. Organic arsenic compounds
11.5. Assessment of the cancer risk for man from exposure to
inorganic arsenic
REFERENCES
NOTE TO READERS OF THE CRITERIA DOCUMENTS
While every effort has been made to present information in the
criteria documents as accurately as possible without unduly delaying
their publication, mistakes might have occurred and are likely to
occur in the future. In the interest of all users of the environmental
health criteria documents, readers are kindly requested to communicate
any errors found to the Division of Environmental Health, World Health
Organization, Geneva, Switzerland, in order that they may be included
in corrigenda which will appear in subsequent volumes.
In addition, experts in any particular field dealt with in the
criteria documents are kindly requested to make available to the WHO
Secretariat any important published information that may have
inadvertently been omitted and which may change the evaluation of
health risks from exposure to the environmental agent under
examination, so that the information may be considered in the event of
updating and re-evaluation of the conclusions contained in the
criteria documents.
WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR ARSENIC
Members
Dr R. Albert, Institute of Environmental Medicine, New York University
Medical Center, New York, NY, USA (Chairman of Subgroup 2)
Dr V. Bencko, Department of General and Environmental Hygiene, Medical
Faculty of Hygiene, Charles University, Prague, Czechoslovakia
Dr G. Corey, Department of Environment Programs, Ministry of Health,
Santiago, Chile
Dr L. Friberg, Departments of Environmental Hygiene of the Karolinska
Institute and of the National Swedish Environment Protection
Board, Stockholm, Sweden (Chairman)
Professor Dr N. Ishinishi, Department of Hygiene, Faculty of Medicine,
Kyushu University, Fukuoka City, Japan (Vice Chairman)
Dr C. Maltoni, Institute of oncology, Bologna, Italya
Dr B. Ordóñez, Undersecretary for Environmental Improvement,
Secretariat for Health and Welfare, Mexico
Professor Dr R. Preussmann, German Cancer Research Center, Institute
of Toxicology and Chemotherapy, Heidelberg, Federal Republic of
Germany
Dr G. Samarawickrama, Department of Community Medicine, Faculty of
Medicine, Peradeniya, Sri Lanka
Dr E. Sandi, Bureau of Chemical Safety, Food Directorate, Health
Protection Branch, Department of National Health & Welfare,
Ottawa, Ontario, Canada (Chairman of Sub group 1)
Dr G. Pershagen, Department of Environmental Hygiene, Karolinska
Institute, Stockholm, Sweden (Rapporteur)
Ms M. Vahter, Department of Environmental Hygiene, National Swedish
Environment Protection Board, Stockholm, Sweden (Rapporteur)
a Unable to attend the Task Group meeting.
Representatives of other organizations
Dr A. Berlin, Commission of the European Communities, Luxembourg
Dr G. F. Nordberg, Commission of the European Communities, Department
of Environmental Hygiene, University of Umeå, Umeå, Sweden
Mr C. Satkunananthan, United Nations Environment Programme, Geneva,
Switzerland
Dr M. Stoeppler, International Union of Pure and Applied Chemistry,
Institute for Chemistry of the Jülich Nuclear Research Facility
Ltd, Jülich, Federal Republic of Germany
Observers
Mr K. W. Nelson, ASARCO Inc., New York, NY USA (representing the
International Center of Industry and Environment)
Mr H. Norin, Department of Environmental Hygiene, National Swedish
Environment Protection Board, Stockholm, Sweden
Dr S.S. Pinto, ASARCO Inc., Tacoma, WA, USA (representing the
International Center of Industry and Environment)
Dr M. Piscator, Department of Environmental Hygiene, Karolinska
Institute, Stockholm, Sweden
Mr R. Svedberg, Boliden Metall AB, Skelleftehamn, Sweden
Secretariat
Mr G. Ozolins, Associate Manager, Environmental Health Criteria and
Standards, Division of Environmental Health, World Health
Organization, Geneva, Switzerland
Mr J. D. Wilbourn, Division of Chemical and Biological Carcinogenesis,
International Agency for Research on Cancer, Lyons, France
CONSULTATION ON THE PREPARATION OF THE ENVIRONMENTAL HEALTH
CRITERIA DOCUMENT ON ARSENIC
STOCKHOLM FROM 4 TO 6 OCTOBER 1978
Participants
Dr V. Bencko, Department of General and Environmental Hygiene, Medical
Faculty of Hygiene, Charles University, Prague, Czechoslovakia
Dr A. Berlin, Commission of the European Communities, Luxembourg
Dr B. Fowler, Environmental Toxicology Branch, National Institute of
Environmental Health Sciences, Research Triangle Park, NC, USA
Dr L. Friberg, Departments of Environmental Hygiene of the Karolinska
Institute and of the National Environment Protection Board,
Stockholm, Sweden (Chairman)
Dr G. Lunde, Central Institute for Industrial Research, Oslo, Norway
Dr G. F. Nordberg, representative of the Commission of the European
Communities, Institute of Community Health and Environmental
Medicine, Odense University, Odense, Denmark
Mr G. Ozolins, Coordinator, Environmental Health Criteria and
Standards, Division of Environmental Health, World Health
Organization, Geneva, Switzerland
Dr G. Pershagen, Department of Environmental Hygiene, Karolinska
Institute, Stockholm, Sweden (Rapporteur)
Dr M. Piscator, Department of Environmental Hygiene, Karolinska
Institute, Stockholm, Sweden
Ms M. Vahter, Department of Environmental Hygiene, National Swedish
Environment Protection Board, Stockholm, Sweden (Rapporteur)
ENVIRONMENTAL HEALTH CRITERIA FOR ARSENIC
Members of the Task Group on Environmental Criteria for Arsenic
met in Stockholm from 28 January to 1 February 1980. The meeting was
opened on behalf of the Director-General by Mr G. Ozolins, Associate
Manager, Environmental Health Criteria and Standards. The Task Group
reviewed and revised the draft criteria document and made an
evaluation of the health risks from exposure to arsenic and its
compounds.
The meeting worked in two subgroups, one on chemical and
environmental aspects and metabolism (subgroup 1) and the other on
effects (subgroup 2). Comments of the subgroups were discussed in
plenary sessions and the conclusions were drawn by the whole group.
The first draft of the biomedical parts of the document was
prepared at the WHO Collaborating Centre for Environmental Health
Effects, Departments of Environmental Hygiene of the Karolinska
Institute and the National Environment Protection Board, Stockholm,
Sweden. Dr G. Pershagen and Ms M. Vahter were primarily responsible
for its preparation. Discussions were held with a group preparing a
report on arsenic for the Health Directorate of the Commission of the
European Communities, Luxembourg and the draft was reviewed and
revised at a consultation arranged by WHO at the Karolinska Institute
in Stockholm from 4 to 6 October, 1978.
The second draft, which was sent out to the national focal points
for environmental health criteria documents, included sections on the
chemical and environmental aspects of arsenic prepared by Dr. R. S.
Braman, Department of Chemistry, University of South Florida, Tampa,
FL, USA.
The third draft was prepared by Dr R. S. Braman and Dr G.
Pershagen based on comments from the national focal points in
Australia, Belgium, Canada, Chile, Finland, Federal Republic of
Germany, Greece, Japan, Mexico, New Zealand, Poland, the United
Kingdom, and the USA, and from the International Labour Office (ILO)
and the American Smelting and Refining Company (ASARCO).
The document, scientifically edited by Dr G. Pershagen and Ms M.
Vahter and reviewed by Dr V. B. Vouk, is based primarily on original
publications listed in the reference section. However, some
comprehensive reviews on the health effects of arsenic including
Fowler (1977), NAS (1977), IARC (1973, 1980), and Pershagen & Vahter
(1979) have also been used.
The possible role of arsenic as an essential element and the
effects of arsine have not been discussed in this document.
Details of the WHO Environmental Health Criteria Programme,
including some of the terms frequently used in the documents, may be
found in the introduction to the Environmental Health Criteria
Programme published together with the environmental health criteria
document on mercury (Environmental Health Criteria 1 -- Mercury, World
Health Organization, Geneva, 1976), and now available as a reprint.
Mrs M. Dahlquist at the WHO Collaborating Centre for Environmental
Health Effects, Stockholm, acted as technical and administrative
assistant and her work is greatly appreciated.
Financial support for the publication of this criteria document
was kindly provided by the 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.
1. SUMMARY AND RECOMMENDATIONS FOR FURTHER RESEARCH
1.1 Summary
1.1.1 Properties, uses and analytical procedures
1.1.1.1 Properties and uses
Arsenic is a ubiquitous element with metalloid properties. Its
chemistry is complex and there are many different compounds of both
inorganic and organic arsenic. In nature, it is widely distributed in
a number of minerals, mainly as the arsenides of copper, nickel, and
iron, or as arsenic sulfide or oxide. In water, arsenic is usually
found in the form of arsenate or arsenite. Methylated arsenic
compounds occur naturally in the environment as the result of
biological activity. The most important commercial compound,
arsenic(III) oxide, is produced as a by-product in the smelting of
copper and lead ores.
Arsenic compounds are mainly used in agriculture and forestry as
pesticides, herbicides, and silvicides; smaller amounts are used in
the glass and ceramics industries and as feed additives.
1.1.1.2 Analytical procedures
If total arsenic has to be determined, the first step usually
consists of complete mineralization. The arsenic can then be measured
directly by, for example, flame or graphite tube atomic absorption
spectrophotometry (AAS). In an ordinary flame, the detection limit is
0.5-1 mg/litre. Using a long-path cell, a detection limit of a few
µg/litre can be obtained.
The most commonly used techniques for the determination of arsenic
involve its transformation into arsine. Subsequent measurements of
arsine can be carried out using, spectrophotometry, flames and
electrothermal devices for AAS, atomic fluorescence (AFS), or atomic
emission spectroscopy (AES).
Spectrophotometry of the silver diethyldithiocarbamate complex of
arsine has been used for several years, and is suitable for
determining arsenic levels in the range of 1-100 µg. Passing the
arsine, generated, for instance, by sodium borohydride, into a heated
tube of an AAS or AES instrument gives an absolute detection limit of
about 0.5 ng. If oxidation can be avoided prior to the arsine
generation step, it is possible to differentiate between As(III) and
As(V) by changing the pH value at this step. Furthermore, cold
trapping of the arsines and separation upon heating can be used for
the separation and detection of inorganic and methylated arsenic
compounds present in natural waters and urine. Other separation
methods include ion exchange chromatography, gas chromatography, and
liquid chromatography.
Neutron activation analysis using radiochemical separation is a
very sensitive method for the determination of arsenic, with detection
limits near 1 ng.
1.1.2 Environmental transport and distribution
Arsenic is mainly transported in the environment by water.
Sedimentation of arsenic in association with iron and aluminium may
sometimes be considerable. In oxygenated water, arsenic usually occurs
as arsenate, but under reducing conditions, for instance, in deep well
waters, arsenite predominates. Methylation of inorganic arsenic to
methyl- and dimethylarsenic acids is associated with biological
activity in water. Some marine organisms have been shown to transform
inorganic arsenic into more complex organic compounds, such as
arsenobetaine, arsenocholine, and arsoniumphospholipids.
In oxygenated soil, inorganic arsenica is present in the
pentavalent form. Under reducing conditions, it is in the trivalent
form. Leaching of arsenate is slow, because of binding to hydrous
oxides of iron and aluminium. There is ample evidence of
biomethylation in the soil and of the release of methylarsines into
the air and high levels of methylated arsenic compound have been
detected in greenhouse air. However, airborne arsenic is mainly
inorganic.
