Arsenic Compounds

ARSENIC COMPOUNDS^(A)

107-02-8

Hazard Summary-Created in April 1992; Revised in January 2000

Arsine is a gas consisting of arsenic and hydrogen. It is extremely toxic to humans, with headaches, vomiting, and abdominal pains occurring within a few hours of exposure. EPA has not classified arsine for carcinogenicity.

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on inhalation chronic toxicity and the RfC for arsine, oral chronic toxicity and the RfD for inorganic arsenic, and the carcinogenic effects of inorganic arsenic including the unit cancer risk for inhalation exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for Arsenic.

Uses

The major use for inorganic arsenic is in wood preservation; arsine is used in the microelectronics industry and in semiconductor manufacture. (2)
Until the 1940s, inorganic arsenic solutions were widely used in the treatment of various diseases, such as syphillis and psoriasis. Inorganic arsenic is still used as an antiparasitic agent in veterinary medicine and in homeopathic and folk remedies in the United States and other countries. (2)

Sources and Potential Exposure

Inorganic arsenic is found throughout the environment; it is released into the air by volcanoes, the weathering of arsenic-containing minerals and ores, and by commercial or industrial processes. (1,2)
For most people, food is the largest source of arsenic exposure (about 25 to 50 micrograms per day [µg/d]), with lower amounts coming from drinking water and air. Among foods, some of the highest levels are found in fish and shelfish; however, this arsenic exists primarily as organic compounds, which are essentially nontoxic. (1)
Elevated levels of inorganic arsenic may be present in soil, either from natural mineral deposits or contamination from human activities, which may lead to dermal or ingestion exposure. (1)
Workers in metal smelters and nearby residents may be exposed to above-average inorganic arsenic levels from arsenic released into the air. (1)
Other sources of inorganic arsenic exposure include burning plywood treated with an arsenic wood preservative or dermal contact with wood treated with arsenic. (2)
Most arsenic poisoning incidents in industry have involved the production of arsine, a short-lived, extremely toxic gas. (3)

Assessing Personal Exposure

Measurement of inorganic arsenic in the urine is the best way to determine recent exposure (within the last 1 to 2 days), while measuring inorganic arsenic in hair or fingernails may be used to detect high-level exposures that occurred over the past 6-12 months. (1)

Health Hazard Information

Acute Effects:

Inorganic Arsenic

Acute inhalation exposure of workers to high levels of arsenic dusts or fumes has resulted in gastrointestinal effects (nausea, diarrhea, abdominal pain), while acute exposure of workers to inorganic arsenic has also resulted in central and peripheral nervous system disorders. (1)

Acute oral exposure to inorganic arsenic, at doses of approximately 600 micrograms per kilogram body weight per day (µg/kg/d) or higher in humans, has resulted in death. Oral exposure to lower levels of inorganic arsenic has resulted in effects on the gastrointestinal tract (nausea, vomiting), central nervous system (CNS) (headaches, weakness, delirium), cardiovascular system (hypotension, shock), liver, kidney, and blood (anemia, leukopenia). (1,2)

Acute animal tests in rats and mice have shown inorganic arsenic to have moderate to high acute toxicity. (5)

Arsine

Acute inhalation exposure to arsine by humans has resulted in death; it has been reported that a half-hour exposure to 25 to 50 parts per million (ppm) can be lethal. (4)

The major effects from acute arsine exposure in humans include headaches, vomiting, abdominal pains, hemolytic anemia, hemoglobinuria, and jaundice; these effects can lead to kidney failure. (4,8)

Arsine has been shown to have extreme acute toxicity from acute animal tests. (5)

Chronic Effects (Noncancer):

Inorganic arsenic

Chronic inhalation exposure to inorganic arsenic in humans is associated with irritation of the skin and mucous membranes (dermatitis, conjunctivitis, pharyngitis, and rhinitis). (1,2)

Chronic oral exposure to inorganic arsenic in humans has resulted in gastrointestinal effects, anemia, peripheral neuropathy, skin lesions, hyperpigmentation, gangrene of the extremities, vascular lesions, and liver or kidney damage. (1,2)

No chronic inhalation exposure studies have been performed in animals for any inorganic arsenic compound. (1)

