After oxygen, silicon is the element most frequently found on earth. It does not occur free in nature, but as an oxide (silica) or silicate (feldspar, kaolinite and so on) in sand, rock and clay. One method of preparation is by heating quartz (SiO₂) with carbon; during this process carbon monoxide is emitted and raw silicon (98% pure) remains. This grade is sufficiently pure for incorporation in alloys—for example, of aluminium and iron—in order to make them harder or less brittle. Pure silicon is prepared by heating raw silicon in chlorine. During this process the volatile compound SiCl₄ occurs and is separated by distillation. If this liquid is heated together with hydrogen, pure silicon is released. This is shaped into rod form, and the last impurities are “floated” out from the rod by successively heating small portions of it to melting point, in an atmosphere of inert gas, such as argon, compounded with any trace elements to be added, which become dissolved in the liquid silicon.

Siloxanes are compounds which contain oxygen in addition to hydrogen, silicon and, usually, carbon (although there are some inorganic siloxanes). Starting from small molecules, they can be built up into large units (polymers), to which various properties (liquidity, elasticity, stability and so on) can be imparted. Siloxanes exist in the form of resins, elastomers (rubbery compounds) or oils.

Uses

It is used as an alloying agent for steel, aluminium, copper, bronze and iron. It is also widely used in semiconductor manufacture and in the production of silanes and organosilicon compounds.

Organosilicon compounds are used in the form of resins, elastomers (rubbery compounds) or oils. Resins are organosilicon compounds which, when mixed with a number of other substances used in the paint industry (hardeners, accelerators and so on), form very stable layers and are readily applicable even on bases to which other paints generally do not adhere well (such as metal surfaces). In addition they are fairly resistant to momentary heating or attack by oxygen, and do not fade much in sunlight. Among other things, these resins are also used as moulding compounds (plastics), and in the manufacture of foams which display good resistance to high temperatures and are useful thermal insulators. Other resins are used as so-called foils (thin layers applied in the electronics industry) because of their low combustibility and good electrical insulating properties even in a damp environment. Silicon resins have numerous applications because of their heat stability and water repellency, and their resistance to solvents, high temperatures and sunlight. Silicon resins are used in paints, varnishes, moulding compounds (plastics), electrical insulation, pressure-sensitive and release coatings, and laminates.

Methyl silicate is a fairly volatile liquid used in the manufacture of television screens. When it is decomposed in water, a transparent layer of silicic acid results, which secures the screen to the glass wall. Ethyl silicate is used as a binding agent for making moulds in special metal-founding processes or as a starting point in chemical synthesis.

Hazards and Their Prevention

This section discusses the hazards of organosilicon compounds. The reader is referred elsewhere in the Encyclopaedia for discussions of the important health effects of exposure to silicates, particularly crystalline silicates. The effects of silicon carbides are also discussed elsewhere.

The toxicological hazards of metallic silicon are not known. For most regulatory purposes it is considered a nuisance dust. When silicon is prepared and purified in the absence of air, the process takes place in a sealed, gas-tight enclosure which should limit exposures. Hazards may arise from the chemicals which are used in conjunction with silicon in various manufacturing processes. There are three types of silicon compounds considered here: silanes, siloxanes and heterosiloxanes.

Silanes. Silanes contain hydrogen and silicon. Most of them are very stable, oily substances which in themselves find but little practical application. If chlorine, nitrogen and so on are added, however, they can be used for chemical synthesis. Both tetrachlorosilane and trichlorosilane, however, are highly reactive compounds that can emit a highly irritant asphyxiating vapour. When they come into contact with water they are decomposed (hydrolysis), giving off hydrogen chloride. Water in the atmosphere can initiate such hydrolysis. The hydrolysis products can be have intense effects on the eyes and respiratory tract. Moreover, trichlorosilane ignites readily. These liquids are treated as corrosive substances and are shipped in quartz ampoules or stainless steel boxes. Spills can be rendered harmless by anhydrous soda.

The siloxane oil vapours can be irritating to the eyes, and it is reported that extremely high concentrations can have serious effects on the respiratory system. By contrast the silicon resin compounds have been considered to be harmless in the past and were widely used as implants in the body.

Elastomers (rubbery compounds). These substances are characterized by their great stability at high (250 °C) and low temperatures (down to -75 °C), and resistance to attack by chemicals. Their chemical inertness is such that they are often used as implant material for blood vessels and so on. Moreover, they do not dissolve in many organic solvents, such as trichloroethylene or acetone. Silicone rubber membranes are easily permeable by gases such as oxygen, even when these are dissolved in water.

It should be noted that there have been major controversies and legal disputes over the effects of silicon breast implants, with noted authorities divided about any possible long-range health hazards.

Oils. These compounds also retain their stability when exposed to extreme changes in temperature. For this reason they are often used as lubricants, since their viscosity remains substantially constant at different temperatures. They are also used as water-repellents, applied for example on walls, textiles or leather. Pressed parts can be easily removed from moulds smeared with these compounds, and they also act as anti-foaming agents (the latter property is inter alia of assistance to chronic bronchitis sufferers, as inhalation of the vapours of these oils aids the evacuation of phlegm). In experimental animals it has been found that these substances are eliminated very slowly from the lungs, but that their presence there causes no adverse reactions. Ointments prepared with silicones are also very well tolerated and, by virtue of their water-repellent properties, contribute to prevention of—or recovery from—contact eczemas, since they prevent contact with substances causing reactions due to hypersensitivity.

Animal experiments also have indicated that if the vapour is inhaled in very high concentrations a fatal narcosis can result; if the exposed animals survived the narcosis, however, complete recovery ensued. Silicone oils irritate the ocular mucosae to a slight extent, giving rise to redness, painfulness and lacrimation; more serious symptoms are induced only by compounds of low molecular weight.