1.1.3 Exposure
Because the metabolic fates and toxicities of arsenic compounds
differ, it is important to distinguish between them in the
environment. The forms of arsenic to which man is actually exposed
have not been considered in detail until recently, mainly because of a
lack of suitable analytical methods.
Airborne concentrations of arsenic in urban areas may range from a
few nanograms to a few tenths of a microgram per cubic metre. Near
point emissions of arsenic, such as smelters, airborne arsenic
concentrations have exceeded 1 µg/m3. Drinking water ordinarily
contains a few micrograms of arsenic per litre or less, mainly in the
form of inorganic compounds. Levels exceeding 1 mg/litre recorded in
some areas, have usually been naturally occurring, but have sometimes
been the result of industrial contamination.
a Abbreviations "inorganic arsenic" and "organic arsenic" mean
"arsenic and its inorganic compounds" and "organic arsenic
compounds", respectively.
Arsenic is present in most foodstuffs in concentrations of less
than 1 mg/kg. However, marine fish may contain arsenic concentrations
of up to 5 mg/kg wet weight and concentrations in some crustacea and
bottom-feeding fish may reach several tens of milligrams per kilogram,
predominantly in the form of organic arsenic. Accumulation of arsenic
in the tissues of poultry and swine can result from the use of some
organic arsenic compounds as feed additives.
Wine and mineral waters can sometimes contain several hundreds of
micrograms of arsenic per litre, probably as a result of the use of
arsenic-containing pesticides. Inorganic forms of arsenic have been
shown to predominate in wine.
The total daily intake of arsenic by man is greatly influenced by
the amount of seafood in the diet, but it is usually less than 0.2 mg
per day. Normally, the daily intake of inorganic arsenic will not
exceed 50 µg. Depending on the content of arsenic in tobacco, an
average smoker may inhale between a few micrograms and 20 µg of
arsenic daily. Some decades ago, when the arsenic content of tobacco
was higher, more than 100 µg might have been inhaled per day. The
chemical form of arsenic in tobacco smoke is not known.
Various arsenic compounds have been used in medicine for many
years. Inorganic trivalent arsenic, often in the form of sodium
arsenite (Fowler's solution) has been used for the treatment of
leukaemia, psoriasis, and as a tonic, frequently at a dose of several
milligrams daily. Some inorganic as well as organic arsenic compounds
are still used in drugs in a number of countries.
Occupational exposure to arsenic mainly occurs through the
inhalation of particles containing arsenic, i.e., among smelter
workers and workers engaged in the production and use of
arsenic-containing pesticides. Concentrations in air ranging from a
few micrograms to more than 1 mg/m3 have been reported.
1.1.4 Metabolism
Studies on animals and man have shown that both trivalent and
pentavalent inorganic arsenic compounds in solution are readily
absorbed after ingestion. Inhalation usually involves particles
containing inorganic arsenic. Most of the inhaled and deposited
arsenic will probably be absorbed from either the respiratory or the
gastrointestinal tract.
The biological half-time of arsenic in rats is long (60 days),
because of its accumulation in erythrocytes. In other animals and in
man, most inorganic arsenic is eliminated at a much higher rate,
mainly via the kidneys. As far as exposure to trivalent arsenic in a
single dose is concerned, both animal and human data indicate an
initial elimination of about 75% in the urine and a few percent in the
faeces during the first days or, at the most, the first week. As for
pentavalent arsenic, a few animal experiments have indicated that
80-90% of a single dose is eliminated during the first 2 days, while
available human data indicate a slower rate of elimination. Animal
data show a somewhat higher retention of arsenic in different organs
after exposure to trivalent arsenic than after exposure to the
pentavalent form. The differences increase with increasing dose
levels.
Placental transfer of inorganic arsenic has been demonstrated in
both experimental animal (rat and hamster) and human studies. In a
study on rats, dimethylarsinic acid was shown to pass through the
placental barrier, the blood values in the fetus being comparable with
those of the mother.
No data are available which indicate that long-term accumulation
of arsenic exists. Some data on mice and rabbits exposed for up to one
year to arsenic indicated that levels of arsenic in the body increased
during the first 2 weeks and then decreased. There are very few data
concerning accumulation in people heavily exposed to inorganic
arsenic, such as industrial populations or populations in areas where
the drinking water contains high levels of arsenic. However, some data
have indicated that arsenic levels in the lungs of smelter workers,
several years after exposure, were 6 times those of controls. The
concentrations of arsenic in human tissues seem to be log-normally
distributed and the highest levels are generally found in hair, skin,
and nails.
In vivo methylation of inorganic arsenic has been demonstrated
in both animals and man. Following ingestion or inhalation of
inorganic arsenic, the major forms of arsenic excreted in human urine
are dimethylarsinic acid and methylarsonic acid accounting for about
65% and 20% of excreted arsenic, respectively. In other species,
methylarsonic acid has only been observed in minimal amounts.
In both animals and man, organic arsenic compounds ingested via
fish and crustacea are readily absorbed from the gastrointestinal
tract and 70%-80% is eliminated within a week, mainly in the urine.
Some data indicate that these compounds are eliminated without being
converted to inorganic arsenic or simple methylated arsenic compounds.
Organic arsenic compounds from other sources show various degrees of
absorption, transformation, and retention.
1.1.5 Normal levels in man and biological indicators
of exposure
In subjects not known to have been exposed to arsenic, whole blood
arsenic levels are in the range of only a few micrograms per litre,
while in persons exposed to water containing high levels of arsenic,
whole blood levels exceeding 50 µg/litre have been reported. No data
are available on the influence of dietary habits on arsenic levels in
blood.
Studies on the metabolism of inorganic arsenic show that in most
animals and man arsenic is taken up readily by the blood and also
rapidly cleared. Arsenic in blood will therefore reflect exposure for
only a short period following absorption and will be highly
time-dependent. If exposure is continuous, as may be the case with
drinking water, it should be possible to find a relationship between
arsenic levels in blood and exposure. However, such studies have not
been carried out.
Effects of arsenic have been seen in a large number of organs in
both animals and man. However, data are not available from which it is
possible to correlate such effects with tissue concentrations, or with
the concentrations in blood. It has not been possible to define a
critical organ for arsenic in the way that the kidney is considered a
critical organ for chronic cadmium intoxication and the central
nervous system for methylmercury intoxication. The short half-time of
arsenic in the blood compared with those in the whole body and
individual organs makes it difficult to establish a relationship
between concentrations of arsenic in blood and the total body burden.
A metabolic model for arsenic has not yet been developed.
Arsenic concentrations in the urine of persons who have not been
excessively exposed to arsenic through, for example, occupation or
dietary habits, have been estimated to range from 10 to 50 µg/litre.
Excretion of up to a few milligrams of arsenic in the urine on the
first day following ingestion of fish with a high arsenic content has
been reported.
Smelter workers exposed to inorganic arsenic compounds may have
urine values of a few hundred micrograms per litre. One study
indicated that the major part of the arsenic was excreted as
dimethylarsinic acid. Increased urinary levels of arsenic have also
been observed in persons living around point sources emitting arsenic.
Urine is a suitable indicator medium for assessment of exposure to
inorganic arsenic, since most studies show that the elimination of
arsenic, in both animals and man, takes place mainly via the kidneys.
A method of assessment must be used that differentiates between the
organic arsenic compounds from sea food and the main metabolites of
inorganic arsenic.
Arsenic levels in the hair of unexposed human adults are usually
below 1 mg/kg. There are no published data to indicate whether
exposure to arsenic in sea food results in increased hair values.
Levels of up to about 80 mk/kg have been recorded in subjects with
chronic arsenic poisoning caused by ingestion of contaminated well
water.
The use of arsenic concentrations in hair as an indicator of
exposure to airborne arsenic is limited, as no reliable method exists
for distinguishing between arsenic from external contamination and
arsenic that has been absorbed and metabolized in the body.
1.1.6 Effects and evaluation of health risks
1.1.6.1 Inorganic arsenic compounds
Acute and subacute effects of arsenic may involve many organ
systems including the respiratory, gastrointestinal, cardiovascular,
nervous, and haematopoietic systems. Unfortunately, in most cases of
human intoxication, the doses and valence states of arsenic have not
been determined. Data from studies on experimental animals indicate
that trivalent inorganic arsenic is more toxic than pentavalent. It is
also evident that arsenic in solution is more toxic than undissolved
arsenic, probably because of better absorption. An ingested dose of
70-180 mg of arsenic (III) oxide has been reported to be fatal in man.
Long-term exposure to inorganic arsenic has been found to give
rise to effects in a large number of organs. However, in general, the
details of human exposure (e.g., type of arsenic compound), have been
inadequate for the establishment of dose-response relationships.
Lesions of the upper respiratory tract including perforation of
the nasal septum, laryngitis, pharyngitis, and bronchitis have
frequently been encountered in workers in the smelting industry
exposed to high levels of arsenic. In general, such lesions have been
reported in instances of prolonged exposure to several hundred
micrograms of arsenic per cubic metre of air and mostly with arsenic
in the trivalent inorganic form. In the case of lower respiratory
tract lesions in workers in the smelting industry, the influence of
concurrent exposure to high levels of sulfur dioxide should be
considered as well as interaction with tobacco smoking.
Inorganic arsenic in the trivalent state can give rise to skin
lesions in man, especially palmo-plantar hyperkeratosis which has a
characteristic appearance. It has been observed in patients under
prolonged medication with Fowler's solution, who have received daily
doses of arsenic of up to 10 mg. In one study, the incidence of
hyperkeratosis was reported to be over 50% in a group of patients,
each of whom had received a total dose of more than 3 g of arsenic.
Palmo-plantar hyperkeratosis has also been reported following
ingestion of arsenic in drinking water (oxidation state not
determined) in some parts of the world including Argentina, China
(Province of Taiwan) and Mexico. Other dermatological symptoms,
including hyperpigmentation, have also appeared in inhabitants of
these areas.
It should be noted that hyperkeratotic lesions of the palms and
soles and hyperpigmentation are very rare among smelter workers
exposed to inorganic arsenic, but have been reported in other
occupational situations. The reason for this discrepancy is not clear
but could be the result of differences in dose.
Disturbances of liver function have been observed in both man and
animals after chronic exposure to inorganic arsenic. An association
between medication with trivalent inorganic arsenic and the
development of portal hypertension in man has been suggested, though
this has not been reported in experimental animals. Indications of
severe hepatic damage resulting in cirrhosis, have come from both
epidemiological and toxicological data. The role of alcohol
consumption in situations of arsenic exposure has, unfortunately, not
been considered in most of the studies.
Evidence of effects on the heart, including minor ECG changes, has
been found in human subjects after exposure to comparatively high
doses of arsenic, which produced other symptoms and signs of
intoxication. These findings have been supported by animal data. A
moderate excess mortality attributed to cardiovascular lesions was
detected in 2 independent epidemiological studies on smelter workers
exposed to high levels of airborne, inorganic arsenic (exposure levels
not given). This finding has not been confirmed in other studies on
workers exposed to arsenic.
Peripheral vascular disturbances have been reported in some areas
of the world where heavy exposure due to ingestion of inorganic
arsenic has occurred, e.g., in Chile, China (Province of Taiwan) and
the Federal Republic of Germany. Exposures have been of the order of
several hundred micrograms to over one milligram daily; the valence
state is not known. Generally, peripheral vascular changes have not
been reported in connexion with occupational exposure to inorganic
arsenic, and, unfortunately, their possible existence in
arsenic-exposed animals has not been considered.
