Arsenic poisoning
Arsenic poisoning is a medical condition that occurs due to elevated levels of arsenic in the body. If arsenic poisoning occurs over a brief period, symptoms may include vomiting, abdominal pain, encephalopathy, and watery diarrhea that contains blood. Long-term exposure can result in thickening of the skin, darker skin, abdominal pain, diarrhea, heart disease, numbness, and cancer.
The most common reason for long-term exposure is contaminated drinking water. Groundwater most often becomes contaminated naturally; however, contamination may also occur from mining or agriculture. It may also be found in the soil and air. Recommended levels in water are less than 10–50 μg/L. Other routes of exposure include toxic waste sites and pseudo-medicine. Most cases of poisoning are accidental. Arsenic acts by changing the functioning of around 200 enzymes. Diagnosis is by testing the urine, blood, or hair.
Prevention is by using water that does not contain high levels of arsenic. This may be achieved by the use of special filters or using rainwater. There is no good evidence to support specific treatments for long-term poisoning. For acute poisonings treating dehydration is important. Dimercaptosuccinic acid or dimercaptopropane sulfonate may be used; but dimercaprol is not recommended, because it tends to increase uptake of other co-occurring toxic heavy metals. Hemodialysis may also be used.
Through drinking water, more than 200 million people globally are exposed to higher-than-safe levels of arsenic. The areas most affected are Bangladesh and West Bengal. Exposure is also more common in people of low income and minorities. Acute poisoning is uncommon. The toxicity of arsenic has been described as far back as 1500 BC in the Ebers papyrus.
Signs and symptoms
Ingesting large amounts of arsenic can cause symptoms similar to food poisoning, with abdominal pain, nausea, vomiting, and diarrhea starting within hours. Bloody diarrhea can cause severe fluid loss, resulting in hypovolemic shock. The heart and nervous system can also be affected, causing disruption to heart rhythms, heart failure, confusion, seizures, brain swelling, coma, and death. Inhaling arsine gas – the most toxic form of arsenic – causes a multisystem disease starting 2 to 24 hours after inhalation. Symptoms include gastrointestinal distress, headache, weakness, difficulty breathing, kidney and liver dysfunction, and the destruction of red blood cells.Chronic ingestion of lower levels of arsenic causes visible changes in the skin, typically hyperpigmentation, but sometimes hypopigmentation or alternating areas of each. Some experience general thickening of the skin on the palms and soles of the feet, or small thickened areas. Around 5% of those affected develop light-colored bands across the fingernail, called Mees' lines. Chronic exposure eventually causes disease across multiple body systems, including peripheral neuropathy, enlargement of the liver and spleen, diabetes, heart disease, cognitive impairment, and damage to the portal vein.
Repeated arsenic exposure also increases the risk for developing several cancers, particularly of the skin, lung, liver, bladder, prostate, and blood vessels. The most common arsenic-induced skin cancer is squamous cell carcinoma in situ which typically occurs 2 to 20 years after arsenic exposure.
Causes
Arsenic poisoning is caused by incidental ingestion or inhalation of arsenic, typically from drinking contaminated well water, eating food cooked in contaminated water, or being exposed to arsenic-containing pesticides, folk medicines, or industrial chemicals. The World Health Organization considers arsenic levels above 10 parts per billion to be unsafe.Groundwater
Arsenic is a ubiquitous naturally occurring chemical element, and the 20th most common element on Earth. Arsenic levels in the groundwater vary from around 0.5 parts per billion to 5000 parts per billion, depending on an area's geologic features, and possible presence on industrial waste. The highest groundwater arsenic levels have been recorded in Brazil, Cambodia, Afghanistan, Australia, and Bangladesh.Arsenic is a ubiquitous element present in American drinking water. In the US, the U.S. Geological Survey estimates that the median groundwater concentration is 1 μg/L or less, although some groundwater aquifers, particularly in the western United States, can contain much higher levels. For example, median levels in Nevada were about 8 μg/L but levels of naturally occurring arsenic as high as 1000 μg/L have been measured in the United States in drinking water. Groundwater associated with volcanics in California contains arsenic at concentrations ranging up to 48,000 μg/L, with arsenic-bearing sulfide minerals as the main source. Geothermal waters on Dominica in the Lesser Antilles also contain concentrations of arsenic >50 μg/L. In Wisconsin, arsenic concentrations of water in sandstone and dolomite aquifers were as high as 100 μg/L. Oxidation of pyrite hosted by these formations was the likely source of the arsenic. In the Piedmont of Pennsylvania and New Jersey, groundwater in Mesozoic age aquifers contains elevated levels of arsenic—domestic well waters from Pennsylvania contained up to 65 μg/L, whereas in New Jersey the highest concentration measured recently was 215 μg/L.