Heterosiloxanes. In addition to silicon, hydrogen and oxygen, heterosiloxanes contain certain other elements such as metals (aluminium, tin, lead and so on) as well as boron or arsenic, etc. They hydrolyze readily and are therefore dangerous to the human body, a major part of which consists of water. Heterosiloxanes are generally formed as intermediate products in chemical syntheses. Methyl silicate and ethyl silicate occupy a special place in this group. Methyl silicate, a fairly volatile liquid, is used in the manufacture of television screens. When it is decomposed in water, a transparent layer of silicic acid results, which secures the screen to the glass wall. Methyl silicate liquid or vapour which reaches the eyes produces no immediate effect, but after 10 to 12 h gives rise to violent ocular pain, accompanied by redness and tears. The cornea becomes opaque, and ulcers can occur, which may result in blindness. If the vapour is inhaled, fatal damage to the lungs or kidneys can ensue. Since contact with the vapour or liquid produces no immediate warning pain, special precautions are required with this substance. Breakage of flasks must be avoided. The eyes must be protected by gas-tight goggles, and the risk of inhalation of vapours in case of spillage, etc., must be avoided by installing an exhaust ventilation system.

Ethyl silicate, which is used as a binding agent for making moulds in special metal-founding processes or as a starting point in chemical syntheses, has a low vapour pressure; this physical property helps reduce exposure. In high concentrations it irritates the mucous membranes and the skin, and in very high concentrations it has proved fatal to animals.

As the molecular weight of the silicates increases, there is a decrease in reactivity.

Silicon and organosilicon compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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Thiols (mercaptans, thioalcohols or sulphydrates) are monofunctional organic sulphydryl compounds, either aliphatic or aromatic, and characterized by the presence of sulphydryl (–SH) groups. Generally, the thiols have a strong, unpleasant odour even at very low concentrations. At equal concentrations the strength of the odour appears to vary inversely with the number of carbon atoms in the molecule, and is essentially absent in 1-dodecane thiol and higher thiols. The most important method for the production of thiols involves the reaction of hydrogen sulphide with olefins or alcohols, at various temperatures and pressures, in combination with a variety of catalysts and promoters including acids, bases, peroxides and metal sulphates. The hydrogen of the –SH group can be replaced by mercury (the word mercaptans is derived from the Latin corpus mercurium captans, meaning entity-seizing mercury) and other heavy metals to form mercaptides.

Naturally occurring thiols exist in all living systems. In living cells, most of the thiols are contributed by the amino acid cysteine and the tripeptide glutathione. Also, methanethiol and ethanethiol occur naturally as “sour” gas at room temperature, while the other thiols are liquids. The C₁ through C₆ alkane thiols and benzenethiol have obnoxious odours at much lower concentrations than do the other thiols.

Organic sulphur compounds can also be formed when a sulphate unit (SO₄) is bound to an organic group. Sulphides and sulphonium salts are formed with two organic groups bonded to a sulphur atom.

Uses

Organic sulphides and sulphates are used in industry as solvents, chemical intermediates, flavouring agents and accelerants for rubber vulcanization and in plating baths for coating metals.

The mercaptans are primarily used as chemical intermediates in the manufacture of jet fuels, insecticides, fungicides, fumigants, dyes, pharmaceuticals and other chemicals, and as adroitness for odourless, toxic gases. Amyl mercaptan (1-pentanethiol), ethyl mercaptan and tert-butyl mercaptan (2-methyl-2-propanethiol) are used as adroitness for natural gas, while propel mercaptan (propanethiol) and methyl mercaptan function as odourants and warning agents for other odourless, toxic gases. Methyl mercaptan is also used as a synthetic flavouring agent and as an intermediate in the manufacture of pesticides, jet fuels, fungicides and plastics. Phenyl mercaptan is an intermediate for insecticides, fungicides and pharmaceuticals. 1-Dodecanethiol (dodecyl mercaptan) is utilized in the manufacture of synthetic rubber, plastics, pharmaceuticals, insecticides, fungicides and nonionic detergents. It also serves as a complexing agent for the removal of metals from wastes.

Thioglycolic acid is used in the production of permanent creases in textiles and in biological media for growing micro-organisms. It finds use in permanent hair wave solutions, plastics, pharmaceuticals, and as a reagent for the detection of iron and other metal ions.

Dimethyl sulphate (sulphuric acid dimethyl ether), an oily, colourless liquid that is slightly soluble in water but more soluble in organic solvents, is used primarily for its methylating properties. It is used in the manufacture of methyl esters, ethers and amines; in dyes, drugs and perfumes; phenol derivatives; and other chemicals. It is also used as a solvent in the separation of mineral oils.

Tetramethylthiuram disulphide (TTD, TMTD, Thiram, thirad, thiuram, Disulphuram), a white or yellow crystal insoluble in water but soluble in organic solvents, is used as a rubber accelerator and vulcanizer, a disinfectant for fruit, seeds, nuts and mushrooms, a bacteriostat for edible oils and fats, and as an ingredient in sun-tan and antiseptic sprays, soaps and lotions. It is also used as a fungicide, a rodent repellent and wood preservative.

Ethylene thiourea (2-imadazolidin ethione) and thiourea serve as components of electroplating baths. Ethylene thiourea also finds use in the dye-stuff and pharmaceutical industries, while thiourea has numerous applications in the photography, textile, cosmetics and paper industries. Thiourea is used to remove stains from negatives and as a fixing agent in photography, hair preparations, dry-cleaning chemicals, paper whiteners and in treatments for boiler water and wastewater, to prepare non-glare mirrors, to prevent brown stain in hemlock wood, as a weighting agent for silk and as a fire retardant for textiles.

