ARSENIC
Anders Permin, Division Manager, PhD
DHI, Centre for Environment and Toxicology
ATV MØDE
ARSEN I GRUNDVAND OG DRIKKEVAND
HELNAN, MARSELIS HOTEL
3. oktober 2007
Background
Arsenic is a semi-metal element in the periodic table with number 33. It is widely distributed
in the Earth’s crust, and has a steel grey metal-like colour. However, arsenic is usually found
in the environment combined with other elements such as oxygen, chlorine, and sulphur.
Arsenic combined with these elements is called inorganic arsenic. Arsenic combined with
carbon and hydrogen is referred to as organic arsenic. Understanding the difference between
inorganic and organic arsenic is important because some of the organic forms are less harmful
than the inorganic forms. Most inorganic and organic arsenic compounds are white or
colourless powders that do not evaporate. They have no smell, and most have no special taste.
Inorganic arsenic occurs naturally in soil and in many kinds of rock, especially in minerals
and ores that contain copper or lead. Arsenic is present in more than 200 mineral species, the
most common of which is arsenopyrite. When these ores are heated in smelters, most of the
arsenic goes up the stack and enters the air as a fine dust1. Smelters may collect this dust and
take out the arsenic as a compound called arsenic trioxide (As2O3). It enters drinking water
supplies from natural deposits in the earth or from agricultural and industrial practices2.
WHO has set the arsenic standard for drinking water at .010 parts per million (10 parts per
billion) to protect consumers served by public water systems from the effects of long-term,
chronic exposure to arsenic3.
Industrial applications
About 90% of all arsenic produced is used as a preservative for wood to make it resistant to
rot and decay. The preservative is copper chromated arsenic (CCA) and the treated wood is
termed as “pressure-treated.” CCA wood still remains widespread in use in many countries. It
was heavily used during the latter half of the 20th century as an outdoor building material,
where there was a risk of rot, or insect infection in untreated wood. Although widespread bans
followed the publication of studies which showed low-level leaching from in-situ wood into
surrounding soil, the most serious risk is probably by the burning of CCA wood. In recent
years fatal animal poisonings have been seen, and serious human poisonings resulting from
the ingestion - directly or indirectly - of wood ash from CCA wood. The lethal human dose is
only approximately 20 grams of ash2.
During the 18th, 19th, and 20th centuries, a number of arsenic compounds have been used as
medicines, including arsphenamine and arsenic trioxide. Arsphenamine as well as
Neosalvarsan was indicated for treatment of syphilis and trypanosomiasis. Arsenic trioxide
has been used in a variety of ways over the past 200 years, but most commonly in the
treatment of cancer. It was also used as Fowler's solution in psoriasis4. In 2000 the Food and
Drug Administration approved Arsenic trioxide for the treatment of patients with acute
promyelocytic leukaemia.
Lead hydrogen arsenate has been used until recently as an insecticide on fruit trees causing
brain damage to the workers. A copper arsenate (Scheele's Green) has been used as a
colouring agent in sweets in the 19th century. In the last half century, monosodium methyl
arsenate (MSMA), a less toxic organic form of arsenic, has replaced lead arsenate's role in
agriculture.
Copper acetoarsenite was used as a green pigment known under many different names,
including 'Paris Green' and 'Emerald Green'. It caused numerous arsenic poisonings of artists.
Emerald Green was a pigment frequently used by Impressionist painters. Cezanne developed
severe diabetes, which is a symptom of chronic arsenic poisoning. Monet's blindness and Van
Gogh's neurological disorders could have been partially due to their use of Emerald Green.
Poisoning by other commonly used substances, including liquor and absinthe, lead pigments,
mercury-based Vermilion, and solvents such as turpentine, could also be a factor in these
cases4.
Contamination of groundwater
Arsenic contamination of groundwater has led to a massive epidemic of arsenic poisoning in
Bangladesh and neighbouring countries. It is estimated that approximately 57 million people
are drinking groundwater with arsenic concentrations elevated above the World Health
Organization's standard of 10 parts per billion3. The arsenic in the groundwater is of natural
origin, and is released from the sediment into the groundwater due to the anoxic conditions of
the subsurface. This groundwater began to be used after NGOs implemented a drinking-water
program based on wells in the 1970ties and 1980ties. This program was designed to prevent
drinking of bacterially contaminated surface waters, but unfortunately the testing for arsenic
in the groundwater failed. Arsenicosis was reported in many other countries and districts in
South East Asia, such as Vietnam, Cambodia, Thailand, Tibet and China. These countries are
thought to have geological environments similarly conducive to generation of high-arsenic
groundwaters as in Bangladesh.
