Toxicity of Heavy Metals (with Symptoms, Effects, Poisoning and Treatment)!
1. Toxicity of Arsenic (As):
The name arsenic is derived from the Latin word arsenicum and the Greek word arsenikon (yellow orpiment). It can also be traced to the Arabic word, Az-zernikh, meaning the orpiment from zerni-zar, the Persian word for gold.
Elemental arsenic is a steel grey, very brittle, crystalline, semi-metallic solid, Arsenic tarnishes in air and is rapidly oxidized to arsenous oxide (As2O3) when health.
Soluble inorganic arsenic salts are highly toxic. The lethal dose of ingested arsenic trioxide is about 1-3 mg (kg body weight)-1 in adults while even lower exposure levels, 1-4 mg day-1, have caused serious health effects, including fatalities, in small children. The Morinage incident, where arsenic-contaminated powdered milk was fed to children, affected 12000 Japanese children and 130 fatalities were recorded.
Symptoms of arsenic intoxication include nausea, headache and severe abdominal pain due to damage to the gastro-intestinal mucous membranes, violent vomiting and diarrhea caused by paralysis of the capillary control in the intestinal tract. Eventually the gastrointestinal epithelium may be sloughed off, followed by a decrease blood volume, decreased blood pressure, disturbed heart action, failure of vital cardiovascular and brain functions and death.
The massive loss of water may lead to renal failure and anuria. Acute arsenic intoxication may also lead to a general paralysis of the capillaries, acute excitability of the brain and death through general paralysis.
Non-fatal acute intoxications may result in damage to the peripheral nervous system, manifested as sensory loss, and due to axonal degeneration. Other symptoms include anemia and leukopenia, fever, anorexia, hepatomegaly and melanosis.
Inhalation of arsenic cause respiratory tract symptoms, such as rhinitis, laryngitis and bronchitis. At high exposure levels, hyperplasia and atrophy in the respiratory tract and perforation of the nasal septum have been reported.
Sub-chronic and chronic exposure to inorganic arsenic has been associated with a reduction in nerve conduction velocity and hepatic injury. Peripheral vascular damage has been observed among people exposed to arsenic in drinking water in Taiwan and Chile. The disease may develop into gangrene of the lower extremities (‘Blackfoot disease’) and the effect appears to be associated with the cumulative dose of arsenic through drinking water.
Ingestion of arsenic induces characteristic changes in skin pigmentation. Areas of hyper- and hypopigmentation are frequently seen on the neck, chest and back. Palmoplantar and popular hyperkeratosis are other dermal manifestations, and these may eventually develop into malignant lesions.
Although Cd is found in foods, the levels are too low to be of any toxicological significance. Cadmium has many industrial uses, for example in electroplating, in low- melting alloys, in low-friction, fatigue-resistant bearing alloys, in solders, in batteries, in pigments, and as a barrier in atomic fission control.
Therefore, it is to be expected that low to moderate Cd content of the environment is widespread. Since chronic exposure to even low levels of trace elements can lead to health problems, Cd is of particular concern to those concerned with environmental quality.
Industrial exposure is the most prevalent cause of chronic and acute Cd toxicity. Chronic toxicity is manifested in humans by anoxia as a result of olfactory nerve damage, kidney dysfunction, and emphysema. Cadmium has also been implicated as a possible cause of lung cancer.
The Cd content of tobacco levels is significant, but there is no experimental evidence linking Cd in tobacco to emphysema and lung cancer. It has also been suggested that Cd may play a role in the production of arteriosclerosis, hypertension, and cardiovascular disease, but the data are limited and contradictory. It is worth noting that the body burden of Cd in smokers in 1.5 – 2 times than that of nonsmokers.
Acute Cd toxicity in humans often leads to pneumonitis ranging from severe to fatal. Vomiting, diarrhea, and prostration are also symptoms of acute Cd poisoning.