Dimethyl sulphide (methyl sulphide) is used as a gas odourant and a food additive. Allyl propyl disulphide is another food additive, and dimethyl sulphoxide (methyl sulphoxide) (DMSO) is a solvent found in industrial cleaners, pesticides, paint and varnish removers, and antifreeze or hydraulic fluid when mixed with water. 2,4-Diaminoanisole sulphate (m-phenylediamine-4-methoxy-sulphate) is used in dyeing furs, and sodium lauryl sulphate (sulphuric acid monododecyl ester sodium salt) is an emulsifying agent used in metal processing, detergents, shampoos, creams, pharmaceuticals and foods.

Hazards

Thiols (mercaptans)

Industrial processes involving the use of thiols present several types of potential problems, including fire and explosion, as well as adverse effects on the health of workers.

Fire and explosion. Most of the thiols are flammable substances. With the alkane thiols, the vapour pressure decreases as the molecular weight increases. At normal work room temperatures the lower molecular weight thiols (C₂ through C₆) may vaporize to form explosive mixtures with air. The mercaptans are typically flammable liquids except for methyl mercaptan, which is a gas. A strong unpleasant odour is their prime characteristic.

Health hazards. Thiols have an intensely disagreeable odour, and contact with the liquid or vapour may cause irritation of the skin, eyes and mucous membranes of the upper respiratory tract. Liquid thiols can also cause contact dermatitis. Benzenethiol appears to have stronger irritating properties than the alkane thiols.

All thiols behave as weak acids, and the predominant biological effect is on the central nervous system. Inhalation is of special concern with the C₁ through C₆ group of alkane thiols, while skin exposure is of greatest concern with the higher thiols (C₇ through C₁₂, C₁₆, C₁₈). Benzenethiol is the most toxic of the thiols normally found in the workplace and has a marked potential for causing eye injury.

Accidental exposure of workers to high concentrations of thiols (greater than 50 ppm) have caused muscular weakness, nausea, dizziness and narcosis. Systemically, methanethiol acts like hydrogen sulphide and may depress the central nervous system, resulting in respiratory paralysis and death. Because hydrogen sulphide is a raw material used or generated in thiol manufacturing plants, special precautions are necessary to prevent its release in hazardous concentrations. After an acute exposure, if death is not immediate, irritation of the lower respiratory tract may result in pulmonary oedema which may be delayed and, if not treated promptly, fatal. Victims who survive may have liver and kidney damage and may suffer from headache, dizziness, staggering gait, nausea and vomiting.

Thioglycolic acid. Pure thioglycolic acid has a pronounced irritant effect on the skin and mucous membranes; in dilute form its irritant action is less pronounced. The salts (ammonium, sodium) of the acid have been reported to cause skin lesions including discreet pruriginous, papulopustular and vesicular eruptions of the neck, ears and shoulders of persons having undergone permanent waving. More rarely, isolated lesions of the deep-burn type and contact eczema of the hands, lower arms, face and neck have been seen in hairdressers.

The thioglycolates widely found in trade have a very low sensitizing action and cause dermatitis by primary irritation. It has been reported, however, that the hydrazide and glycolics esters of thioglycolic acid have a pronounced sensitizing action and have resulted in numerous cases of contact eczema amongst hairdressers. As a consequence, the sale of preparations containing the hydrazide was stopped in Germany. Thioglycolic acid derivatives have also, on rare occasions, caused perionyxis and dry skin of the hands in hairdressers. When dermatitis is encountered in a hairdresser, however, thought should also be given to the other products used in permanent waving, excessive alkalinity, and sodium hydrosulphide impurities.

Thioglycolic acid has a high degree of acute toxicity. The oral LD₅₀ of the undiluted acid in rats has been reported as less than 50 mg/kg. It is rapidly absorbed through the skin and, in the rabbit, 60% is excreted in the urine within 24 hours in the form of inorganic sulphate or neutral sulphur.

Prevention. Hairdressers should use thioglycolic acid or its derivatives only in dilute solutions with a pH near to neutral. In Switzerland, for example, they are permitted to use only 7.5% solutions with a maximum pH of 7.5 or 9% solutions with a maximum pH of 8. When applying the solution, the hairdresser should protect his or her hands by the use of rubber or plastic gloves, and eye contact should be avoided. The solution should be neutralized as quickly as possible, and flushed away at the first indication of irritation.

Hairdressers using these products should be informed of the hazards involved and should be alert for early signs of trouble (i.e., burning sensations, itching and so on). These preparations should not be used if there is any pre-existing skin irritation. In hairdressing salons, ventilation should be sufficient to prevent the material from accumulating in the atmosphere in the form of mist.

Sulphates and sulphides

Dimethyl sulphate is an extremely hazardous poison. Its toxicity is derived from its alkylating properties and its hydrolysis to sulphuric acid and methyl alcohol. The liquid is highly irritating to skin and mucous membranes. In the skin it causes blisters which are typically slow-healing and may result in scars, and numbness which may persist for months. Irritation of the eye may result in tearing (lacrimation), light sensitivity (photophobia), conjunctivitis and keratitis; in severe cases, corneal opacities and permanent impairment of vision have occurred. In addition to acute irritation of the respiratory tract, it may cause delayed pulmonary oedema, bronchitis and pneumonitis. The effect of the vapour on trigeminal, laryngeal and vagal nerve endings may result in bradycardia or tachycardia and pulmonary vasodilatation.

Long-term effects are seen only rarely and are usually limited to respiratory and ocular difficulties.

Dimethyl sulphate has been shown to be carcinogenic in the rat both directly and following prenatal exposure. The inhalation of 1 ppm was followed by urinary excretion of methylpurines showing a non-specific alkylation of DNA. The International Agency for Research on Cancer (IARC) classifies dimethyl sulphate as a Group 2A chemical, probably carcinogenic to humans.

