Friday, 11 February 2011 04:10


Gunnar Nordberg

Occurrence and Uses

In nature, Indium (In) is widely distributed and occurs most frequently together with zinc minerals (sphalerite, marmatite, christophite), its chief commercial source. It is also found in the ores of tin, manganese, tungsten, copper, iron, lead, cobalt and bismuth, but generally in amounts of less than 0.1%.

Indium is generally used in industry for surface protection or in alloys. A thin coat of indium increases the resistance of metals to corrosion and wear. It prolongs the life of moving parts in bearings and finds wide use in the aircraft and automobile industries. It is used in dental alloys, and its “wettability” makes it ideal for plating glass. Because of its resistance to corrosion, indium is utilized extensively in making motion picture screens, cathode ray oscilloscopes and mirrors. When joined with antimony and germanium in an extremely pure combination, it is widely used in the manufacture of transistors and other sensitive electronic components. Radioisotopes of indium in compounds such as indium trichloride and colloidal indium hydroxide are used in organic scanning and in the treatment of tumours.

In addition to the metal, the most common industrial compounds of indium are the trichloride, used in electroplating; the sesquioxide, used in glass manufacture; the sulphate; and the antimonide and the arsenide used as semiconductor material.


No cases have been reported of systemic effects in humans exposed to indium. Probably the greatest current potential hazard comes from the use of indium together with arsenic, antimony and germanium in the electronics industry. This is due primarily to the fumes given off during welding and soldering processes in the manufacture of electronic components. Any hazard arising from the purification of indium is probably attributable to the presence of other metals, such as lead, or chemicals, such as cyanide, used in the electroplating process. Exposure of the skin to indium does not seem to present a serious hazard. The tissue distribution of indium in various chemical forms has been studied by administration to laboratory animals.

The sites of highest concentration were kidney, spleen, liver and salivary glands. After inhalation, widespread lung changes were observed, such as interstitial and desquamative pneumonitis with consequent respiratory insufficiency.

The results of animal studies showed that the more soluble salts of indium were very toxic, with lethality occurring after administration of less than 5 mg/kg by way of parenteral routes of injection. However, after gavage, indium was poorly absorbed and essentially non-toxic. Histophathological studies indicated that death was due primarily to degenerative lesions in the liver and kidney. Minor changes in the blood have also been noted. In chronic poisoning by indium chloride the main change is a chronic interstitial nephritis with proteinuria. The toxicity from the more insoluble form, indium sesquioxide, was only moderate to slight, requiring up to several hundred mg/kg for lethal effect. After administration of indium arsenide to hamsters, the uptake in various organs differed from the distribution of ionic indium or arsenic compounds.

Safety and Health Measures

Preventing the inhalation of indium fumes by the use of correct ventilation appears to be the most practical safety measure. When handling indium arsenide, safety precautions such as those applied for arsenic should be observed. In the field of nuclear medicine, correct radiation safety measures must be followed when handling radioactive indium isotopes. Intoxication in rats from indium-induced hepatic necrosis has been reduced considerably by administration of ferric dextran, the action of which is apparently very specific. The use of ferric dextran as a prophylactic treatment in humans has not been possible owing to a lack of serious cases of industrial exposures to indium.



Friday, 11 February 2011 04:23


Gunnar Nordberg

Iridium (Ir) belongs to the platinum family. Its name derives from the colours of its salt, which are reminiscent of a rainbow (iris). Although it is very hard and the most corrosion-resistant metal known, it is attacked by some salts.

Occurrence and Uses

Iridium occurs in nature in the metallic state, usually alloyed with osmium (osmiridium), platinum or gold, and it is produced from these minerals. The metal is used to manufacture crucibles for chemical laboratories and to harden platinum. Recent in vitro studies indicate the possible effects of iridium on Leishmania donovani and the trypanocidal activity of iridium against Trypanosoma brucei. Ir is used in industrial radiology and is a gamma emitter (0.31 MeV at 82.7%) and beta emitter (0.67 MeV at 47.2%). 192Ir is a radioisotope which has also been used for clinical treatment, particularly cancer therapy. It is one of the most frequently used isotopes in interstitial brain irradiation.


Very little is known about the toxicity of iridium and its compounds. There has been little opportunity to note any adverse human effects since it is used only in small amounts. All radioisotopes are potentially harmful and must be treated with appropriate safeguards required for handling radioactive sources. Soluble iridium compounds such as iridium tribromide and tetrabromide and iridium trichloride could present both toxic effects of the iridium or the halogen, but data as to its chronic toxicity are unavailable. Iridium trichloride has been reported to be a mild irritant to the skin and is positive in eye irritation test. Inhaled aerosol of metallic iridium is deposited in the upper respiratory ways of rats; the metal is then quickly removed via the gastrointestinal tract, and approximately 95% can be found in the faeces. In humans the only reports are those concerning radiation injuries due to accidental exposure to 192Ir.

Safety and Health Measures

A radiation safety and medical surveillance programme should be in place for persons responsible for nursing care during interstitial brachytherapy. Radiation safety principles include exposure reduction by time, distance and shielding. Nurses who care for brachytherapy patients must wear radiation monitoring devices to record the amount of exposure. To avoid industrial radiography accidents, only trained industrial radiographers should be allowed to handle radionuclides.



Friday, 11 February 2011 04:24


Gunnar Nordberg

Adapted from ATSDR 1995.

Occurrence and Uses

Lead ores are found in many parts of the world. The richest ore is galena (lead sulphide) and this is the main commercial source of lead. Other lead ores include cerussite (carbonate), anglesite (sulphate), corcoite (chromate), wulfenite (molybdate), pyromorphite (phosphate), mutlockite (chloride) and vanadinite (vanadate). In many cases the lead ores may also contain other toxic metals.

Lead minerals are separated from gangue and other materials in the ore by dry crushing, wet grinding (to produce a slurry), gravity classification and flotation. The liberated lead minerals are smelted by a three-stage process of charge preparation (blending, conditioning, etc.), blast sintering and blast furnace reduction. The blast-furnace bullion is then refined by the removal of copper, tin, arsenic, antimony, zinc, silver and bismuth.