In laboratory animals, Cd produces reduced growth, kidney and liver damage, brain hemorrhages, skeletal decalcification, and testicular necrosis. Rats develop hypertension as a result of Cd ingestion. It is not clear whether the hypertension results primarily from kidney damage (which involves lesions in the renal arterial system, glomeruli, and the tubular system) or from the fact that low concentrations of Cd increase pressure response to norepinephrine. The latter result has been demonstrated in isolated arterial strips, and it should be noted that higher concentrations of Cd have the opposite effect.
The main biochemical finding in Cd toxicity is proteinuria as a result of renal damage. It has been postulated that the proteinuria results from Cd transport to the proximal tubules by metallothionein (a low molecular weight 211- and Cd-binding protein). In the tubules Cd acts upon enzymes that are responsible for reabsorption. Although the significance of the finding is unknown, tryptophan is not found in the low molecular weight proteins of serum and urine from the urine of humans with tubular proteinuria.
Cadmium affects the activities of several enzymes. Enhanced activity of δ- aminolevulinic acid dehydratase, pyruvate -dehydrogenase, and pyruvate decarboxylase have been noted, while depressed activity of 8-aminolevulinic acid synthetase, alcohol dehydrogenase, arylsulfatase, and lipoamide dehydrogenase result from Cd intoxication.
There is no known nutritional requirement for Hg and most of the Hg present in foods results from environmental contamination. Because it has many uses, there are numerous opportunities for contamination of food, air, and water with Hg. Elemental Hg is used in thermometers, barometers, diffusion pumps, Hg vapor lamps, electrical switches, dental fillings, paints, batteries, catalysts, and the manufacture of chlorine.
Mercury salts are used as medicine, paint pigments, explosive detonators, and in the manufacture of paper. Organic Hg compounds are used as fungicides for seed treatment and in the manufacture of certain types of plastic.
The body’s ability to eliminate Hg is limited, and therefore Hg is a cumulative poison. Reduced elimination appears to result from a high affinity of the tissues for Hg rather than poor excretion, since excretion kinetics are first orders. Mercury can be absorbed through the gastrointestinal and respiratory tracts and through the skin.
Elemental and organic Hg compounds are volatile, and only small quantities are needed to saturate the atmosphere. Both elemental and organic Hg compounds pass the blood- brain barrier, and thus can induce central nervous system symptomology. Methyl Hg compounds is particularly dangerous since tissue retention is even longer than for other forms of Hg. As a consequence, elemental and organic Hg compounds need to be handled with extreme caution.
Symptoms of Hg intoxication are varied. They range from excessive salivation and diarrhea to tremors, ataxia, irritability, dizziness, moodiness, and depression. Acute exposure to elemental Hg by inhalation results in pulmonary edema and the symptoms closely resemble influenza. If not immediately fatal, recovery is usually complete.
Chronic exposure can lead to symptoms of central nervous system involvement. The character of the Mad Hatter in Alice in Wonderland is derived from the fact that hat makers often suffered from neurological disorders resulting from the use of mercuric nitrate to treat felt. Mercury poisoning has also been observed in dental technicians and industrial workers.
Several epidemic-type outbreaks of organic Hg poisoning have been described in the literature. These have occurred in Pakistan, Guatemala, and Iraq as a result of human consumption of seed grains treated with organic Hg. Minamata disease occurred in Japan as a result of local inhabitants consuming fish and shellfish from Minamata Bay, into which a local plastics factory had been dumping methyl Hg.
Mercury compounds are highly reactive and can interact with various chemical groupings of proteins and nucleic acids. The binding of Hg to sulfhydryl groups of membrane proteins causes an inactivation of membrane ATPase and a blockage of glucose transport into the cell. Mercury also reacts with phosphoryl groups – of membranes, sulfhydryl, amino, and carboxyl groups of enzymes, and phosphoryl groups and bases of nucleic acids.
Exposure to Pb occurs in many forms, in addition to that of industrial hazards. Although Pb intake from paints, water pipes, tin, cans, and insecticides has decreased, exposure to other forms of Pb such as in motor vehicle exhausts and tobacco smoke has either stabilized or increased. Intake of Pb paint by children is still a problem in poor urban, neighborhoods where Pb-containing painted surfaces still remain.
