Wednesday, 09 February 2011 04:36


Rate this item
(0 votes)

Gunnar Nordberg

There are three major groups of arsenic (As) compounds:

  1. inorganic arsenic compounds
  2. organic arsenic compounds
  3. arsine gas and substituted arsines.


    Occurrence and Uses

    Arsenic is found widely in nature and most abundantly in sulphide ores. Arsenopyrite (FeAsS) is the most abundant one.

    Elemental arsenic

    Elemental arsenic is utilized in alloys in order to increase their hardness and heat resistance (e.g., alloys with lead in shot-making and battery grids). It is also used in the manufacture of certain types of glass, as a component of electrical devices and as a doping agent in germanium and silicon solid-state products.

    Trivalent inorganic compounds

    Arsenic trichloride (AsCl3) is used in the ceramics industry and in the manufacturing of chlorine-containing arsenicals. Arsenic trioxide (As2O3), or white arsenic, is useful in the purification of synthesis gas and as a primary material for all arsenic compounds. It is also a preservative for hides and wood, a textile mordant, a reagent in mineral flotation, and a decolourizing and refining agent in glass manufacture. Calcium arsenite (Ca(As2H2O4)) and cupric acetoarsenite (usually considered Cu(COOCH3)2 3Cu(AsO2)2) are insecticides. Cupric acetoarsenite is also used for painting ships and submarines. Sodium arsenite (NaAsO2) is employed as a herbicide, a corrosion inhibitor, and as a drying agent in the textile industry. Arsenic trisulphide is a component of infrared-transmitting glass and a dehairing agent in the tanning industry. It is also used in the manufacturing of pyrotechnics and semiconductors.

    Pentavalent inorganic compounds

    Arsenic acid (H3AsO4·½H2O) is found in the manufacture of arsenates, glass making and wood-treating processes. Arsenic pentoxide (As2O5), an herbicide and a wood preservative, is also used in the manufacture of coloured glass.

    Calcium arsenate (Ca3(AsO4)2) is used as an insecticide.

    Organic arsenic compounds

    Cacodylic acid ((CH3)2AsOOH) is used as a herbicide and a defoliant. Arsanilic acid (NH2C6H4AsO(OH)2) finds use as a grasshopper bait and as an additive in animal feeds. Organic arsenic compounds in marine organisms occur in concentrations corresponding to a concentration of arsenic in the range 1 to 100 mg/kg in marine organisms such as shrimp and fish. Such arsenic is mainly made up of arsenobetaine and arsenocholine, organic arsenic compounds of low toxicity.

    Arsine gas and the substituted arsines. Arsine gas is used in organic syntheses and in the processing of solid-state electronic components. Arsine gas may also be generated inadvertently in industrial processes when nascent hydrogen is formed and arsenic is present.

    The substituted arsines are trivalent organic arsenical compounds which, depending on the number of alkyl or phenyl groups that they have attached to the arsenic nucleus, are known as mono-, di- or tri-substituted arsines. Dichloroethylarsine (C2H5AsCl2), or ethyldichloroarsine, is a colourless liquid with an irritant odour. This compound, like the following one, was developed as a potential chemical warfare agent.

    Dichloro(2-chlorovinyl-)arsine (ClCH:CHAsCl2), or chlorovinyldichloroarsine (lewisite), is an olive-green liquid with a germanium-like odour. It was developed as a potential warfare agent but never used. The agent dimercaprol or British anti-lewisite (BAL) was developed as an antidote.

    Dimethyl-arsine (CH3)2AsH, or cacodyl hydride and trimethylarsine (CH3)3As), or trimethylarsenic, are both colourless liquids. These two compounds can be produced after metabolic transformation of arsenic compounds by bacteria and fungi.


    Inorganic arsenic compounds

    General aspects of toxicity. Although it is possible that very small amounts of certain arsenic compounds may have beneficial effects, as indicated by some animal studies, arsenic compounds, particularly the inorganic ones, are otherwise regarded as very potent poisons. Acute toxicity varies widely among compounds, depending on their valency state and solubility in biological media. The soluble trivalent compounds are the most toxic. Uptake of inorganic arsenic compounds from the gastrointestinal tract is almost complete, but uptake may be delayed for less soluble forms such as arsenic trioxide in particle form. Uptake after inhalation is also almost complete, since even less soluble material deposited on the respiratory mucosa, will be transferred to the gastrointestinal tract and subsequently taken up.

