Gunnar Nordberg

Magnesium (Mg) is the lightest structural metal known. It is 40% lighter than aluminium. Metallic magnesium can be rolled and drawn when heated between 300 and 475 ºC, but is brittle below this temperature and is apt to burn if heated much above it. It is soluble in, and forms compounds with, a number of acids, but is not affected by hydrofluoric or chromic acids. Unlike aluminium, it is resistant to alkali corrosion.

Occurrence and Uses

Magnesium does not exist in a pure state in nature, but is generally found in one of the following forms: dolomite (CaCO₃·MgCO₃), magnesite (MgCO₃), brucite (Mg(OH)₂), periclase (MgO), carnallite (KClMgCl₂·6H₂O) or kieserite (MgSO₄·H₂O). In addition, it is found as a silicate in asbestos and talc. Magnesium is so widely distributed over the earth that facilities for processing and transporting the ore are often the determining factors in selecting a site for mining.

Magnesium is used, mainly in alloy form, for components of aircraft, ships, automobiles, machinery and hand tools for which both lightness and strength are required. It is used in the manufacture of precision instruments and optical mirrors, and in the recovery of titanium. Magnesium is also extensively used in military equipment. Because it burns with such intense light, magnesium is widely used in pyrotechnics, signal flares, incendiary and tracer bullets, and in flash bulbs.

Magnesium oxide has a high melting point (2,500 ºC) and is often incorporated into the linings of refractories. It is also a component of animal feeds, fertilizers, insulation, wallboard, petroleum additives and electrical heating rods. Magnesium oxide is useful in the pulp and paper industry. In addition, it serves as an accelerator in the rubber industry and as a reflector in optical instruments.

Other important compounds include magnesium chloride, magnesium hydroxide, magnesium nitrate and magnesium sulphate. Magnesium chloride is a component of fire extinguishers and ceramics. It is also an agent in fireproofing wood and textile and paper manufacture. Magnesium chloride is a chemical intermediate for magnesium oxychloride, which is used for cement. A mixture of magnesium oxide and magnesium chloride forms a paste which is useful for floors. Magnesium hydroxide is useful for the neutralization of acids in the chemical industry. It is also used in uranium processing and in sugar refining. Magnesium hydroxide serves as a residual fuel-oil additive and an ingredient in toothpaste and antacid stomach powder. Magnesium nitrate is used in pyrotechnics and as a catalyst in the manufacture of petrochemicals. Magnesium sulphate has numerous functions in the textile industry, including weighting cotton and silk, fireproofing fabrics, and dyeing and printing calicos. It also finds use in fertilizers, explosives, matches, mineral water, ceramics and cosmetic lotions, and in the manufacture of mother-of-pearl and frosted papers. Magnesium sulphate increases the bleaching action of chlorinated lime and acts as a water-correcting agent in the brewing industry and a cathartic and analgesic in medicine.

Alloys. When magnesium is alloyed with other metals, such as manganese, aluminium and zinc, it improves their toughness and resistance to strain. In combination with lithium, cerium, thorium and zirconium, alloys are produced which have an enhanced strength-to-weight ratio, along with considerable heat-resisting properties. This renders them invaluable in the aircraft and aerospace industries for the construction of jet engines, rocket launchers and space vehicles. A large number of alloys, all containing over 85% magnesium, are known under the general name of Dow metal.

Hazards

Biological roles. As an essential ingredient of chlorophyll, the magnesium requirements of the human body are largely supplied by the consumption of green vegetables. The average human body contains about 25 g of magnesium. It is the fourth most abundant cation in the body, after calcium, sodium and potassium. The oxidation of foods releases energy, which is stored in the high-energy phosphate bonds. It is believed that this process of oxidative phosphorylation is carried out in the mitochondria of the cells and that magnesium is necessary for this reaction.

Experimentally produced magnesium deficiency in rats leads to a dilation of the peripheral blood vessels and later to hyperexcitability and convulsions. Tetany similar to that associated with hypocalcaemia occurred in calves fed only milk. Older animals with magnesium deficiency developed “grass staggers”, a condition which appears to be associated with malabsorption rather than with a lack of magnesium in the fodder.

Cases of magnesium tetany resembling those caused by calcium deficiency have been described in humans. In the reported cases, however, a “conditioning factor”, such as an excessive vomiting or fluid loss, has been present, in addition to inadequate dietary intake. Since this tetany clinically resembles that caused by calcium deficiency, a diagnosis can be made only by determining the blood levels of calcium and magnesium. Normal blood levels range from 1.8 to 3 mg per 100 cm³, and it has been found that persons tend to become comatose when the blood concentration approaches 17 mg per cent. “Aeroform tumours” due to the evolution of hydrogen have been produced in animals by introducing finely divided magnesium into the tissues.

Toxicity. Magnesium and alloys containing 85% of the metal may be considered together in their toxicological properties. In industry, their toxicity is regarded as low. The most frequently used compounds, magnesite and dolomite, may irritate the respiratory tract. However, the fumes of magnesium oxide, as those of certain other metals, can cause metal fume fever. Some investigators have reported a higher incidence of digestive disorders in magnesium plant workers and suggest that a relationship may exist between magnesium absorption and gastroduodenal ulcers. In foundry-casting magnesium or high-magnesium alloys, fluoride fluxes and sulphur-containing inhibitors are used in order to separate the molten metal from the air with a layer of sulphur dioxide. This prevents burning during the casting operations, but the fumes of fluorides or of sulphur dioxide could present a greater hazard.

The greatest danger in handling magnesium is that of fire. Small fragments of the metal, such as would result from grinding, polishing or machining, can readily be ignited by a chance spark or flame, and as they burn at a temperature of 1,250ºC, these fragments can cause deep destructive lesions of the skin. Accidents of this type have occurred when a tool was sharpened on a wheel which was previously used to grind magnesium alloy castings. In addition, magnesium reacts with water and acids, forming combustible hydrogen gas.