Tetramethylthiuram disulphide (TTD). Exposure to TTD is by inhalation of its dust, spray or mist. Local effects result from irritation of mucous membranes: conjunctivitis, rhinitis, sneezing, cough. TTD ranges high among substances giving rise to contact hypersensitivity, perhaps reflecting the frequent use of rubber in domestic, medical and industrial utensils. It may produce contact dermatitis, erythema and urticaria; skin sensitivity is confirmed by patch testing.

Workers exposed to TTD have shown an intolerance to alcohol, manifested by flushing of the face, palpitation, rapid pulse, hypotension and dizziness. These effects are thought to be due to the blocking of the oxidation of acetaldehyde. (The diethyl homologue of TTD is marketed under the name of Antabuse as a drug to be administered to chronic alcoholics in the hope that the severely disagreeable symptoms that follow their ingestion of alcohol will condition them against breaking their abstinence.)

Intoxication due to inhalation or ingestion of TTD results in nausea, vomiting, diarrhoea, ataxia, hypothermia, hypotonia and, finally, ascending paralysis with death from respiratory failure. Toxicity is greater in the presence of fats, oils and fat solvents. TTD is metabolically converted to carbon disulphide, to which the neurologic and cardiovascular effects are attributed.

Safety and Health Measures

Open flames and other ignition sources should be excluded from areas where flammable sulphur compounds (e.g., thiols), especially the more volatile ones, are used. Emergency procedures and routine work practices should emphasize proper handling, containment of spills, and the use of proper protective equipment, such as respirators and eye goggles. Spills of thiols should be neutralized with a household bleach solution and flushed with an abundant flow of water. The primary purpose of control measures is to reduce the potential for inhalation or skin contact with thiols, with special emphasis on the eyes. Whenever feasible, control at the source of exposure should be implemented; this may involve enclosure of the operation and/or the use of local exhaust ventilation. Where such engineering controls are not sufficient to reduce airborne concentrations to acceptable levels, respirators may be necessary to prevent pulmonary irritation and systemic effects. At low concentrations (less than 5 ppm) a chemical cartridge respirator with a half-mask facepiece and organic vapour cartridges can be used. At high concentrations, supplied air respirators, with a full facepiece, are necessary.

Safety showers, eyewash fountains and fire extinguishers should be located in areas where appreciable amounts of thiols are used. Handwashing facilities, soap and ample amounts of water should be made available to involved employees.

Treatment. Affected employees should, as necessary, be removed from emergency situations and if the eyes or skin have been contaminated they should be lavaged with water. Contaminated clothing should be promptly removed. If high concentrations are inhaled, hospitalization and observation should be continued for at least 72 hours because of the potential delayed onset of severe pulmonary oedema. Therapeutic measures should follow those suggested for respiratory irritants.

Protective measures are similar to those for sulphur dioxide. They include the wearing of impervious clothing, aprons, gloves, goggles and boots by those working where liquid thiols are likely to be spilled or splashed.

All industrial operations involving the use of dimethyl sulphate should be carried out in fully enclosed systems, and established procedures for the handling of human carcinogens should be followed. Arrangements should be made for proper disposal of any spillage, and workers should be strictly forbidden to attempt to clean up massive spillages such as may occur in the event of container breakage until the area has been thoroughly washed down. Many accidents with dimethyl sulphate have been the result of hasty and uninformed clean-up attempts.

Organic sulphur compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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Sulphur is found in the native state in certain volcanic regions, or in the combined state as metal sulphides (pyrites, galena, blende, cinnabar), sulphates (anglesite, gypsum) or in the form of hydrogen sulphide in certain sources of water or natural gas. At one time, the mined sulphur-bearing rock was heated to melting point in primitive furnaces dug in the ground or in masonry furnaces open at the top (Sicilian calcaroni), the sulphur-bearing rock being covered with a layer of lag to prevent contact with the air. In both cases, some of the natural sulphur is itself consumed as fuel.

Elemental sulphur is largely extracted from petroleum refining. In some countries, sulphur is recovered as a by-product in the production of copper, lead and zinc, from their sulphur minerals; it is also obtained by roasting iron pyrites for the production of sulphuric acid.

Uses

Sulphur is used for the production of sulphuric acid, sulphates, hyposulphites, carbon disulphide and so on, in match manufacture, rubber vulcanization, electron melting and incendiary-bomb manufacture; it is used in agriculture to combat plant parasites and in the treatment of wine. It is also used as a bleaching agent for pulp and paper, textiles and dried fruit. Sulphur is a component of anti-dandruff shampoos, a binder and asphalt extender for road paving, an electric insulator, and a nucleating agent in photographic film.

Sulphur dioxide serves primarily as an intermediate in the production of sulphuric acid, but is also encountered in the production of paper pulp, starch, sulphites and thiosulphates. It is used as a bleaching agent for sugar, fibres, leather, glues and sugar liquor; in organic synthesis it is used as the starting point for numerous substances such as carbon disulphide, thiophene, sulphones and sulphonates; it is employed as a preservative in the wine and food industries. In combination with ammonia and atmospheric moisture, it forms artificial ammonium sulphite mists used to protect crops against night frost. Sulphur dioxide is used as a disinfectant in breweries, a depressant in the flotation of sulphide ores, an extractive solvent in oil refining, a cleaning agent for tile drains, and a tanning agent in the leather industry.

Sulphur trioxide is used as an intermediate in the manufacture of sulphuric acid and oleum for sulphonation, in particular, of dyes and dye-stuffs, and for the production of anhydrous nitric acid and explosives. Solid sulphur trioxide is marketed under such names as Sulphan and Triosul, and is used primarily for sulphonation of organic acids. Sulphur tetrafluoride is a fluorinating agent. Sulphur hexafluoride serves as a gaseous insulator in high-voltage electric installations. Sulphyryl fluoride is used as an insecticide and a fumigant.

Sulphur hexafluoride and trioxychlorofluoride are used in insulation material for high-voltage systems.