    Occupational exposure to inorganic arsenic compounds through inhalation, ingestion or skin contact with subsequent absorption may occur in industry. Acute effects at the point of entry may occur if exposure is excessive. Dermatitis may occur as an acute symptom but is more often the result of toxicity from long-term exposure, sometimes subsequent to sensitization (see the section “Long-term exposure (chronic poisoning)”).

    Acute poisoning

    Exposure to high doses of inorganic arsenic compounds by a combination of inhalation and ingestion may occur as a result of accidents in industries where large amounts of arsenic (e.g., arsenic trioxide), are handled. Depending on dose, various symptoms may develop, and when doses are excessive, fatal cases may occur. Symptoms of conjunctivitis, bronchitis and dyspnoea, followed by gastrointestinal discomfort with vomiting, and subsequently cardiac involvement with irreversible shock, may occur in a time course of hours. Arsenic in blood was reported to be above 3 mg/l in a case with fatal outcome.

    With exposure to sub-lethal doses of irritant arsenic compounds in air (e.g., arsenic trioxide), there may be symptoms related to acute damage to the mucous membranes of the respiratory system and acute symptoms from exposed skin. Severe irritation of the nasal mucosae, larynx and bronchi, as well as conjunctivitis and dermatitis, occur in such cases. Perforation of the nasal septum can be observed in some individuals only after a few weeks following exposure. A certain tolerance against acute poisoning is believed to develop upon repeated exposure. This phenomenon, however, is not well documented in the scientific literature.

    Effects due to accidental ingestion of inorganic arsenicals, mainly arsenic trioxide, have been described in the literature. However, such incidents are rare in industry today. Cases of poisoning are characterized by profound gastrointestinal damage, resulting in severe vomiting and diarrhoea, which may result in shock and subsequent oliguria and albuminuria. Other acute symptoms are facial oedema, muscular cramps and cardiac abnormalities. Symptoms may occur within a few minutes following exposure to the poison in solution, but may be delayed for several hours if the arsenic compound is in solid form or if it is taken with a meal. When ingested as a particulate, toxicity is also dependent on solubility and particle size of the ingested compound. The fatal dose of ingested arsenic trioxide has been reported to range from 70 to 180 mg. Death may occur within 24 hours, but the usual course runs from 3 to 7 days. Acute intoxication with arsenic compounds is usually accompanied by anaemia and leucopenia, especially granulocytopenia. In survivors these effects are usually reversible within 2 to 3 weeks. Reversible enlargement of the liver is also seen in acute poisoning, but liver function tests and liver enzymes are usually normal.

    In individuals surviving acute poisoning, peripheral nervous disturbances frequently develop a few weeks after ingestion.

    Long-term exposure (chronic poisoning)

    General aspects. Chronic arsenic poisoning may occur in workers exposed for a long time to excessive concentrations of airborne arsenic compounds. Local effects in the mucous membranes of the respiratory tract and the skin are prominent features. Involvement of the nervous and circulatory system and the liver may also occur, as well as cancer of the respiratory tract.

    With long-term exposure to arsenic via ingestion in food, drinking water or medication, symptoms are partly different from those after inhalation exposure. Vague abdominal symptoms—diarrhoea or constipation, flushing of the skin, pigmentation and hyperkeratosis—dominate the clinical picture. In addition, there may be vascular involvement, reported in one area to have given rise to peripheral gangrene.

    Anaemia and leucocytopenia often occur in chronic arsenic poisoning. Liver involvement has been more commonly seen in persons exposed for a long time via oral ingestion than in those exposed via inhalation, particularly in vineyard workers considered to have been exposed mainly through drinking contaminated wine. Skin cancer occurs with excess frequency in this type of poisoning.

    Vascular disorders. Long-term oral exposure to inorganic arsenic via drinking water may give rise to peripheral vascular disorders with Raynaud’s phenomenon. In one area of Taiwan, China, peripheral gangrene (so-called Blackfoot disease) has occurred. Such severe manifestations of peripheral vascular involvement have not been observed in occupationally exposed persons, but slight changes with Raynaud’s phenomenon and an increased prevalence of low peripheral blood presssure on cooling have been found in workers exposed for a long time to airborne inorganic arsenic (doses of absorbed arsenic are given below.