Rice and seafood
Organic arsenic is less harmful than inorganic arsenic. Seafood is a common source of the less toxic organic arsenic in the form of arsenobetaine.In the United States, Schoof et al. estimated an average adult intake of 3.2 μg/day, with a range of 1–20 μg/day. Estimates for children were similar. Food also contains many organic arsenic compounds. The key organic arsenic compounds that can be routinely found in food include monomethylarsonic acid, dimethylarsinic acid, arsenobetaine, arsenocholine, arsenosugars, and arsenolipids. DMAsV or MMAsV can be found in various types of fin fish, crabs, and mollusks, but often at very low levels.
Arsenobetaine is the major form of arsenic in marine animals and is considered nontoxic. Arsenocholine, which is mainly found in shrimp, is chemically similar to arsenobetaine, and is considered to be "essentially nontoxic". Although arsenobetaine is little studied, available information indicates it is not mutagenic, immunotoxic, or embryotoxic. Arsenosugars and arsenolipids have recently been identified. Exposure to these compounds and their toxicological implications are currently being studied. Arsenosugars are detected mainly in seaweed but are also found to a lesser extent in marine mollusks. Studies addressing arsenosugar toxicity, however, have largely been limited to in vitro studies, which show that arsenosugars are significantly less toxic than both inorganic arsenic and trivalent methylated arsenic metabolites.
It has been found that rice is particularly susceptible to the accumulation of arsenic from soil. Rice grown in the United States has an average 260 ppb of arsenic, according to a study; but U.S. arsenic intake remains far below World Health Organization-recommended limits. China has set a standard for arsenic limits in food, as levels in rice exceed those in water.
Air
The European Commission reports that levels of arsenic in air range 0–1 ng/m3 in remote areas, 0.2–1.5 ng/m3 in rural areas, 0.5–3 ng/m3 in urban areas, and up to about 50 ng/m3 in the vicinity of industrial sites. Based on these data, the European Commission estimated that in relation to food, cigarette smoking, water, and soil, air contributes less than 1% of total arsenic exposure.Pesticides
The use of lead arsenate pesticides has been effectively eliminated for over 50 years. However, due to the pesticide's environmental persistence, it is estimated that millions of acres of land remain contaminated with lead arsenate residues. This presents a potentially significant public health concern in some areas of the United States, where large areas of land used historically as orchards have been converted into residential developments.Some modern uses of arsenic-based pesticides still exist. Chromated copper arsenate has been registered for use in the United States since the 1940s as a wood preservative, protecting wood from insects and microbial agents. In 2003, manufacturers of chromated copper arsenate initiated a voluntary recall of residential wood treated with the chemical. The Environmental Protection Agency Act 2008 final report stated that chromated copper arsenate is still approved for use in nonresidential applications, such as in marine facilities, utility poles, and sand highway structures.
Copper smelting
Exposure studies in the copper smelting industry are much more extensive and have established definitive links between arsenic, a by-product of copper smelting, and lung cancer via inhalation. Dermal and neurological effects were also increased in some of these studies. Although as time went on, occupational controls became more stringent and workers were exposed to reduced arsenic concentrations, the arsenic exposures measured from these studies ranged from about 0.05 to 0.3 mg/m3 and are significantly higher than airborne environmental exposures to arsenic.Pathophysiology
Arsenic interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenase complex, which catalyzes the oxidation of pyruvate to acetyl-CoA by NAD+. With the enzyme inhibited, the energy system of the cell is disrupted resulting in cellular apoptosis. Biochemically, arsenic prevents the use of thiamine resulting in a clinical picture resembling thiamine deficiency. Poisoning with arsenic can raise lactate levels and lead to lactic acidosis. Low potassium levels in the cells increase the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide.Arsenic in cells clearly stimulates the production of hydrogen peroxide. When the H2O2 reacts with certain metals such as iron or manganese, it produces a highly reactive hydroxyl radical. Inorganic arsenic trioxide found in ground water particularly affects voltage-gated potassium channels,
disrupting cellular electrolytic function resulting in neurological disturbances, cardiovascular episodes such as prolonged QT interval, neutropenia, high blood pressure,
central nervous system dysfunction, anemia, and death.
Arsenic has also been shown to induce cardiac hypertrophy by activating certain transcription factors involved in pathologically remodeling the heart. Tissue culture studies have shown that arsenic compounds block both IKr and Iks channels and, at the same time, activate IK-ATP channels. Arsenic compounds also disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. These metabolic interferences lead to death from multi-system organ failure, probably from necrotic cell death, not apoptosis. A post mortem reveals brick red colored mucosa, due to severe hemorrhage. Although arsenic causes toxicity, it can also play a protective role.