Lead poisoning has been reported in the southern United States as a result of consumption of non-tax-paid, distilled alcoholic beverages commonly known as moonshine whiskey. Old auto radiators, which contain Pb, Cd, and Zn, are often used to distill illegal whiskey. Storage of acidic foods in cans in which solder is exposed or in crockery with Pb-containing glazes has also been reported to result in increased Pb concentration in the food.
Symptoms of Pb poisoning include abdominal pain, anemia, and lesions of the central and peripheral nervous systems. The lesions of the central nervous system cause behavioral problems. The anemia is characterized by a larger than normal number of erythrocytes and is of the hypochromic, microcytic type.
The principal biochemical effect of Pb intoxication in humans and animals is defective hemoglobin synthesis. Lead inhibits Fe incorporation into protoporphyrin, which results in lower heme concentrations and higher protoporphyrin concentrations in erythrocytes. Excretion of coproporphyrin is increased, and the Fe content of the blood plasma and bone marrow is elevated.
Lead also interferes with an earlier step in heme, synthesis by inhibiting 8-aminolevulinic acid dehydratase, which converts δ- aminolevulinic acid to porphobilinogen. The resulting increase in δ-aminolevulinic acid in blood and urine is a sensitive indicator plumbism of. In advanced Pb poisoning, synthesis of the globin moiety of hemoglobin is also inhibited.
The Na, K-APTase of red cell membranes is inhibited by Pb. Serum levels of transaminases and aldolase are increased by Pb exposure, while the serum levels of alkaline phosphatase and cholinesterase are decreased. Lead can also inhibit enzymes with a single, functional sulfhydryl group, but the effect of Pb on sulfhydryl groups is not as marked as that of Hg or Cd.
Lead interferes with tryptophan metabolism, probably by inhibiting monoamine oxidase (MAO). The inhibition of MAO by tetraethyl lead blocks serotonin catabolism in the brain, and the increased serotonin levels may account for some of the psychological and nerve function impairment.
5. Toxicity of Aluminium (Al):
Alum was used by the Greeks and Romans as a astringent in medicine and as a mordant in dyeing. The metal was isolated by Wohler in 1827. The element was named aluminium, derived from the Latin word salurnen or alum, in the early nineteenth century, although the American Chemical Society has used the name aluminium in their publications since 1925.
The element is mainly obtained from the mineral bauxite. Aluminium and aluminium alloys are appreciated owing to their strength and lightness and they have found a multitude of applications, including the manufacture of cooking utensils, aircrafts and rockets. Natural aluminium minerals are also used for water purification and aluminium salts have found use in antacids and antiperspirants.
The intake of aluminium in the form of antacids, although exceeding the normal dietary intake levels by two or three orders of magnitude, has not been associated with adverse health effects. The gastro-intestinal uptake of aluminium is generally very low but can be enhanced in the presence of citrate. Aluminium is a potential neurotoxic agent in humans. Cases of encephalopathy have been recorded in patients receiving dialysis treatment for renal failure.
The dialysis fluids used contained high concentrations of aluminium, usually above 200 igl-1. The pathogenic role of aluminium in the onset and progression of Alzheimer’s disease is controversial and not supported by available data. Occupational exposure to aluminium compounds has been associated with pulmonary fibrosis and irritant-induced asthma. However, the exposure situations are usually complex and involve other compounds that may contribute to the observed effects.
6. Toxicity of Beryllium (Be):
The name of the element can be derived from the Greek words beryllos and beryl. Beryllium was discovered as the oxide by Vauquelin in 1798 and the metal was independently isolated in 1828 by Wohler and Bussy. Aquamarine and emerald are precious forms of the mineral beryl.
Exposure to beryllium is primarily an occupational health problem. Massive exposure (>100 ig m-3) to airborne beryllium causes acute beryllium disease, characterized by chemical pneumonitis, which may be fatal (WHO, 1990b). Long-term exposure to lower concentrations of beryllium may cause chronic beryllium disease, a form of granulomatous interstitial pneumonitis with symptoms including dyspnea, cough and reduced pulmonary function.