Metallic lead is used in the form of sheeting or pipes where pliability and resistance to corrosion are required, such as in chemical plants and the building industry; it is used also for cable sheathing, as an ingredient in solder and as a filler in the automobile industry. It is a valuable shielding material for ionizing radiations. It is used for metallizing to provide protective coatings, in the manufacture of storage batteries and as a heat treatment bath in wire drawing. Lead is present in a variety of alloys and its compounds are prepared and used in large quantities in many industries.

About 40% of lead is used as a metal, 25% in alloys and 35% in chemical compounds. Lead oxides are used in the plates of electric batteries and accumulators (PbO and Pb3O4), as compounding agents in rubber manufacture (PbO), as paint ingredients (Pb3O4) and as constituents of glazes, enamels and glass.

Lead salts form the basis of many paints and pigments; lead carbonate and lead sulphate are used as white pigments and the lead chromates provide chrome yellow, chrome orange, chrome red and chrome green. Lead arsenate is an insecticide, lead sulphate is used in rubber compounding, lead acetate has important uses in the chemical industry, lead naphthenate is an extensively used dryer and tetraethyllead is an antiknock additive for gasoline, where still permitted by law.

Lead alloys. Other metals such as antimony, arsenic, tin and bismuth may be added to lead to improve its mechanical or chemical properties, and lead itself may be added to alloys such as brass, bronze and steel to obtain certain desirable characteristics.

Inorganic lead compounds. Space is not available to describe the very large number of organic and inorganic lead compounds encountered in industry. However, the common inorganic compounds include lead monoxide (PbO), lead dioxide (PbO2), lead tetroxide (Pb3O4), lead sesquioxide (Pb2O3), lead carbonate, lead sulphate, lead chromates, lead arsenate, lead chloride, lead silicate and lead azide.

The maximum concentration of the organic (alkyl) lead compounds in gasolines is subject to legal prescriptions in many countries, and to limitation by the manufacturers with governmental concurrence in others. Many jurisdictions have simply banned its use.


The prime hazard of lead is its toxicity. Clinical lead poisoning has always been one of the most important occupational diseases. Medico-technical prevention has resulted in a considerable decrease in reported cases and also in less serious clinical manifestations. However, it is now evident that adverse effects occur at exposure levels hitherto regarded as acceptable.

Industrial consumption of lead is increasing and traditional consumers are being supplemented by new users such as the plastics industry. Hazardous exposure to lead, therefore, occurs in many occupations.

In lead mining, a considerable proportion of lead absorption occurs through the alimentary tract and consequently the extent of the hazard in this industry depends, to some extent, on the solubility of ores being worked. The lead sulphide (PbS) in galena is insoluble and absorption from the lung is limited; however, in the stomach, some lead sulphide may be converted to slightly soluble lead chloride which may then be absorbed in moderate quantities.

In lead smelting, the main hazards are the lead dust produced during crushing and dry grinding operations, and lead fumes and lead oxide encountered in sintering, blast-furnace reduction and refining.

Lead sheet and pipe are used principally for the constructon of equipment for storing and handling sulphuric acid. The use of lead for water and town gas pipes is limited nowadays. The hazards of working with lead increase with temperature. If lead is worked at temperatures below 500 °C, as in soldering, the risk of fume exposure is far less than in lead welding, where higher flame temperatures are used and the danger is higher. The spray coating of metals with molten lead is dangerous since it gives rise to dust and fumes at high temperatures.

The demolition of steel structures such as bridges and ships that have been painted with lead-based paints frequently gives rise to cases of lead poisoning. When metallic lead is heated to 550 °C, lead vapour will be evolved and will become oxidized. This is a condition that is liable to be present in metal refining, the melting of bronze and brass, the spraying of metallic lead, lead burning, chemical plant plumbing, ship breaking and the burning, cutting and welding of steel structures coated with paints containing lead tetroxide.

Routes of entry

The main route of entry in industry is the respiratory tract. A certain amount may be absorbed in the air passages, but the main portion is taken up by the pulmonary bloodstream. The degree of absorption depends on the proportion of the dust accounted for by particles less than 5 microns in size and the exposed worker’s respiratory minute volume. Increased workload therefore results in higher lead absorption. Although the respiratory tract is the main route of entry, poor work hygiene, smoking during work (pollution of tobacco, polluted fingers while smoking) and poor personal hygiene may considerably increase total exposure mainly by the oral route. This is one of the reasons why the correlation between the concentration of lead in workroom air and lead in blood levels often is very poor, certainly on an individual basis.

Another important factor is the level of energy expenditure: the product of concentration in air and of respiratory minute volume determines lead uptake. The effect of working overtime is to increase exposure time and reduce recovery time. Total exposure time is also much more complicated than official personnel records indicate. Only time analysis in the workplace can yield relevant data. The worker may move around the department or the factory; a job with frequent changes in posture (e.g., turning and bending) results in exposure to a great range of concentrations. A representative measure of lead intake is almost impossible to obtain without the use of a personal sampler applied for many hours and for many days.

Particle size. Since the most important route of lead absorption is by the lungs, the particle size of industrial lead dust is of considerable significance and this depends on the nature of the operation giving rise to the dust. Fine dust of respirable particle size is produced by processes such as the pulverizing and blending of lead colours, the abrasive working of lead-based fillers in automobile bodies and the dry rubbing-down of lead paint. The exhaust gases of gasoline engines yield lead chloride and lead bromide particles of 1 micron diameter. The larger particles, however, may be ingested and be absorbed via the stomach. A more informative picture of the hazard associated with a sample of lead dust might be given by including a size distribution as well as a total lead determination. But this information is probably more important for the research investigator than for the field hygienist.

Biological fate

In the human body, inorganic lead is not metabolized but is directly absorbed, distributed and excreted. The rate at which lead is absorbed depends on its chemical and physical form and on the physiological characteristics of the exposed person (e.g., nutritional status and age). Inhaled lead deposited in the lower respiratory tract is completely absorbed. The amount of lead absorbed from the gastrointestinal tract of adults is typically 10 to 15% of the ingested quantity; for pregnant women and children, the amount absorbed can increase to as much as 50%. The quantity absorbed increases significantly under fasting conditions and with iron or calcium deficiency.

Once in the blood, lead is distributed primarily among three compartments—blood, soft tissue (kidney, bone marrow, liver, and brain), and mineralizing tissue (bones and teeth). Mineralizing tissue contains about 95% of the total body burden of lead in adults.