Potency
The LD50 for pure arsenic is 763 mg/kg body weight (by ingestion) and 13 mg/kg (by
intraperitoneal injection). For a 70 kg human, this is about 53 grams. However, compounds
containing arsenic can be significantly more toxic.
Toxicity
Arsenic and many of its compounds are extremely potent poisons. Arsenic disrupts ATP
production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits
succinate dehydrogenase and by competing with phosphate it uncouples oxidative
phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration,
and ATP synthesis. Hydrogen peroxide production is also increased, which might form
reactive oxygen species and oxidative stress. These metabolic interferences lead to death from
multi-system organ failure probably from necrotic cell death, not apoptosis. A post mortem
reveals brick red coloured mucosa, due to severe haemorrhage.
Elemental arsenic and arsenic compounds are classified as "toxic" and "dangerous for the
environment" in the European Union under directive 67/548/EEC.
The IARC recognizes arsenic and arsenic compounds as group 1 carcinogens, and the EU lists
arsenic trioxide, arsenic pentoxide and arsenate salts as category 1 carcinogens5.
Arsenic is known to cause arsenicosis due to its manifestation in drinking water, “the most
common species being arsenate [HAsO42- ; As(V)] and arsenite [H3AsO3 ; As(III)]”. The
ability of arsenic to undergo redox conversion between As(III) and As(V) makes its
availability in the environment possible. The study of chemolithoautotrophic As(III) oxidizers
and the heterotrophic As(V) reducers can help the understanding of the oxidation and/or
reduction of arsenic.
Human exposure to arsenic can cause both short and long term health effects. Short or acute
effects can occur within hours or days of exposure. Long or chronic effects occur over many
years. Most cases of arsenic-induced toxicity in humans are due to exposure to inorganic
arsenic, and there is an extensive database on the human health effects of the common arsenic
oxides and oxyacids. Although there may be some differences in the potency of different
chemical forms (e.g., arsenites tend to be somewhat more toxic than arsenates), these
differences are usually minor. Exposures of humans near hazardous waste sites could involve
inhalation of arsenic dusts in air, ingestion of arsenic in water, food, or soil, or dermal contact
with contaminated soil or water. By the inhalation route, the most sensitive effect of inorganic
arsenic is an increased risk of lung cancer, although respiratory irritation, nausea, and skin
effects may also occur. There are only a few quantitative data on noncancer effects in humans
exposed to inorganic arsenic by the inhalation route. However, it appears that such effects are
unlikely below a concentration of about 0.1–1.0 mg As/m3. Animal data similarly identify
effects on the respiratory system as the primary noncancer effect of inhaled inorganic arsenic
compounds, although only a few studies are available. Only limited data on the effects of
inhaled organic arsenic compounds in humans or animals are available; these studies are
generally limited to high-dose, short-term exposures, which result in frank effects2.
Relatively little information is available on effects due to direct dermal contact with inorganic
arsenicals, but several studies indicate the chief effect is local irritation and dermatitis, with
little risk of other adverse effects2.
The database for the oral toxicity of inorganic arsenic is extensive, containing a large number
of studies of orally-exposed human populations. These studies have identified effects on
virtually every organ or tissue evaluated, although some end points appear to be more
sensitive than others. The available data from humans identify the skin as the most sensitive
noncancer end point of long-term oral arsenic exposure. Typical dermal effects include
hyperkeratinisation of the skin (especially on the palms and soles), formation of multiple
hyperkeratinised corns or warts, and hyperpigmentation of the skin with interspersed spots of
hypopigmentation. Oral exposure data from studies in humans indicate that these lesions
typically begin to manifest at exposure levels of about 0.002–0.02 mg As/kg/day. At these
exposure levels, peripheral vascular effects are also commonly noted, including cyanosis and
gangrene. Other reported cardiovascular effects of oral exposure to inorganic arsenic include
increased incidences of high blood pressure and circulatory problems. In addition to dermal
and cardiovascular effects, oral exposure to inorganic arsenic may result in effects on other
organ systems. Nausea, vomiting, and diarrhoea are very common symptoms in humans
following oral exposure to inorganic arsenicals, both after acute high-dose exposure and after
repeated exposure to lower doses; these effects are likely due to a direct irritation of the
gastrointestinal mucosa. Acute, high-dose exposure can lead to encephalopathy, with clinical
signs such as confusion, hallucinations, impaired memory, and emotional lability, while longterm exposure to lower levels can lead to the development of peripheral neuropathy
characterized by a numbness in the hands and feet that may progress to a painful "pins and
needles" sensation. A recent study also reported decreases in intelligence scores of arsenicexposed children2.