Slivers of magnesium penetrating the skin or entering deep wounds could cause “aeroform tumours” of the type already mentioned. This would be rather exceptional; however, wounds contaminated with magnesium are very slow to heal. Fine dust from the buffing of magnesium could be irritating to the eyes and respiratory passages, but it is not specifically toxic.

Safety and Health Measures

As with any potentially hazardous industrial process, constant care is needed in handling and working magnesium. Those engaged in casting the metal should wear aprons and hand protection made of leather or some other suitable material to protect them against the “spatter” of small particles. Transparent face shields should also be worn as face protection, especially for the eyes. Where workers are exposed to magnesium dust, contact lenses should not be worn and eyewash facilities should be immediately available. Workers machining or buffing the metal should wear overalls to which small fragments of the metal will not adhere. Sufficient local exhaust ventilation is also essential in areas where magnesium oxide fumes may develop, in addition to good general ventilation. Cutting tools should be sharp, as blunt ones may heat the metal to the point of ignition.

Buildings in which magnesium is cast or machined should be constructed, if possible, of non-flammable materials and without ledges or protuberances on which magnesium dust might accumulate. The accumulation of shavings and “swarf” should be prevented, preferably by wet sweeping. Until final disposal, the scrapings should be collected in small containers and placed apart at safe intervals. The safest method for disposal of magnesium waste is probably wetting and burying.

Since the accidental ignition of magnesium presents a serious fire hazard, fire training and adequate firefighting facilities are essential. Workers should be trained never to use water in fighting such a blaze, because this merely scatters the burning fragments, and may spread the fire. Among the materials which have been suggested for the control of such fires are carbon and sand. Commercially prepared firefighting dusts are also available, one of which consists of powdered polyethylene and sodium borate.

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Gunnar Nordberg

Occurrence and Uses

Manganese (Mn) is one of the most abundant elements in the earth’s crust. It is found in soils, sediments, rocks, water and biological materials. At least a hundred minerals contain manganese. Oxides, carbonates and silicates are the most important among manganese-containing minerals. Manganese can exist in eight oxidation states, the most important being +2, +3, and +7. Manganese dioxide (MnO₂) is the most stable oxide. Manganese forms various organometallic compounds. Of major practical interest is methylcyclopentadienyl manganese tricarbonyl CH₃C₅H₄Mn(CO)₃, often referred to as MMT.

The most important commercial source of manganese is manganese dioxide (MnO₂), which is found naturally in sedimentary deposits as pyrolusite. Two other types of deposit can be distinguished: carbonate accumulations, which are usually composed mainly of rhodocrosite (MnCO₃), and stratiform deposits. However, only the sedimentary deposits are significant, and those are usually worked by opencast techniques. Sometimes underground mining is necessary, and room and pillar extraction is carried out; seldom is there any call for the techniques used in deep metal mining.

Manganese is used in the production of steel as a reagent to reduce oxygen and sulphur and as an alloying agent for special steels, aluminium and copper. It is used in the chemical industry as an oxidizing agent and for the production of potassium permanganate and other manganese chemicals. Manganese is used for electrode coating in welding rods and for rock crushers, railway points and crossings. It also finds use in the ceramics, match, glass and dyestuff industries.

Several manganese salts are used in fertilizers and as driers for linseed oil. They are also utilized for glass and textile bleaching and for leather tanning. MMT has been used as a fuel-oil additive, a smoke inhibitor, and as an antiknock gasoline additive.

Hazards

Absorption, distribution and excretion

In occupational situations manganese is primarily absorbed by inhalation. Manganese dioxide and other manganese compounds which occur as volatile by-products of metal refining are practically insoluble in water. Thus, only particles small enough to reach the alveoli are eventually absorbed into the blood. Large inhaled particles may be cleared from the respiratory tract and swallowed. Manganese may also enter the gastrointestinal tract with contaminated food and water. The rate of absorption can be influenced by a dietary level of manganese and iron, the type of manganese compound, iron deficiency and age. However, the risk of intoxication by this route is not great. Absorption of manganese through the skin is negligible.

After inhalation, or after parenteral and oral exposure, the absorbed manganese is rapidly eliminated from the blood and distributed mainly to the liver. The kinetic patterns for blood clearance and liver uptake of manganese are similar, indicating that these two manganese pools rapidly enter equilibrium. Excess metal may be distributed to other tissues such as kidneys, small intestine, endocrine glands and bones. Manganese preferentially accumulates in tissues rich in mitochondria. It also penetrates the blood-brain barrier and the placenta. Higher concentrations of manganese are also associated with pigmented portions of the body, including the retina, pigmented conjunctiva and dark skin. Dark hair also accumulates manganese. It is estimated that the total body burden for manganese is between 10 and 20 mg for a 70 kg male. The biological half-life for manganese is between 36 and 41 days, but for manganese sequestered in the brain, the half-life is considerably longer. In the blood, manganese is bound to proteins.

The organic compound MMT is rapidly metabolized in the body. The distribution seems to be similar to that seen after exposure to inorganic manganese.

Bile flow is the main route of excretion of manganese. Consequently, it is eliminated almost entirely with faeces, and only 0.1 to 1.3% of daily intake with urine. It seems that biliary excretion is the main regulatory mechanism in the homeostatic control of manganese in the body, accounting for a relative stability of manganese content in tissues. After exposure to the organic compound MMT, excretion of manganese goes to a large extent with urine. This has been explained as a result of biotransformation of the organic compound in the kidney. As a metalloprotein compound of some enzymes, manganese is an essential element for humans.

Exposure

Intoxication by manganese is reported in mining and processing of manganese ores, in the production of manganese alloys, dry-cell batteries, welding electrodes, varnishes and ceramic tiles. Mining of ore can still present important occupational hazards, and the ferromanganese industry is the next most important source of risk. The operations that produce the highest concentrations of manganese dioxide dust are those of drilling and shotfiring. Consequently, the most dangerous job is high-speed drilling.