The disease may have an immunological component. Recently, it was proposed that a genetic modification of the major histocompatibility complex allele HLA-DPB1 may be used as a biomarker of susceptibility to chronic beryllium disease.
The name originates from the German Weisse Masse (white mass), later transformed to Wisuth and Bisemutum. The element was confused with lead and tin in early times but shown to be distinct from lead in 1753 by Claude Geoffrey the Younger.
Bismuth is found in nature as the pure element and the oxide (Bi2O3) and sulphide (Bi2S3) and is mainly used in alloys but also a pigment in cosmetic preparations. Bismuth salts have been used medicinally in the treatment of gastric ulcers (bismuth subcitrate) and diarrhea (bismuth subsalicylate).
Reports on bismuth toxicity in humans are mainly found in connection with its therapeutic use. Nephropathies, encephalopathy, arthrosis, damage to the oral epithelium (gingivitis, stomatitis) and melanosis have been observed in patients treated with Bi- containing preparations. The effects depended on the type of preparations used.
During the mid-1970s, reports from France and Australia showed a form of bismuth-associated encephalopathy of known aetiology. The clinical symptoms described in both countries (confusion, tremor, motor disturbances) were similar and developed after prolonged therapy (from 4 weeks to 30 years) with high doses (0.7 – 20 g day/1) of mainly bismuth sub-nitrate (France) and bismuth subgallate (Australia).
The effects were often reversible and disappeared after ceasation of Bi therapy, although fatalities were also reported. In a review of 63 cases of bismuth-associated encephalopathy, blood bismuth levels of 170-2850 μg l-1 were reported among the patients. An epidemiological study saw no correlation between encephalopathy, and age, type of bismuth compound administered, dose or length of treatment.
Constipation was more prevalent as a therapeutic indication among the encephalopathy patients, whereas diarrhea and colon disease were more frequent among the controls (bismuth therapy without encephalopathy). The data suggested that the intestinal micro-flora may be of importance for the absorption of bismuth.
Chromium takes its name from the Greek word for colour, chroma. The element was discovered by Vauquelin in 1797.
Major sources of chromium exposure are chromated steel, cement, leather goods, and welding fumes. Chromium is a cause of occupational allergic contact dermatitis and the trivalent form of chromium [Cr(III)] is considered to be the sensitizing agent. Hexavalent chromium may be released from chromium metal by the corrosive action of sweat and penetrate the skin. Cr(VI) is subsequently reduced to Cr(III). Inhalation of corrosive Cr(VI) compounds may lead to ulceration and perforation of the nasal septum.
Acute exposure to chromium cases death preceded by nausea, vomiting, shock and coma. Intravascular hemolysis and acute renal failure have also been reported from ingestion of potassium dichromate. Chronic exposure causes respiratory effects viz.- ulcerated preformation of nasal septum, irritation of mucous membranes and general bronchospasm. Effects of chromium on skin are well known. Chromium ulcers or chrome holes are characteristic lesions.
Hexavalent chromium is much more toxic than trivalent. In fact trivalent chromium has such a low order of toxicity that a wide margin of safety exists between the amounts ordinarily ingested and those likely to induce deleterious effects. Cats tolerate 1000 mg/day and rats showed no adverse effects from 100 mg/kg diet.
Lifetime exposure to 5 mg/liter of chromium (III) in the drinking water induced no toxic effects in rats and mice, and exposure of mice for three generations to chromium oxide at levels up to 20 ppm of the diet had no measurable effect on mortality, morbidity, growth, or fertility.
Chronic exposure to chromate dust has been correlated with increased incidence of lung cancer, and oral administration of 50 ppm of chromate has been associated with growth depression and liver and kidney damage in experimental animals.
9. Toxicity of Nickel (Ni):
The name of the element is derived from the German word Kupftrnickel meaning ‘Old Nick’s (= Satan’s) copper’. Nickel was discovered by Cronstedt in 1751.