Many of these compounds are used in the dye-stuff, chemical, leather, photography, rubber and metalworking industries. Sodium metabisulphite, sodium trisulphite, sodium hydrosulphite, ammonium sulphate, sodium thiosulphate, calcium sulphate, sulphur dioxide, sodium sulphite and potassium metabisulphite are additives, preservatives and bleaching agents in the food industry. In the textile industry, sodium trisulphite and sodium sulphite are bleaching agents; ammonium sulphate and ammonium sulphamate are used for flameproofing; and sodium sulphite is used for printing cotton. Ammonium sulphate and carbon disulphide are used in the viscose silk industry, and sodium thiosulphate and sodium hydrosulphite are bleaching agents for pulp and paper. In addition, ammonium sulphate and sodium thiosulphate are tanning agents in the leather industry, and ammonium sulphamate is used for flameproofing wood and treating cigarette paper.

Carbon disulphide is a solvent for waxes, lacquers, oils and resins, as well as a flame lubricant for cutting glass. It is used for the cold vulcanization of rubber and for generating petroleum catalysts. Hydrogen sulphide is an additive in extreme-pressure lubricants and cutting oils, and a by-product of petroleum refining. It is used in ore reduction and for the purification of hydrochloric acid and sulphuric acid.

Hazards

Hydrogen sulphide

Hydrogen sulphide is a flammable gas which burns with a blue flame, giving rise to sulphur dioxide, a highly irritating gas with a characteristic odour. Mixtures of hydrogen sulphide and air in the explosive range may explode violently; since the vapours are heavier than air, they may accumulate in depressions or spread over the ground to a source of ignition and flash back. When exposed to heat, it decomposes to hydrogen and sulphur, and when in contact with oxidizing agents such as nitric acid, chlorine trifluoride and so on, it may react violently and ignite spontaneously. Extinguishing agents recommended for the fighting of hydrogen sulphide fires include carbon dioxide, chemical dry powder and water sprays.

Health hazards. Even at low concentrations, hydrogen sulphide has an irritant action on the eyes and respiratory tract. Intoxication may be hyperacute, acute, subacute or chronic. Low concentrations are readily detected by the characteristic rotten-egg odour; however, prolonged exposure dulls the sense of smell and makes the odour a very unreliable means of warning. High concentrations can rapidly deaden the sense of smell. Hydrogen sulphide enters the body through the respiratory system and is rapidly oxidized to form compounds of low toxicity; there are no accumulation phenomena, and elimination occurs through the intestine, urine and the expired air.

In cases of slight poisoning, following exposure to from 10 to 500 ppm, a headache may last several hours, pains in the legs may be felt and rarely there may be loss of consciousness. In moderate poisoning (from 500 to 700 ppm) there will be loss of consciousness lasting a few minutes, but no respiratory difficulty. In cases of severe poisoning the subject drops into a profound coma with dyspnoea, polypnoea and a slate-blue cyanosis until breathing restarts; there are tachycardia and tonic-clonic spasms.

Inhalation of massive quantities of hydrogen sulphide will rapidly produce anoxia resulting in death by asphyxia; epileptiform convulsions may occur and the individual falls apparently unconscious, and may die without moving again. This is a syndrome characteristic of hydrogen sulphide poisoning in sewer workers; however, in such cases, exposure is often due to a mixture of gases including methane, nitrogen, carbon dioxide and ammonia.

In subacute poisoning, the signs may be nausea, stomach distress, foetid eructations, characteristic “rotten-egg” breath, and diarrhoea. These digestive-system disorders may be accompanied by balance disorders, vertigo, dryness and irritation of the nose and throat with viscous and mucopurulent expectoration and diffuse rales and ronchi.

There have been reports of retrosternal pain similar to that found in angina pectoris, and the electrocardiogram may show the characteristic trace of myocardial infarction, which, however, disappears quite rapidly. The eyes are affected by palpebral oedema, bulbar conjunctivitis and mucopurulent secretion with, perhaps, a reduction in visual acuity—all of these lesions usually being bilateral. This syndrome is known to sugar and sewer workers as “gas eye”. A variety of other systemic effects have been reported, including headaches, asthenia, eye disorders, chronic bronchitis and a grey-green line on the gums; as in acute poisoning, the ocular lesions are said to predominate, with paralysis, meningitis, polyneuritis and even behavioural problems.

In rats, exposure to hydrogen sulphide has given rise to teratogenic effects.

Metabolism and pathology. Hydrogen sulphide has a general toxic action. It inhibits Warburg’s respiratory enzyme (cytochrome oxidase) by binding iron, and the oxydo-reduction processes are also blocked. This inhibition of enzymes essential for cellular respiration may be fatal. The substance has a local irritant action on the mucous membranes since, on contact with moisture, it forms caustic sulphides; this may also occur in the lung parenchyma as a result of combination with tissue alkalis. Experimental research has shown that these sulphides may enter into the circulation, producing respiratory effects such as polypnoea, bradycardia and hypertension, by their action on the vasosensitive, reflexogenic zones of the carotid nerves and Hering’s nerve.

Post-mortem examination in a number of cases of hyperacute poisoning has revealed pulmonary oedema and congestion of various organs. A characteristic autopsy feature is the odour of hydrogen sulphide that emanates from the dissected corpse. Other features of note are the haemorrhages of the gastric mucosae, and the greenish colour of the upper regions of the intestine and even of the brain.

Carbon disulphide

The first cases of carbon disulphide poisoning were observed during the nineteenth century in France and Germany in connection with the vulcanization of rubber. After the First World War, the production of viscose rayon expanded, and with it the incidence of acute and chronic poisoning from carbon disulphide, which has remained a serious problem in some countries. Acute and, more often, chronic poisoning still occur, although improvements in technology and hygienic conditions in plants have virtually eliminated such problems in a number of countries.