The lead in mineralizing tissues accumulates in subcompartments that differ in the rate at which lead is resorbed. In bone, there is both a labile component, which readily exchanges lead with the blood, and an inert pool. The lead in the inert pool poses a special risk because it is a potential endogenous source of lead. When the body is under physiological stress such as pregnancy, lactation or chronic disease, this normally inert lead can be mobilized, increasing the lead level in blood. Because of these mobile lead stores, significant drops in a person’s blood lead level can take several months or sometimes years, even after complete removal from the source of lead exposure.

Of the lead in the blood, 99% is associated with erythrocytes; the remaining 1% is in the plasma, where it is available for transport to the tissues. The blood lead not retained is either excreted by the kidneys or through biliary clearance into the gastrointestinal tract. In single-exposure studies with adults, lead has a half-life, in blood, of approximately 25 days; in soft tissue, about 40 days; and in the non-labile portion of bone, more than 25 years. Consequently, after a single exposure a person’s blood lead level may begin to return to normal; the total body burden, however, may still be elevated.

For lead poisoning to develop, major acute exposures to lead need not occur. The body accumulates this metal over a lifetime and releases it slowly, so even small doses, over time, can cause lead poisoning. It is the total body burden of lead that is related to the risk of adverse effects.

Physiological effects

Whether lead enters the body through inhalation or ingestion, the biologic effects are the same; there is interference with normal cell function and with a number of physiological processes.

Neurological effects. The most sensitive target of lead poisoning is the nervous system. In children, neurological deficits have been documented at exposure levels once thought to cause no harmful effects. In addition to the lack of a precise threshold, childhood lead toxicity may have permanent effects. One study showed that damage to the central nervous system (CNS) that occurred as a result of lead exposure at age 2 resulted in continued deficits in neurological development, such as lower IQ scores and cognitive deficits, at age 5. In another study that measured total body burden, primary school children with high tooth lead levels but with no known history of lead poisoning had larger deficits in psychometric intelligence scores, speech and language processing, attention and classroom performance than children with lower levels of lead. A 1990 follow-up report of children with elevated lead levels in their teeth noted a sevenfold increase in the odds of failure to graduate from high school, lower class standing, greater absenteeism, more reading disabilities and deficits in vocabulary, fine motor skills, reaction time and hand-eye coordination 11 years later. The reported effects are more likely caused by the enduring toxicity of lead than by recent excessive exposures because the blood lead levels found in the young adults were low (less than 10 micrograms per deciliter (μg/dL)).

Hearing acuity, particularly at higher frequencies, has been found to decrease with increasing blood lead levels. Hearing loss may contribute to the apparent learning disabilities or poor classroom behavior exhibited by children with lead intoxication.

Adults also experience CNS effects at relatively low blood lead levels, manifested by subtle behavioural changes, fatigue and impaired concentration. Peripheral nervous system damage, primarily motor, is seen mainly in adults. Peripheral neuropathy with mild slowing of nerve conduction velocity has been reported in asymptomatic lead workers. Lead neuropathy is believed to be a motor neuron, anterior horn cell disease with peripheral dying-back of the axons. Frank wrist drop occurs only as a late sign of lead intoxication.

Haematological effects. Lead inhibits the body’s ability to make hemoglobin by interfering with several enzymatic steps in the heme pathway. Ferrochelatase, which catalyzes the insertion of iron into protoporphyrin IX, is quite sensitive to lead. A decrease in the activity of this enzyme results in an increase of the substrate, erythrocyte protoporphyrin (EP), in the red blood cells. Recent data indicate that the EP level, which has been used to screen for lead toxicity in the past, is not sufficiently sensitive at lower levels of blood lead and is therefore not as useful a screening test for lead poisoning as previously thought.

Lead can induce two types of anaemia. Acute high-level lead poisoning has been associated with hemolytic anaemia. In chronic lead poisoning, lead induces anemia by both interfering with erythropoiesis and by diminishing red blood cell survival. It should be emphasized, however, that anemia is not an early manifestation of lead poisoning and is evident only when the blood lead level is significantly elevated for prolonged periods.

Endocrine effects. A strong inverse correlation exists between blood lead levels and levels of vitamin D. Because the vitamin D-endocrine system is responsible in large part for the maintenance of extra- and intra-cellular calcium homeostasis, it is likely that lead impairs cell growth and maturation and tooth and bone development.

Renal effects. A direct effect on the kidney of long-term lead exposure is nephropathy. Impairment of proximal tubular function manifests in aminoaciduria, glycosuria and hyperphosphaturia (a Fanconi-like syndrome). There is also evidence of an association between lead exposure and hypertension, an effect that may be mediated through renal mechanisms. Gout may develop as a result of lead-induced hyperuricemia, with selective decreases in the fractional excretion of uric acid before a decline in creatinine clearance. Renal failure accounts for 10% of deaths in patients with gout.

Reproductive and developmental effects. Maternal lead stores readily cross the placenta, placing the foetus at risk. An increased frequency of miscarriages and stillbirths among women working in the lead trades was reported as early as the end of the 19th century. Although the data concerning exposure levels are incomplete, these effects were probably a result of far greater exposures than are currently found in lead industries. Reliable dose-effect data for reproductive effects in women are still lacking today.

Increasing evidence indicates that lead not only affects the viability of the foetus, but development as well. Developmental consequences of prenatal exposure to low levels of lead include reduced birth weight and premature birth. Lead is an animal teratogen; however, most studies in humans have failed to show a relationship between lead levels and congenital malformations.

The effects of lead on the male reproductive system in humans have not been well characterized. The available data support a tentative conclusion that testicular effects, including reduced sperm counts and motility, may result from chronic exposure to lead.

Carcinogenic effects. Inorganic lead and inorganic lead compounds have been classified as Group 2B, possible human carcinogens, by the International Agency for Research on Cancer (IARC). Case reports have implicated lead as a potential renal carcinogen in humans, but the association remains uncertain. Soluble salts, such as lead acetate and lead phosphate, have been reported to cause kidney tumors in rats.

Continuum of signs and symptoms associated with lead toxicity

Mild toxicity associated with lead exposure includes the following:

  • myalgia or paresthesia
  • mild fatigue
  • irritability
  • lethargy
  • occasional abdominal discomfort.


