Arsenic
Arsenic compounds are found in a select group of industrial, commercial, and pharmaceutical products. Use of arsenic as a wood preservative in industrial applications (eg, marine timbers and utility poles) accounts for two-thirds of domestic consumption, but former widespread use in new lumber sold for residential purposes (eg, decks, fencing, play structures) ended with a voluntary ban effective at the end of 2003. Arsenic-treated lumber used in residential structures and objects created before 2004 has not been officially recalled or removed. Virtually all arsenic in pesticides and herbicides in the United States has been withdrawn or subject to phaseout with the exception of the limited use of monosodium methane arsonate (MSMA) as an herbicide. Phenylarsenic compounds are used as feed additives for poultry and swine, and poultry litter used as a soil amendment may contain low levels of soluble arsenic. IV arsenic trioxide, reintroduced to the US Pharmacopoeia in 2000, is used as a drug for cancer chemotherapy. Inorganic arsenic is used in the production of nonferrous alloys, semiconductors, and certain types of glass. Inorganic arsenic is sometimes found in folk remedies and tonics, particularly from Asian sources. Artesian well water can be contaminated by inorganic arsenic from natural geologic deposits, and elevated levels of arsenic may be encountered in mine tailings and sediments and coal fly ash. Arsine, a hydride gas of arsenic, is discussed in Arsine.
Mechanism of toxicity. Arsenic compounds may be organic or inorganic and may contain arsenic in either a pentavalent (arsenate) or a trivalent (arsenite) form. Once absorbed, arsenicals exert their toxic effects through multiple mechanisms, including inhibition of enzymatic reactions vital to cellular metabolism, induction of oxidative stress, and alteration in gene expression and cell signal transduction. Although arsenite and arsenate undergo in vivo biotransformation to less toxic pentavalent monomethyl and dimethyl forms, there is evidence that the process also forms more toxic trivalent methylated compounds.
Soluble arsenic compounds, which are well absorbed after ingestion or inhalation, pose the greatest risk for acute human intoxication.
Inorganic arsenic dusts (eg, arsenic trioxide) may exert irritant effects on the skin and mucous membranes. Contact dermatitis has also been reported. Although the skin is a minor route of absorption for most arsenic compounds, systemic toxicity has resulted from industrial accidents involving percutaneous exposure to highly concentrated liquid formulations.
The chemical warfare agent lewisite (dichloro [2-chlorovinyl] arsine) is a volatile vesicant liquid that causes immediate severe irritation and necrosis to the eyes, skin, and airways (see also Warfare Agents–Chemical).
Arsenate and arsenite are known human carcinogens by both ingestion and inhalation.
Toxic dose. The toxicity of arsenic compounds varies considerably with the valence state, chemical composition, and solubility. Humans are generally more sensitive than other animals to the acute and chronic effects of arsenicals.
Inorganic arsenic compounds. In general, trivalent arsenic (As3+) is 2–10 times more acutely toxic than pentavalent arsenic (As5+). However, overexposure to either form produces a similar pattern of effects, requiring the same clinical approach and management.
Acute ingestion of as little as 100–300 mg of a soluble trivalent arsenic compound (eg, sodium arsenite) can be fatal.
The lowest observed acute effect level (LOAEL) for acute human toxicity is approximately 0.05 mg/kg, a dose associated with GI distress in some individuals.
Death attributable to malignant arrhythmias has been reported after days to weeks of cancer chemotherapy regimens in which arsenic trioxide at a dosage of 0.15 mg/kg/d was administered IV.
Repeated ingestion of approximately 0.04 mg/kg/d can result in GI distress and hematologic effects after weeks to months and peripheral neuropathy after 6 months to several years. Lower chronic exposures, approximately 0.01 mg/kg/d, can result in characteristic skin changes (initially spotted pigmentation, followed within years by palmar-plantar hyperkeratosis) after intervals of 5–15 years.
The US National Research Council (2001) estimated that chronic ingestion of drinking water containing arsenic at a concentration of 10 mcg/L can be associated with an excess lifetime cancer risk greater than 1 in 1000. The latency period for development of arsenic-induced cancer is probably a decade or longer.
Organic arsenic.
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