Hazardous Chemical Information System (HCIS)

Arsenic and soluble compounds, (as As)

Exposure Standard first adopted in 1990

Carcinogen category notice: Category 1. Established human carcinogen known to be carcinogenic to humans. There is sufficient evidence to establish a causal association between human exposure to these substances and the development of cancer. See Chapter 13: Guidance Note on the Interpretation of Exposure Standards for Atmospheric Contaminants in the Occupational Environment, published by Worksafe Australia.

No standard should be applied without reference to Guidance on the interpretation of Workplace exposure standards for airborne contaminants.

Documentation notice: National Occupational Health and Safety Commission documentation available for these values.

Carcinogen Category 1 (Confirmed Human Carcinogen)

1. IDENTITY

2. CHEMICAL AND PHYSICAL PROPERTIES

Arsenic is an element with atomic number of 33. The most common form of the element is a silver-grey brittle crystalline solid. Given below are some of its properties:

When arsenic is heated in air, it will burn and form a white smoke consisting of arsenic trioxide (As203).

3. MAJOR INDUSTRIAL USES

Elemental or metallic arsenic is utilised as an alloying agent for heavy metals, in special solders, and as a doping agent in silicon and germanium solid state products.

Many arsenic compounds have found commercial applications. The arsenites (trivalent arsenic compounds, for example, calcium arsenite) are important herbicides and wood preservatives. Some arsenates (pentavalent arsenic compounds, for example, calcium arsenate) are used as insecticides and pigments. Many organic compounds have been employed in medicine, or as war gases.

4. GENERAL HEALTH EFFECTS

4.1 Acute Effects

Acute arsenical poisoning due to inhalation is exceedingly rare in the workplace. When it does occur, it produces respiratory tract symptoms (cough, chest pain and dyspnoea), giddiness, headache, and extreme general weakness, followed by gastrointestinal symptoms including epigastric pain, vomiting and diarrhoea (1) .

4.2 Chronic Effects

Chronic signs of toxicity in workers exposed to arsenic compounds are related chiefly to the skin, mucous membranes, gastrointestinal and nervous systems, and far less commonly to disorders of the circulatory system and liver (2) .

Chronic poisoning from inhalation exposure has been described as having three phases based on signs and symptoms (1) :

First phase: The worker complains of weakness, loss of appetite, some nausea, occasional vomiting, a sense of heaviness in the stomach, and some diarrhoea.

Second Phase: The worker complains of conjunctivitis, and a catarrhal state of the mucous membranes of the nose, larynx and respiratory passages. Coryza, hoarseness, and mild tracheobronchitis may occur. Perforation of the nasal septum is common, and is probably the most typical lesion of the upper respiratory tract in occupational exposure to arsenical dust. Skin lesions, eczematoid and allergic in type, are common.

Third Phase: The worker complains of symptoms of peripheral neuritis, initially of hands and feet, which is essentially sensory. In more severe cases, motor paralyses occur; the first muscles affected are usually the toe extensors and the peronei. In only the most severe cases will paralysis of flexor muscles of the feet or the extensor muscles of hands occur.

5. METABOLISM AND ABSORPTION

Airborne arsenic particles deposited in the respiratory tract seem to be rapidly taken up from the lung; however, their absorption rates are not known in humans (3) . Most arsenic derivatives are rapidly excreted in the urine but some of the absorbed arsenic is widely distributed in the tissues including the liver, abdominal viscera, bone, skin, and particularly the hair and nails (2) .

6. TERATOGENICITY

Teratogenic effects of arsenic have frequently been reported in laboratory animals exposed to single high doses (4) . Schroeder & Mitchener (5) exposed three generations of mice to low doses of arsenic (5mg As/kg diet), but did not find any abnormalities other than reduced litter size.

Human data on the teratogenicity of arsenic are very rare and the data available are usually confounded by variables such as exposure to other metals. However, as inorganic arsenic crosses the human placenta (6) and there is evidence of teratogenesis at high doses in animals, arsenic at high doses should be considered a potential teratogen in humans.

7. MUTAGENICITY

A number of studies have indicated an effect of arsenic on human chromosomes, both in vivo (7) and in vitro (8,9) . There is evidence that in experimental systems it induces chromosome aberrations and sister chromatid exchanges and that it affects DNA repair mechanisms (4,10) . However, there is no evidence available to correlate these effects with levels of workplace exposure.