    Dermatological disorders. Arsenical skin lesions differ somewhat, depending on the type of exposure. Eczematoid symptoms of varying degrees of severity do occur. In occupational exposure to mainly airborne arsenic, skin lesions may result from local irritation. Two types of dermatological disorders may occur:

    1. an eczematous type with erythema (redness), swelling and papules or vesicles
    2. a follicular type with erythema and follicular swelling or follicular pustules.


      Dermatitis is primarily localized on the most heavily exposed areas, such as the face, back of the neck, forearms, wrists and hands. However, it may also occur on the scrotum, the inner surfaces of the thighs, the upper chest and back, the lower legs and around the ankles. Hyperpigmentation and keratoses are not prominent features of this type of arsenical lesions. Patch tests have demonstrated that the dermatitis is due to arsenic, not to impurities present in the crude arsenic trioxide. Chronic dermal lesions may follow this type of initial reaction, depending on the concentration and duration of exposure. These chronic lesions may occur after many years of occupational or environmental exposure. Hyperkeratosis, warts and melanosis of the skin are the conspicuous signs.

      Melanosis is most commonly seen on the upper and lower eyelids, around the temples, on the neck, on the areolae of the nipples and in the folds of the axillae. In severe cases arsenomelanosis is observed on the abdomen, chest, back and scrotum, along with hyperkeratosis and warts. In chronic arsenic poisoning, depigmentation (i.e., leukoderma), especially on the pigmented areas, commonly called “raindrop” pigmentation, also occurs. These chronic skin lesions, particularly the hyperkeratoses, may develop into pre-cancerous and cancerous lesions. A transverse striation of the nails (so-called Mees lines) also occurs in chronic arsenical poisoning. It should be noted that the chronic skin lesions may develop long after cessation of exposure, when arsenic concentrations in skin have returned to normal.

      Mucous membrane lesions in chronic arsenic exposure is most classically reported as perforation of the nasal septum after inhalation exposure. This lesion is a result of irritation of the mucous membranes of the nose. Such irritation also extends to the larynx, trachea and bronchi. Both in inhalation exposure and in poisoning caused by repeated ingestion, dermatitis of the face and eyelids sometimes extends to keratoconjunctivitis.

      Peripheral neuropathy. Peripheral nervous disturbances are frequently encountered in survivors of acute poisoning. They usually start within a few weeks after the acute poisoning, and recovery is slow. The neuropathy is characterized by both motor dysfunction and paresthaesia, but in less severe cases only sensory unilateral neuropathy may occur. Often the lower extremities are more affected than the upper ones. In subjects recovering from arsenical poisoning, Mees lines of the fingernails may develop. Histological examination has revealed Wallerian degeneration, especially in the longer axons. Peripheral neuropathy also may occur in industrial arsenic exposure, in most cases in a subclinical form that can be detected only by neurophysiological methods. In a group of smelter workers with long-term exposure corresponding to a mean cumulative total absorption of approximately 5 g (maximal absorption of 20 g), there was a negative correlation between cumulative absorption of arsenic and nerve conduction velocity. There were also some light clinical manifestations of peripheral vascular involvement in these workers (see above). In children exposed to arsenic, hearing loss has been reported.

      Carcinogenic effects. Inorganic arsenic compounds are classified by the International Agency for Research on Cancer (IARC) as lung and skin carcinogens. There is also some evidence to suggest that persons exposed to inorganic arsenic compounds suffer a higher incidence of angiosarcoma of the liver and possibly of stomach cancer. Cancer of the respiratory tract has been reported in excess frequency among workers engaged in the production of insecticides containing lead arsenate and calcium arsenate, in vine-growers spraying insecticides containing inorganic copper and arsenic compounds, and in smelter workers exposed to inorganic compounds of arsenic and a number of other metals. The latency time between onset of exposure and the appearance of cancer is long, usually between 15 and 30 years. A synergistic action of tobacco smoking has been demonstrated for lung cancer.