The signs and symptoms associated with moderate toxicity include:

  • arthralgia
  • general fatigue
  • difficulty concentrating
  • muscular exhaustibility
  • tremor
  • headache
  • diffuse abdominal pain
  • vomiting
  • weight loss
  • constipation.


The signs and symptoms of severe toxicity include:

  • paresis or paralysis
  • encephalopathy, which may abruptly lead to seizures, changes in consciousness, coma and death
  • lead line (blue-black) on gingival tissue
  • colic (intermittent, severe abdominal cramps).


Some of the haematological signs of lead poisoning mimic other diseases or conditions. In the differential diagnosis of microcytic anaemia, lead poisoning can usually be ruled out by obtaining a venous blood lead concentration; if the blood lead level is less than 25 μg/dL, the anaemia usually reflects iron deficiency or haemoglobinopathy. Two rare diseases, acute intermittent porphyria and coproporphyria, also result in haeme abnormalities similar to those of lead poisoning.

Other effects of lead poisoning can be misleading. Patients exhibiting neurological signs due to lead poisoning have been treated only for peripheral neuropathy or carpal tunnel syndrome, delaying treatment for lead intoxication. Failure to correctly diagnose lead induced gastrointestinal distress has led to inappropriate abdominal surgery.

Laboratory evaluation

If pica or accidental ingestion of lead-containing objects (such as curtain weights or fishing sinkers) is suspected, an abdominal radiograph should be taken. Hair analysis is not usually an appropriate assay for lead toxicity because no correlation has been found between the amount of lead in the hair and the exposure level.

The probability of environmental lead contamination of a laboratory specimen and inconsistent sample preparation make the results of hair analysis difficult to interpret. Suggested laboratory tests to evaluate lead intoxication include the following:

  • CBC with peripheral smear
  • blood lead level
  • erythrocyte protoporphyrin level
  • BUN and creatinine level
  • urinalysis.


CBC with peripheral smear. In a lead-poisoned patient, the haematocrit and haemoglobin values may be slightly to moderately low. The differential and total white count may appear normal. The peripheral smear may be either normochromic and normocytic or hypochromic and microcytic. Basophilic stippling is usually seen only in patients who have been significantly poisoned for a prolonged period. Eosinophilia may appear in patients with lead toxicity but does not show a clear dose-response effect.

It is important to note that basophilic stippling is not always seen in lead poisoned patients.

Blood lead level. A blood lead level is the most useful screening and diagnostic test for lead exposure. A blood lead level reflects lead’s dynamic equilibrium between absorption, excretion and deposition in soft- and hard-tissue compartments. For chronic exposures, blood lead levels often underrepresent the total body burden; nevertheless, it is the most widely accepted and commonly used measure of lead exposure. Blood lead levels srespond relatively rapidly to abrupt or intermittent changes in lead intake (e.g., ingestion of lead paint chips by children) and, within a limited range, bear a linear relationship to those intake levels.

Today, the average blood lead level in the US population, for example, is below 10 μg/dL, down from an average of 16 μg/dL (in the 1970s), the level before the legislated removal of lead from gasoline. A blood lead level of 10 μg/dL is about three times higher than the average level found in some remote populations.

The levels defining lead poisoning have been progressively declining. Taken together, effects occur over a wide range of blood lead concentrations, with no indication of a threshold. No safe level has yet been found for children. Even in adults, effects are being discovered at lower and lower levels as more sensitive analyses and measures are developed.

Erythrocyte protoporhyrin level. Until recently, the test of choice for screening asymptomatic populations at risk was erythrocyte protoporphyrin (EP), commonly assayed as zinc protoporphyrin (ZPP). An elevated level of protoporphyrin in the blood is a result of accumulation secondary to enzyme dysfunction in the erythrocytes. It reaches a steady state in the blood only after the entire population of circulating erythrocyles has turned over, about 120 days. Consequently, it lags behind blood lead levels and is an indirect measure of long-term lead exposure.

The major disadvantage of using EP (ZPP) testing as a method for lead screening is that it is not sensitive at the lower levels of lead poisoning. Data from the second US National Health and Nutrition Examination Survey (NHANES II) indicate that 58% of 118 children with blood lead levels above 30 μg/dL had EP levels within normal limits. This finding shows that a significant number of children with lead toxicity would be missed by reliance on EP (ZPP) testing alone as the screening tool. An EP (ZPP) level is still useful in screening patients for iron deficiency anaemia.

Normal values of ZPP are usually below 35 μg/dL. Hyperbilirubinaemia (jaundice) will cause falsely elevated readings when the haematofluorometer is used. EP is elevated in iron deficiency anaemia and in sickle cell and other haemolytic anaemias. In erythropoietic protoporphyria, an extremely rare disease, EP is markedly elevated (usually above 300 μg/dL).

BUN, creatinine and urinalysis. These parameters may reveal only late, significant effects of lead on renal function. Renal function in adults can also be assessed by measuring the fractional excretion of uric acid (normal range 5 to 10%; less than 5% in saturnine gout; greater than 10% in Fanconi syndrome).

Organic lead intoxication

The absorption of a sufficient quantity of tetraethyllead, whether briefly at a high rate or for prolonged periods at a lower rate, induces acute intoxication of the CNS. The milder manifestations are those of insomnia, lassitude and nervous excitation which reveals itself in lurid dreams and dream-like waking states of anxiety, in association with tremor, hyper-reflexia, spasmodic muscular contractions, bradycardia, vascular hypotension and hypothermia. The more severe responses include recurrent (sometimes nearly continuous) episodes of complete disorientation with hallucinations, facial contortions and intense general somatic muscular activity with resistance to physical restraint. Such episodes may be converted abruptly into maniacal or violent convulsive seizures which may terminate in coma and death.

Illness may persist for days or weeks, with intervals of quietude readily triggered into over-activity by any type of disturbance. In these less acute cases, fall in blood pressure and loss of body weight are common. When the onset of such symptomatology follows promptly (within a few hours) after brief, severe exposure to tetraethyllead, and when the symptomatology develops rapidly, an early fatal outcome is to be feared. When, however, the interval between the termination of brief or prolonged exposure and the onset of symptoms is delayed (by up to 8 days), the prognosis is guardedly hopeful, although partial or recurrent disorientation and depressed circulatory function may persist for weeks.

