The therapeutic use of arsenic (arsenic trioxide) for acute promyelocytic leukemia (APL), as well as its emergence as a significant environmental toxin, has renewed interest in its pharmacology and toxicology. The role of arsenic in our pharmacopeia may expand; its efficacy in treating various other leukemias, lymphomas, and multiple myeloma is being studied.142 This chapter predominantly discusses the properties and toxicity of inorganic arsenic, the most prevalent toxic form.
Arsenic poisoning can be unintentional, suicidal, homicidal, occupational, environmental, or iatrogenic.95,96,126,148 Mass poisonings have occurred. Nearly 400 residents of Hong Kong fell ill after eating contaminated bread from the Esing Bakery in 1857; two bakery foremen were thought to have tampered with the recipe.79 The 1900 Staffordshire beerepidemic in England saw 6000 beer drinkers fall ill and 70 die from beer brewed with sugar made with arsenic-contaminated sulfuric acid.95 In Wakayama, Japan, 67 people were poisoned by eating intentionally contaminated curry at a festival in 1998.200 In 2003, the largest recent outbreak of arsenic poisoning in the United States occurred in New Sweden, Maine, when intentionally adulterated church coffee resulted in the death of one parishioner and the hospitalization of an additional 15 victims.16 Arsenic trioxide reemerged as a treatment for acute promyelocytic leukemia in the 1990s after physicians in Harbin, China, found a high remission rate in patients given Ailing-1, a crude arsenic trioxide infusion.111,236
Contaminated soil, water, and food are the primary sources of arsenic for the general population. Pentavalent arsenic is the most common inorganic form in the environment.49 Inorganic arsenic exposure from food is generally low and usually occurs from soil-derived foods such as rice and produce.29,177,227,235 Exposure to organic arsenic compounds of low toxicity occurs from consumption of algae, fish, and shellfish. In the past 2 decades, consumption of contaminated water has emerged as the primary cause of large-scale outbreaks of chronic arsenic toxicity. Arsenic leaches from certain minerals and ores, as well as from industrial waste.133 In Bangladesh, millions of people have been poisoned by drinking water from wells contaminated with arsenic leached from ground minerals.151 Ironically, the wells were dug to obtain safer groundwater. Hydroarsenicism has also been reported in Chile, Taiwan, Brazil, India, Mexico, and Argentina.32,43,49,89,133,151,216 In 2001, the US Environmental Protection Agency decreased the maximum contaminant level of arsenic in drinking water to 10 parts per billion (ppb), or 10 μg/L, after statistical modeling indicated an increased risk of lung and bladder cancer from water contaminated with arsenic at the formerly acceptable level of 50 ppb.57 The World Health Organization also recommends a maximum concentration of 10 ppb.
Arsenic is a metalloid that exists in multiple forms: elemental, gaseous (arsine), organic, and inorganic [(As3+ [trivalent, or arsenite] and As5+ [pentavalent, or arsenate])]. Tables 88–1 and 88–2 list ...