      Long-term exposure to inorganic arsenic via drinking water has been associated with an increased incidence of skin cancer in Taiwan and in Chile. This increase has been shown to be related to concentration in drinking water.

      Teratogenic effects. High doses of trivalent inorganic arsenic compounds may cause malformations in hamsters when injected intravenously. With regard to human beings there is no firm evidence that arsenic compounds cause malformations under industrial conditions. Some evidence, however, suggests such an effect in workers in a smelting environment who were exposed simultaneously also to a number of other metals as well as other compounds.

      Organic arsenic compounds

      Organic arsenicals used as pesticides or as drugs may also give rise to toxicity, although such adverse effects are incompletely documented in humans.

      Toxic effects on the nervous system have been reported in experimental animals following feeding with high doses of arsanilic acid, which is commonly used as a feed additive in poultry and swine.

      The organic arsenic compounds that occur in foodstuffs of marine origin, such as shrimp, crab and fish, are made up of arsinocholine and arsinobetaine. It is well known that the amounts of organic arsenic that are present in fish and shellfish can be consumed without ill effects. These compounds are quickly excreted, mainly via urine.

      Arsine gas and the substituted arsines. Many cases of acute arsine poisoning have been recorded, and there is a high fatality rate. Arsine is one of the most powerful haemolytic agents found in industry. Its haemolytic activity is due to its ability to cause a fall in erythrocyte-reduced glutathion content.

      Signs and symptoms of arsine poisoning include haemolysis, which develops after a latent period that is dependent on the intensity of exposure. Inhalation of 250 ppm of arsine gas is instantly lethal. Exposure to 25 to 50 ppm for 30 minutes is lethal, and 10 ppm may be lethal after longer exposures. The signs and symptoms of poisoning are those characteristic of an acute and massive haemolysis. Initially there is a painless haemoglobinuria, gastrointestinal disturbance such as nausea and possibly vomiting. There may also be abdominal cramps and tenderness. Jaundice accompanied by anuria and oliguria subsequently occurs. Evidence of bone marrow depression may be present. After acute and severe exposure, a peripheral neuropathy may develop and can still be present several months after poisoning. Little is known about repeated or chronic exposure to arsine, but since the arsine gas is metabolized to inorganic arsenic in the body, it can be assumed that there is a risk for symptoms similar to those in long-term exposure to inorganic arsenic compounds.

      The differential diagnosis should take account of acute haemolytic anaemias that could be caused by other chemical agents such as stibine or drugs, and secondary immunohaemolytic anaemias.

      The substituted arsines do not give rise to haemolysis as their main effect, but they act as powerful local and pulmonary irritants and systemic poisons. The local effect on the skin gives rise to sharply circumscribed blisters in the case of dichloro(2-chlorovinyl-)arsine (lewisite). The vapour induces marked spasmodic coughing with frowzy or blood-stained sputum, progressing to acute pulmonary oedema. Dimercaprol (BAL) is an effective antidote if given in the early stages of poisoning.

      Safety and Health Measures

      The most common type of occupational arsenic exposure is to inorganic arsenic compounds, and these safety and health measures are mainly related to such exposures. When there is a risk of exposure to arsine gas, particular attention needs to be paid to accidental leaks, since peak exposures for short intervals may be of special concern.

      The best means of prevention is to keep exposure well below accepted exposure limits. A programme of measurement of air-concentrations of arsenic is thus of importance. In addition to inhalation exposure, oral exposure via contaminated clothes, hands, tobacco and so on should be watched, and biological monitoring of inorganic arsenic in urine may be useful for evaluation of absorbed doses. Workers should be supplied with suitable protective clothing, protective boots and, when there is a risk that the exposure limit for airborne arsenic will be exceeded, respiratory protective equipment. Lockers should be provided with separate compartments for work and personal clothes, and adjacent sanitary facilities of a high standard should be made available. Smoking, eating and drinking at the workplace should not be allowed. Pre-employment medical examinations should be carried out. It is not recommended to employ persons with pre-existing diabetes, cardiovascular diseases, anaemia, allergic or other skin diseases, neurologic, hepatic or renal lesions, in arsenic work. Periodic medical examinations of all arsenic-exposed employees should be performed with special attention to possible arsenic-related symptoms.