Considering the dependence of deposition sites and solubility rate of particle size, the dangerous effect of exposure is closely related to the particle size composition of manganese aerosol. There is also evidence that aerosols formed by condensation may be more harmful than those formed by disintegration, which can be connected again with the difference in particle size distribution. The toxicity of different manganese compounds appears to depend on the type of manganese ion present and on the oxidation state of manganese. The less oxidized the compound, the higher the toxicity.

Chronic manganese poisoning (manganism)

Chronic manganese poisoning can take either a nervous or pulmonary form. If the nervous system is attacked, three phases can be distinguished. During the initial period, diagnosis may be difficult. Early diagnosis, however, is critical because cessation of exposure appears to be effective in arresting the course of the disease. Symptoms include indifference and apathy, sleepiness, loss of appetite, headache, dizziness and asthenia. There may be bouts of excitablity, difficulty in walking and coordination, and cramps and pains in the back. These symptoms can be present in varying degrees and appear either together or in isolation. They mark the onset of the disease.

The intermediate stage is marked by the appearance of objective symptoms. First the voice become monotonous and sinks to a whisper, and speech is slow and irregular, perhaps with a stammer. There is fixed and hilarious or dazed and vacant facies, which may be attributable to an increase in the tonus of the facial muscles. The patient may abruptly burst into laughter or (more rarely) into tears. Although the faculties are much decayed, the victim appears to be in a perpetual state of euphoria. Gestures are slow and awkward, gait is normal but there may be a waving movement of the arms. The patient is unable to run and can walk backwards only with difficulty, sometimes with retropulsion. Inability to perform rapid alternating movements (adiadochokinesia) may develop, but neurological examination displays no changes except, in certain cases, exaggeration of the patellar reflexes.

Within a few months, the patient’s condition deteriorates noticeably and the various disorders, especially those affecting the gait, grow steadily more pronounced. The earliest and most obvious symptom during this phase is muscular rigidity, constant but varying in degree, which results in a very characteristic gait (slow, spasmodic and unsteady), the patient putting his or her weight on the metatarsus and producing a movement variously described as “cock-walk” or “hen’s gait”. The victim is totally incapable of walking backwards and, should he or she try to do so, falls; balance can hardly be preserved, even when trying to stand with both feet together. A sufferer can turn round only slowly. There may be tremor, frequently in the lower limbs, even generalized.

The tendinous reflexes, rarely normal, become exaggerated. Sometimes there are vasomotor disorders with sudden sweating, pallor or blushing; on occasion there is cyanosis of the extremities. The sensory functions remain intact. The patient’s mind may work only slowly; writing becomes irregular, some words being illegible. There may be changes in the pulse rate. This is the stage at which the disease becomes progressive and irreversible.

Pulmonary form. Reports of “manganese pneumoconiosis” have been contested in view of the high silica content of the rock at the site of exposure; manganese pneumonia has also been described. There is also controversy over the correlation between pneumonia and manganese exposure unless manganese acts as an aggravating factor. In view of its epidemic character and severity, the disease may be a non-typical viral pneumopathy. These manganic pneumonias respond well to antibiotics.

Pathology. Some authors maintain that there are widespread lesions to the corpus striatum, then to the cerebral cortex, the hippocampus and corpora quadrigemina (in the posterior corpora). However, others are of the opinion that the lesions to the frontal lobes provide a better explanation for all the symptoms observed than do those observed in the basal ganglia; this would be confirmed by electroencephalography. The lesions are always bilateral and more or less symmetrical.

Course. Manganese poisoning ultimately becomes chronic. However, if the disease is diagnosed while still at the early stages and the patient is removed from exposure, the course may be reversed. Once well established, it becomes progressive and irreversible, even when exposure is terminated. The nervous disorders show no tendency to regress and may be followed by deformation of the joints. Although the severity of certain symptoms may be reduced, gait remains permanently affected. The patient’s general condition remains good, and he or she may live a long time, eventually dying from an intercurrent ailment.

Diagnosis. This is based primarily on the patient’s personal and occupational history (job, length of exposure and so on). However, the subjective nature of the initial symptoms makes early diagnosis difficult; consequently, at this stage, questioning must be supplemented by information supplied by friends, colleagues and relatives. During the intermediate and full-blown stages of the intoxication, occupational history and objective symptoms facilitate diagnosis; laboratory examinations can provide information for supplementing the diagnosis.

Haematological changes are variable; on the one hand, there may be no changes at all, whereas, on the other, there may be leucopenia, lymphocytosis and inversion of leucocyte formula in 50% of cases, or increase in haemoglobin count (considered as the first sign of poisoning) and slight polycythaemia.

There is diminished urinary excretion of 17-ketosteroids, and it may be assumed that the adrenal function is affected. Albumin level in the cerebrospinal fluid is increased, often to a marked degree (40 to 55 and even 75 mg per cent). Digestive and hepatic symptoms are non-indicative; there is no sign of hepatomegalia or splenomegalia; however, accumulation of manganese in the liver may result in metabolic lesions which seem to be related to the patient’s endocrinological condition and may be influenced by the existence of neurological lesions.

Differential diagnosis. There may be difficulty in distinguishing between manganese poisoning and the following diseases: nerve syphilis, Parkinson’s disease, disseminated sclerosis, Wilson’s disease, hepatic cirrhosis and Westphal-Strümpell’s disease (pseudo-sclerosis).

Safety and Health Measures

The prevention of manganese poisoning is primarily a question of suppression of manganese dusts and fumes. In mines, dry drilling should always be replaced by wet drilling. Shotfiring should be carried out after the shift so that the heading can be well ventilated before the next shift starts up. Good general ventilation at source is also essential. Airline respiratory protection equipment as well as independent respirators have to be used in specific situations to avoid excessive short-term exposures.

