Arsenic Health Article

ARSENIC

Arsenic (As) is a silver-gray metal that gained much of its notoriety because of its historical use as a human poison (approximately 70 to 180 milligrams of arsenic is fatal to an adult). Arsenic is present in the earth's crust at an average concentration of 2 to 5 mg/kg, with low levels commonly found in the air, water, and soil. In the eighteenth and nineteenth centuries, arsenic was used as a preservative in animal hides, and as an ingredient in pigments, dyes, glass, pharmaceuticals, and pesticides.

In the first half of the twentieth century, arsenic was used in pharmaceuticals intended to treat syphilis (e.g., arsphenamine), skin diseases (e.g., Fowler's solution, a 1% potassium arsenate solution), and parasites (e.g., Pearson's Arsenical Solution). Arsenic is still used as an ingredient in pesticides, wood preservatives, copper and lead alloys, glass, semiconductor devices, and veterinary medicines.

Although arsenic is found in nature in its elemental form (arsenic metal), it occurs most commonly in inorganic or organic compounds. Common inorganic arsenic compounds are trivalent arsenic (e.g., arsenite, H₃AsO₃) and pentavalent arsenic (e.g., arsenate, H₂AsO₄, HAsO₄²). Common organic arsenic compounds are monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA, also known as cacodylic acid), and roxarsone.

Adverse health effects are dependent on the chemical form and physical state of the specific arsenic compound. In general, organic arsenic is less acutely toxic than inorganic arsenic. The health effects of arsenic are widely variable, and are primarily due to differences in the oxidation state of the two predominant forms: trivalent arsenite and pentavalent arsenate. Several organic arsenicals that accumulate in fish and shellfish are essentially nontoxic. Human exposure to arsenic compounds occurs primarily in occupational settings and by the ingestion of contaminated drinking water and seafood. Arsenic toxicity due to natural contamination of drinking water has been recently noted as a significant public health problem in Bangladesh. Predominant adverse health effects associated with acute arsenic exposure include fever, melanosis, hepatomegaly, cardiac arrhythmia, peripheral neuropathy, nephrotoxicity, diarrhea and vomiting, and, at sufficiently high doses (70 to 180 milligrams for an adult), death. Chronic exposure to arsenic may lead to neurotoxicity (evidenced by sensory changes, paresthesia, and muscle weakness), cancer (basal cell and squamous cell carcinoma of the skin, lung cancer, or bladder cancer), cardiovascular effects (including "blackfoot disease," so called because the soles of the feet and toes turn black with gangrene), skin disorders such as hyperpigmentation, and birth defects.

Arsine gas is a potent hemolytic agent. The International Agency for Cancer Research (IARC) and the U.S. Environmental Protection Agency (EPA) classify arsenic as a carcinogen based upon epidemiological evidence demonstrating a causal association between arsenic exposure and specific cancers, such as skin cancer and lung cancer. Arsenic can accumulate in hair and nails, and measurement of arsenic levels in these tissues may be a useful indicator of past exposures, while measurement of urine is considered a good indicator of current arsenic exposure. Arsenic is primarily excreted from the body in urine (30 to 85% of absorbed arsenic is excreted via urine). Scientists have puzzled for decades over arsenic's mechanism of carcinogenicity due to the discordance between the results of human and animal bioassays. Animals appear to be substantially less susceptible to arsenic-induced toxicity than humans. Investigations in animals have suggested that inorganic arsenic can be an essential trace element in some animals. In contrast, arsenic has not been determined to be an essential trace element in humans.

MARGARET H. WHITAKER

BRUCE A. FOWLER

(SEE ALSO: Carcinogen; Heavy Metals)