Inorganic arsenic can exert chronic effects on the peripheral
nervous system in man. The only information on these effects as far as
occupational exposure is concerned comes from case reports, and
exposure levels have not been given. It is obviously difficult to draw
any conclusions from such reports. Disturbances of CNS function were
reported in Japanese youths, 15 years after they had been exposed as
infants to inorganic arsenic in average daily doses of 3.5 mg for
about one month. The effects included severe hearing loss and
electroencephalographic abnormalities. CNS effects have also been
reproduced in animals. Children living near a coal-fired power plant,
which emitted large amounts of arsenic, were reported to have moderate
hearing losses, but such effects were not confirmed in another
instance of exposure to elevated levels of inorganic arsenic in
ambient air. Ingestion of moderate amounts of inorganic arsenic at
levels of a few hundred micrograms daily in drinking water (length of
exposure and valence state of arsenic unknown) has been associated
with abnormal electromyographic findings in one study. This effect
might serve as a sensitive indicator of arsenic intoxication, but the
association must be identified and evaluated elsewhere before any
definite conclusions can be drawn.
Because inorganic trivalent arsenic has an effect on the
haematopoietic system, it has been used for several decades as a
therapeutic agent for various forms of leukaemia, often in doses of
several milligrams dally. The impaired resistance to viral infections,
associated with arsenic exposure in some animal studies, should be
noted, when considering the high frequency of chronic cough,
bronchopulmonary disease, and lip herpes observed in persons exposed
to arsenic in water in Chile. The lack of evidence of these effects in
other studies on human subjects is worth noting. Animal data suggest
that arsenic exposure may have chronic effects on the kidneys, but
this has not been confirmed for human exposure situations.
There are both in vivo and in vitro studies indicating effects
of inorganic arsenic on human chromosomes. An increased frequency of
chromosomal aberrations has been found among persons exposed to
arsenic, mainly in the trivalent form, through medication. Similar
findings have been reported among workers exposed to arsenic. However,
the exposure of these workers to other toxic substances may have been
of importance.
Several studies have indicated that inorganic arsenic affects DNA
repair mechanisms.
Human data on the teratogenicity of inorganic arsenic are lacking.
One epidemiological study on the offspring of women working at a
copper smelter, where high levels of airborne arsenic were registered
in some workplaces, pointed towards an increased frequency of
malformations and spontaneous abortions. Since exposure to several
other toxic substances also took place, no conclusions can be drawn as
to the specific role of arsenic.
Results of studies on hamsters, rats, and mice have shown that
high doses of both trivalent and pentavalent inorganic arsenic induce
teratogenic effects. The high doses used in these studies make it
difficult to judge how significant such animal data are for man.
There is substantial epidemiological evidence of respiratory
carcinogenicity in association with exposure to mainly inorganic
arsenic in the manufacture of arsenic-containing insecticides.
However, conclusions cannot be drawn on the carcinogenic potential of
trivalent versus pentavalent inorganic compounds since exposure to
both forms occurred in these workplaces. A possible association
between the use of pesticides containing arsenic, often in the form of
arsenate, in vineyards and orchards, and in an increased risk of lung
cancer has been found, but the data are not conclusive.
The carcinogenic potential of inorganic arsenic in smelter
environments is evident from many epidemiological studies. One report
revealed a roughly linear relationship between cumulative arsenic
exposure and lung cancer risk. Although exposure data are uncertain,
it is estimated that exposure to airborne arsenic levels of about
50 µg/m3 (probably mostly arsenic (III) oxide) for more than 25 years
could result in a nearly 3-fold increase in the mortality rate of
cancer in the respiratory tract after the age of 65 years.
Exposure to inorganic arsenic can cause skin cancer, mainly
tumours of low malignancy. This has been observed following ingestion
of arsenic in drinking water or drugs resulting in a total intake of
several grams of arsenic over a number of decades. The form of arsenic
in drinking water has yet to be elucidated, but in medication it has
most often been inorganic trivalent arsenic.
The association between arsenic and tumours of other organs, most
notably the liver and lymphatic and haematopoietic system, needs
further confirmation.
At present, no definite evidence exists to show that inorganic
arsenic compounds are carcinogenic in animals. This holds true as far
as both tumour initiation and promotion are concerned. Results of four
studies on rats and mice, however, suggest that arsenic plays a role
in the development of tumours of the lung and the haemapoietic system.
An attempt has been made to assess the risk of cancer of the lung
and skin from low doses of arsenic by extrapolating data concerning
the risks from relatively high doses.
1.1.6.2 Organic arsenic compounds
Medication with some organic arsenic compounds such as
[4-[2-amino-2 oxoethyl]-amino]-phenyl] arsonic acid (tryparsamide),
has induced side-effects, mainly in the central nervous system. These
include encephalopathy and optic atrophy. Toxic effects on the nervous
system have been reproduced in experimental animals fed high doses of
arsanilic acid, which is commonly used as a feed additive for poultry
and swine. Limited data indicate that the toxicity of the organic
arsenic compounds present in seafood is low.
No conclusive evidence of carcinogenic activity has been reported
for any of the organoarsenic compounds tested in experimental animals.
1.2 Recommendations For Further Research
1.2.1 Sampling and analysis
A number of important problems remain to be solved in the
following areas:
(a) sampling of arsenic in air;
(b) pretreatment of samples with special attention to seafood
arsenic; and
(c) differentiation between the various arsenic species, including
the identification of the arsenic compounds in seafood.
The development of reference materials for biological specimens is
recommended and interlaboratory calibration exercises should be
performed.
1.2.2 Exposure
There are only a few dose-response relationships established for
the exposure of man to arsenic, mainly because of a lack of reliable
exposure data. More data are therefore needed on the exposure levels
of arsenic in both general and occupational environments. Continuous
monitoring of arsenic in foodstuffs, especially poultry and pork, is
required in view of the use of arsenic compounds as feed additives.
It is important not only to get quantitative measurements of the
dose but also to determine the chemical form of arsenic. Such
qualitative information is lacking for most foodstuffs as well as for
cigarette smoke. In fish and crustacea, most of the arsenic has been
reported to be in an organic form. However, data on the chemical form
of arsenic in seafood from water polluted with inorganic arsenic are
required, as fish probably cannot convert inorganic arsenic to organic
arsenic compounds.
More studies are needed to understand the volatilization of
arsenic into the air. The effect of naturally occurring oxidants such
as ozone and nitrogen oxides on volatilized arsines is of particular
interest. The oxidants may demethylate methylarsenic compounds and
convert them to inorganic forms. The arsenic forms found over the open
oceans and in remote regions also need to be determined to assess the
impact of volatilization on global transport.
1.2.3 Metabolism and indicators of exposure
In the evaluation of health effects, arsenic has generally been
treated as such without any reference to its chemical form, e.g.,
trivalent or pentavalent inorganic arsenic. Though it has been shown
that both forms are methylated in vivo, possible quantitative
differences have not been studied. Thus, the rate, extent, and
mechanism of biomethylation of different forms of arsenic should be
further investigated. Conversion of As(V) to the more toxic As(III) in
the body has been indicated in some studies, but data are not
conclusive. This needs to be further investigated together with the
possibility of in vivo oxidation. Data on the biotransformation of
arsenic compounds are also needed for the identification of biological
indicators of exposure to these compounds.
Further efforts should be made to establish a suitable animal
model for arsenic.
More data are required on the concentrations of arsenic in human
organs in high-exposure groups, including those heavily exposed to
seafood arsenic. It has been shown at autopsies that smelter workers
may retain arsenic in their lungs for several years after cessation of
exposure. It is important to study the nature of this arsenic.
More data are also needed on possible interactions between arsenic
and nutrients in the human diet as well as interactions between
arsenic and other pollutants in the human environment.
1.2.4 Effects
Dose-response data on various health effects caused by exposure to
arsenic are generally very scanty or nonexistent. Damage to the liver
and the cardiovascular and nervous systems, reported in some chronic
exposure situations, needs to be validated in future studies. In many
instances, animal models would be of use. Sensitive indicators of
arsenic exposure have been suggested such as the urinary excretion of
uroporphyrin or electromyographic abnormalities, but further
confirmation is needed.
It has been demonstrated recently that the two major metabolites
formed after exposure to inorganic arsenic compounds are methylarsonic
acid and dimethylarsinic acid. It is important to study the toxicity
of these compounds. Man is also exposed to large amounts of organic
arsenic compounds through consumption of some seafoods. Though the
acute toxicity of these compounds must be considered to be low, there
are very limited data on possible long-term effects. Studies should be
carried out on both human subjects and on animals.
Severe effects of exposure to arsenic have been demonstrated in
Japan in the form neurological effects and in Chile and China
(Province of Taiwan) in the form of severe vascular disorders. There
is a need to carry out followup studies using modern epidemiological
techniques. In order to elucidate the cardiovascular diseases,
including peripheral vascular disease in Chile and China (Province of
Taiwan), it is recommended that WHO should initiate an internationally
coordinated study.
Although there is strong epidemiological evidence that inorganic
arsenic is carcinogenic for man, more work is needed to determine if
this is true for both valence forms. Conclusive animal data are not
available. Further epidemiological investigations concerning the
relationship between exposure to arsenic and cancer of the lung and
skin should be undertaken in both ambient and occupational exposure
situations, because of the considerable uncertainty concerning
dose-response relationships.
Health effects of arsenic in industry have generally been seen
where exposure to arsenic has been combined with exposure to other
metals and irritating substances, such as sulfur dioxide. Possible
synergism in relation to the carcinogenic activity of arsenic should
be investigated in epidemiological studies as well as in experimental
systems.
Some data indicate that arsenic may induce effects in the human
reproductive system. More studies in this field are needed.
In this document, pulmonary cancer and skin cancer have been
regarded as the critical effects in man for long-term exposure to
inorganic arsenic through inhalation and oral exposure, respectively.
There is still considerable uncertainty regarding the effects of
different chemical forms of arsenic and dose-response relationships
and it is recommended that these questions should be studied further,
both in industry and in the general environment. Studies should
comprise both human epidemiological and experimental animal studies.
There is also a need for further investigation of the mutagenic
activity of different arsenic compounds.
2. PROPERTIES AND ANALYTICAL PROCEDURES
2.1 Chemical and Physical Properties of Arsenic Compounds
There are many different forms of inorganic and organic arsenic.
The most important forms for the evaluation of health effects are
shown in Table 1.
2.1.1 Inorganic arsenic compounds
The most important commercial compound is arsenic (III) oxide, the
molecular formula of which is generally accepted to be As4O6, at
temperatures up to 1073°C. This compound is recovered from copper
smelters as a by-product of copper production. The arsenic in
naturally occurring metal arsenides and arsenic sulfides is
volatilized and oxidized during the ore roasting process and condenses
as the trioxide in flues. Arsenic-containing coal also produces
chiefly arsenic(III) oxide, when it is combusted. Arsenic(III) oxide
has a reasonably low boiling point (465°C) and will sublime at lower
temperatures (Durrant & Durrant, 1966; Carapella, 1973). Its vapour
pressure at ambient temperatures is significant, a fact which is
important in its transport and distribution in the environment
(Lao et al., 1974). If data on the vapour pressure of arsenic(III)
oxide are extrapolated to 25°C, the saturating concentration of
arsenic(III) oxide is 0.6 µg/m3.