A high standard of personal hygiene is essential, and personal cleanliness and adequate sanitary facilities, clothing and time must be provided so that compulsory showering after work, a change of clothes and a ban on eating at the workplace can be effected. Smoking at work should be prohibited as well.

Periodic measurements of exposure levels should be performed, and attention should be given to the size distribution of airborne manganese. Contamination of drinking water and food as well as workers’ dietary habits ought to be considered as a potential additional source of exposure.

It is inadvisable for workers with psychological or neurological disorders to be employed in work associated with exposure to manganese. Nutritional deficiency states may predispose to anaemia and thus increase susceptibility to manganese. Therefore workers suffering from such deficiencies have to be kept under strict surveillance. During the anaemic state, subjects should avoid exposure to manganese. The same relates to those suffering from lesions of the excretory organs, or from chronic obstructive lung disease. A study has suggested that long-term manganese exposure may contribute to the development of chronic obstructive lung disease, particularly if the exposure is combined with smoking. On the other hand impaired lungs may be more susceptible to the potential acute effect of manganese aerosols.

During the periodic medical examinations the worker should be screened for symptoms which might be connected with the subclinical stage of manganese poisoning. In addition, the worker should be examined clinically, particularly with a view to detecting early psychomotor changes and neurological signs. Subjective symptoms and abnormal behaviour may often constitute the only early indications of health impairment. Manganese can be measured in blood, urine, stools and hair. Estimation of the extent of manganese exposure by means of manganese concentration in urine and blood did not prove to be of great value.

The average manganese blood level in exposed workers seems to be of the same order as that in non-exposed persons. Contamination during sampling and analytical procedures may at least partly explain a rather wide range found in literature particularly for blood. The use of heparin as an anticoagulant is still quite common although the manganese content in heparin may exceed that in blood. The mean concentration of manganese in urine of non-exposed people is usually estimated to be between 1 and 8 mg/l, but values up to 21 mg/l have been reported. Daily manganese intake from human diets varies greatly with the amount of unrefined cereals, nuts, leafy vegetables and tea consumed, owing to their relatively high content of manganese, and thus affects the results of normal manganese content in biological media.

A manganese concentration of 60 mg/kg of faeces and higher has been suggested as indicative of occupational exposure to manganese. Manganese content in hair is normally below 4 mg/kg. As the determination of manganese in urine, which is often used in practice, has not yet been validated enough for assessment of individual exposure, it can be used only as a group indicator of the mean level of exposure. Collection of the stool and the analysis of manganese content is not easy to perform. Our present knowledge does not include any other reliable biological parameter which might be used as an indicator of individual exposure to manganese. Thus the assessment of workers’ exposure to manganese still has to rely on manganese air levels. There is also very little reliable information about the correlation between the manganese content in the blood and urine and the findings of neurological symptoms and signs.

Persons with the signs of manganese intoxication should be removed from exposure. If the worker is removed from exposure shortly after the onset of symptoms and signs (before the fully developed stage of manganism) many of the symptoms and signs will disappear. There may be some residual disturbances, however, particularly in speech and gait.

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F. William Sunderman, Jr.

Occurrence and Uses

Metal carbonyls have the general formula Me_x(CO)_y, and are formed by combination of the metal (Me) with carbon monoxide (CO). Physical properties of some metal carbonyls are listed in table 1. Most are solids at ordinary temperatures, but nickel carbonyl, iron pentacarbonyl and ruthenium pentacarbonyl are liquids, and cobalt hydrocarbonyl is a gas. This article focuses on nickel carbonyl, which, because of its volatility, exceptional toxicity and industrial importance merits special attention in regard to occupational toxicology. Since iron pentacarbonyl and cobalt hydrocarbonyl also have high vapour pressures and potential for inadvertant formation, they warrant serious consideration as possible occupational toxicants. Most metal carbonyls react vigorously with oxygen and oxidizing substances, and some ignite spontaneously. Upon exposure to air and light, nickel carbonyl decomposes to carbon monoxide and particulate nickel metal, cobalt hydrocarbonyl decomposes to cobalt octacarbonyl and hydrogen, and iron pentacarbonyl decomposes to iron nonacarbonyl and carbon monoxide.

Table 1. Physical properties of some metal carbonyls

*Decomposition starts at temperature shown.

Source: Adapted from Brief et al. 1971.

Metal carbonyls are used in isolating certain metals (e.g., nickel) from complex ores, for producing carbon steel, and for metallizing by vapour deposition. They are also used as catalysts in organic reactions (e.g., cobalt hydrocarbonyl or nickel carbonyl in olefin oxidation; cobalt octacarbonyl for the synthesis of aldehydes; nickel carbonyl for the synthesis of acrylic esters). Iron pentacarbonyl is used as a catalyst for various organic reactions, and is decomposed to make finely powdered, ultra pure iron (so-called carbonyl iron), which is used in the computer and electronics industries. Methycyclopentadienyl manganese tricarbonyl (MMT) (CH₃C₅H₄Mn(CO)₃) is an antiknock additive to gasoline and is discussed in the article “Manganese”.

Health Hazards

The toxicity of a given metal carbonyl depends on the toxicity of carbon monoxide and of the metal from which it is derived, as well as the volatility and instability of the carbonyl itself. The principal route of exposure is inhalation, but skin absorption can occur with the liquid carbonyls. The relative acute toxicity (LD₅₀ for the rat) of nickel carbonyl, cobalt hydrocarbonyl and iron pentacarbonyl may be expressed by the ratio 1:0.52:0.33. Inhalation exposures of experimental animals to these substances induce acute interstitial pneumonitis, with pulmonary oedema and capillary damage, as well as injury to the brain, liver and kidneys.

Judging from the sparse literature on their toxicity, cobalt hydrocarbonyl and iron pentacarbonyl rarely pose health hazards in industry. None the less, iron pentacarbonyl can be formed inadvertently when carbon monoxide, or a gas mixture containing carbon monoxide, is stored under pressure in steel cylinders or fed through steel pipes, when illuminating gas is produced by petroleum reforming, or when gas welding is carried out. Presence of carbon monoxide in emission discharges from blast furnaces, electric arc furnaces and cupola furnaces during steel-making can also lead to the formation of iron pentacarbonyl.