The initial diagnosis is suggested by a valid history of significant exposure to tetraethyllead, or by the clinical pattern of the presenting illness. It may be supported by the further development of the illness, and confirmed by evidence of a significant degree of absorption of tetraethyllead, provided by analyses of urine and blood which reveal typical findings (i.e., a striking elevation of the rate of excretion of lead in the urine) and a concurrently negligible or slight elevation of the concentration of lead in the blood.

Lead Control in the Working Environment

Clinical lead poisoning has historically been one of the most important occupational diseases, and it remains a major risk today. The considerable body of scientific knowledge concerning the toxic effects of lead has been enriched since the 1980s by significant new knowledge regarding the more subtle subclinical effects. Similarly, in a number of countries it was felt necessary to redraft or modernize work protective measures enacted over the last half-century and more.

Thus, in November 1979, in the US, the Final Standard on Occupational Exposure to Lead was issued by the Occupational Safety and Health Administration (OSHA) and in November 1980 a comprehensive Approved Code of Practice was issued in the United Kingdom regarding the control of lead at work.

The main features of the legislation, regulations and codes of practice emerging in the 1970s concerning the protection of the health of workers at work involved establishing comprehensive systems covering all work circumstances where lead is present and giving equal importance to hygiene measures, ambient monitoring and health surveillance (including biological monitoring).

Most codes of practice include the following aspects:

  • assessment of work which exposes persons to lead
  • information, instruction and training
  • control measures for materials, plant and processes
  • use and maintenance of control measures
  • respiratory protective equipment and protective clothing
  • washing and changing facilities and cleaning
  • separate eating, drinking and smoking areas
  • duty to avoid spread of contamination by lead
  • air monitoring
  • medical surveillance and biological tests
  • keeping of records.


Some regulation, such as the OSHA lead standard, specifies the permissible exposure limit (PEL) of lead in the workplace, the frequency and extent of medical monitoring, and other responsibilities of the employer. As of this writing, if blood monitoring reveals a blood lead level greater than 40 μg/dL, the worker must be notified in writing and provided with medical examination. If a worker’s blood lead level reaches 60 μg/dL (or averages 50 μg/dL or more), the employer is obligated to remove the employee from excessive exposure, with maintenance of seniority and pay, until the employee’s blood lead level falls below 40 μg/dL (29 CFR 91 O.1025) (medical removal protection benefits).

Safety and Health Measures

The object of precautions is first to prevent the inhalation of lead and secondly to prevent its ingestion. These objects are most effectively achieved by the substitution of a less toxic substance for the lead compound. The use of lead polysilicates in the potteries is one example. The avoidance of lead carbonate paints for the painting of the interiors of buildings has proved very effective in reducing painters’ colic; effective substitutes for lead for this purpose have become so readily available that it has been considered reasonable in some countries to prohibit the use of lead paint for the interiors of buildings.

Even if it is not possible to avoid the use of lead itself, it is still possible to avoid dust. Water sprays may be used in large quantities to prevent the formation of dust and to prevent it from becoming airborne. In lead smelting, the ore and the scrap may be treated in this way and the floors on which it has been lying may be kept wet. Unfortunately, there is always a potential source of dust in these circumstances if the treated material or floors are ever allowed to become dry. In some instances, arrangements are made to ensure that the dust will be coarse rather than fine. Other specific engineering precautions are discussed elsewhere in this Encyclopaedia.

Workers who are exposed to lead in any of its forms should be provided with personal protective equipment (PPE), which should be washed or renewed regularly. Protective clothing made of certain man-made fibres retains much less dust than cotton overalls and should be used where the conditions of work render it possible; turn-ups, pleats and pockets in which lead dust may collect should be avoided.

Cloakroom accommodation should be provided for this PPE, with separate accommodation for clothing taken off during working hours. Washing accommodation, including bathing accommodation with warm water, should be provided and used. Time should be allowed for washing before eating. Arrangements should be made to prohibit eating and smoking in the vicinity of lead processes and suitable eating facilities should be provided.

It is essential that the rooms and the plant associated with lead processes should be kept clean by continuous cleaning either by a wet process or by vacuum cleaners. Where, in spite of these precautions, workers may still be exposed to lead, respiratory protective equipment should be provided and properly maintained. Supervision should ensure that this equipment is maintained in a clean and efficient condition and that it is used when necessary.

Organic lead

Both the toxic properties of organic lead compounds, and their ease of absorption, require that contact of the skin of workers with these compounds, alone or in concentrated mixtures in commercial formulations or in gasoline or other organic solvents, must be scrupulously avoided. Both technological and management control are essential, and appropriate training of workers in safe work practices and the use of PPE is required. It is essential that atmospheric concentrations of alkyl lead compounds in the workplace air should be maintained at extremely low levels. Personnel should not be allowed to eat, smoke or keep unsealed food or beverages at the workplace. Good sanitary facilities, including showers, should be provided and workers should be encouraged to practise good personal hygiene, especially by showering or washing after the work shift. Separate lockers should be supplied for working and private clothes.



Friday, 11 February 2011 04:27


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.


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.



Friday, 11 February 2011 04:28


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.


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.


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.



Friday, 11 February 2011 04:40

Metal Carbonyls (especially Nickel Carbonyl)

F. William Sunderman, Jr.

Occurrence and Uses

Metal carbonyls have the general formula Mex(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


Mol. Wt.

Sp. Gr.

M.P. (ºC)

B.P. (ºC)

V.P. (25ºC) 

mm Hg




















very low




















approx. 140*













approx. 150*



*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.


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.



Friday, 11 February 2011 04:31


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.


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.



Friday, 11 February 2011 21:08


Gunnar Nordberg

Occurrence and Uses

Molybdenum (Mo) is widely distributed throughout the earth’s crust, but it is mined in only a limited number of countries due to the rarity of bodies of sufficiently high quality molybdenite ore (MoSO2). A certain amount of molybdenum is obtained as a by-product in the processing of copper ore. Coal-electrical power plants can be significant sources of molybdenum. Molybdenum is an essential trace element.

Molybdenum forms a large variety of commercially useful compounds in which it displays the valence numbers 0, +2, +3, +4, +5 and +6. It readily changes valence states (disproportionates) with only minor changes in external conditions. It has a strong tendency to form complexes; with the exception of the sulphides and halides, very few other simple compounds of molybdenum exist. The +6 molybdenum forms isopoly- and heteropoly- acids.