The solubility of arsenic(III) oxide in water is fairly low, about
2% at 25°C and 8.2% at 98°C (Durrant & Durrant, 1966). The resulting
solution is slightly acidic and contains arsenous acid (H3AsO3).
Arsenic(III) oxide is highly soluble in either hydrochloric acid or in
alkali. In aqueous solution, arsenic is usually in the form of the
arsenate or arsenite.
Alkali earth metals combine with arsenate anions to form salts
that are only slightly soluble; consequently arsenic tends to form a
precipitate frequently in association with phosphates.
Reported pKa values for arsenous and arsenic acids are: HAsO2,
pKa 9.23; H3AsO4, pKa1 2.20, pKa2 6.97, pKa3 11.53 (Flis et al.,
1959).
Arsenates and arsenic acid are strong oxidants and may for
example, oxidize I-ion to I-3. In air saturated water, arsenic(V)
compounds should predominate, but arsenic(III) compounds have been
shown to exist under these conditions. Sulfides of arsenic predominate
under reducing systems in the presence of reduced forms of sulfur
(Ferguson & Gavis, 1972). Reduction by organic matter of arsenic(III)
and sulfate ions in the sediments of aquatic systems is likely to be
responsible for the formation of both metallic arsenic and arsenic
sulfides at the same location. Lead arsenate, copper arsenate,
copper(II) acetate meta-arsenate (Paris Green), and calcium arsenate,
all of which have been used as insecticides, are only slightly soluble
in water.
The halides of arsenic and arsine are not found in the environment
but are important in organoarsenic chemistry and in chemical analysis.
Arsenic(III) chloride, for example, is formed when arsenic(III) oxide
is treated with concentrated hydrochloric acid (Durrant & Durrant,
1966). It is easily hydrolyzed by water. Arsenic halides are rapidly
hydrolized and easily alkylated by a number of organic alkylating
agents, such as the Grignard reagents.
2.1.2 Organic arsenic compounds
The organic chemistry of arsenic is extensive. Carbon-arsenic
bonds are quite stable under a variety of environmental conditions of
pH and oxidation potential. Some methylarsenic compounds, such as di-
and trimethylarsines, occur naturally as a consequence of biological
activity. In water solutions, these may undergo oxidation to the
corresponding methylarsenic acids. These and other higher organic
arsenic compounds such as arsenobetaine and arsenocholine, which are
found in marine organisms, are very resistant to chemical degradation
(Lauwerys et al., 1979).
Methylarsonic acid is a difunctional acid, with pKa1 4.1, pKa2
8.7, that forms soluble salts with alkali metals. Dimethylarsinic
acid, which acts as a monofunctional weak acid, pKa 6.2, also forms
fairly soluble alkali metal salts. The alkylarsenic acids can undergo
reduction to the corresponding arsines, a reaction important in
analysis. They also react with hydrogen sulfide and alkanethiols to
produce sulfur derivatives such as (CH3)2AsS SH (NAS, 1977). It
appears likely that the reduction of dimethylarsinic acid and its
subsequent reaction with thiols may be a key to its involvement in
biological activity.
The alkylchloroarsines are reasonably stable with respect to
hydrolysis but quite reactive with reduced compounds of sulfur. One
such compound, 2-chlorovinylarsine dichloride (Lewisite), has been
used as a war gas.
An extensive review of the chemical and physical properties of
organoarsenic compounds has been made by Doak & Freedman (1970).
2.2 Analytical Procedures
2.2.1 Sampling and sample treatment
Arsenic poses some special problems in sampling not experienced in
the determination of other trace elements. Water, urine, and
biologically active samples should either be analysed within a few
hours or frozen and stored (Andreae, 1977; Feldman 1979). Low
concentrations of arsenic compounds found in natural waters slowly
decrease with time, unless stabilized in some manner to prevent
adsorptive losses. The biomethylation of inorganic arsenic in a
biologically active sample can cause a change in its composition.
Since environmental analyses often involve trace concentrations,
sample treatment frequently includes some type of preconcentration
prior to analysis. Conversion of arsenic to arsine, co-precipitation
with iron(III) hydroxide, distillation as arsenic(III) chloride, or
extraction are typical examples of the approaches used.
2.2.1.1 Natural waters
Sea water and fresh natural waters are generally analysed without
oxidative treatment prior to a preconcentration step, when the
molecular forms of arsenic are to be analysed. If the preconcentration
step or the final steps in the analytical method require the
conversion of organoarsenic compound to an inorganic form, oxidation
procedures may be necessary. An acid-potassium persulfate preoxidation
method (Pierce et al., 1976) and a method involving ultraviolet (UV)
have both been automated (Fishman & Spencer, 1977). Acid-permanganate
oxidation was found to be effective in the conversion of
dimethylarsinic acid to inorganic arsenic (Sandhu & Nelson, 1978).
Arsine generation followed by cold trapping in liquid nitrogen is
a technique that can be used with or without prior oxidation (Braman
et al., 1977; Siemer & Koteel, 1977). Arsine generation has long been
used as a first step in the determination of arsenic in water samples,
prior to spectrophotometric analysis of the complex formed with
silverdiethyldithiocarbamate (SDDC) (Skonieczny & Hahn, 1978). A
recent adaptation of this method is the analysis for the SDDC complex
by graphite tube furnace AAS which gives an improved detection limit
of about 10 ng (Shaikh & Tallman, 1977). Arsenic has been separated
from samples by volatilization as the trichloride or tribromide. A
recent application combines distillation as the chloride with anodic
stripping voltametry (Davis et al., 1978).
A number of coprecipitation methods have been reported for the
preconcentration of arsenic from water followed by different methods
of analysis. Iron(III) hydroxide (Portmann & Riley, 1964) and
hydroxides of zirconium and cerium (Plotnikov & Usatova, 1964) are
among the many coprecipitants that have been studied. Thionalide has
also been used in the coprecipitation of arsenic from sea water
(Portmann & Riley, 1964) with 95% efficiency, but the procedure is
slow, requiring much sample handling, a problem with all of the
precipitation methods.
2.2.1.2 Air
Air sampling for trace amounts of arsenic in the environment has
mainly been confined to sampling the particulate phase. It is likely
that many different types of particulate filters are satisfactory for
this type of sampling, though arsenic is usually associated with small
size particles.
As the estimated saturated concentration of arsenic(III) oxide in
air at 25°C is about 600 ng/m3, it is possible that, when air
concentrations are below this level, arsenic(III) oxide collected on a
filter may evaporate or may not be collected completely. Results of
laboratory work using filters and pure arsenic(III) oxide in air
support this theory (Lao et al., 1974; Walsh et al., 1977b).
Nevertheless, in studies using a filter impregnated with ethyleneimine
in glycerol which is 65% efficient in trapping arsenic(III) oxide
vapour, it was shown that the major portion of arsenic in air (78-99%)
could be collected on untreated, 0.4 micrometer pore size,
polycarbonate type filters (Nuclepore Co.). Millipore membrane filters
have also given satisfactory results (Walsh et al., 1977b). This was
found to be the case for both ambient air samples containing low
levels of arsenic and near-smelter air samples containing high levels.
Approximately 15% of the arsenic in the air collected was found to be
in a vapour form that was not collected on untreated filters. These
results agree with those of Johnson & Braman (1975a) who also found
that approximately 15% of the collected arsenic was volatile.
Vapour forms of arsenic in air, particularly the arsines, can be
preconcentrated from air onto silver-coated glass beads (Johnson &
Braman, 1975a). Even if oxidized after adsorption, the identity of the
compound is not lost. For example, dimethylarsine, if present, can
only be oxidized to dimethylarsinic acid. Adsorbed compounds can be
desorbed using dilute sodium hydroxide (Braman et al., 1977).
2.2.1.3 Biological materials
Samples of biological materials to be analysed for total arsenic
are generally completely oxidized prior to analysis. A number of
oxidation methods have been studied, the majority of which involved
the use of oxidizing acids or persulfates. The completeness of the
oxidation has however seldom been checked. Perhaps the best oxidizing
procedure involves the use of a mixture of sulfuric and nitric acids
(Chu et al., 1972), a mixture of sulfuric, nitric, and perchloric
acids (Christian & Feldman, 1970) or hydrogen peroxide (Samsahl,
1967). Dry ashing with magnesium oxide or magnesium nitrate has been
successfully applied in the analyses of a variety of biological
samples (Snell & Snell, 1945; Evans & Bandermer, 1954). Other methods
with fewer contamination problems or losses of arsenic are the Parr
bomb (Beamish & Collins, 1934) and the Carius oxidation (Day, 1964)
techniques. Schoeninger flask oxidation has been used in the oxidation
of dried tissue samples (Schwedt & Russel, 1972). The proper
preanalytical treatment for samples of certain marine organisms
containing compounds such as arsenobetaine has yet to be established
(Edmonds, et al., 1977).
There has been some success in analysing homogenized samples
without oxidation by treating them with hydrochloric acid (Kingsley &
Schaffert, 1951) or sodium hydroxide (Johnson & Braman, 1975b) prior
to analysis. This approach is particularly necessary if the molecular
forms of arsenic present are to be identified. In no case has the
accuracy of the analyses been unequivocally determined.
Various methylarsenic compounds have been determined in human
urine samples without pretreatment (Braman, et al., 1977; Crecelius,
1977b).
2.2.2 Analytical methods
2.2.2.1 Methods for total arsenic
One early very common method for the determination of total
arsenic was the Gutzeit method (Vogel, 1955).
Spectrophotometry using the silver diethyldithiocarbamate (SDDC)
complex of arsine is the classical method for determining arsenic in
the 1-100 microgram range (Vasak & Sedivec, 1952). Arsenic is reduced
to arsine by either granular zinc in hydrochloric acid or by sodium
borohydride. Arsine reacts with SDDC in pyridine and the absorption of
the red coloured complex is read at 533 nm. Methylarsine and
dimethylarsine, but not trimethylarsine, form SDDC complexes which
absorb at 533 nm, but their complexes have lower molar absorptivities.
A large number of studies can be found in the literature
concerning the use of the SDDC method as it is often designated a
standard method of analysis (Stratton & Whitehead, 1962). Some more
recent papers include one in which the somewhat disagreeable pyridine
solvent was replaced by L-erythro-2-(methylamine)-1-phenylpropan-1-ol
(L-ephedrine) in chloroform (Hundley & Underwood, 1970; Gastiner,
1972; Kopp, 1973). Ionic interference in the SDDC procedure has been
studied by Sandhu & Nelson (1978).
The arsenate ion reacts with ammonium molybdate to form a complex
which, when reduced, gives a blue colour (Portmann & Riley, 1964).
Under favourable conditions, the limit of detection is near 0.1 µg. An
adaptation of the method has been used to determine the amounts of
phosphate, arsenate, and arsenite in sea water (Johnson & Pilson,
1972). The method is applicable to sea water samples with arsenic
concentrations below 3 × 10-6 mol/litre. Precision is of the order of
± 0.015 × 10-6 mol/litre.