Safety and Health Measures

Special precautions are mandatory in the storage of metal carbonyls; their handling must be mechanized to the maximum degree, and decanting should be avoided wherever possible. Vessels and piping should be purged with an inert gas (e.g., nitrogen, carbon dioxide) before being opened, and carbonyl residues should be burnt or neutralized with bromine water. Where there is an inhalation hazard, workers should be provided with airline respirators or self-contained breathing apparatus. Workshops should be fitted with down-draught ventilation.

Nickel Carbonyl

Nickel carbonyl (Ni(CO)₄) is mainly used as an intermediate in the Mond process for nickel refining, but it is also used for vapour-plating in the metallurgical and electronics industries and as a catalyst for synthesis of acrylic monomers in the plastics industry. Inadvertent formation of nickel carbonyl can occur in industrial processes that use nickel catalysts, such as coal gasification, petroleum refining and hydrogenation reactions, or during incineration of nickel-coated papers that are used for pressure-sensitive business forms.

Hazards

Acute, accidental exposure of workers to inhalation of nickel carbonyl usually produces mild, non-specific, immediate symptoms, including nausea, vertigo, headache, dyspnoea and chest pain. These initial symptoms usually disappear within a few hours. After 12 to 36 hours, and occasionally as long as 5 days after exposure, severe pulmonary symptoms develop, with cough, dyspnoea, tachycardia, cyanosis, profound weakness and often gastrointestinal symptoms. Human fatalities have occurred 4 to 13 days after exposure to nickel carbonyl; deaths have resulted from diffuse interstitial pneumonitis, cerebral hemorrhage or cerebral oedema. In addition to pathologic lesions in the lungs and brain, lesions have been found in liver, kidneys, adrenals and spleen. In patients who survive acute nickel carbonyl poisoning, pulmonary insufficiency often causes protracted convalescence. Nickel carbonyl is carcinogenic and teratogenic in rats; the European Union has classified nickel carbonyl as an animal teratogen. Processes that use nickel carbonyl constitute disaster hazards, since fire and explosion can occur when nickel carbonyl is exposed to air, heat, flames or oxidizers. Decomposition of nickel carbonyl is attended by additional toxic hazards from inhalation of its decomposition products, carbon monoxide and finely particulate nickel metal.

Chronic exposure of workers to inhalation of low atmospheric concentrations of nickel carbonyl (0.007 to 0.52 mg/m³) can cause neurological symptoms (e.g., insomnia, headache, dizziness, memory loss) and other manifestations (e.g., chest tightness, excessive sweating, alopecia). Electroencephalographic abnormalities and elevated serum monoamine oxidase activity have been observed in workers with chronic exposures to nickel carbonyl. A synergistic effect of cigarette smoking and nickel carbonyl exposure on the frequency of sister-chromatid exchanges was noted in a cytogenetic evaluation of workers with chronic exposure to nickel carbonyl.

Safety and Health Measures

Fire and explosion prevention. Because of its flammability and tendency to explode, nickel carbonyl should be stored in tightly closed containers in a cool, well-ventilated area, away from heat and oxidizers such as nitric acid and chlorine. Flames and sources of ignition should be prohibited wherever nickel carbonyl is handled, used or stored. Nickel carbonyl should be transported in steel cylinders. Foam, dry chemical, or CO₂ fire extinguishers should be used to extinguish burning nickel carbonyl, rather than a stream of water, which might scatter and spread the fire.

Health protection. In addition to the medical surveillance measures recommended for all nickel-exposed workers, persons with occupational exposures to nickel carbonyl should have biological monitoring of nickel concentration in urine specimens on a regular basis, typically monthly. Persons who enter confined spaces where they might possibly be exposed to nickel carbonyl should have self-contained breathing apparatus and a suitable harness with lifeline tended by another employee outside the space. Analytical instruments for continuous atmospheric monitoring of nickel carbonyl include (a) Fourier-transform infrared absorption spectroscopes, (b) plasma chromatographs and (c) chemiluminescent detectors. Atmospheric samples can also be analysed for nickel carbonyl by (d) gas chromatography, (e) atomic absorption spectrophotometry and (f) colourimetric procedures.

Treatment. Workers suspected to have been acutely exposed to nickel carbonyl should be immediately removed from the exposure site. Contaminated clothing should be removed. Oxygen should be administered and the patient kept at rest until seen by a physician. Each voiding of urine is saved for nickel analysis. The severity of acute nickel carbonyl poisoning correlates with the urine nickel concentrations during the first 3 days after exposure. Exposures are classified as “mild” if the initial 8-h specimen of urine has a nickel concentration less than 100 µg/l, “moderate” if the nickel concentration is 100 to 500 µg/l, and “severe” if the nickel concentration exceeds 500 µg/l. Sodium diethyldithiocarbamate is the drug of choice for chelation therapy of acute nickel carbonyl poisoning. Ancillary therapeutic measures include bed rest, oxygen therapy, corticosteroids and prophylactic antibiotics. Carbon monoxide poisoning may occur simultaneously and requires treatment.

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Gunnar Nordberg

Inorganic Mercury

Mercury combines readily with sulphur and halogens at ordinary temperatures and forms amalgams with all metals except iron, nickel, cadmium, aluminium, cobalt and platinum. It reacts exothermically (generates heat) with alkaline metals, is attacked by nitric acid but not by hydrochloric acid and, when hot, will combine with sulphuric acid.

Inorganic mercury is found in nature in the form of the sulphide (HgS) as cinnabar ore, which has an average mercury content of 0.1 to 4%. It is also encountered in the earth’s crust in the form of geodes of liquid mercury (in Almadén) and as impregnated schist or slate (e.g., in India and Yugoslavia).

