Arsenic (symbol As) is a chemical element with athomic number 33 and mass number 74.92.
It is an allotropic metalloid and can be found in different forms:
- metalloidal (semimetallic)
- in molecular non metallic form (yellow) As4
- as arsenide and in arsenate compounds (more commonly), non metallic
It's a natural element usually found in soil and minerals.
It can get into air, water and the ground from wind blown dust. It may also get into water from runoff. Humans are exposed to arsenic through air, drinking water, and food (meat, fish, and poultry); poultry is usually the largest source of food based arsenic injestion due to usage of certain antibiotics in chicken feed. Arsenic was also found in wine if arsenic pesticides are used in the vineyard.
Industries that use inorganic arsenic and its compounds include wood preservation, glass production, nonferrous metal alloys, pesticides, and electronic semiconductor manufacturing. Inorganic arsenic is also found in coke oven emissions associated with the smelter industry.
Occupational exposure to arsenic may occur with copper or lead smelting and wood treatment, among workers involved in the production or application of pesticides containing organic arsenicals.
Arsenic is well absorbed (more than 50% of the taken dose) by oral and inhalatory routes, widely distributed and excreted in urine and feces.
The remaining non-excreted arsenic (= 10%) accumulates in cells, which over time can lead to cancer.
Inorganic As can pass placenta and cause fetal damage.
Organic arsenical compounds are considered less toxic than inorganic ones. In fact they are less absorbed, detoxified by liver methylation and easily eliminated.
In the liver, the metabolism of arsenic involves enzymatic and non-enzymatic methylation, the most frequently excreted metabolite (= 90%) in the urine of mammals is dimethylarsinic acid (DMA).
In humans inorganic arsenic is reduced nonenzymatically, from pentavalent to trivalent state using glutathione (GSH), or enzymatically.
Research has shown that arsenites (trivalent forms) have a higher acute toxicity than arsenates (pentavalent forms).
Metabolism and toxicity of arsenic: A human carcinogen
WAY OF ACTION
Main toxic effects are caused by inorganic As:
- As (V): uncouples oxidative phosphorylation by competing with inorganic phosphate and blocking ATP synthesis (As+ADP -> unstable arsenate)
- As (III): binds to sulfhydryl groups (R-SH), thus reacts with a variety of proteins and inhibits their activity (e.g: pyruvate dehydrogenase, glutathione reductase and thioredoxin reductase)
Arsenite inhibits not only the formation of Acetyl-CoA but also the enzyme succinic dehydrogenase.
Arsenate can replace phosphate in many reactions.
Therefore, arsenic poisoning kills by allosteric inhibition of essential metabolic enzymes, leading to death from multi organ failure. It primarily inhibits enzymes that require lipoic acid as a cofactor, such as pyruvate and alpha-ketoglutarate dehydrogenase.
Tissue culture studies have shown that arsenic blocks potassium dependent voltage channels.
It particularly affects both IKr and Iks channels and activates IK-ATP channels, disrupting cellular electrolytic function resulting in neurological disturbances, prolonged q-t interval, central nervous system dysfunction and death.
Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress.
The toxicity of arsenic and its compounds is not highly variable. The acute minimal lethal dose of arsenic in adults is estimated to be 70 to 200 mg or 1 mg/kg/day. Most reported arsenic poisonings are not caused by elemental arsenic, but by one of arsenics compounds, especially arsenic trioxide, which is approximately 500 times more toxic than pure arsenic.
- Acute toxicity (inorganic As)
nausea, vomiting (greenish or yellowish, sometimes streaked with blood), abdominal pains
circulatory system: vasodilatation, increased permeability, edema, dehydration, hypotension, letal shock
gastroenteric system: diarrhea (sometimes haematic, because of vesicles formation and rupture with epithelial damage)
kidneys: glomerular and tubular damage, proteinuria
PNS: peripheral sensitive and motorial neuropathy
CNS: encefalopathy caused by orgnic damage, delirium, coma
bone marrow: pancitopenia
liver: steatosis, necrosis, cirrhosis
Chronic exposure to inorganic arsenic may lead to hypertension, vasospasm, involuntary muscular dysfunction and weakness (including incontinence), Mees lines on nails (white), "milk and roses", skin hiperpigmentation due to anemia and vasodilatation, garlic breath odor, liver and neuro- toxicity, hyperkeratosis, diabetes (related to alteration of voltage dependent potassium channels due in part to the function of insulin and potassium in the cellular metabolism of glucose). It may also lead to skin, bladder, kidney, liver, lung, and prostate cancers.
Uncommon. As is neurotoxic and causes organic damage for SH groups inibition in white and gray matter.
- Arsine (AsH3) intoxication
Inhalatory absorption. Arsine combinet with haemoglobine and causes hemolitic episodes. Emoglobinuria with dark urines, jaundice, astenia, headache, progressive tubular damage, acute renal failure.
There are tests available to diagnose poisoning by measuring arsenic in blood, urine, hair, and fingernails. The urine test is the most reliable test for arsenic exposure within the last few days. Urine testing needs to be done within 24–48 hours for an accurate analysis of an acute exposure. Tests on hair and fingernails can measure exposure to high levels of arsenic over the past 6–12 months. These tests can determine if one has been exposed to above-average levels of arsenic. They cannot predict, however, whether the arsenic levels in the body will affect health.
Immediatly: vomiting induction, gastric lavage, activated charcoal with a cathartic (such as sorbitol). Aggressive therapy with intravenous fluid and electrolyte replacement in an intensive-care setting may be life-saving.
Dimecaprol is the chelating agent of choice and is administered intramuscularly at an initial dose of 3 to 5 mg/kg on the following schedule: every 4 h for 2 days, every 6 h on the third day, and every 12 h thereafter for 10 days. Succimer is sometimes an effective alternative, particularly if adverse reactions to dimercaprol develop (such as nausea, vomiting, headache, increased blood pressure, and convulsions). In cases of renal failure, doses should be adjusted carefully, and hemodialysis may be needed to remove the chelating agent-arsenic complex.
Exchange transfusion, haemodialysis.
Arsine gas poisoning should be treated supportively with the goals of maintaining renal function and circulating red-cell mass.