Atomic absorption spectrophotometry (AAS) is gaining in popularity
as a method for the determination of total arsenic. Sensitivity of the
ordinary flame type AAS for arsenic in solution is comparatively poor,
detection limits are in the 0.5-1 mg/litre range (Holak, 1969;
Kirkbright & Ranson, 1971). When an electrodeless discharge lamp and
an argon-air-hydrogen flame are used, the detection limit is reduced
to 0.1 mg/litre (Menis & Rains, 1969). With a long-path cell, the
detection limit is about 6 µg/litre (Ando et al. 1969). Arsine can
also be passed into a heated graphite or quartz furnace mounted in an
AAS instrument. The arsine can be continuously passed through the
atomizer (Smith, 1975; Siemer et al., 1976) or collected in a cold
trap and passed through rapidly when the cold trap in heated (Griffin
et al., 1975; McDaniel et al., 1976). This second technique provides
the best detection limits which are in the fraction of a ng range
(Siemer & Koteel, 1977).
Neutron activation analysis is one of the more sensitive
analytical methods. The arsenic-75 isotope is converted to arsenic-76
by thermal neutron absorption. Detection limits are near 1 ng, but the
method is susceptible to interference, particularly from sodium. There
have been many applications of this method in the analyses of
biological samples (Takeo & Shibuya, 1972; Heydorn & Damsgaard, 1973;
Maruyama & Komiya, 1973; Orvini, et al., 1974), water (Ray & Johnson,
1972) and particulate matter in air (Walsh et al., 1977b). Activated
sample solutions are frequently subjected to separation to eliminate
interfering radioisotopes (Gallorini, et al., 1978).
The determination of trace amounts of arsenic has also been
performed using differential pulse polarography and anodic stripping
voltametry (Arnold & Johnson, 1969; Myers & Osteryoung, 1973; Davis,
et al., 1978). The second of these methods was applied to biological
samples that were wet ashed with nitric, sulfuric, and perchloric
acids before distillation of arsenic as arsenic(III) chloride. The
detection limit was in the ng range. Some of the organoarsenic
compounds are also electroactive (Elton & Gieger, 1978) but no
practical methods for environmental analyses have appeared since mg/kg
concentrations are required to observe responses.
A variety of other analytical methods have been successfully used
for the determination of trace amounts of arsenic. Among these are:
atomic emission spectroscopy (Kirkbright et al., 1973; Braman et al.,
1977; Robbins et al., 1979), X-ray fluorescence (Thomson, 1975), and
isotope dilution mass spectrometry (Zeman et al., 1964).
Recently an electron spectroscopic method (ESCA) has been reported
in which arsine collected on filter surfaces was analysed (Carvalho &
Hercules, 1978). Detection limits were in the ng range so that
preconcentration resulted in further reduction of detection limits to
sub µg/kg.
A recent enzyme method gave reasonable results in the
0.02-2.0 mg/kg range (Goode & Matthews, 1978).
Very recently, a small interlaboratory comparison study on the
determination of total urinary arsenic was performed with the
participation of 4 laboratories using different analytical procedures
(NAA and AAS). Ten samples containing arsenic concentrations of
between 0.001 and 1 mg/litre were examined (Buchet et al., in press).
2.2.2.2 Analyses for specific arsenic compounds
Low concentrations of inorganic arsenic(III) and arsenic(V) in sea
water can be determined using the molybdenum blue method (Johnson &
Pilson, 1972). Inorganic arsenic(III) and (V) can be separated by
direct extraction with toluene of acidified aqueous solutions
containing, for example, cysteine (Lauwerys et al., 1979).
Differentiation between arsenic(III) and arsenic(V) is also possible
using pH sensitive, selective reduction with sodium borohydride
followed by atomic emission spectroscopy or AAS detection. Inorganic
and methylarsenic compounds are reduced according to the reactions
shown in Table 2. By buffering at pH 4, reduction of arsenic(V) is
avoided. At pH 1.5, all compounds are reduced. The methylarsine
compounds produced may be cold trapped, separated, and detected
individually. Cold trapping and separation on heating, with detection
by d.c. discharge in helium, has been used in the determination of
arsenic in natural water, human urine (Braman et al., 1977; Crecelius,
1977b) and sea water (Johnson & Braman, 1975b; Andreae, 1977) at µg/kg
and sub µg/kg concentrations. The detector cell has recently been
studied and improved (Feldman & Batistoni, 1977) as has the analysis
train (Crecelius, 1978).
Table 2. Reduction reactions of inorganic and methylarsenic compounds
Compound pKa1 pH Product B.P.
arsenous acid (meta) 9.23 < 7 AsH3 -55°C
(HAsO2)
arsenic acid (ortho) 2.20 > 4.0 no reaction
(H3AsO4) 1.5 AsH3 -55°C
methylarsonic acid 4.1 > 5.0 little reaction
(CH3AsO(OH)2) 1.5 CH3AsH2 2°C
dimethylarsinic acid 6.2 1.5 (CH3)2AsH 36°C
((CH3)AsO(OH))
trimethylarsine oxide -- 1.5 (CH3)3As 70°C
(CH3)3AsO
phenylarsonic acid 1.5 C6H5AsH2 148°C
(C6H5AsO(OH)2)
p-aminophenyl arsinic -- 1.5 H3+ N C6H4 AsH2 --
acid (arsanilic acid)
p-H2N-C6H4AsO(OH)2
Gas chromatographic detection of arsines trapped in cold toluene
solvent using a microwave stimulated plasma detector has been
developed by Talmi & Norvell (1975). The detection limits of this
method are excellent (about 20 pg).
The electrochemical reactions of dimethylarsinic acid and
trimethylarsine were studied by Elton & Geiger (1978). Dimethylarsinic
acid may be converted to its iodide and determined by gas
chromatography (Söderquist, et al., 1974) but the method is not
applicable to the same wide range of arsenic compounds as the
hydride-generating procedures.
Arsenic has been determined in marine organisms (Portmann & Riley,
1964). Substantial efforts have been made to identify the different
organic arsenic compounds and, only recently, arsenobetaine was
identified in rock lobsters (Edmonds et al., 1977) and
arsenophospholipids in algae (Cooney et al., 1978). Analytical methods
for the determination of these compounds are not well developed. Thin
layer chromatography was used in studies by Lunde (1977), the results
of which indicated the possible presence of several as yet
unidentified organic arsenic compounds.
Analytical methods for the determination of total arsenic and
different forms of arsenic in human biological materials have recently
been reviewed by Lauwerys et al. (1979).
3. SOURCES AND OCCURRENCE OF ARSENIC IN THE ENVIRONMENT
3.1 Natural Occurrence
3.1.1 Rocks, soils, and sediments
Arsenic is widely distributed in a large number of minerals. The
highest mineral concentrations generally occur as arsenides of copper,
lead, silver, or gold or as the sulfide. Major arsenic-containing
minerals are arsenopyrite (FeAsS), realgar (As4S4), and orpiment
(As2S3). The arsenic content of the earth's crust is 1.5-2 mg/kg; it
ranks 20th in abundance in relation to other elements (NAS, 1977).
Oxidized forms of arsenic are usually found in sedimentary deposits.
The elemental oxidation state, though stable in reducing environments,
is rarely found. Table 3 gives some ranges of the arsenic contents of
crustal materials. Although the values shown are generally low,
mineralized zones of sulfidic ores may contain much higher
concentrations of arsenic.
Table 3. Arsenic in crustal materialsa
Type Range
As (mg/kg)
Igneous rocks
ultrabasic 0.3-16
basalts 0.06-113
andesites 0.5-5.8
granitic 0.2-13.8
silicic, volcanic 0.2-12.2
Sedimentary rocks
limestones 0.1-20
sandstones 0.6-120
shales and clay 0.3-490
phosphorites 0.4-188
a From: NAS (1977).
High levels of arsenic may also occur in some coals. The average
arsenic content of coal in the USA was estimated at 1-10 mg/kg (Davis
& Associates, 1971). In some coal mined in Czechoslovakia, the
concentration of arsenic has been shown to be as high as 1500 mg/kg
(Cmarko, 1963).
Uncontaminated soils were found to contain arsenic levels between
0.2 and 40 mg/kg, while arsenic-treated soils contained up to
550 mg/kg (Walsh & Keeney, 1975). The soil in the city of Antofagasta,
Chile, contains natural levels of arsenic of about 3.2 mg/kg (Borgono
& Greiber, 1972). In the Comarca Lagunera, Mexico, values between 3
and 9 mg/kg were found at the soil surface and more than 20 mg/kg,
deep down (Gonzalez, 1977).
Peat may contain considerable quantities of arsenic. Minkkinen &
Yliruokanen (1978) found maximum arsenic concentrations in various
Finnish peat bogs of between 16 and 340 mg/kg dry peat.
The natural level of arsenic in sediments is usually below
10 mg/kg dry weight (Crecelius, 1974). Bottom sediments can become
substantially contaminated by arsenic from man-made sources. Levels of
up to 10 000 mg/kg dry weight were found in bottom sediments near a
copper smelter in Washington, USA (Crecelius, 1974).
3.1.2 Air
Airborne particulate matter has been shown to contain both
inorganic and organic arsenic compounds (Johnson & Braman, 1975a;
Attrep & Anirudahn, 1977). Crecelius (1974) showed that only 35% of
the inorganic arsenic in rain from an urban area was present as
arsenite; however, some post-sampling oxidation could not be excluded.
In studies by Johnson & Braman (1975a), methylarsines made up
approximately 20% of the total arsenic in ambient air from rural and
urban areas.
In unpolluted areas, airborne arsenic concentrations ranging from
less than one to a few nanograms per cubic metre have been reported
(Peirson, et al., 1974; Johnson & Braman, 1975a; Walsh, et al., 1977b;
Beavington & Cawse, 1978; Brimblecombe, 1979).
3.1.3 Water
Arsenic occurs in both inorganic and organic forms in water
(Braman & Foreback, 1973; Crecelius, 1974). The main organic arsenic
species, methylarsonic acid and dimethylarsinic acid, are generally
present in smaller amounts than the inorganic forms, arsenite and
arsenate. The chemistry of arsenic in the aqueous environment has been
reviewed by Ferguson & Gavis (1972).
The arsenic contents of surface waters in unpolluted areas vary
but typical values seem to be a few micrograms per litre or less. In a
study of river waters in the USA, about 80% of the samples contained
levels of less than 0.01 mg/litre (Durum et al., 1971). Quentin &
Winkler (1974) found an average value of 0.003 mg/litre in river water
and 0.004 mg/litre in lake water in the Federal Republic of Germany. A
mean arsenic concentration of 0.0025 mg/litre was reported in some
Norwegian rivers (Lenvik et al., 1978). Much higher values have been
reported from some areas including Antofagasta, Chile, where the
average arsenic level in a river water supply of drinking water
between 1958 and 1970 was 0.8 mg/litre (Borgono et al., 1977).
The oxidation state of arsenic in surface waters in various parts
of the world remains largely unknown. Braman & Foreback (1973) found
that the ratio of trivalent to pentavalent inorganic arsenic ranged
from < 0.06 to 6.7 in a few uncontaminated surface water samples
containing between 0.0025 and 0.0030 mg As/litre. About 8% of the
total arsenic in 2 samples of well-aerated stream water (0.014 and
0.06 mg/litre, respectively) was reported by Clement & Faust (1973) to
be in the trivalent form. In anaerobic reservoirs, all of the arsenic
present (0.14-1.3 mg As/litre) seemed to be in this form.