Over 90% of the molybdenum produced is used as an alloying element for iron, steel and non-ferrous metals, mainly because of its heat-resisting properties; the rest is used in chemicals and lubricants. As a steel alloy, molybdenum is utilized in the electric, electronics, military and automobile industries and in aeronautical engineering. Another important use of molybdenum is in the production of inorganic molybdenum pigments, dyes and lakes. Small but increasing amounts of molybdenum are used as trace elements in fertilizers.

The most important molybdenum chemical is molybdenum trioxide (MoO3), made from roasting the sulphide ore. Pure molybdenum trioxide is used in chemical and catalyst manufacture. The technical product is added to steel as an alloying agent. Molybdenum trioxide also serves as a catalyst in the petroleum industry and as a component of ceramics, enamels and pigments. Molybdenum disulphide (MoS2) is employed as a heat-resistant lubricant or a lubricant additive. Molybdenum hexacarbonyl (Mo(CO)6) is the starting product for the manufacture of organomolybdenum dyes. It is increasingly used for molybdenum plating by thermal decomposition.

Molybdenum compounds are widely used as catalysts or catalyst activators or promoters, especially for hydrogenation-cracking, alkylation and reforming in the petroleum industry. They are employed as laboratory reagents (phosphomolybdates). In addition, molybdenum compounds are used in electroplating and in tanning.


In the processing and industrial utilization of molybdenum and its compounds there may be exposure to dusts and fumes of molybdenum and its oxides and sulphides. This exposure may occur, especially where high-temperature treatment is being carried out as, for example, in an electric furnace. Exposure to molybdenum disulphide lubricant spray, molybdenum hexacarbonyl and its breakdown products during molybdenum plating, molybdenum hydroxide (Mo(OH)3) mist during electroplating, and molybdenum trioxide fumes which sublime above 800 °C may all prove hazardous to health.

Molybdenum compounds are highly toxic based on animal experiments. Acute poisoning causes severe gastrointestinal irritation with diarrhoea, coma and deaths from heart failure. Pneumoconiosis-like effects in the lungs have been reported in animal studies. Workers exposed to pure molybdenum or to molybdenum oxide (MoO3) (concentration of 1 to 19 mg Mo/m3) over a period of 3 to 7 years have suffered from pneumoconiosis. Inhalation of molybdenum dust from alloys or carbides can cause “hard metal lung disease”.

There is a wide degree of variation in the hazard resulting from exposure. Insoluble molybdenum compounds (e.g., molybdenum disulphide and many of the oxides and halides) are characterized by low toxicity; however, the soluble compounds (i.e., those in which molybdenum is an anion, such as sodium molybdenate—Na2MoO4·2H2O) are considerably more toxic and should be handled with care. Likewise, precautions should be taken to prevent over-exposure to freshly generated molybdenum fumes as in the thermal decomposition of molybdenum hexacarbonyl.

Exposure to molybdenum trioxide produces irritation of the eyes and the mucous membranes of the nose and throat. Anaemia is a characteristic feature of molybdenum toxicity, with low haemoglobin concentrations and reduced red-cell counts.

High dietary levels of molybdenum in cattle were found to produce deformities in the joints of the extremities. Among chemists handling molybdenum and tungsten solutions, an abnormally high frequency of cases of gout have been reported, and a correlation has been found between the content of molybdenum in food, the incidence of gout, uricaemia and xanthine oxidase activity.

Safety Measures

While working with molybdenum in industry, proper local exhaust ventilation should be employed to collect fumes at their source. Respirators may be worn when engineering and work practices have failed, when such controls are in the process of being installed, for operations requiring entry into tanks or closed vessels, or in emergencies. In the paint, printing and coatings industries, local and general exhaust ventilation as well as safety glasses, protective clothing, face shields and acceptable respirators should be used to reduce exposure for workers handling molybdenum-based dry ingredients for inorganic and organic colours.



Friday, 11 February 2011 21:12


F. William Sunderman, Jr.

Nickel (Ni) compounds of interest include nickel oxide (NiO), nickel hydroxide (Ni(OH)2), nickel subsulphide (Ni3S2), nickel sulphate (NiSO4) and nickel chloride (NiCl2). Nickel carbonyl (Ni(CO)4) is considered in a separate article on metal carbonyls.

Occurrence and Uses

Nickel (Ni) comprises 5 to 50% of the weight of meteorites and is found in ores in combination with sulphur, oxygen, antimony, arsenic and/or silica. Ore deposits of commercial importance are principally oxides (e.g., laterite ores containing mixed nickel/iron oxides) and sulphides. Pentlandite ((NiFe)9S8), the major sulphide mineral, is commonly deposited in association with pyrrhotite (Fe7S6), chalcopyrite (CuFeS2) and small amounts of cobalt, selenium, tellurium, silver, gold and platinum. Substantial deposits of nickel ores are found in Canada, Russia, Australia, New Caledonia, Indonesia and Cuba.

Since nickel, copper and iron occur as distinct minerals in the sulphide ores, mechanical methods of concentration, such as flotation and magnetic separation, are applied after the ore has been crushed and ground. The nickel concentrate is converted to nickel sulphide matte by roasting or sintering. The matte is refined by electrowinning or by the Mond process. In the Mond process, the matte is ground, calcined and treated with carbon monoxide at 50 °C to form gaseous nickel carbonyl (Ni(CO)4), which is then decomposed at 200 to 250 °C to deposit pure nickel powder. Worldwide production of nickel is approximately 70 million kg/year.

More than 3,000 nickel alloys and compounds are commercially produced. Stainless steel and other Ni-Cr-Fe alloys are widely used for corrosion-resistant equipment, architectural applications and cooking utensils. Monel metal and other Ni-Cu alloys are used in coinage, food-processing machinery and dairy equipment. Ni-Al alloys are used for magnets and catalyst production (e.g., Raney nickel). Ni-Cr alloys are used for heating elements, gas turbines and jet engines. Alloys of nickel with precious metals are used in jewellery. Nickel metal, its compounds and alloys have many other uses, including electroplating, magnetic tapes and computer components, arc-welding rods, surgical and dental prostheses, nickel-cadmium batteries, paint pigments (e.g., yellow nickel titanate), moulds for ceramic and glass containers, and catalysts for hydrogenation reactions, organic syntheses and the final methanation step of coal gasification. Occupational exposures to nickel also occur in recycling operations, since nickel-bearing materials, especially from the steel industry, are commonly melted, refined and used to prepare alloys similar in composition to those that entered the recycling process.


