Arsenic Poisoning

• Arsenic is an element (metalloid) that can combine with organic and inorganic substances.
• Inorganic arsenic is arsenic alone or combined with inorganic substances that are very toxic to most biological systems, including humans.
• Organic arsenic is arsenic combined with organic substances and may be non-toxic or far less toxic to many biologic systems than inorganic arsenic.
• Symptoms of arsenic poisoning vary with the type and concentration of the poison. Inorganic arsenic may cause abdominal pains, destruction of red blood cells (hemolysis), shock, and death quickly. Lower concentrations of inorganic arsenic and organic arsenic cause far less severe symptoms.
• Diagnosis of arsenic poisoning is made by determining inorganic and organic levels of arsenic in the blood and urine.
• Treatment of arsenic poisoning in acute toxic poisonings needs to begin quickly; treatment involves removal of arsenic by dialysis, chelating agents, replacement of red blood cells, and if ingested, bowel cleansing.
• Acute toxic inorganic arsenic poisoning has only a fair to poor outcome. Chronic poisoning has a better outcome.
• Arsenic is found in groundwater, many chemicals, and foods. If arsenic is in the organic form, it is likely nontoxic or weakly toxic to humans, but inorganic arsenic can also be found in similar locations and materials and in high concentrations in industrial processes. In 2013, the FDA made recommendations that less than 10 parts per billion of arsenic was acceptable for levels in apple juice. Levels for arsenic have yet to be FDA approved for rice (still under study), although groundwater levels that provide arsenic to rice are FDA set at less than 10 parts per billion.

Arsenic is a grey-appearing chemical element (atomic number 33, symbol "As" in the periodic table) also termed a metalloid. Arsenic can exist in a metallic state in three forms (yellow, black, and gray; with gray predominating) and in ionic forms. Arsenic is considered to be a heavy metal, and arsenic toxicity shares some features with poisonings by other heavy metals. Historically, arsenic has been used as a medicinal agent, a pigment, a pesticide, and an agent with intent to harm (use with criminal intent). Up until 2003, arsenic (in the form of chromated copper arsenate) was used in the U.S. as a treatment to prevent insect infestation of wood used in buildings. In 2003 the use of this compound was banned by the U.S. Environmental Protection Agency.

Arsenic is mixed with copper or leads to strengthening alloys containing these materials. Arsenic and some of its compounds react with proteins, mainly the thiol portions, and uncouples the process of oxidative phosphorylation, thus inactivating most cellular functions. Consequently, arsenic and some of the substances it combines with are deadly poisons to most biological systems, except for a few bacterial species. Arsenic is used in making insecticides and weed killers. Arsenic is also thought to be carcinogenic, meaning that it has the potential to cause cancer.

Arsenic can be found as a contaminant in food and water sources. Shellfish and other seafood, as well as fruits, vegetables, and rice; are the foods most commonly contaminated. Arsenic poisoning typically occurs as a result of industrial exposure, from contaminated wine or illegally distilled spirits, or in cases of malicious intent.

Inorganic arsenic is metallic or a metalloid element that forms a number of poisonous compounds. In industry, it can be found in a gaseous form termed arsine gas that is very toxic when inhaled. Inorganic arsenic is found in nature at low levels mostly compounded with oxygen, chlorine, and sulfur. These are called inorganic arsenic compounds. Inorganic arsenic compounds are much more poisonous to most biological systems (animals, plants, humans) than organic arsenic (see below).

Inorganic arsenic occurs in nature in the soil, copper and lead ore deposits, and water, but usually in low concentrations. However, it can become more concentrated when industrial processes use it to make wood preservatives, metal compounds, or organic arsenic-containing compounds such as insecticides, weed killers, and other compounds. If such compounds are burned, inorganic arsenic can be released into the air and later settle on the ground or in water and either remain in the inorganic form or combine with organic material.

Organic arsenic is any compound that is made from a chemical combination of the element arsenic with any organic compound (compounds containing a large amount of carbon). These are often termed arsenical organic compounds.

Most frequently, organic arsenic is a component used in making insecticides, weed killers, and other compounds. Organic arsenic usually is not poisonous to humans but may be poisonous to humans in high concentrations. In general, organic arsenic is usually far less poisonous than inorganic arsenic.

People can be exposed to arsenic by inhaling it, by consuming contaminated foods, water, or beverages, or by skin contact. We are normally exposed to trace amounts of arsenic in the air and water, and in food. People may be exposed to higher levels if they live near industrial areas that currently or formerly contained arsenic compounds. Areas with known high concentrations of arsenic in the drinking water are also associated with greater exposure.

Acute or immediate symptoms of a toxic level of exposure to arsenic may include the following:

• Vomiting
• Abdominal pain
• Diarrhea
• Dark urine (termed black water urine)
• Dehydration
• Cardiac problems
• Hemolysis (destruction of red blood cells)
• Vertigo
• Delirium
• Shock
• Death

Long-term exposures to arsenic lower than toxic levels can lead to skin changes (darkening or discoloration, redness, swelling, and hyperkeratosis (skin bumps that resemble corns or warts). Whitish lines (Mees' lines) may appear in the fingernails. Both sensory and motor nerve defects can develop. Additionally, liver and kidney function may be affected.