Penrose et al. (1977) reported that sea-water ordinarily contains
arsenic concentrations ranging from 0.001-0.008 mg/litre. Levels of
about 0.002 mg/litre have been reported by Onishi (1969) and Johnson &
Braman (1975b). The major chemical form of arsenic appears to be the
thermodynamically stable arsenate ion; even so, arsenite often
accounts for one third of the total arsenic (Johnson, 1972; Andreae,
1978).
Clement & Faust (1973) analysed water from 2 groundwater supplies
with very high levels of arsenic (224 and 280 mg/litre) and found that
about 50% was present as arsenic(III). In a groundwater-fed stream,
26% of the total arsenic (0.08 mg/litre) was in the form of trivalent
arsenic. Arsenic speciation has also been performed on well water
samples from an area in Alaska containing high levels of arsenic
(Harrington et al., 1978). In 5 samples containing arsenic
concentrations ranging from 0.52 to 3.6 mg/litre, between 3% and 39%
of the arsenic present was trivalent, the rest being pentavalent. No
methylated arsenic compounds could be detected.
High levels of arsenic have been found in waters from areas of
thermal activity. Thermal waters in New Zealand have been shown to
contain up to 8.5 mg/litre (Ritchie, 1961). Geothermal water in Japan
contained arsenic levels of 1.8-6.4 mg/litre and neighbouring streams
contained about 0.002 mg/litre (Nakahara et al., 1978).
The chemical forms of arsenic in thermal water from New Zealand
were investigated by Aggelt & Aspell (1978). In the geothermal bores,
more than 90% of the arsenic was present in the trivalent form.
However, in a river flowing through the area, the pentavalent form was
predominant but some seasonal variation in the ratio between the two
valence states was indicated.
3.1.4 Biota
The sorption of arsenate ions in the soil by iron and aluminum
components, greatly restricts the availability of arsenic to plants
(Walsh et al., 1977a). The arsenic content of plants grown on soils
that had never been treated with arsenic-containing pesticides varied
from 0.01 to about 5 mg/kg dry weight (NAS, 1977). Plants grown on
arsenic-contaminated soils may, however, contain considerably higher
levels, especially in the roots (Walsh & Keeney, 1975; Grant & Dobbs,
1977; Wauchope & McWhorter, 1977). Some grasses growing on soils
containing high levels of arsenic have been found to have elevated
arsenic contents (Porter & Peterson, 1975). Andersson & Nilsson (1972)
reported that arsenic in soils treated with sewage sludge was highly
available to plants, but only a few samples were analysed. In
contrast, Furr et al. (1976) claimed that soil arsenic is not readily
available to plants.
Marine algae and seaweed usually contain considerable amounts of
arsenic. Lunde (1970) showed values of 10-100 mg/kg dry weight in
marine algae from the Norwegian coast. The degree of enrichment was
found to be between 1500 and 5000 compared with the level of arsenic
in the growth medium (Lunde, 1973a). Similar and even higher
enrichment ratios were reported for fresh water plants in the Waikato
River, New Zealand (Reay, 1972). The elevated arsenic concentrations
in the water (0.03-0.07 mg/litre) gave rise to concentrations of up to
971 mg As/kg dry weight in aquatic plants.
3.2 Industrial Production and Uses of Arsenic
3.2.1 Industrial production
Based on the limited data available (US Bureau of Mines, 1975;
Nelson, 1977), it can be estimated that the total world production in
1975 was around 60 000 tonnes. This production seems to be stable. The
main producers are: China, France, Federal Republic of Germany,
Mexico, Namibia, Peru, Sweden, USA, and USSR. These countries account
for about 90% of the production. For a more detailed discussion of
production of arsenic and its compounds, see IARC (1980).
Arsenic(III) oxide, the major basic chemical of the arsenic
industry, is emitted as a by-product in smelting, mainly of copper and
lead ores. It is recovered from the flue dust in a reasonably pure
form.
3.2.2 Uses of arsenic compounds
Arsenic compounds are mainly used in agriculture and forestry
(NAS, 1977). Much smaller amounts are used in the glass and ceramics
industry and as feed additives and drugs. The use pattern for
arsenic(III) oxide in 1975-78 has been reported as follows:
manufacture of agricultural chemicals (pesticides), 82%; glass and
glassware, 8%; industrial chemicals, copper and lead alloys, and
pharmaceuticals, 10% (US Bureau of Mines, 1979).
In agriculture, compounds such as lead arsenate, copper
acetoarsenite, sodium arsenite, calcium arsenate, and organic arsenic
compounds are used as pesticides. Substantial amount of methylarsonic
acid and dimethylarsinic acid are used as selective herbicides. These
herbicides are particularly necessary for the control of Johnson grass
(Sorghum halepense) in cotton fields. They are also used to treat
other weeds such as sandbur ( Cenchrus sp.), cocklebur
( Xanthium sp.) and crabgrass in lawns (Weed Science Society of
America, 1974). Dimethylarsinic acid is used as a silvicide in forest
control and workers may be exposed to the compound and its volatile
reaction products in the soil (Wagner & Weswig, 1974). Dimethylarsinic
acid was the Agent Blue used in Viet Nam as a defoliant for military
purposes.
Chromated copper arsenate, sodium arsenate, and zinc arsenate are
used as wood preservatives (Lansche, 1965). When these compounds are
applied under pressure they react with the wood to create water
insoluble compounds. The preserved timber is resistant to both fungal
and insect attack (Dobbs et al., 1976). The use of arsenic in wood
preservatives is increasing.
Some phenylarsenic compounds such as arsanilic acid are used as
feed additives for poultry and swine and to combat certain diseases in
chickens.
Small amounts of arsenic compounds continue to be used as drugs in
some countries. Other applications of arsenic are found in metallurgy,
where it is used to dope germanium and silicon or in the production of
gallium arsenide or indium arsenide.
3.2.3 Sources of environmental pollution
The burning of coal and smelting of metals are major sources of
arsenic in air. A British study showed yearly average concentrations
in suspended matter in town air of 0.04-0.14 µg/m3 (Goulden et al.,
1952). In Prague, Vondracek (1963) found a winter mean concentration
in air of 0.56 µg/m3 and a summer mean of 0.07 µg/m3. In urban areas
in the USA, air concentrations of arsenic ranged from below the
detection limit (0.01 µg/m3) to 0.36 µg/m3 on a quarterly average
basis in 1964 (Sullivan, 1969). In 1974, about 200 of the 280 US
National Air Surveillance Network sites recorded quarterly average
concentrations below 0.001 µg/m3 (Thompson, 1977). Only 13 sites,
mainly highly urbanized areas and smelter locations, showed levels
exceeding 0.02 µg/m3.
In the vicinity of smelters, levels of arsenic in air exceeding
1 µg/m3 have been recorded. Rozenshtein (1970) found levels of
airborne arsenic, given as arsenic(III) oxide, of 0.7-2.5 µg/m3
(i.e., 0.5-1.9 µg As/m3) within 4 km of a copper smelter in the USSR.
Data were not given on the duration of sampling. In the USA, quarterly
average levels of up to 1.4 µg/m3 were reported in El Paso, Texas, at
the site of a large copper smelter (Sullivan, 1969). Near a copper
smelter in Tacoma, Washington, monthly averages of arsenic in air of
up to 1.46 µg/m3 were recorded (Nelson, 1977) and a maximum 24-h
concentration of 7.9 µg/m3 was reported by Roberts, et al. (1977).
Daily mean concentrations of up to 1.6 µg/m3 were found in the air
near a smelter in Romania (Gabor & Coldea, 1977). Auermann et al.
(1977) reported airborne arsenic concentrations in a polluted region
of the German Democratic Republic ranging from 0.9-1.5 µg/m3 (average
0.9 µg As/m3; duration of sampling not stated). In the vicinity of a
Canadian gold mine, where ore was roasted, annual mean arsenic
concentrations in ambient air ranged from 0.06 to 0.09 µg/m3 between
1973 and 1975 (Hazra & Prokupok, 1977). Individual 24-h arsenic
concentrations varied from less than 0.01 to 3.91 µg/m3. The
concentrations of arsenic in flue dust from a coal-fired power plant
in Czechoslovakia ranged from 43 to 110 mg/kg (Zdrazil & Picha, 1966).
In fly ash from 24 US coal-fired power plants, the arsenic
concentrations ranged between 2.3 and 312 mg/kg (Kaakinen et al.,
1975; Furr et al., 1977).
In the stack dust from nonferrous smelting operations, arsenic is
predominantly in the trivalent inorganic form (Crecelius, 1974,
Rosehart & Chu, 1975). No conclusive data on the extent of oxidation
of airborne trivalent arsenic are available at present.
A thorough study has been made of arsenic in the environs of a
copper smelter near Tacoma, WA, USA (Crecelius, 1974). Dated segments
of sediment cores showed that the arsenic buildup started with the
operation of the smelter. Less than 30% of the arsenic entering
neighbouring waterways accumulated in the sediments. The remaining 70%
presumably left the location in solution. Elevated concentrations of
arsenic were found in water in locations within 2-4 km of the smelter.
Analyses of air, rain water, and snow all indicated elevated arsenic
levels in the Tacoma, Washington area, attributable to the smelter
effluent. Levels of up to 380 mg/kg (dry weight) were found in top
soil in the vicinity of the plant.
A similar pattern, was observed in a study of the distribution of
arsenic from a copper smelter in Sweden (Lindau, 1977). The arsenic
concentrations in air a few kilometres from the smelter were higher
than normal, as were arsenic levels in the soil, moss, and nearby
natural water bodies.
Suzuki et al. (1974) reported concentrations of arsenic of up to
2470 mg/kg in soil near a smelter in Japan.
Attrep & Anirudhan (1977) found a quarterly average total arsenic
concentration in air of 0.08 µg/m3 in an area polluted by arsenic
from defoliants. About half of the airborne arsenic was in the form of
organic arsenic compounds. Four years later, during a season of low
arsenic use, a monthly average of 0.009 µg/m3 was detected in the
same area. At this time, only about 15% of total airborne arsenic was
in the form of organoarsenic compounds.
Burning of wood treated with arsenic-containing preservatives,
mainly inorganic pentavalent compounds, can result in the release of
arsenic into the atmosphere. The concentration of arsenic in the
combustion fumes is closely related to the temperature. Smouldering of
wood, treated with inorganic arsenic salts, at a temperature of 415°C
resulted in volatilization of 8.6% of the total arsenic in the wood
(Watson, 1958). When wood treated with a preservative containing
inorganic pentavalent arsenic salts was burned at temperatures of
700-800°C, about 50% of the arsenic was present in the ashes (the rest
was mainly in the smoke), while at 1000°C only about 15% remained in
the ashes (Öhman, 1960).
The use of geothermal energy can result in severe arsenic
contamination. Crecelius, et al. (1976) found that the natural arsenic
level 0.002 mg/litre had increased 1000 times in a water reservoir in
which some of the discharge from a Mexican geothermal power plant was
emitted. Between 6% and 51% of the total arsenic in this reservoir was
present as trivalent inorganic arsenic and the rest as pentavalent.
The emissions of arsenic into the environment from the plant totalled
about 60 kg/day. In El Salvador, water from a reservoir near a
geothermal power plant contained an arsenic level of 8.9 mg/litre
(Jernelöv et al., 1976).
Arsenic is also present in trace amounts in fertilizers. In a
recent study, it was reported that concentrations of up to several
hundred mg/kg were present in some instances (Senesi et al., 1979).