Some studies have suggested that inorganic arsenic is an essential dietary nutrient in goats, chicks, and rats. However, no comparable data are available for humans. EPA has concluded that essentiality, although not rigorously established, is plausible. (1,6)

EPA has not established a Reference Concentration (RfC) for inorganic arsenic. (6)

The California Environmental Protection Agency (CalEPA) has established a chronic inhalation reference level of 0.00003 milligrams per cubic meter (mg/m³) based on developmental effects in mice. The CalEPA reference exposure level is a concentration at or below which adverse health effects are not likely to occur. It is not a direct estimator of risk, but rather a reference point to gauge the potential effects. At lifetime exposures increasingly greater than the reference exposure level, the potential for adverse health effects increases. (7)

The Reference Dose (RfD) for inorganic arsenic is 0.0003 milligrams per kilogram body weight per day (mg/kg/d) based on hyperpigmentation, keratosis, and possible vascular complications in humans. The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of deleterious noncancer effects during a lifetime. (6)

EPA has medium confidence in the study on which the RfD for inorganic arsenic was based because, although an extremely large number of people were included in the assessment (>40,000), the doses were not well characterized and other contaminants were present. The supporting human toxicity database, while extensive, is somewhat flawed and, consequently, EPA has assigned medium confidence to the RfD. (6)

Arsine

No information is available on the chronic effects of arsine in humans.

The RfC for arsine is 0.00005 mg/m³ based on increased hemolysis, abnormal red blood cell morphology, and increased spleen weight in rats, mice, and hamsters. (4)

EPA has medium confidence in the RfC based on: (1) high confidence in the studies on which the RfC for arsine was based because the sample sizes were adequate, statistical significance was reported, concentration dose-response relationships were documented, three species were investigated, and both a no-observed-adverse-effect level (NOAEL) and a lowest-observed-adverse-effect level (LOAEL) were identified, and (2) medium confidence in the database because while there were three inhalation animal studies and a developmental/reproductive study, there were no data available on human exposure. (4)

Reproductive/Developmental Effects:

Inorganic arsenic

Several studies have suggested that women who work in, or live near, metal smelters may have higher than normal spontaneous abortion rates, and their children may exhibit lower than normal birthweights. However, these studies are limited because they were designed to evaluate the effects of smelter pollutants in general, and are not specific for inorganic arsenic. (1)

Ingested inorganic arsenic can cross the placenta in humans, exposing the fetus to the chemical. (2)

Oral animal studies have reported inorganic arsenic at very high doses to be fetotoxic and to cause birth defects. (1)

Arsine

Human studies have indicated higher than expected spontaneous abortion rates in women in the microelectronics industry who were exposed to arsine. However, these studies have several limitations, including small sample size and exposure to other chemicals in addition to arsine. (4)

Cancer Risk:

Inorganic arsenic

Human, inhalation studies have reported inorganic arsenic exposure to be strongly associated with lung cancer. (1,2,6)

Ingestion of inorganic arsenic in humans has been associated with an increased risk of nonmelanoma skin cancer and also to an increased risk of bladder, liver, and lung cancer. (1,6)

Animal studies have not associated inorganic arsenic exposure via the oral route with cancer, and no cancer inhalation studies have been performed in animals for inorganic arsenic. (1)

EPA has classified inorganic arsenic as a Group A, human carcinogen. (6)

EPA used a mathematical model, using data from an occupational study of arsenic-exposed copper smelter workers, to estimate the probability of a person developing cancer from continuously breathing air containing a specified concentration of inorganic arsenic. EPA calculated an inhalation unit risk estimate of 4.3 × 10^-3(µg/m³)^-1. EPA estimates that, if an individual were to continuously breathe air containing inorganic arsenic at an average of 0.0002 µg/m³(2 x 10^-7 mg/m³) over his or her entire lifetime, that person would theoretically have no more than a one-in-a-million increased chance of developing cancer as a direct result of breathing air containing this chemical. Similarly, EPA estimates that continuously breathing air containing 0.002 µg/m³ (2 x 10^-6 mg/m³) would result in not greater than a one-in-a-hundred thousand increased chance of developing cancer, and air containing 0.02 µg/m³ (2 x 10^-5 mg/m³) would result in not greater than a one-in-ten thousand increased chance of developing cancer. For a detailed discussion of confidence in the potency estimates, please see IRIS. (6)

