Toxicity of Arsenic 2231 Human

Arsenic is a metal that can generate multiple adverse health effects because of the many chemical forms it takes. Arsine gas (AsH3) is the most toxic compound having a fatal dose of 250 mg/m3 at an exposure time of 30 min (Bissen and Frimmel 2003a). The lethal dose (LD50) for arsenic trioxide is 34.5 mg/kg (fatal dose for adults: 120300 mg), sodium arsenite 4.5 mg/kg, sodium arsenate 14-18 mg/kg, monomethylar-sonic acid 1,800 mg/kg, dimethylarsinic acid 1,200 mg/kg, and trimethylarsine 8,000 mg/kg (Yamauchi and Fowler 1994; Bissen and Frimmel 2003a).

As(III) is absorbed faster in biological systems than As(V), however both the oxidation states are reported to inhibit the energy-linked functions of the mitochondria. As(III) compounds have a high affinity to sulfhydryl groups in proteins and can cause deactivation of enzymes. As(V) competes with phosphate in cell reactions and can uncouple oxidative phosphorylation so that the high-energy - bonds of adenosine triphosphate are not conserved (Gorby 1994; Squibb and Fowler 1993; Pontius et al. 1994; Bissen and Frimmel 2003a).

Arsenic can cause both acute and chronic poisoning. Chronic arsenic poisoning involves non-specific symptoms such as weakness, loss of reflexes, weariness, gastritis, colitis, anorexia, weight loss, and hair loss. Long-term exposure through food or air results in hyperkeratosis, hyperpigmentation, cardiovascular diseases, disturbance in the peripheral vasculature and nervous systems, circulatory disorders, brittle loose nails with transverse white bands across the nails called Mees lines, eczema, suffering from liver and kidney disorder. Arsenic is deposited in hair, skin, nails, and bones (Vahter 1983; Hindmarsh and Mc Curdy 1986; Lu 1990; Hall 2002; Bissen and Frimmel 2003a).

Acute arsenic poisoning may cause vomiting, dryness of the mouth and throat, muscle cramps, colicky abdominal pain, tingling of the hands and feet, circulatory disorders, and nervous weakness, the skin may become cold and clammy, hallucinations, delirium, and diarrhoea may also appear, fatal shock can develop due to renal failure. Death may result within a short time due to hepatic failure, renal failure, or heart attack (Gorby 1994; Bissen and Frimmel 2003a). The human body can detoxify the inorganic arsenic compounds As(III) and As(V) by methylation to a certain amount to reduce the affinity of arsenic for tissue. The possibility of methylation of arsenic is limited to an arsenic uptake of 400-500 mg/day (Pontius et al. 1994; Bissen and Frimmel 2003a). Arsenic compounds are excreted in the urine after 3-4 days (Yamauchi and Fowler 1994; Pontius et al. 1994; Bissen and Frimmel 2003a). The individual sensitivity to arsenic differs. Humans who are not accustomed to the consumption of arsenic die at an arsenic uptake between 0.1 and 0.3 g/day. However, chronic arsenic consumption reportedly increased the tolerance to 1 g/day H3AsO3 without manifestations of acute poisoning (Morton and Dunnette 1994; Bissen and Frimmel 2003a).

Arsenic is found to inhibit the repair of DNA damage. It is also carcinogenic as uptake of arsenic causes lung cancer, bladder cancer, renal cancer, liver cancer, and skin cancer (Bates et al. 1992; Pontius 1994; Kessel et al. 2002; Roy and Saha 2002; Bissen and Frimmel 2003a).

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