Extraction. Mercury ore is extracted by underground mining, and mercury metal is separated from the ore by roasting in a rotary kiln or shaft furnace, or by reduction with iron or calcium oxide. The vapour is carried off in the combustion gases and is condensed in vertical tubes.

The most important uses of metallic mercury and its inorganic compounds have included the treatment of gold and silver ores; the manufacture of amalgams; the manufacture and repair of measurement or laboratory apparatus; the manufacture of incandescent electric bulbs, mercury vapour tubes, radio valves, x-ray tubes, switches, batteries, rectifiers, etc.; as a catalyst for the production of chlorine and alkali and the production of acetic acid and acetaldehyde from acetylene; chemical, physical and biological laboratory research; gold, silver, bronze and tin plating; tanning and currying; feltmaking; taxidermy; textile manufacture; photography and photogravure; mercury-based paints and pigments; and the manufacture of artificial silk. Some of these uses have been discontinued because of the toxic effects that the mercury exposure exerted upon workers.

Organic Mercury Compounds

Organic compounds of mercury may be considered as the organic compounds in which the mercury is chemically linked directly to a carbon atom. Carbon-mercury bonds have a wide range of stability; in general, the carbon-to-mercury bond in aliphatic compounds is more stable than that in aromatic compounds. According to one reliable estimate, more than 400 phenyl mercurials and at least that number of alkyl mercury compounds have been synthesized. The three most important groups in common usage are the alkyls, the aromatic hydrocarbons or aryls and the alkoxyalkyls. Examples of aryl mercury compounds are phenylmercuric acetate (PMA), nitrate, oleate, propionate and benzoate. Most available information is about PMA.

Uses. All the important uses of the organic mercury compounds depend on the biological activity of these substances. In medical practice organic mercury compounds are used as antiseptics, germicides, diuretics and contraceptives. In the field of pesticides they serve as algicides, fungicides, herbicides, slimacides and as preservatives in paints, waxes and pastes; they are used for mildew suppression, in antifouling paints, in latex paints and in the fungus-proofing of fabrics, paper, cork, rubber and wood for use in humid climates. In the chemical industry they act as catalysts in a number of reactions and the mercury alkyls are used as alkylating agents in organic syntheses.

Hazards

Absorption and effects: Inorganic and metallic mercury

Vapour inhalation is the main route for the entry of metallic mercury into the body. Around 80% of inhaled mercury vapour is absorbed in the lung (alveoli). Digestive absorption of metallic mercury is negligible (lower than 0.01% of the administered dose). Subcutaneous penetration of metallic mercury as the result of an accident (e.g. the breakage of a thermometer) is also possible.

The main routes of entry of inorganic mercury compounds (mercury salts) are the lungs (atomization of mercury salts) and the gastrointestinal tract. In the latter case, absorption is often the result of accidental or voluntary ingestion. It is estimated that 2 to 10% of ingested mercury salts are absorbed through the intestinal tract.

Skin absorption of metallic mercury and certain of its compounds is possible, although the rate of absorption is low. After entry into the body, metallic mercury continues to exist for a short time in metallic form, which explains its penetration of the blood-brain barrier. In blood and tissues metallic mercury is rapidly oxidized to Hg²⁺ mercury ion, which fixes to proteins. In the blood, inorganic mercury is also distributed between plasma and red blood cells.

The kidney and brain are the sites of deposition following exposure to metallic mercury vapours, and the kidney following exposure to inorganic mercury salts.

Acute poisoning

The symptoms of acute poisoning include pulmonary irritation (chemical pneumonia), perhaps leading to acute pulmonary oedema. Renal involvement is also possible. Acute poisoning is more often the result of accidental or voluntary ingestion of a mercury salt. This leads to severe inflammation of the gastrointestinal tract followed rapidly by renal insufficiency due to necrosis of the proximal convoluted tubules.

The severe chronic form of mercury poisoning encountered in places like Almadén up until the early 20th century, and which presented spectacular renal, digestive, mental and nervous disorders and terminated in cachexia, was eliminated by means of preventive measures. However, a chronic, “intermittent” poisoning in which periods of active intoxication are interspersed between periods of latent intoxication can still be detected among mercury miners. In the latent periods, symptoms remit to such a degree that they are visible only on close search; only the neurological manifestations persist in the form of profuse sweating, dermographia and, to some extent, emotional instability.

A condition of “micromercurialism” characterized by functional neurosis (frequent hysteria, neurasthenia, and mixed forms), cardiovascular lability and secretory neurosis of the stomach has also been described.

Digestive system. Gingivitis is the most common gastrointestinal disorder encountered in mercury poisoning. It is favoured by poor oral hygiene and is accompanied by an unpleasant, metallic or bitter taste in the mouth. Ulceromembranous stomatitis is much less common and is normally found in persons already suffering from gingivitis who have accidentally inhaled mercury vapours. This stomatitis commences with the subjective symptoms of gingivitis with increased salivation (mercurial ptyalism) and coating of the tongue. Eating and drinking produce a burning sensation and discomfort in the mouth, the gums become increasingly inflamed and swollen, ulcers appear and there is spontaneous bleeding. In acute cases, there is high fever, inflammation of the submaxillary ganglions and extremely fetid breath. Alveolodental periostitis has also been observed.

There may be a bluish line on the tooth edge of the gums, in particular in the vicinity of infected areas; this line is, however, never encountered in persons without teeth. Slate-grey punctiform pigmentation of the oral mucosae—the vestibular side of the gums (usually those of the lower jaw), the palate, and even the inside of the cheeks—has also been observed.

Recurrent gingivitis affects the supporting tissues of the teeth, and in many cases the teeth have to be extracted or merely fall out. Other gastrointestinal disorders encountered in mercury poisoning include gastritis and gastroduodenitis.

Non-specific pharyngitis is relatively common. A rarer manifestation is that of Kussmaul’s pharyngitis which presents as a bright-red coloration of the pharynx, tonsils and soft palate with fine arborisation.