Data on the effects of oral exposure to inorganic arsenic on reproductive end points in humans
are not available. Animal data suggest that arsenic may cause changes to reproductive organs
of both sexes, including decreased organ weight and increased inflammation of reproductive
tissues, although these changes may be secondary effects. However, these changes do not
result in a significant impact on reproductive ability. Chronic exposure of humans to
inorganic arsenic in the drinking water has been associated with excess incidence of
miscarriages, stillbirths, preterm births, and infants with low birth weights, although doseresponse data are not presently available for these effects. Animal studies of oral inorganic
arsenic exposure have reported developmental effects, but generally only at concentrations
that also resulted in maternal toxicity2.
Arsenic is a known human carcinogen by both the inhalation and oral exposure routes. By the
inhalation route, the primary tumour types are respiratory system cancers, although a few
reports have noted increased incidence of tumours at other sites, including the liver, skin, and
digestive tract. In humans exposed chronically by the oral route, skin tumours are the most
common type of cancer. In addition to skin cancer, there are a number of case reports and
epidemiological studies that indicate that ingestion of arsenic also increases the risk of
internal tumours (mainly of bladder and lung, and to a lesser extent, liver, kidney, and
prostate)1,2.
Non-cancer effects can include thickening and discoloration of the skin, stomach pain,
nausea, vomiting; diarrhoea; numbness in hands and feet; partial paralysis; and blindness.
Clinical symptoms
Symptoms include violent stomach pains in the region of the bowels; tenderness and pressure;
retching; vomiting; sense of dryness and tightness in the throat; thirst; hoarseness and
difficulty of speech; the matter vomited, greenish or yellowish, sometimes streaked with
blood; diarrhoea; tenesmus; sometimes excoriation of the anus; urinary organs occasionally
affected with violent burning pains and suppression; convulsions and cramps; clammy sweats;
lividity of the extremities; countenance collapsed; eyes red and sparkling; delirium; death.
Some of these symptoms may be absent where the poisoning results from inhalation, as of
arseniuretted hydrogen.
Symptoms of arsenic poisoning start with mild headaches and can progress to lightheadedness
and usually, if untreated, will result in death.
Arsenicosis - chronic arsenic poisoning from drinking water
Chronic arsenic poisoning results from intake of drinking water with high levels of arsenic
over a long period. Effects include changes in skin colour, formation of hard patches on the
skin, skin cancer, lung cancer, cancer of the kidney and bladder, and can lead to gangrene.
Non-carcinogenic chronic effects include liver injury—jaundice and cirrhosis;—peripheral
vascular disease involving blueness of the extremities; Raynaud's syndrome; blackfoot disease
(a type of gangrene); anemia, resulting from impaired haeme biosynthesis; and hyperkeratosis
of the skin.
Arsenic in seafood
Concerns about the adverse effects of chronic arsenic exposure have focused on contaminated
drinking water and airborne workplace exposures; the risks of naturally occurring arsenic in
foods have received less attention. About 90% of the arsenic in US diets comes from seafood,
of which only a small proportion occurs in inorganic forms; the great majority consists of
complex organic compounds that generally have been regarded as non-toxic. However, recent
studies of seafood have documented formation of metabolites carcinogenic in some rodents6.
Treatment and testing
Chemical and synthetic methods are now used to treat arsenic poisoning. Dimercaprol and
Succimer are chelating agents which sequester the arsenic away from blood proteins and are
used in treating acute arsenic poisoning. The most important side-effect is hypertension. One
way to test for arsenic poisoning is by checking hair follicles. If arsenic is in the bloodstream,
it will enter hair and remain there for many years.
References
1. Anonymous. Arsenic and arsenic compounds. 224 vol., 2001:1-501
2. U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICESPublic Health
ServiceAgency for Toxic Substances and Disease Registry. Draft
Toxicological Profile For Arsenic. 2005.
3. Anonymous. Arsenic fact sheet. 2007.
4. Anonymous. Arsenic. www.wikipedia.org . 2007.
5. Anonymous. Some Drinking-water Disinfectants and Contaminants, including
Arsenic. 2004. IARC Monographs on the Evaluation of Carcinogenic
Risks to Humans.
6. Borak J, Hosgood HD. Seafood arsenic: implications for human risk assessment.
Regul Toxicol Pharmacol. 2007; 47:204-212