EPA has calculated an oral cancer slope factor of 1.5 (mg/kg/d)^-1 for inorganic arsenic. (6)

Arsine

No cancer inhalation studies in humans or animals are available for arsine. (1)

EPA has not classified arsine for carcinogenicity. (4)

Physical Properties

Inorganic arsenic is a naturally occurring element in the earth's crust.(1)
Pure inorganic arsenic is a gray-colored metal, but inorganic arsenic is usually found combined with other elements such as oxygen, chlorine, and sulfur. (1)
The chemical symbol for inorganic arsenic is As, and it has an atomic weight of 74.92 g/mol. (3)
The chemical formula for arsine is AsH₃, and it has a molecular weight of 77.95 g/mol. (8)
Arsine is a colorless gas with a disagreeable garlic odor. (8)
Arsenic combined with elements such as oxygen, chlorine, and sulfur forms inorganic arsenic; inorganic arsenic compounds include arsenic pentoxide, arsenic trioxide, and arsenic acid. Arsenic combined with carbon and hydrogen forms organic arsenic; organic arsenic compounds include arsanilic acid, arsenobetaine, and dimethylarsinic acid. (1)

Conversion Factors (only for the gaseous form):
To convert concentrations in air (at 25°C) from ppm to mg/m³: mg/m³ = (ppm) × (molecular weight of the compound)/(24.45). For inorganic arsenic: 1 ppm = 3.06 mg/m³. For arsine: 1 ppm = 3.19 mg/m³. To convert concentrations in air from µg/m³ to mg/m³: mg/m³ = (µg/m³) × (1 mg/1,000 µg).

Health Data from Inhalation Exposure (Inorganic Arsenic)

ACGIH TLV--American Conference of Governmental and Industrial Hygienists' threshold limit value expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effects.
NIOSH IDLH--National Institute of Occupational Safety and Health's immediately dangerous to life or health concentration; NIOSH recommended exposure limit to ensure that a worker can escape from an exposure condition that is likely to cause death or immediate or delayed permanent adverse health effects or prevent escape from the environment.
NIOSH REL ceiling value--NIOSH's recommended exposure limit ceiling; the concentration that should not be exceeded at any time.
OSHA PEL--Occupational Safety and Health Administration's permissible exposure limit expressed as a time-weighted average; the concentration of a substance to which most workers can be exposed without adverse effect averaged over a normal 8-h workday or a 40-h workweek.

The health and regulatory values cited in this factsheet were obtained in December 1999.
^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.
^bRegulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice. OSHA numbers are regulatory, whereas NIOSH and ACGIH numbers are advisory.
^cThe LOAEL is from the critical study used as the basis for the CalEPA chronic reference exposure level.

References

Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Arsenic (Draft). U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1998.
Agency for Toxic Substances and Disease Registry (ATSDR). Case Studies in Environmental Medicine. Arsenic Toxicity. U.S. Public Health Service, U.S. Department of Health and Human Services, Altanta, GA. 1990.
U.S. Environmental Protection Agency. Health Assessment Document for Inorganic Arsenic. EPA/540/1-86/020. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Washington, DC. 1984.
U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Arsine. National Center for Environmental Assessment, Office of Research and Development, Washington, DC. 1999.
U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.
U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Arsenic. National Center for Environmental Assessment, Office of Research and Development, Washington, DC. 1999.
California Environmental Protection Agency (CalEPA). Technical Support Document for the Determination of Noncancer Chronic Reference Exposure Levels. Draft for Public Comment. Office of Environmental Health Hazard Assessment, Berkeley, CA. 1997.
M. Windolz. The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals. 10th ed. Merck and Co., Rahway, NJ. 1983.
American Conference of Governmental Industrial Hygienists (ACGIH). 1999 TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents. Biological Exposure Indices. Cincinnati, OH. 1999.
Occupational Safety and Health Administration (OSHA). Occupational Safety and Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations. 29 CFR 1910.1000. 1998.
National Institute for Occupational Safety and Health (NIOSH). Pocket Guide to Chemical Hazards. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention. Cincinnati, OH. 1997.

A. * This fact sheet addresses the toxicity of the inorganic arsenic compounds as well as the toxicity of the gaseous arsenic trihydride: arsine.

Arsenic Compounds