Arsenic exposure over the long term has also been associated with the development of certain cancers, and arsenic has been classified as a carcinogen by the Environmental Protection Agency (EPA). Studies of people in parts of Southeast Asia and South America where there has been a high level of arsenic in the drinking water have reported an increased risk of developing cancers of the bladder, kidney, lung, and skin. Organic arsenic compounds are not as toxic as inorganic compounds and are not believed to be linked to cancer.

The history of the patient is very important as exposures are most often from industrial accidents so other people (coworkers, rescue personnel) may be exposed and not realize they may have some risk also. People exposed to toxic levels of arsenic may have breath and urine that smells like garlic as a clue to their diagnosis. Most doctors that suspect arsenic (or other metal or metalloid poisonings) will request lab studies such as blood cell counts and serum electrolytes such as calcium and magnesium; if there is evidence of hemolysis (blood cell destruction), a type of screening for a potential blood transfusion is done.

 There are rapid urine "spot" tests available to diagnose elevated levels of arsenic, but they usually don't distinguish between organic and inorganic arsenic. The patient's blood and urine will be sent for analysis for arsenic; a result of > 50 micrograms/L is considered elevated, but acute toxic exposures may result in levels 5 to 100 times or more than those which are considered "elevated."

A speciation test (determines levels of inorganic versus organic arsenic) is required in all cases in which total urine arsenic is elevated since inorganic arsenic is so toxic. Electrocardiograms (ECG, EKG) and nerve conduction tests are often done in any type of suspected arsenic exposure. Tests for other toxins or toxic overdoses (for example, Tylenol ingestion) may also be done.

Acute toxic inorganic arsenic exposure and arsine gas exposure can rapidly result in death, and there are only a few ways to possibly save the patient's life. Hemodialysis can remove arsenic from the bloodstream, but only before it binds to the tissues so there is only a short time window for this treatment to work. Similarly, arsine binds to and causes rapid destruction of red blood cells, so blood transfusions and exchange transfusions may help the patient.

In addition, if the arsenic was ingested, stomach or bowel irrigation may be attempted, but there is no good data to indicate these will be successful. Consultation with a nephrologist and a toxicologist as soon as possible is recommended; other consultants may need to be called (hematologist, psychiatrist, or others).

Chelation therapy (the use of drugs that selectively bind and effectively inactivate substances) is usually begun quickly through an intravenous line. The drug and the bound arsenic are then excreted through the urine. The chelation drug of choice is Dimercaprol (also termed BAL in oil); Succimer (DMSA) has also been used successfully, and Dimerval (DMPS) may also work as a chelator, but it is not readily available in the U.S.

If the patient survives an acute toxic exposure, most will develop some degree of nerve damage to the peripheral nerves (sensory and motor disturbances); many survivors may have cardiac, liver, renal, and skin problems; the prognosis is fair to poor. Chronic poisoning and organic arsenic exposure have better outcomes with fewer and less severe problems.

People may be exposed through work in a metal foundry, mining, glass production, the semiconductor industry, in criminal attempts at murder by poisoning, suicide attempts, and as biological warfare agents.

• Arsenic has been found to contaminate such common items as wine, glues, and pigments.
• Arsenic is commonly found in many foods both in its relatively nontoxic organic form and also in the more toxic inorganic form. Consequently, such foods need to be tested for both inorganic and organic arsenic levels.
• Arsenic has been reported in milk and dairy products, beef, pork, poultry, and cereal.
• Arsenic is also often found in rice, representing a potentially serious source of exposure in certain at-risk populations (especially children).
• Many water sources in the world have high levels of arsenic in them, both due to normal arsenic leaching out of the ground and from mining and industrial waste.

Recent examples of concerns about arsenic have surfaced because of its presence in apple juice. In most studies, various sources of apple juice tested by the government and consumer labs have found that most (over 95% tested) contain a very small amount of arsenic (less than 10 parts per billion) and are safe to drink (in contrast to a TV show that raised alarms about consuming apple juice). However, the FDA qualified their findings by indicating in July 2013, new standards would apply and any juice that contained 10 or more parts per billion (the same level set for safe groundwater) would not be permitted to be sold in the US. This is lower than the previously approved level of fewer than 23 parts per billion approved in 2008. Nonetheless, other groups suggest that only juice containing less than 3 parts per billion be FDA approved.

Two other sources of arsenic, especially of some concern for children, are groundwater and subsequently rice that is grown in such groundwater. Rice is a common food for children but to date, there are no regulations about the levels of arsenic that are considered safe for consumption. The FDA and the EPA are currently collecting data to make a recommendation about safe levels but many groups are pushing the FDA to act soon. The groups claim some private laboratories have detected that a single adult serving of some commercially available rice can give about 1.5 times the amount of permissible arsenic in one liter of water (under 10 parts per billion), so action on permissible arsenic levels should be done quickly. In 2013, the CDC recommends only about 2 cups of cooked rice per individual (adult) per week.