      Determination of the level of inorganic arsenic and its metabolites in urine allows estimation of the total dose of inorganic arsenic taken up by various exposure routes. Only when inorganic arsenic and its metabolites can be specifically measured is this method useful. Total arsenic in urine may often give erroneous information about industrial exposure, since even a single meal of fish or other marine organisms (containing considerable amounts of non-toxic organic arsenic compound) may cause greatly elevated urinary arsenic concentrations for several days.


      Arsine gas poisoning. When there is reason to believe that there has been considerable exposure to arsine gas, or upon observation of the first symptoms (e.g., haemoglobinuria and abdominal pain), immediate removal of the individual from the contaminated environment and prompt medical attention are required. The recommended treatment, if there is any evidence of impaired renal function, consists of total-replacement blood transfusion associated with prolonged artificial dialysis. Forced diuresis has proved useful in some cases, whereas, in the opinion of most authors, treatment with BAL or other chelating agents seems to have only limited effect.

      Exposure to the substituted arsines should be treated in the same way as inorganic arsenic poisoning (see below).

      Poisoning by inorganic arsenic. If there has been exposure to doses that can be estimated to give rise to acute poisoning, or if severe symptoms from the respiratory system, the skin or the gastrointestinal tract occur in the course of long-term exposures, the worker should immediately be removed from exposure and treated with a complexing agent.

      The classical agent which has been used most widely in such situations is 2,3-dimercapto-1-propanol or British anti-lewisite (BAL, dimercaprol). Prompt administration in such cases is vital: to obtain maximal benefit such treatment should be given within 4 hours of poisoning. Other pharmaceuticals which may be used are sodium 2,3-dimercaptopropanesulphonate (DMPS or unithiol) or meso-2,3-dimercaptosuccinic acid (DMSA). These drugs are less likely to give side effects and are believed to be more effective than BAL. Intravenous administration of N-acetylcysteine has been reported in one case to be of value; in addition, general treatment, such as prevention of further absorption by removal from exposure and minimizing absorption from the gastrointestinal tract by gastric lavage and administration by gastric tube of chelating agents or charcoal, is mandatory. General supportive therapy, such as maintenance of respiration and circulation, maintenance of water and electrolyte balance, and control of nervous system effects, as well as elimination of absorbed poison through haemodialysis and exchange transfusion, may be used if feasible.

      Acute skin lesions such as contact dermatitis and mild manifestations of peripheral vascular involvement, such as Raynaud’s syndrome, usually do not require treatment other than removal from exposure.



      Read 5308 times Last modified on Saturday, 30 July 2022 23:15
      More in this category: « Antimony Barium »

      " DISCLAIMER: The ILO does not take responsibility for content presented on this web portal that is presented in any language other than English, which is the language used for the initial production and peer-review of original content. Certain statistics have not been updated since the production of the 4th edition of the Encyclopaedia (1998)."


      Metals: Chemical Properties and Toxicity References

      Agency for Toxic Substances and Disease Registry (ATSDR). 1995. Case Studies in Environmental Medicine: Lead Toxicity. Atlanta: ATSDR.

      Brief, RS, JW Blanchard, RA Scala, and JH Blacker. 1971. Metal carbonyls in the petroleum industry. Arch Environ Health 23:373–384.

      International Agency for Research on Cancer (IARC). 1990. Chromium, Nickel and Welding. Lyon: IARC.

      National Institute for Occupational Safety and Health (NIOSH). 1994. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 94-116. Cincinnati, OH: NIOSH.

      Rendall, REG, JI Phillips and KA Renton. 1994. Death following exposure to fine particulate nickel from a metal arc process. Ann Occup Hyg 38:921–930.

      Sunderman, FW, Jr., and A Oskarsson,. 1991. Nickel. In Metals and their compounds in the environment, edited by E Merian, Weinheim, Germany: VCH Verlag.

      Sunderman, FW, Jr., A Aitio, LO Morgan, and T Norseth. 1986. Biological monitoring of nickel. Tox Ind Health 2:17–78.

      United Nations Committee of Experts on the Transport of Dangerous Goods. 1995. Recommendations on the Transport of Dangerous Goods, 9th edition. New York: United Nations.