Human health hazards from occupational exposures to nickel compounds generally fall into three major categories:

  1. allergy
  2. rhinitis, sinusitis and respiratory diseases
  3. cancers of the nasal cavities, lungs and other organs.


The health hazards from nickel carbonyl are considered separately, in the article on metal carbonyls.

Allergy. Nickel and nickel compounds are among the most common causes of allergic contact dermatitis. This problem is not limited to persons with occupational exposure to nickel compounds; dermal sensitization occurs in the general population from exposures to nickel-containing coins, jewellery, watch cases and clothing fasteners. In nickel-exposed persons, nickel dermatitis usually begins as a papular erythema of the hands. The skin gradually becomes eczematous, and, in the chronic stage, lichenification frequently develops. Nickel sensitization sometimes causes conjunctivitis, eosinophilic pneumonitis, and local or systemic reactions to nickel-containing implants (e.g., intraosseous pins, dental inlays, cardiac valve prostheses and pacemaker wires). Ingestion of nickel-contaminated tap water or nickel-rich foods can exacerbate hand eczema in nickel-sensitive persons.

Rhinitis, sinusitis and respiratory diseases. Workers in nickel refineries and nickel electroplating shops, who are heavily exposed to inhalation of nickel dusts or aerosols of soluble nickel compounds, may develop chronic diseases of the upper respiratory tract, including hypertrophic rhinitis, nasal sinusitis, anosmia, nasal polyposis and perforation of the nasal septum. Chronic diseases of the lower respiratory tract (e.g., bronchitis, pulmonary fibrosis) have also been reported, but such conditions are infrequent. Rendall et al. (1994) reported the fatal acute exposure of a worker to inhalation of particulate nickel from a metal arc process; the authors stressed the importance of wearing protective equipment while using metal arc processes with nickel wire electrodes.

Cancer. Epidemiological studies of nickel-refinery workers in Canada, Wales, Germany, Norway and Russia have documented increased mortality rates from cancers of the lung and nasal cavities. Certain groups of nickel-refinery workers have also been reported to have increased incidences of other malignant tumours, including carcinomas of the larynx, kidney, prostate or stomach, and sarcomas of soft tissues, but the statistical significance of these observations is questionable. The increased risks of cancers of the lungs and nasal cavities have occurred primarily among workers in refinery operations that entail high nickel exposures, including roasting, smelting and electrolysis. Although these cancer risks have generally been associated with exposures to insoluble nickel compounds, such as nickel subsulphide and nickel oxide, exposures to soluble nickel compounds have been implicated in electrolysis workers.

Epidemiological studies of cancer risks among workers in nickel-using industries have generally been negative, but recent evidence suggests slightly increased lung cancer risks among welders, grinders, electroplaters and battery makers. Such workers are often exposed to dusts and fumes that contain mixtures of carcinogenic metals (e.g., nickel and chromium, or nickel and cadmium). Based on an evaluation of epidemiological studies, the International Agency for Research on Cancer (IARC) concluded in 1990: “There is sufficient evidence in humans for the carcinogenicity of nickel sulphate and of the combinations of nickel sulphides and oxides encountered in the nickel refining industry. There is inadequate evidence in humans for the carcinogenicity of nickel and nickel alloys.” Nickel compounds have been classified as carcinogenic to humans (Group 1), and metallic nickel as possibly carcinogenic to humans (Group 2B).

Renal effects. Workers with high exposures to soluble nickel compounds may develop renal tubular dysfunction, evidenced by increased renal excretion of β2-microglobulin (β2M) and N-acetyl-glucosaminidase (NAG).

Safety and Health Measures

A general protocol for health surveillance of workers exposed to nickel was proposed in 1994 by the Nickel Producers Evironmental Research Association (NiPERA) and the Nickel Development Institute (NiDI). The key elements are as follows:

Pre-placement assessment. The goals of this examination are to identify pre-existing medical conditions that may influence hiring and job placement, and to provide baseline data for subsequent functional, physiological or pathological changes. The assessment includes (i) detailed medical and occupational history, focusing on lung problems, exposures to lung toxins, past or present allergies (particularly to nickel), asthma and personal habits (e.g., smoking, alcohol consumption), (ii) complete physical examination, with attention to respiratory and skin problems and (iii) determination of the respiratory protective equipment that may be worn.

Chest x ray, pulmonary function tests, audiometric tests and vision tests may be included. Skin patch testing for nickel sensitivity is not routinely performed, because such tests could possibly sensitize the subject. If the organization conducts a biological monitoring programme for nickel-exposed workers (see below), baseline nickel concentrations in urine or serum are obtained during the pre-placement assessment.

Periodic assessment. The goals of periodic medical examinations, typically performed annually, are to monitor the worker’s general health and to address nickel-associated concerns. The examination includes the history of recent illnesses, symptom review, physical examination and re-evaluation of the worker’s ability to use the respiratory protective equipment required for particular tasks. Pulmonary symptoms are assessed by a standard questionnaire for chronic bronchitis. Chest x ray may be legally required in some countries; pulmonary function tests (e.g., forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) are generally left to the physician’s discretion. Periodic cancer detection procedures (e.g., rhinoscopy, nasal sinus x rays, nasal mucosal biopsy, exfoliative cytological studies) may be indicated in workers with high-risk exposures in nickel refining.

Biological monitoring. Analyses of nickel concentrations in urine and serum samples may reflect the recent exposures of workers to metallic nickel and soluble nickel compounds, but these assays do not furnish reliable measures of the total body nickel burden. The uses and limitations of biological monitoring of nickel-exposed workers have been summarized by Sunderman et al. (1986). A technical report on analysis of nickel in body fluids was issued in 1994 by the Commission on Toxicology of the International Union of Pure and Applied Chemistry (IUPAC). The National Maximum Workplace Concentration Committee (NMWCC) of the Netherlands proposed that urine nickel concentration 40 µg/g creatinine, or serum nickel concentration 5 µg/l (both measured in samples obtained at the end of a working week or a work shift) be considered warning limits for further investigation of workers exposed to nickel metal or soluble nickel compounds. If a biological monitoring programme is implemented, it should augment an environmental monitoring programme, so that biological data are not used as a surrogate for exposure estimates. A standard method for the analysis of nickel in workplace air was developed in 1995 by the UK Health and Safety Executive.