4. ENVIRONMENTAL TRANSPORT AND DISTRIBUTION
4.1 General
Most environmental transformations of arsenic appear to occur in
the soil, in sediments, in plants and animals, and in zones of
biological activity in the oceans. Biomethylation and bioreduction are
probably the most important environmental transformations of the
element, since they can produce organometallic species that are
sufficiently stable to be mobile in air and water. However, the
biomethylated forms of arsenic produced are subject to oxidation and
bacterial demethylation back to inorganic forms.
The biomethylation of arsenic was first recognized long ago when
arsines were produced from cultures of a fungus Scopulariopsis
brevicaulis (Challenger, 1945). This work was done in an
investigation of poisoning incidents attributed to arsenic-containing
wall paper -- thought to contain Paris Green colouring pigment. It was
eventually ascertained that methylarsines were the toxic agents. More
recently, the methylation of arsenic by methanogenic bacteria (McBride
& Wolfe, 1971) and by reaction with methylcobalamine (Schrauzer
et al., 1972) or L-methionine-methyl-d3 (Cullen et al., 1977) has
been demonstrated in laboratory work. McBride et al. (1978) reported
that dimethylarsine was mainly produced by anaerobic organisms, while
trimethylarsine resulted from aerobic methylation. The following
mechanism for the methylation of arsenate has been proposed by
Challenger (1945) and McBride et al. (1978).
2e CH3+ 2e CH3+
AsVO43- --->ÄsIIIO33- --->CH3AsVO32- --->CH3ÄsIIIO22- --->
--O2- --O2-
2e CH3+ 2e
(CH3)2AsVO2- --->(CH3)2ÄsIIIO- --->(CH3)3AsVO --->(CH3)3ÄsIII
--O2- --O2-
The proposed mechanism indicates that As(V) has to be reduced to
As(III) before being methylated.
4.2 Aquatic Systems
Studies on the molecular forms of arsenic compounds in sea water
have been reported. The concentration ratio As(III)/As(V) was found to
be 0.18 in some Sargasso sea water (Johnson & Braman, 1975b).
Fluctuations in the As(III)/As(V) ratio from 0.02 to 0.09 in the
saline water of Naragansett Bay appeared to be associated with
phytoplankton activity (Johnson & Burke, 1978). Sea water samples off
southern California also exhibited a variable As(III)/As(V) ratio,
again associated with biological activity (Andreae, 1977). In some
instances, the arsenic(III) concentrations exceeded those of
arsenic(V). The same type of biological activity was observed in
natural fresh waters (Braman & Foreback, 1973; Clement & Faust, 1973).
It is evident that the presence of arsenic(III) compounds is the
result of some reductive activity, which could be either biological or
a non-biological effect of dissolved organic matter on arsenic(V).
The oxidation rate of arsenic(III) in Sargasso seawater was
studied under carefully controlled laboratory conditions by Johnson &
Pilson (1975). Temperature, pH, salinity, and the presence of light
all influenced the rate of arsenite oxidation.
The finding of methylarsenic acids in seawater and fresh natural
water is evidence that arsenic goes through reactions other than
simple oxidation or reduction. In both sea and fresh water, the
occurrence of methylarsenic compounds is associated with phytoplankton
activity. In fresh water, the levels of methylarsenic compounds were
especially high in locations where nutrients from fertilizers
(presumably, also containing arsenic) had built up in lakes and ponds.
There is little evidence that sediments play a substantial role in the
methylation of arsenic (Braman, 1975). Sediment samples from two
natural water environments did not contain unusually large amounts of
methylarsenic compounds.
The analysis of biota associated with Sargassum weed indicated
that substantial amounts of arsenic were present in forms other than
the inorganic or methylarsenic forms (Johnson & Braman, 1975b). Only
small amounts of methylarsenic acid type compounds were present in the
organisms.
The involvement of arsenic in the biochemistry of marine organisms
through production of arsenobetaine, arsenocholine, and
arsenophospholipids is a new and only partially explored aspect of the
local cycle. Much work has been done in an effort to identify arsenic
compounds in marine organisms (Edmonds et al., 1977; Irgolic et al.,
1977; Lunde, 1977; Penrose et al., 1977; Cooney et al., 1978).
4.3 Air-soil Systems
It has already been mentioned (section 3) that large quantities of
arsenic compounds are used in agriculture and are initially
distributed in the soil. This is an important aspect of arsenic
distribution in the environment. The occurrence and distribution of
arsenic in soils and plants have been reviewed by Walsh et al.
(1977a). Arsenic is converted to arsenates except under highly
reducing conditions. Arsenate ions are readily sorbed by hydrous
oxides of iron and aluminum and thus leaching of arsenate is slow.
Absorption appears to be a major factor in the retention of arsenic in
soils.
Slow removal of arsenic from the soil is of concern, when old
orchards previously treated with arsenic are used for crop growing
(Bishop & Chisholm, 1962). High arsenic levels can cause a depression
in plant growth but the amounts required to produce this effect depend
on the plant species. Bioaccumulation of arsenic in food crops is not
particularly high.
Methylarsines are released into the air from soil treated with
various arsenic compounds. Dimethylarsine and trimethylarsine were
detected over grass areas treated with the methylarsenic compounds,
soon after application. Methylarsines evolved much more slowly from
grass treated with sodium arsenite (Braman, 1975). Despite these
observations in locations where arsenic was obviously volatilized into
the air following biomethylation, the amounts of methylarsenic
compounds actually found in unpolluted air appear to be small. In one
study, approximately 15% of the total arsenic in outdoor air was in a
methylated form (Johnson & Braman, 1975a). The total arsenic was much
greater in greenhouse air than in ambient air outside and the
methylarsenic forms were much in excess of inorganic forms.
A proposed model of an air-soil arsenic system is shown in
Fig. 1. The system has little chance of being in apparent equilibrium,
since air transport of transpired volatile arsenic is rapid, compared
with evolution rates. Because of lack of data concerning arsenic
compounds in air, especially in locations with arsenic-rich soils, the
rates of evolution and buildup of arsenic in air are not known. A
pseudo-equilibrium can be approached if the air transported into a
site is equivalent to the air transported away from a site. This cycle
is similar to one developed for an agronomic ecosystem, in which
arsenic pesticides were the input (Sandberg & Allen, 1975). The most
important translocation factors were absorption by soil and oxidation,
uptake by vegetation, and volatilization after biomethylation.
5. LEVELS OF EXPOSURE TO ARSENIC AND ITS COMPOUNDS
Identification of the form in which arsenic occurs has only
recently become part of the determination of arsenic in various
environmental media. Generally, only total arsenic concentrations have
been measured. In several reports however, the concentration of
arsenic has been expressed as arsenic(III) oxide, even though the
exact nature of the compound has not been determined. An attempt has
been made in this section to distinguish between the various forms of
arsenic, where sufficient knowledge exists. Unless specifically noted,
the concentrations given in this section refer to elemental arsenic.
The levels should be considered tentative as, in most instances, the
accuracy of the analytical methods has not been assured.
5.1 General Population Exposure through Air, Drinking-Water,
Food, and Beverages
5.1.1 Air
From data on air concentrations of arsenic in unpolluted areas
(section 3.1.2), it can be calculated that the amount of arsenic
inhaled per day is about 0.05 µg or less (assuming that about 20 m3
of air is inhaled per day). However, in areas where coal with a high
arsenic content is used in power plants, or in the vicinity of
smelters, the intake of arsenic may be considerably higher. Airborne
arsenic levels of about 1 µg/m3, have been detected in such areas,
(section 3.2.3), which would result in the inhalation of approximately
20 µg of arsenic per day.
The amount of arsenic absorbed from the lungs depends on particle
size and the chemical form of the arsenic. Analysis of arsenic in
airborne fly ash from coal-fired power plants indicated that the
highest concentration was associated with respirable particles. On a
mass basis, 76% of the arsenic present was recovered from particles
with a diameter of less than 7.3 µm (Natusch et al., 1974).
5.1.2 Drinking-water
The natural concentration of total arsenic in drinking-water
varies in different parts of the world. McCabe et al. (1970)
investigated more than 18 000 community water supplies in the USA and
found that less than 1% had arsenic levels exceeding 0.01 mg/litre. In
a report by Grantham & Jones (1977) on arsenic concentrations in water
from more than 800 wells in Nova Scotia, Canada, 13% had arsenic
levels exceeding 0.05 mg/litre. Apparently, some of these wells had
been contaminated by gold-mining activities in previous years. In some
areas where chronic arsenic poisoning has occurred, levels exceeding
1 mg/litre have been recorded in well water. In the region of Cordoba,
Argentina, Arguello et al. (1938) reported maximum levels of arsenic
of between 0.9 and 3.4 mg/litre. Artesian well water in the Tainan
county of the Province of Taiwan contained up to 1.8 mg/litre (Kuo,
1968). Well waters in Oregon also contained elevated levels of arsenic
(0.07-1.7 mg/litre) (Goldblatt, et al., 1963).
Drinking-water can be severely contaminated through industrial
operations. In the city of Torreon, Mexico, Espinosa González (1963)
reported that levels of arsenic in drinking-water from a deep well
ranged from 4 to 6 mg/litre. In Niigata, Japan, waste water from a
factory producing arsenic sulfide contaminated nearby well water, and
arsenic levels up to 3 mg/litre were recorded (Terada, 1960). Leaching
of arsenic from coal preparation wastes and fly ash from coal-fired
power plants may also result in the contamination of water (Williams,
et al., 1977; Chu, et al., 1978).
When considering exposure through drinking water, it is important
to ensure that exposures are assessed for water delivered from the
consumer's tap. Conventional flocculation treatment using either
aluminum or ferric salts removes a high proportion, at least, of
arsenic(V) (Gulledge & O'Connor, 1973).
5.1.3 Food and beverages
Arsenic levels in food, with the exception of some seafoods, are
generally well below 1 mg/kg wet weight (Westöö & Rydälv, 1974).
Marine fish on an average contain below 5 mg/kg wet weight (LeBlanc &
Jackson, 1973; Lunde, 1973b; Leatherland & Burton, 1974; Kennedy,
1976; Stoeppler & Mohl, 1980). Certain bottom feeding fish, crustacea
and shellfish may contain arsenic concentrations of several tens of
milligrams per kilo (Westöö & Rydälv, 1972; Crecelius, 1974; Munro
et al., 1974). Arsenic concentrations of between 0.6 and 58 mg/kg dry
weight, have been found in some food supplements prepared from kelp
(Walkiw & Douglas, 1975). Edible seaweed, a common product in Japan,
has been reported to contain arsenic levels ranging from 19 to
172 mg/kg dry weight with a mean concentration of 112 mg/kg (Watanabe
et al., 1979). The use of some organic arsenic compounds as feed
additives for poultry and swine may lead to accumulation of arsenic in
certain organs (Ledet et al., 1973; Calvert, 1975) (section 6.2.2.2)
and limits of tolerance have been established in the USA for edible
by-products from chickens, turkeys, and swine (Jelinek & Corneliussen,
1977).
Most of the arsenic in marine organisms occurs in the form of
either fat-soluble or water-soluble organoarsenic compounds (Lunde,
1975). The water-soluble compounds are characterized by high chemical
stability. Lunde (1973b) separated inorganic and organic arsenic in
some fish and crustacea from the Norwegian Atlantic coast. The
concentrations of inorganic arsenic (including organic-bound arsenic
degradable by 6.6 M hydrochloric acid) ranged from 1.0 to 2.5 mg/kg
and those of organoarsenic compounds from 3 to 37 mg/kg. Seafood
arsenic, i.e., the major organic arsenic compounds found in seafood,
is not degradable by this treatment. Crecelius (1977b) did not find
any increase in human urinary excretion of inorganic or of simple
methylated arsenic compounds, i.e., methylarsenic acid and
dimethylarsenic acid, following the ingestion of 2 mg of arsenic in
crab meat. This indicated that the inorganic arsenic content of the
crab meat was very low (<1% of the arsenic).