Nervous system involvement may occur with or without gastrointestinal symptoms and may evolve in line with two main clinical pictures: (a) fine-intention tremor reminiscent of that encountered in persons suffering from multiple sclerosis; and (b) Parkinsonism with tremor at rest and reduced motor function. Usually one of these two conditions is dominant in the over-all clinical picture which may be further complicated by morbid irritability and pronounced mental hyperactivity (mercurial erethism).

Mercurial Parkinsonism presents a picture of unsteady and staggering gait, absence of balance-recovery reflexes and hypotonia; vegetative symptoms are slight with mask-like facies, sialorrhea, etc. However, Parkinsonism is usually encountered in milder forms, in particular as micro-Parkinsonism.

The most frequently encountered symptoms resemble those presented by persons with multiple sclerosis, except that there is no nystagmus and the two conditions have a different serology and different clinical courses. The most striking feature is tremor which is usually a late symptom but may develop prior to stomatitis.

Tremor usually disappears during sleep, although sudden generalized cramps or contractions may occur; however, it always increases under emotional stress and this is such a characteristic feature that it provides firm grounds for a diagnosis of mercury poisoning. Tremor is particularly pronounced in situations where the patient feels embarrassed or ashamed; often he or she will have to eat in solitude since otherwise he would be incapable of raising food to his lips. In its most acute form, the tremor may invade all the voluntary muscles and be continuous. Cases still occur in which the patient has to be strapped down to prevent him falling out of bed; such cases also present massive, choreiform movements sufficient to wake the patient from his sleep.

The patient tends to utter his words in staccato fashion, so that his sentences are difficult to follow (psellismus mercurialis); when a spasm ceases, the words come out too fast. In cases more reminiscent of parkinsonism, speech is slow and monotonous and the voice may be low or completely absent; spasmodic utterence is, however, more common.

A highly characteristic symptom is a desire for sleep, and the patient often sleeps for long periods although lightly and is frequently disturbed by cramps and spasms. However, insomnia may occur in some cases.

Loss of memory is an early and dementia a terminal symptom. Dermographia and profuse sweating (for no obvious reason) are frequently encountered. In chronic mercury poisoning, the eyes may show the picture of “mercurialentis” characterized by a light-grey to dark, reddish-grey discoloration of the anterior capsule of the crystalline lens due to the deposition of finely divided particles of mercury. Mercurialentis can be detected by examination with a slit-lamp microscope and is bilateral and symmetrical; it usually appears some considerable time before the onset of general signs of mercury poisoning.

Chronic exposure

Chronic mercury poisoning usually starts insidiously, which makes the early detection of incipient poisoning difficult. The main target organ is the nervous system. Initially, suitable tests can be used to detect psychomotor and neuro-muscular changes and slight tremor. Slight renal involvement (proteinuria, albuminuria, enzymuria) may be detectable earlier than neurological involvement.

If excessive exposure is not corrected, neurological and other manifestations (e.g., tremor, sweating, dermatography) become more pronounced, associated with changes in behaviour and personality disorders and, perhaps, digestive disorders (stomatitis, diarrhoea) and a deterioration in general status (anorexia, weight loss). Once this stage has been reached, termination of exposure may not lead to total recovery.

In chronic mercury poisoning, digestive and nervous symptoms predominate and, although the former are of earlier onset, the latter are more obvious; other significant but less intense symptoms may be present. The duration of the period of mercury absorption preceding the appearance of clinical symptoms depends on the level of absorption and individual factors. The main early signs include slight digestive disorders, in particular, loss of appetite; intermittent tremor, sometimes in specific muscle groups; and neurotic disorders varying in intensity. The course of intoxication may vary considerably from case to case. If exposure is terminated immediately upon the appearance of the first symptoms, full recovery usually occurs; however, if exposure is not terminated and the intoxication becomes firmly established, no more than an alleviation of symptoms can be expected in the majority of cases.

Kidney. There have been studies over the years on the relationships between renal function and urinary mercury levels. The effects of low-level exposures are still not well documented or understood. At higher levels (above 50 μg/g (micrograms per gram) abnormal renal function (as evidenced by N-acetyl-B-D-glucosaminidase (NAG), which is a sensitive indicator of damage to the kidneys) have been observed. The NAG levels were correlated with both the urinary mercury levels and the results of neurological and behavioural testing.

Nervous system. Recent years have seen the development of more data on low levels of mercury, which are discussed in more detail in the chapter Nervous system in this Encyclopaedia.

Blood. Chronic poisoning is accompanied by mild anaemia sometimes preceded by polycythaemia resulting from bone marrow irritation. Lymphocytosis and eosinophilia have also been observed.

Organic Mercury Compounds

Phenylmercuric acetate (PMA). Absorption may occur through inhalation of aerosols containing PMA, through skin absorption or by ingestion. The solubility of the mercurial and the particle size of the aerosols are determining factors for the extent of absorption. PMA is more efficiently absorbed by ingestion than are inorganic mercuric salts. Phenylmercury is transported mainly in blood and distributed in the blood cells (90%), accumulates in the liver and is there decomposed into inorganic mercury. Some phenylmercury is excreted in the bile. The main portion absorbed in the body is distributed in the tissues as inorganic mercury and accumulated in the kidney. On chronic exposure, mercury distribution and excretion follow the pattern seen on exposure to inorganic mercury.

Occupational exposure to phenylmercury compounds occurs in the manufacture and handling of products treated with fungicides containing phenylmercury compounds. Acute inhalation of large amounts may cause lung damage. Exposure of the skin to a concentrated solution of phenylmercury compounds may cause chemical burns with blistering. Sensitization to phenylmercury compounds may occur. Ingestion of large amounts of phenylmercury may cause renal and liver damage. Chronic poisoning gives rise to renal damage due to accumulation of inorganic mercury in the renal tubules.

