Concise and comprehensive toxicological review paper on arsenic

Toxicological report: Arsenic
Name
Course
Professor
Date
1 Introduction
Millions of people worldwide are affected by toxicity caused by Arsenic metal. Contamination cause by arsenic is a global issue. This happens when arsenic which naturally occurs in geological sources leach into water bodies and aquifers and contaminates drinking water. Mining and other manufacturing industries are also sources of arsenic toxicity. In addition, conventional medicines also contain this toxicity. Arsenic trioxide is also used for medicinal purpose in the treatment of severe promyelocytic leukemia. Absorption in to the body occurs in two ways; assimilation from the small intestines and from skin contact and inhalation. The former is the major way in which arsenic enters the body. Arsenic poisons the body by disabling enzyme functions. Up to 200 enzymes are effected mostly those associated with DNA synthesis and repair and provision of cellular energy. Symptoms of acute arsenic poisoning include abdominal pain, nausea, diarrhea, and vomiting. This often affects multiple systems in the body since it is carcinogenic. Arsenic prone areas in the world include Bangladesh and West Bengal in India. These two regions are the most hit with about 79 million people exposed to arsenic in Bangladesh and 40 million in West Bengal. The world health organization allows a maximum of 50 μg/l ingestion of arsenic in drinking water. However in these regions the amounts ingested exceed this amount. There is no treatment for acute arsenic poisoning as at now but scientists have come up with antioxidants even though their workability has not been proved. The most effective way to control arsenic poisoning is by avoiding unsafe drinking water or switching to better water supply (National Academy Press.52, 1999). 
2 CHEMISTRY AND TOXICITY
Arsenic exists in two oxidation states either in trivalent or pentavalent form. This is arsenite (As2O3 ) and arsenate (As2O5) respectively. Arsenic in the trivalent form is said to be more toxic than in pentavalent form up to 60 times. It is important to comprehend that toxicity only arises from inorganic arsenic since the organic arsenic is non toxic. Toxicity by inorganic arsenic alters DNA replication and repair by deactivating enzymes associated with it. Arsenic replaces phosphate in the body in cases of ATP among other high energy compounds. Another way arsenic poisons the body is by producing reactive oxygen intermediates (Federal Register 2001). This usually happens during the redox cycle and metabolic oxidation involved with the preoxidation of fat and damaging of the DNA. This is often triggered by trivalent arsenic such as sulfhydryl when it accumulates in major organs and tissues like lungs, liver, kidney, spleen, skin and hair.
3 TOXICOKINETICS
Arsenic Exposure
There are many ways by which individuals are exposed to arsenic depending on their environment. Mostly exposure occurs by ingestion of arsenic from contaminated water. In addition exposure includes inhalation, and through contact with the skin. In food, the occurrence of arsenic is as non toxic organic compounds. Among the common sources include fish, algae and sea food. Even though these organic compounds increase the amount of arsenic in the blood stream they are usually excreted from the body in their former state. The intake of arsenic through solid food is high as compared to its intake through liquids and drinking water. Agricultural products are the means by which arsenic enters the plant food chain. In addition, the use of contaminated irrigated water or arsenic based fertilizers is other means by which arsenic enters the food chain (Gosselin 12, 2008).
Absorption
Arsenic absorption usually occurs in the small intestines. This involves an elcetrogenic process with a proton(H +) gradient. An environment with a suitable pH of 5.0 is perfect for the absorption of arsenic. This is in exception of the small bowel`s milieu which has a pH of about 7.0 because of the secretion of pancreatic bicarbonate.
Metabolism and Excretion
Once arsenic is absorbed into the body it goes through hepatic biomethylation. The outcome of this process is the formation of monomethylarsonic acid and dimethylarsinic acid. Even these acids are not toxic they cannot be ruled out as harmless. Almost half of the ingested amount of arsenic may find its way out of the body mostly through urine after approximately four days. In the urine, the dominant acids are Dimethylarsinic at about 70% in comparison to monomethylarsonic acid. Also some amount of inorganic arsenic is also excreted in its former state. Following acute poisoning, the liver and kidney exhibit the highest concentration of arsenic in accordance to electrothermal atomic absorption spectrometry. This is different from chronic ingestion whereby accumulation occurs in the liver, lungs, kidney and heart. Traces of arsenic will also be found in the muscles, nervous system and the spleen. In the long run most of this deposits are cleared but significant amounts remain in the tissues harboring keratin; nails ,skin and hair.