Treatment. When a group of workers accidently drank water heavily contaminated with nickel chloride and nickel sulphate, conservative treatment with intravenous fluids to induce diuresis was effective (Sunderman et al. 1988). The best therapy for nickel dermatitis is avoidance of exposure, with special attention to work hygienic practices. Therapy of acute nickel carbonyl poisoning is discussed in the article on metal carbonyls.



Friday, 11 February 2011 21:14


Gunnar Nordberg

Occurrence and Uses

Niobium (Nb) is found together with other elements including titanium (Ti), zirconium (Zr), tungsten (W), thorium (Th) and uranium (U) in ores such as tantalite-columbite, fergusonite, samarskite, pyrochlore, koppite and loparite. The largest deposits are located in Australia and Nigeria, and during the last few years extensive deposits have been discovered in Uganda, Kenya, Tanzania and Canada.

Niobium is widely used in the electrovacuum industry and also in the manufacture of anodes, grids, electrolytic condensers and rectifiers. In chemical engineering, niobium is used as a corrosion-proof material for heat exchangers, filters, needle valves and so on. High-quality cutting tools and magnetic materials are made from niobium alloys. Ferroniobium alloy is used in thermonuclear appliances.

Niobium and its refractory alloys are utilized in the field of rocket technology, in the supersonic aircraft industry, interplanetary flight equipment and in satellites. Niobium is also used in surgery.


During the mining and concentration of niobium ore and processing of the concentrate, the workers may be exposed to general hazards, such as dust and fumes, which are typical for these operations. In the mines, the action of dust may be aggravated by exposure to radioactive substances such as thorium and uranium.


Much of the information about the behaviour of niobium in the body is based on studies of the radioisotope pair 95Zr-95Nb, a common nuclear fission product. 95Nb is the daughter of 95Zr. One study investigated cancer incidence among niobium mine workers exposed to radon and thoron daughters and found an association between lung cancer and cumulative alpha-radiation.

Intravenous and intraperitoneal injections of niobium (radioactive) and its compounds showed a fairly uniform distribution through the organism, with a tendency to accumulate in the liver, kidneys, spleen and bone marrow. The elimination of radioactive niobium from the organism can be hastened appreciably by the injection of massive doses of zirconium nitrate. After intraperitoneal injections of stable niobium in the form of potassium niobate, the LD50 for rats was 86 to 92 mg/kg and for mice 13 mg/kg. Metallic niobium is not absorbed from the stomach or intestines. The LD50 of niobium pentachloride in these organs was 940 mg/kg for rats, while the corresponding figure for potassium niobate was 3,000 mg/kg. Niobium compounds administered intravenously, intraperitoneally or per os produce a particularly pronounced effect on the kidneys. This effect can be attenuated by preventive medication with ascorbic acid. Oral intake of niobium pentachloride furthermore causes acute irritation of the mucous membranes of the gullet and stomach, and liver changes; chronic exposure during 4 months causes temporary blood changes (leukocytosis, prothrombin deficiency).

Inhaled niobium is retained in the lung, which is the critical organ for dust. Daily inhalation of niobium nitride dust at a concentration of 40 mg/m3 of air leads within a few months to signs of pneumoconiosis (while there are no noticeable signs of toxic action): thickening of the interalveolar septa, development of considerable amounts of collagenous fibres in the peribronchial and perivascular tissue, and desquamation of the bronchial epithelium. Analogous changes develop upon intratracheal administration of niobium pentoxide dust; in this case dust is found even in the lymph nodes.

Safety and Health Measures

Atmospheric concentrations of the aerosols of niobium alloys and compounds that contain toxic elements such as fluorine, manganese and beryllium, should be strictly controlled. During the mining and concentration of niobium ore containing uranium and thorium, the worker should be protected against radioactivity. Proper engineering design including adequate ventilation with fresh air is necessary to control dust in mine air. In the extraction of pure niobium from its compounds by powder metallurgy, the workplaces must be kept free from niobium dust and fumes, and workers must be protected against chemicals such as caustic alkalis and benzene. In addition, regular medical examinations which include lung function tests are recommended.



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Part I. The Body
Part II. Health Care
Part III. Management & Policy
Part IV. Tools and Approaches
Part V. Psychosocial and Organizational Factors
Part VI. General Hazards
Part VII. The Environment
Part VIII. Accidents and Safety Management
Part IX. Chemicals
Using, Storing and Transporting Chemicals
Minerals and Agricultural Chemicals
Metals: Chemical Properties and Toxicity
Part X. Industries Based on Biological Resources
Part XI. Industries Based on Natural Resources
Part XII. Chemical Industries
Part XIII. Manufacturing Industries
Part XIV. Textile and Apparel Industries
Part XV. Transport Industries
Part XVI. Construction
Part XVII. Services and Trade
Part XVIII. Guides

Metals: Chemical Properties and Toxicity References

Agency for Toxic Substances and Disease Registry (ATSDR). 1995. Case Studies in Environmental Medicine: Lead Toxicity. Atlanta: ATSDR.

Brief, RS, JW Blanchard, RA Scala, and JH Blacker. 1971. Metal carbonyls in the petroleum industry. Arch Environ Health 23:373–384.

International Agency for Research on Cancer (IARC). 1990. Chromium, Nickel and Welding. Lyon: IARC.

National Institute for Occupational Safety and Health (NIOSH). 1994. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 94-116. Cincinnati, OH: NIOSH.

Rendall, REG, JI Phillips and KA Renton. 1994. Death following exposure to fine particulate nickel from a metal arc process. Ann Occup Hyg 38:921–930.

Sunderman, FW, Jr., and A Oskarsson,. 1991. Nickel. In Metals and their compounds in the environment, edited by E Merian, Weinheim, Germany: VCH Verlag.

Sunderman, FW, Jr., A Aitio, LO Morgan, and T Norseth. 1986. Biological monitoring of nickel. Tox Ind Health 2:17–78.

United Nations Committee of Experts on the Transport of Dangerous Goods. 1995. Recommendations on the Transport of Dangerous Goods, 9th edition. New York: United Nations.