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Arsenic

Arsenic is a natural component of the earth’s crust and is widely distributed throughout the environment. Arsenic exists in trivalent and pentavalent forms, as well as methylated compounds, monomethylarsonic acid and dimethylarsenic acid. All of these forms are toxic, but the trivalent form is the most potent. The biologic half-life of inorganic arsenic is 4 to 6 hours, while the biologic half-life of the methylated metabolites is 20 to 30 hours. 

Organic forms, such as the arsenobetaine and arsenocholine found in shellfish, cod, haddock and other seafood, are nontoxic.Organic arsenic is completely excreted within 1 to 2 days after ingestion and there are no residual toxic metabolites. The biologic half-life of organic arsenic is 4 to 6 hours.

Normally, humans consume 5 to 25 ug of arsenic each day as part of their normal diet.  Arsenics greatest threat to public health occurs from contaminated groundwater. According to the World Health Organization an arsenic level of less than 10 ug per liter in drinking water is needed to reduce the risks associated with long-term arsenic exposure.

Symptoms can develop within minutes to hours after acute exposure to high levels of inorganic arsenic. The earliest symptoms typically begin in the gastrointestinal tract with vomiting, abdominal pain, and severe watery diarrhea that results in dehydration and hypotension. Gastrointestinal hemorrhage can also occur. Patients may hypersalivate and have a garlicky odor on their breath. Acute encephalopathy may develop over several days, with delirium, seizures, and progression to coma. Severe cases may progress to renal impairment, liver dysfunction, adult respiratory distress syndrome, and cardiac dysfunction. 

Patients who survive the initial illness may develop chronic complications. Hepatitis and pancytopenia may develop within the first week. Bone marrow suppression reaches a maximum at 2 to 3 weeks. Painful peripheral neuropathy typically develops 1 to 3 weeks after exposure and may not respond to chelation therapy. Arsenic poisoning has been associated with reactivation of varicella–zoster virus. Long-term exposure to arsenic has been associated with an increased risk of cancer, particularly skin, bladder, and lung cancer. 

Exposure to inorganic arsenic can result in urine arsenic levels greater than1000 ug per gram of creatinine that remain elevated for weeks. Urine levels above 1,000 mcg/g indicate significant exposure. Ingestion of seafood containing organic forms of arsenic typically result in urine concentrations above 200 ug/g and decline to less than 35 ug/g in 24 to 48 hours. 

Because inorganic arsenic is rapidly cleared from blood by glomerular filtration, a random urine collection is the preferred specimen for detection of arsenic exposure. Urine tests measure total arsenic level, including both toxic inorganic arsenic compounds and nontoxic organic arsenic compounds found in fish, other seafood, and other foods. Ideally, a urine specimen should be obtained after a patient has abstained from eating fish for 48 to 72 hours. If a specimen has arsenic concentrations greater than 35 ug/g of creatinine, then a 24-hour urine collection should be fractionated to distinguish toxic inorganic from nontoxic organic arsenic. 

Chelation therapy with dimercaprol or succimer is recommended if urine levels of inorganic arsenic are elevated. Although chelation therapy increases urinary clearance of arsenic, it may not prevent progression of peripheral neuropathy.

Urine arsenic levels are measured by inductively coupled plasma-mass spectrometry (ICP-MS).Urine total arsenic concentration is normally less than 35 mcg arsenic per gram creatinine (<35 mcg/g). Reference value for inorganic arsenic is <20 ug per 24 hour urine collection.

Reference

G. Lindenmayer et al. A Sickening Tale. N Engl J Med 2018;379:75-80

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