Carbon disulphide is primarily a neurotoxic poison; therefore those symptoms indicating central and peripheral nervous system damage are the most important. It was reported that concentrations of 0.5 to 0.7 mg/l (160 to 230 ppm) caused no acute symptoms in humans, 1 to 1.2 mg/l (320 to 390 ppm) were bearable for several hours, with the appearance of headaches and unpleasant feelings after 8 hours of exposure; at 3.6 mg/l (1,150 ppm) giddiness set in; at 6.4 to 10 mg/l (2,000 to 3,000 ppm) light intoxication, paraesthesia and irregular breathing occurred within 1/2 to 1 hour. At concentrations of 15 mg/l (4,800 ppm), the dose was lethal after 30 minutes; and at even higher concentrations, unconsciousness occurred after several inhalations.

Acute poisoning occurs mainly after accidental exposures to very high concentrations. Unconsciousness, frequently rather deep, with extinction of cornea and tendon reflexes, occurs after only a short time. Death sets in by a blockage of the respiratory centre. If the patient regains consciousness, motor agitation and disorientation follow. If he or she recovers, frequently late sequellae include psychic disturbances as well as permanent damage to the central and peripheral nervous systems. Subacute cases of poisoning usually occur from exposure to concentrations of more than 2 mg/l. They are manifested mainly in mental disorders of the manic-depressive type; more frequent at lower concentrations, however, are cases of polyneuritis.

Chronic poisoning begins with weakness, fatigue, headache, sleep disturbances, often with frightening dreams, paraesthesia and weakness in the lower extremities, loss of appetite and stomach illness. Neurological symptoms are also seen, and impotence is rather frequent. Continued exposure may give rise to polyneuritis, which is said to appear after working in concentrations of 0.3 to 0.5 mg/l for several years; an early sign is the dissociation of tendon reflexes in lower extremities. Damage to the brain nerves is less frequent, but neuritis n. optici and vestibular and sense-of-smell disturbances have been observed.

In exposed workers, disorders occur in the male reproductive system (hypo- and asthenospermia), and excretion of 17-ketosteroids, 17-hydroxycorticosteroids and androsteron decreases during exposure. In women menstrual disturbances, metrorrhagia and more frequent abortions have been described. Carbon disulphide passes the placenta. Animals have demonstated foetotoxic and teratogenic effects at levels of 32 ppm and higher.

The relationship between carbon disulphide and atherosclerosis is a topic of special interest. Prior to the Second World War, not much attention was paid to this pattern, but thereafter, when classic carbon disulphide poisoning ceased to occur in many countries, several authors noted the development of atherosclerosis of the brain vessels in younger workers in viscose rayon plants.

Ophthalmodynamographic studies in young workers who were exposed to carbon disulphide concentrations of 0.2 to 0.5 mg/l for several years, showed that the retinal systolic and diastolic blood pressure was higher than that of the brachial artery. This increase was due to arterial hypertension in the brain, and it was reported that arterial spasms appeared before subjective complaints. Rheoencephalography has been recommended for assessment of brain vessel function. Changes in resistance are caused by arterial pulsation, especially of intracranial vessels, and could therefore lead to the discovery of possible increased rigidity or spasms of cranial vessels. In Japanese workers a higher incidence of small, round, retinal haemorrhages and microaneurysms was observed.

In chronically exposed men, arteriolocapillary hyalinosis was found, which represents a special type of carbon disulphide arteriosclerosis. Therefore, carbon disulphide may be assumed to be a contributing factor to the origin of this sclerosis, but not a direct cause. This hypothesis, as well as the results of biochemical examinations, seems to be supported further by reports about the significant increase of atherosclerosis, frequently in younger persons who were exposed to carbon disulphide. With regard to the kidneys, it seems that glomerulosclerosis of the Kimmelstiel-Wilson type is more frequent in persons exposed to carbon disulphide than in others. British, Finnish and other investigators have shown that there is increased mortality from coronary heart disease in male workers exposed for many years to relatively low carbon disulphide concentrations.

The absorption of carbon disulphide through the respiratory tract is rather high, and about 30% of the inhaled quantity is retained when a steady state of inhalation is reached. The time required for the establishment of this state varies in length from rather short, to several hours if light physical work is done. After termination of exposure, part of the carbon disulphide is rapidly excreted through the respiratory tract. The length of the desaturation period depends on the degree of exposure. Approximately 80 to 90% of the absorbed carbon disulphide is metabolized in the body with the formation of dithiocarbamates and possible further cyclization to thiazolidane. Owing to the nucleophilic character of carbon disulphide, which reacts especially with —SH, —CH, and —NH₂ groups, perhaps other metabolites are formed too.

Carbon disulphide is also absorbed through the skin in considerable amounts, but less than through the respiratory tract. Dithiocarbamates easily chelate many metals such as copper, zinc, manganese, cobalt and iron. Increased zinc content has been demonstrated in the urine of animals and humans exposed to carbon disulphide. It is also believed that a direct reaction takes place with some of the metals contained in metalloenzymes.

Liver microsome tests have demonstrated the formation of carbon oxysulphide (COS) and atomic sulphur which is bound covalently to microsomal membranes. Other authors have found in rats that carbon disulphide after oxidative decomposition binds primarily to protein P-450. In urine it is excreted in a fraction of 1% as carbon disulphide; of the retained amount it is excreted to about 30% as inorganic sulphates, the remainder as organic sulphates and some unknown metabolites, one of which is thiourea.

It is assumed that the reaction of carbon disulphide with vitamin B₆ is very important. B₆ metabolism is impaired, which is manifested by enhanced excretion of xanthurenic acid and decreased excretion of 4-pyridoxine acid, and further in a reduced serum pyridoxine level. It appears that copper utilization is disturbed as indicated by the reduced level of ceruloplasmin in exposed animals and humans. Carbon disulphide interferes with serotonin metabolism in the brain by inhibiting certain enzymes. Furthermore, it has been reported that it inhibits the clearing factor (lipase activated by heparin in the presence of -lipoproteins), thus interfering with the clearing of fat from blood plasma. This may result in the accumulation of cholesterol and lipoid substances in vessel walls and stimulate the atherosclerotic process. However, not all reports about the inhibition of the clearing factor are so convincing. There are many, although often contradictory, reports about the behaviour of lipoproteins and cholesterol in the blood and organs of animals and humans exposed to carbon disulphide for a long time, or poisoned by it.