Wine may contain appreciable amounts of arsenic. Noble et al.
(1976) found concentrations between 0.02 and 0.11 mg/litre in 9 US
wines produced between 1949 and 1974. Crecelius (1977a) also
investigated the levels and forms of arsenic in some US table wines.
In over half of the samples, levels greatly exceeded 0.05 mg/litre
(tentative limit in the international drinking water standards
published by WHO). Most of the arsenic present was in the trivalent
form. Arsenate was also found, but no methylated species were
detected. This study indicated that considerable reduction from
arsenate to arsenite occurred during the fermentation of grape juice
by wine yeast. It is probable that the arsenic in the wines originated
mainly from the arsenic-containing insecticides used on the grapes.
Elevated arsenic levels have been found in some bottled mineral
waters. Zoeteman & Brinkmann (1976) reported a mean arsenic
concentration of 0.021 mg/litre (range <0.001-0.19 mg/litre) in
bottled mineral waters sold in countries within the European
Community. In an investigation on lager beers from various countries,
none of the samples contained more than 0.02 mg/litre (Binns et al.,
1978).
5.1.4 Tobacco
The content of arsenic in tobacco grown on soils not treated with
arsenic compounds is usually below 3 mg/kga a (Satterlee, 1956;
Bailey et al., 1957; Hjern, 1961; Griffin et al., 1975). During the
first part of this century, the use of arsenic insecticides, mainly in
the USA, brought about a steady increase in the content of arsenic in
a The weight of a cigarette is approximately 1 g.
tobacco products. In the 1950s, levels of up to 52 mg/kg, given as
As(III) oxide (40 mg As/kg) were found in American cigarettes (Holland
& Acevedo, 1966). However, during the last 20 years the concentrations
of arsenic have decreased to below 8 mg/kg, because of a great
reduction in the use of inorganic arsenic compounds in agriculture. Of
the total arsenic originally present in cigarettes, 10-15% was
recovered in the main stream smoke, the remainder mainly being
distributed in the ash and butt (Thomas & Collier, 1945). Cigarettes
in Japan have been reported to contain arsenic levels of less than
1 mg/kg (Maruyama et al., 1970). The chemical form of arsenic in the
smoke has yet to be elucidated.
5.1.5 Drugs
Both inorganic and organic arsenic compounds have been widely used
in medicine. Arsenical Solution, also called Liquor Arsenicalis,
Solutio Kalii Arsenitis or Fowler's Solution, contained arsenic(III)
oxide dissolved in potassium hydroxide, neutralized with hydrochloric
acid and diluted with chloroform water (Martindale, 1977). The arsenic
administered was thus in the form of arsenite. The drug ordinarily
contained an arsenic concentration of 7.6 g/litre and the daily dose
of arsenic was sometimes as high as 10 mg (Pearson & Ponds, 1971). It
was used for the treatment of leukaemia, psoriasis, chronic bronchial
asthma, and as a tonic. Other preparations described in the Extra
Pharmacopoeia by Martindale (1977) include various pastes containing
inorganic arsenic in combination with other drugs, such as cocaine or
procaine. Sodium arsenate was formerly used in the treatment of
chronic skin diseases, some parasitic diseases, and anaemia
(Martindale, 1977). Pearson's Arsenical Solution, which contained
about 0.5% arsenic in the form of arsenate, has been included in
several pharmacopoeias. The recommended dose was 1-10 mg of the
arsenate (0.2-2.4 mg As) with a maximum of 20 mg in 24 h. Drugs
containing inorganic arsenic compounds are being phased out and
replaced by more effective and less toxic drugs.
Salvarsan (arsphenamine), an organic arsenic compound containing
32% arsenic, was formerly used in the treatment of syphilis
(Martindale, 1977). Because of the difficulties in preparing it for
injection and because of its high toxicity, it was replaced by
neoarsphenamine. The recommended dose used to be 100-600 mg (32-192 mg
As) administered intravenously. Antibiotics have finally replaced
these drugs. Some organic arsenic compounds including carbarsone,
melarsoprol, and tryparsamide, are still in use in human medicine,
mainly as antiparasitic drugs.
5.1.6 Total daily intake in the general population
Daily intake of arsenic from ambient air and water will ordinarily
be of the order of a few micrograms, predominantly in the inorganic
form (section 5.1.1 and 5.1.2).
As mentioned previously, the total daily dietary intake of arsenic
depends, to a great extent, on the amount of seafood in the diet. A
seafood meal may lead to the ingestion of several milligrams of
arsenic, predominantly in organic forms. The daily intake of total
arsenic in Japan has been reported to be between 0.07 and 0.17 mg
(Nakao, 1960). The US Food and Drug Administration has monitored
arsenic in foodstuffs since 1967 (Jelinek & Corneliussen, 1977). Data
from this programme indicate that the total daily intake of arsenic
has decreased from about 0.05-0.1 mg per day in the late sixties to
0.01-0.02 mg per day in 1972-74. Most of the arsenic was found in the
group "meat, fish, and poultry". From analysis of composites of food
representing the Canadian diet during 1970-73, it was estimated that
the total intake of arsenic was 0.025-0.035 mg daily (Smith et al.,
1972, 1973, 1975). Hamilton & Minski (1973) estimated the total intake
of arsenic in the United Kingdom to be about 0.1 mg/day, based on
analysis of diets containing fish. The considerable variations in the
estimated dietary arsenic intake can be expected because of
differences in the amounts of seafood in the diets investigated.
Moreover, in neither of the reports was a distinction made between the
amount of inorganic and organic arsenic consumed. Because of
differences in metabolism and toxicity (sections 6, 7, and 8), it is
important to distinguish between inorganic and organic forms of
arsenic.
During the 1950s, the smoking of some tobacco, especially from the
US, may have led to inhalation of more than 0.1 mg of arsenic daily.
At present, the arsenic content of most tobacco is much lower and it
can be estimated that less than 0.02 mg may be inhaled by an average
smoker.
Data on the urinary excretion of various arsenic compounds in
individuals not excessively exposed to arsenic can be helpful for
deducing daily intake figures. Inorganic arsenic will be excreted
mainly as inorganic and simple methylated arsenic compounds
(Crecelius, 1977b). Smith et al. (1977) found an average urinary
concentration of these forms of arsenic of 17.5 µg/litre in 41 male
workers in the USA without known occupational exposure to arsenic.
This would correspond to an intake of 0.025-0.040 mg of inorganic
arsenic per day.
5.2 Occupational Exposure
Occupational exposure to arsenic compounds takes place mainly
among workers, especially those involved in the processing of copper,
gold, and lead ores. Occupational exposure may also occur among
workers using or producing arsenic-containing pesticides.
Unfortunately, very few data exist on the actual air levels of arsenic
to which persons in such occupations have been exposed. This is also
the case for wood treatment plant workers and carpenters, who may
become exposed to inorganic arsenic compounds (mainly pentavalent)
through their use as wood preservatives (section 3.2.2).
In a plant where sodium arsenite was being manufactured, Perry et
al. (1948) found mean air arsenic concentrations of between 0.078 and
1.034 mg/m3 around various workstations during sampling times of
"10 minutes or more". The respirable fraction (< 5 µm) of the airborne
arsenic ranged from 20% to 38% by mass. Ott et al. (1974) reported
airborne arsenic levels in 1943 of 0.18 to 18 mg/m3 in the packaging
department of a plant where lead arsenate and calcium arsenate
insecticides were produced. In 1952, airborne arsenic levels ranged
between 0.26 and 40.8 mg/m3 in another workplace at the plant. In the
workroom air of a factory producing lead arsenate, Horiguchi et al.
(1976) found levels ranging from 0.01 to 0.9 mg/m3 during the years
1959-70.
When the airborne arsenic in a Swedish copper smelter was
measured, the average concentrations near the roasters, reverberatory
furnaces, and in the converter hall ranged between 0.06 and 2 mg/m3
during sampling times of "several hours" (Lundgren, 1954). No data
were given on the size distribution of the airborne arsenic-containing
particles. At the same Swedish copper smelter Carlsson (1976) found
weighted 8-h average concentrations at different workplaces of between
0.002 mg and 0.23 mg/m3 in the air inhaled by the workers (i.e.,
after filtration in a respirator). The highest exposures were found
among the roasterworkers. Kodama et al. (1976) measured airborne
arsenic concentrations in a copper refinery, where arsenic(III) oxide
was being manufactured. They found levels of between 0.006 and
0.012 mg/m3 when the ventilation was normal, and up to 0.2 mg/m3
when the ventilation was shut off. Around the furnaces in the copper
smelter, average concentrations of between 0.001 and 0.012 mg/m3 were
reported, and around the furnaces in a ferronickel smelter, the
corresponding concentrations were between 0.002 and 0.005 mg/m3.
Smith et al. (1977) described a study at a US copper smelter where
airborne particulate matter was collected in personal exposure
samplers. The concentrations were found to be log-normally
distributed, with a geometric mean of 0.053 mg/m3 in a high exposure
group (i.e., workers in the baghouse, flue, cotterell, stack, and
reverberatory furnace areas). Workers in the concerter area were
exposed to 0.046 mg/m3 (geometric mean). In the high exposure area,
only 32% of the airborne arsenic was respirable (< 5 µm), compared
with over 80% in the converter area. Pinto et al. (1976) reported an
overall mean airborne arsenic concentration of 0.05 mg/m3 (range
0.003-0.3 mg/m3) in the working environment of 24 smelter workers
wearing personal air samplers on 5 consecutive days.
Airborne arsenic particulate matter in smelters is generally
assumed to consist primarily of arsenic(III) oxide. However, it is
probable that some of the arsenic is firmly bound to other metals,
especially in the reverberatory furnace. There is also evidence of the
presence of arsenic sulfides (Smith et al., 1976). The form in which
arsenic is present clearly depends, to a great extent, on the
characteristics of the industrial process involved, such as the
temperature, humidity, and other elements present. More work is
urgently needed to characterize the arsenic compounds by form and size
distribution.
Workers may be exposed to airborne arsenic in cutting and sawing
operations on wood treated with arsenic-containing preservatives.
Arsenault (1977) found concentrations of arsenic in air of 0.043-
0.36 mg/m3 originating from the sawing of wood treated with copper,
chromium, and arsenic salts. The duration of measurement was 100 min.
Only about 5% of the dust particles (on a mass basis) were less than
10 µm.
6. METABOLISM OF ARSENIC
The metabolism of arsenic in man is very complex since the fate of
arsenic compounds in the human body varies with the type of compound.
The metabolism of a compound also varies with animal species, for
example, the metabolism of arsenic in the rat is unique and quite
different from that in man or other mammals. The rat is therefore not
a suitable model for most metabolic pathways in man and the emphasis
in this document has been placed, as much as possible, on data
concerning other experimental animals.
6.1 Inorganic Arsenic
The metabolism of inorganic arsenic depends on its chemical form.
Possible changes in the different forms of inorganic arsenic before
the time of exposure should be considered. Even co