4 TOXICODYNAMICS
Acute Toxicity
Acute toxicity of arsenic often happens accidentally for instance when an individual ingests insecticide or pesticide. Suicide is another method but is less common. If the amount of ingested arsenic is small at about 5mg the result will be vomiting and diarrhea. This is temporary and lasts for not more than 12 hours. Seeking treatment is not necessary unless the individual becomes dehydrated. If the amount of arsenic ingested falls anywhere between 100 and 300 mg, the situation becomes life threatening. According to The Risk Assessment Information System database, a deadly amount of inorganic arsenic ingested is 0.6mg/kg/day. Demise occurs usually from 24 hours to four days depending on the amount taken. Initial symptoms usually associated with the gastrointestinal system include abdominal pain, nausea, vomiting, and lots of loose and watery diarrhea. Other features include excessive salivation, acute psychosis, skin rushes and even seizures (Gosselin 20, 2008).
Peripheral neuropathy is the most apparent neurological manifestation that may last for upto two years. It may lead to rapid and severe ascending weakness requiring mechanical ventilation. Another common manifestation is encephalopathy, possibility of arsenic poisoning if its aetiology is uncertain. Encephalopathy has been caused by intravenous administration of arsphenamine, its basis is thought to be due to hemorrhage. There have been reports of metabolic changes with acute arsenic toxicity. Also acidosis has occurred a particular patient while in cattle, hypoglycemia and hypocalcaemia has been experienced. The best known indicator of acute poisoning on recent ingestion i.e. one to two days is through urinary arsenic concentration.
Chronic Toxicity
This is as a result of long-termarsenic toxicity, it often leads to multisystem disease the most severe one being malignancy. The various effects of arsenic toxicity or rather the clinical features vary between individuals, geographical areas and population groups. Apparently it is still unclear on the factors that affect the occurrence of a particular clinical manifestation or the particular body that is targeted, hence the wide range of clinical features from a person exposed to this chronic toxicity. Its onset comes with non-specific symptom of sore throat, abdominal pain, and diarrhea. Various organs are affected, this is as discussed below.
* Skin
Several skin changes may occur with longterm exposure. A common feature is dermatological changes and the primary clinical diagnosis is often based on hyperpigmentation, solar keratosis and palmar. Both palmar and solar keratosis is classified as of significant diagnostic criterion. Physically keratosis may appear as either discrete nodules or as uniform thickening. As for hyperpigmentation, it may occur as diffuse dark brown spots or sometimes as less discrete darkening of the skin that has the likeness of a rain drop. Bowen`s disease which is an arsenic associated form of cancer is uncommon with Asians, this may be due to their high skin melanin content and also the significant increased exposure to sunlight i.e. ultraviolet radiation. To those with non-melanin pigmented skin arsenic may cause a basal cell carcinoma. The dormant period after exposure may be up to 60 years has been revealed in sheep dip workers, vineyard workers using arsenic pesticides and also from taking contaminated wine. In the transverse white lines in the fingernails and the toenails is another manifestation of arsenic in keratin rich areas (Gosselin 29, 2008).
* Gastrointestinal system
As earlier stated, diarrhea is a major onset signal of acute arsenic toxicity. In this case it occurs inrecurrent bouts and may be associated with retching. One may be suspected of arsenic ingestion if other symptoms such as changes in skin and neuropathy are also present.
* Cardiovascular System
Diseases in this system are often reported in smelter workers due to arsenic exposure. It causes hypersensitive heart disease, hypertension due to exposure to arsenic well water,ischaemic heart disease in "arseniasis- hyperendemic villages" is lin...