Impaired glucose tolerance of the chemical diabetes type has also been observed. It is elicited by the elevated level of xanthurenic acid in serum, which, as was demonstrated in experiments, forms a complex with insulin and reduces its biological activity. Neurochemical studies have demonstrated changed catecholamine levels in the brain as well as in other nervous tissues. These findings show that carbon disulphide changes the biosynthesis of catecholamines, probably by inhibiting dopamine hydroxylase by chelating enzymatic copper.

Examination of animals poisoned by carbon disulphide revealed a variety of neurologic changes. In humans the changes included serious degeneration of the grey matter in the brain and cerebellum, changes in the pyramid system of pons and spinal cord, degenerative changes of peripheral nerves and disintegration of their sheaths. Also described were atrophy, hypertrophy and hyalin degeneration of muscle fibres.

Sulphur and sulphur dioxide

Extraction of sulphur-bearing rock can lead to the inhalation of the high concentrations of sulphur dust in sulphur mines and may have harmful effects on the respiratory system. In sulphur mining, at the beginning of exposure, the miner suffers from upper respiratory tract catarrh, with cough, and expectoration which is mucoid and may even contain grains of sulphur. Asthma is a frequent complication.

The acute effects of inhalation of sulphur and its inorganic compounds include upper respiratory system effects (catarrhal inflammation of the nasal mucosae, which may lead to hyperplasia with abundant nasal secretion). Tracheobronchitis is a frequent occurrence, with shortness of breath (dyspnoea), persistent cough and expectoration which may sometimes be streaked with blood. There may also be irritation of the eyes, with lacrimation, photophobia, conjunctivitis and blepharoconjunctivitis; cases of damage to the crystalline lens have also been described, with the formation of opacities and even cataract and focal chorioretinitis.

The skin may be subject to erythematous and eczematous lesions and signs of ulceration, especially in the case of workers whose hands are in prolonged or repeated contact with powdered sulphur or sulphur compounds, as for example in bleaching and decolouring processes in the textile industry.

Sulphur dioxide is one of the most widely encountered contaminants in the workplace environment. It is released in considerable quantities in the manufacture of sulphuric acid, liquid sulphur dioxide and cast iron, in the refining of sulphur-rich minerals (copper, lead, zinc and so on) and from the combustion of sulphur-rich coal. It is also found as a contaminant in the production of cellulose, sugar and superphosphates, in food preserving, petroleum refining, bleaching, disinfecting and so on.

Sulphur dioxide is an irritant gas, and its effect is due to the formation of sulphurous and sulphuric acids on contact with moist mucosae. It may enter the body via the respiratory tract or, following dilution in the saliva, it may be swallowed and enter the gastro-intestinal tract in the form of sulphurous acid. Certain authors believe that it can enter the body via the skin. Due to its high solubility, sulphur dioxide is rapidly distributed throughout the body, producing metabolic acidosis with a reduction in the blood alkali reserve and compensatory elimination of ammonia in the urine and alkali in the saliva. The general toxic action is demonstrated by protein and carbohydrate metabolism disorders, vitamin B and C deficiency and oxidase inhibition. In the blood, sulphuric acid is metabolized to sulphates which are excreted in the urine. It is probable that the absorption of large quantities of sulphur dioxide has a pathological effect on the haemopoietic system and may produce methaemoglobin.

Acute poisoning results from the inhalation of very high concentrations of sulphur dioxide and is characterized by intense irritation of the conjunctivae and upper respiratory tract mucosae with dyspnoea and cyanosis followed rapidly by consciousness disorders. Death may ensue as a result of suffocation due to reflex spasm of the larynx, sudden circulatory arrest in the lungs, or shock.

In industry, sulphur dioxide poisoning is usually of a chronic nature. The substance’s local irritant action on the mucous membranes produces a sensation of burning, dryness and pain in the nose and throat, altered sense of smell, and causes secretion (which may be blood-streaked), nasal haemorrhage, and dry or productive cough, perhaps with bloody sputum. Gastric troubles have also been reported. Objective signs and symptoms include pronounced hyperaemia accompanied by oedema of the mucous membranes of the nose, pharyngeal walls, tonsils and, in some cases, also the larynx. Chronic conjunctivitis can be observed. In the more advanced stages, the process becomes atrophic, with dilation of the blood vessels in certain regions. Ulceration of the nasal septum, which bleeds readily, may also be observed. Persons who have a long history of exposure to high concentrations of sulphur dioxide may suffer from chronic bronchitis accompanied by emphysema. The initial symptoms are a reduction in vital capacity to the detriment of residual volume, compensatory hyperventilation and a reduction in oxygen consumption.

These manifestations often precede the radiological stage, which presents with dense and enlarged hilar shadows, gross reticulation produced by peribronchitis and, in some cases, bronchiectasis and even nodular appearances. These changes are bilateral and more evident in the median and basal regions.

Both behavioural and nervous system disorders may occur, probably due to the general toxic effect of sulphur dioxide on the body.

The mouth can be affected, with dental caries, peridontal and gingival disorders present. Patients may complain of rapid and painless dental destruction, loss of fillings, and increased tooth sensitivity to temperature changes. Objective symptoms include loss of brilliance, and enamel striation and yellowing.

Sulphur dioxide causes skin irritation which is aggravated by perspiration, and this may be attributed to the conversion of sulphur dioxide to sulphurous acid from contact with sweat.