8. CARCINOGENICITY

Epidemiological studies clearly indicate that exposure to arsenic increases the incidence of skin, lung, liver and lymphoid cancer in humans

(11) . However, as animal studies designed to confirm the carcinogenic potential of arsenic have been largely negative, the question as to whether it is a direct carcinogen is unresolved. It has been proposed that it may be a co-promotor or co-carcinogen (that is, a potentiator of the carcinogenic process).

Lung cancer is the primary cause of concern with chronic inhalation of arsenic in the workplace. An excess of deaths due to respiratory cancer has been observed among workers exposed to inorganic arsenic in the production and use of pesticides, gold mining, and in the smelting of nonferrous metals, especially copper

(4) .

The uncertainty involved in estimating past exposure in epidemiological studies makes it difficult to relate risk to exposure levels. However, a number of organisations have undertaken detailed analyses of these studies and have produced the following assessments of elevated risk:

9. OVERSEAS EXPOSURE STANDARDS

On the basis of risk assessment, both OSHA(U.S.) and NIOSH(U.S.) (12) have recommended an exposure standard of 10ug/m3 (as As) for inorganic arsenic. Ontario (Canada) has adopted a TWA of 10ug/m3 and a 15-minute standard of 50ug/m3 with an exemption for the construction and mining industries. Sweden's standard is set at 50ug/m3. The HSE(U.K.) has adopted a maximum exposure limit of 200ug/m3, pending consideration of the impact of a 50ug/m3 limit on the industry. The ACGIH, in adopting a TLV of 200ug/m3, however, stated that as there was a lack of data on which to unequivocally base an exposure standard, there were insufficient grounds to reduce the TLV (13) . Levels set in a number of other countries are equal to or greater than that set by the ACGIH.

10. RECOMMENDATIONS FOR EXPOSURE STANDARD

After reviewing the relevant data, the Exposure Standards Working Group recommends that arsenic and its soluble compounds be assigned the designation Carcinogen Category 1 (Confirmed Human Carcinogen). The reader is encouraged to review the section on Carcinogens in the Guidance Note on the Interpretation of Exposure Standards for Atmospheric Contaminants in the Occupational Environment, for guidance on the classification system of carcinogens.

The Working Group also recommends a time-weighted average exposure standard of 0.05mg/m3 (as As), believing that according to risk assessment, this level can significantly reduce the number of cases of cancer resulting from exposure to arsenic.

REFERENCES

1. Sittig M, Handbook of Toxic and Hazardous Chemicals and Carcinogens, 2nd ed., Noyes Publications, New Jersey, pp 86-90, 1985

2. Clayton G D & Clayton F E (ed), Patty's Industrial Hygiene and Toxicology, 3rd revised edition, Vol 2A, John Wiley and Sons, New York, pp 1517-1528, 1981

3. Kirsch-Voiders M, Mutagenicity, Carcinogenicity and Teratogenicity of Industrial Pollutants, Plenum Press, New York, pp 64-70, 1984

4. World Health Organisation, Environmental Health Criteria 18: Arsenic, WHO, Geneva, 1981

5. Schroeder H A & Mitchener M, "Toxic effects of trace elements on the reproduction of mice and rats", Arch Environ Health, 23, 102-106, 1971

6. Lugo Get al, "Acute maternal arsenic intoxication with neonatal death", Am J Dis Child, 117, 328-330, 1969

7. Petres Jet al, "Effects of arsenic cell metabolism and cell proliferation: Cytogenic and biochemical studies", Environ Health Perspect, 19, 223-227, 1977

8. Oppenheim J J & Fishbein W N, "Induction of chromosome breaks in cultured normal human leukocytes by potassium arsenite, hydroxyurea and related compounds", Cancer Res, 25, 980-985, 1965

9. Paton G R & Allison A C, "Chromosome damage in human cell cultures induced by metal salts", Mutat Res, 16, 332-336, 1972

10. National Board of Occupational Safety and Health, Scientific Basis for Swedish Occupational Standards V, Sweden, 1984

11. International Agency for Research on Cancer, IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol 23, Some Metals and Metallic Compounds, IARC, Lyon, pp 39-141, 1980

12. National Institute for Occupational Safety and Health, Criteria for a Recommended Standard: Occupational Exposure to Inorganic Arsenic, NIOSH, Washington, DC, 1975

13. American Conference of Governmental Industrial Hygienists, Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th edition, ACGIH, Ohio, 1986

Footnotes:

Documentation notice:

Entries carrying a notice for National Occupational Health and Safety Commission documentation indicate that these substances have been reviewed in detail by the Exposure Standards Expert Working Group and that documentation supporting the adopted national values is available in the National Commission's Documentation of the Exposure Standards [NOHSC:10003(1995)].