Exposure to nickel and its salts is regarded as one of the most common causes of human skin sensitization and allergic contact dermatitis. Dermal exposure to nickel may occur through jewellery, wrist watches with metal backs, coins and jeans buttons. The prime cause of nickel sensitization is ear piercing in combination with nickel-containing jewellery.
The risk of sensitization has led to the adoption of nickel release limits for jewellery and other metal objects in close skin contact. It has been shown that exposure to nickel generates nickel-specific T-lymphocytes, probably mediated by nickel interaction with the major histocompatibility class II-peptide complex.
Cobalt was isolated by the Swedish chemist Georg Brandt in the middle of the eighteenth century, although compounds containing cobalt were used already in ancient Egypt. Kobold was a name applied during the sixteenth century to ores eventually found to be toxic, arsenic-bearing cobalt ores.
Cobalt is essential to humans in the form of cyanocobalamin (vitamin B12). Cobalamins function in rearrangement (adenosylcobalamin) and methyl transfer (methyl cobalamin) reactions. Vitamin B12 is essential for the production of red blood cells.
Intoxications (cardiomyopathies) due to its use as foam stabilizer in beer were described by Bonenfant et al. (1967). Inhalation of cobalt-containing dust may cause respiratory irritation and ‘hard-metal’ pneumoconiosis, developing into interstitial fibrosis.
The element was discovered in prehistoric times and has its name from the island of Cyprus (Latin: cuprum). Copper is an essential trace element and necessary for the functioning of several enzymes involved in electron transfer (cytochrome oxidase), free radical defence (catalase, superoxide dismutase) and melanin formation (tyrosinase). Copper is also essential for the utilization of iron and formation of haemoglobin.
Intoxication by copper salts results in vomiting, hypertension, coma and death. Excess hepatic copper causes hepatitis leading to cirrhosis, hepatic failure and ultimately death. The liver shows pericentral necrosis. Copper may initiate lipid peroxidation through hydroxyl radical formation in a mechanism analogous to the Haber-Weiss cycle.
The chemical name stems from the Latin word ferrum. The use of iron is prehistoric and the element is mentioned in Genesis- Tubal-Cain, seven generations from Adam, was ‘an instructor of every artefact in brass and iron’. The most common ore is magnetite (Fe2O3).
Carbon steel is an alloy of iron with carbon, and alloy steels are carbon steels with additives such as nickel, chromium and vanadium, hepatic necrosis and renal failure. Primary hemochromatosis is a disease with autosomal recessive inheritance characterized by an increased absorption of iron in the gastrointestinal tract resulting in chronic iron overload, hepatic portal fibrosis and ultimately cirrhosis.
The defect has been localized to chromosome 6 closely linked to the HLA locus. Redox cycling of iron may lead to hydroxyl radical formation and lipid peroxidation, which have been implicated as crucial events in iron toxicity.
The name is derived from the word selene, the Greek name for moon. Selenium was discovered by Berzelius in 1817. The element was associated with tellurium, named after Tellus, the Earth. Selenium is obtained from byproducts during refining of copper and in sulphuric acid production.
The content of selenium in crops, the main human source of exposure, largely depends on the selenium content of the soil, which varies substantially around the world. An average daily requirement of selenium of about 0.4 ig (kg body weight)-1 for adults has been calculated by the WHO (1996).
A number of toxic manifestations due to acute or chronic exposure to selenium have been demonstrated in animals and man. Negative health signs (brittle hair and nails, prolonged plasma prothrombin time, skin lesions and changes in perpheral nerves) have been observed at daily intake exceeding 750 – 850 ig Se.
The mechanism(s) remain unclear, although several hypotheses including disturbances in sulphur metabolism, glutathione depletion and redox cycling of selenium metabolites have been presented. Based primarily on the studies performed in a seleniferous region in China, a maximum safe dietary selenium intake of 400 ig day-1 for adults has been suggested by WHO (1996).