Available clinical data do not permit extensive conclusions about dose-response relationships. They suggest, however, that phenylmercury compounds are less toxic than inorganic mercury compounds or long-term exposure. There is some evidence of mild adverse effects on the blood.

Alkyl mercury compounds. From a practical point of view, the short-chained alkyl mercury compounds, like methylmercury and ethylmercury, are the most important, although some exotic mercury compounds, generally used in laboratory research, have led to spectacular rapid deaths from acute poisoning. These compounds have been extensively used in seed treatment where they have been responsible for a number of fatalities. Methylmercuric chloride forms white crystals with a characteristic odour, while ethylmercury chloride; (chloroethylmercury) forms white flakes. Volatile methylmercury compounds, like methylmercury chloride, are absorbed to about 80% upon inhalation of vapour. More than 95% of short-chained alkyl mercury compounds is absorbed by ingestion, although the absorption of methylmercury compounds by the skin can be efficient, depending on their solubility and concentration and the condition of the skin.

Transport, distribution and excretion. Methylmercury is transported in the red blood cells ( 95%), and a small fraction is bound to plasma proteins. The distribution to the different tissues of the body is rather slow and it takes about four days before equilibrium is obtained. Methylmercury is concentrated in the central nervous system and especially in grey matter. About 10% of the body burden of mercury is found in the brain. The highest concentration is found in the occipital cortex and the cerebellum. In pregnant women methylmercury is transferred in the placenta to the foetus and especially accumulated in the foetal brain.

Hazards of organic mercury

Poisoning by alkyl mercury may occur on inhalation of vapour and dust containing alkyl mercury and in the manufacture of the mercurial or in handling the final material. Skin contact with concentrated solutions results in chemical burns and blistering. In small agricultural operations there is a risk of exchange between treated seed and products intended for food, followed by involuntary intake of large amounts of alkyl mercury. On acute exposure the signs and symptoms of poisoning have an insidious onset and appear with a latency period which may vary from one to several weeks. The latency period is dependent on the size of the dose—the larger the dose, the shorter the period.

On chronic exposure the onset is more insidious, but the symptoms and signs are essentially the same, due to the accumulation of mercury in the central nervous system, causing neuron damage in the sensory cortex, such as visual cortex, auditory cortex and the pre- and post-central areas. The signs are characterized by sensory disturbances with paresthaesia in the distal extremities, in the tongue and around the lips. With more severe intoxications ataxia, concentric constrictions of the visual fields, impairment of hearing and extrapyramidal symptoms may appear. In severe cases chronic seizures occur.

The period in life most sensitive to methylmercury poisoning is the time in utero; the foetus seems to be between 2 and 5 times more sensitive than the adult. Exposure in utero results in cerebral palsy, partly due to inhibition of the migration of neurons from central parts to the peripheral cortical areas. In less severe cases retardation in the psychomotor development has been observed.

Alkoxyalkyl mercury compounds. The most common alkoxyalkyl compounds used are methoxyethyl mercury salts (e.g., methoxyethylmercury acetate), which have replaced the short-chain alkyl compounds in seed treatment in many industrial countries, in which the alkyl compounds have been banned due to their hazardousness.

The available information is very limited. Alkoxyalkyl compounds are absorbed by inhalation and by ingestion more efficiently than inorganic mercury salts. The distribution and excretion patterns of absorbed mercury follow those of inorganic mercury salts. Excretion occurs through the intestinal tract and the kidney. To what extent unchanged alkoxyalkyl mercury is excreted in humans is unknown. Exposure to alkoxyalkyl mercury compounds can occur in the manufacture of the compound and in handling the final product(s) treated with the mercurial. Methoxyethyl mercury acetate is a vesicant when applied in concentrated solutions to the skin. Inhalation of methoxyethyl mercury salt dust may cause lung damage, and chronic poisoning due to long-term exposure may give rise to renal damage.

Safety and Health Measures

Efforts should be made to replace mercury with less hazardous substances. For example, the felt industry may employ non-mercurial compounds. In mining, wet drilling techniques should be used. Ventilation is the main safety measure and if it is inadequate, the workers should be provided with respiratory protective equipment.

In industry, wherever possible, mercury should be handled in hermetically sealed systems and extremely strict hygiene rules should be applied at the workplace. When mercury is spilt, it very easily infiltrates into crevices, gaps in the floor and workbenches. Due to its vapour pressure, a high atmospheric concentration may occur even following seemingly negligible contamination. It is therefore important to avoid the slightest soiling of work surfaces; these should be smooth, non-absorbent and slightly tilted towards a collector or, failing this, have a metal grill over a gutter filled with water to collect any drops of spilt mercury which fall through the grill. Working surfaces should be cleaned regularly and, in the event of accidental contamination, any drops of mercury collected in a water trap should be drawn off as rapidly as possible.

Where there is a danger of mercury volatilizing, local exhaust ventilation (LEV) systems should be installed. Admittedly, this is a solution which is not always applicable, as is the case in premises producing chlorine by the mercury cell process, in view of the enormous vaporization surface.

Work posts should be planned in such a way as to minimize the number of persons exposed to mercury.

Most exposure to organic mercury compounds involves mixed exposure to mercury vapour and the organic compound, as the organic mercury compounds decompose and release mercury vapour. All technical measures pertaining to exposure to mercury vapour should be applied for exposure to organic mercury compounds. Thus, contamination of clothes and/or parts of the body should be avoided, as it may be a dangerous source of mercury vapour close to the breathing zone. Special protective work clothes should be used and changed after the workshift. Spray painting with paint containing mercurials requires respiratory protective equipment and adequate ventilation. The short-chained alkyl mercury compounds should be eliminated and replaced whenever possible. If handling cannot be avoided, an enclosed system should be used, combined with adequate ventilation, to limit exposure to a minimum.

Great care must be exercised in preventing the contamination of water sources with mercury effluent since the mercury can be incorporated into the food chain, leading to disasters such as that which occurred in Minamata, Japan.

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