The initial upper and lower respiratory tract symptoms may regress with suitable treatment and removal from exposure to all sources of respiratory tract inflammation; however, the prognosis is poor for the advanced forms—especially when accompanied by bronchiectasis and right heart deficiency.

The chronic effects consist mainly of bronchopulmonary disease which, after several years, may be complicated by emphysema and bronchiectasis. The maxillary and frontal sinuses may be affected; involvement is usually bilateral, and pansinusitis may be observed in some cases. X-ray examination of the respiratory system reveals irregular opacities, especially in the medial basal region; the apical regions are not usually affected. In certain cases, nodulation has been observed. Stratigraphy shows that the accentuation of pulmonary pattern depends on pulmonary vascular repletion.

Lung function examination has shown changes in pulmonary ventilation, increased oxygen consumption, reduced expiratory volume per second and increased residual volume. Pulmonary carbon dioxide diffusion capacity was also impaired. The disorders are often of a spasmodic nature. Levels of blood sulphur may be higher than normal; there is increased urinary excretion of sulphates and a rise in the ratio of total to organic sulphur.

Sulphur dust and sulphur dioxide are definitely at the origin of the chronic bronchitis. They irritate the mucous membranes and produce obstructive reactions. The possibility of sulphur-induced pulmonary sclerosis has been much discussed, and sulphur pneumoconiosis (“thiopneumoconiosis”) was described for the first time a century ago. However, experimental research and autopsy findings have shown that sulphur produces chronic bronchopulmonary disease without the formation of true nodular fibrosis and without any feature characteristic of silicosis.

Other sulphur compounds

Sulphur trioxide. The vapour pressure of sulphur trioxide rises rapidly with increasing temperatures and, when the a-form melts, the pressure rise is explosive; consequently transport and storage containers must withstand pressures of 10 to 15 atm. Sulphur trioxide reacts vigorously and highly exothermically with water to produce hydrosulphuric acid. When exposed to moist air, it fumes and forms a mist of sulphuric acid which eventually fills all the available space; it also corrodes metals. It is a powerful oxidizing agent and, in the liquid phase, carbonizes organic materials.

Wherever it is used in gaseous, liquid or solid form, or when oleum or hot sulphuric acid is being employed, sulphur trioxide will pollute the working environment. Sulphur dioxide in air will be oxidized by atmospheric oxygen to produce sulphur trioxide.

It enters the body through the respiratory tract and acts both as a local irritant and general toxic agent in a similar manner to sulphur dioxide, although its irritant action is more pronounced. It causes chronic respiratory tract damage and may degrade alkaline reserves and carbohydrate and protein metabolism; it is metabolized to sulphate in the blood and eliminated in the urine in the same way as sulphur dioxide.

The toxic action of oleum on the body is similar to that of sulphuric acid, but the objective signs and symptoms are more pronounced. Safety and health measures for sulphur trioxide are similar to those described for sulphur dioxide.

Carbonyl sulphide (COS). Carbonyl sulphide is encountered in the native state in volcanic gases and sulphurous waters. It is produced by the reaction of dilute sulphuric acid on ammonium thiocyanate. Carbonyl sulphide is known for its high toxicity. It has been found that it produces serious nervous-system impairment with narcotic effects in high concentrations and has an irritant action.

It is a potent oxidizing substance and should be handled appropriately.

Sulphur tetrafluoride, sulphur pentafluoride (S₂F₁₀), disulphur decafluoride, sulphuryl fluoride
(SO₂F₂), sulphuric oxyfluoride and thionyl fluoride (SOF₂) are all irritant substances capable of causing pulmonary oedema in concentrations exceeding the exposure limits, because of their absence of water solubility. The most dangerous is sulphur pentafluoride, which in the presence of moisture hydrolyzes into hydrogen fluoride and sulphur dioxide; its irritant action is considered more severe than that of phosgene, not only as regards the dose, but also because pulmonary haemorrhages may be associated with lung oedema. Sulphuryl fluoride appears to act mainly as a convulsant agent on laboratory animals.

The safety and health measures to be taken in exposure to sulphur pentafluoride are the same as those recommended for the most severe irritant compounds. The other fluorinated sulphur compounds should be treated like sulphur dioxide.

Sulphur chloride is a flammable liquid which gives rise to a moderate fire hazard associated with the evolution of the dangerous decomposition products sulphur dioxide and hydrogen chloride. It is a fuming, corrosive liquid which is dangerous to the eyes; the vapour is irritating to the lungs and mucous membrane. In contact with the skin, the liquid can cause chemical burns. It should be handled under the maximum degree of enclosure and workers should be provided with personal protective equipment including eye protective equipment and respiratory protective equipment.

Sulphuryl chloride is formed by the direct combination of sulphur dioxide and chlorine in the presence of a catalyst which may be charcoal, camphor or acetic anydride. It is also obtained by heating chlorosulphonic acid, with mercuric sulphate, antimony or tin as catalyst. It is used in the manufacture of pharmaceuticals and dye-stuffs, and generally in organic synthesis as a chlorinating, dehydrating or acylating agent.

Sulphuryl chloride is a corrosive liquid which, in contact with the body, can cause burns; the vapour is a respiratory irritant. The precautions are similar to those recommended for sulphur chloride.

Safey and Health Management

Airborne sulphur dust is a fire and explosion hazard; there is also the danger of insidious release of sulphur dioxide leading to the inhalation of irritant vapours. Vapours given off during the melting of sulphur may contain sufficient hydrogen sulphide and carbon disulphide to permit ignition of the air/vapour mixture on contact with a hot surface; such an ignition may result in the transmission of flames to the molten sulphur.

The main hazards in the handling, transport and storage of molten sulphur are related to the flammability of the substance and the possible giving off, during cooling, of hydrogen sulphide, which is even more readily flammable and is explosible in air at concentrations ranging between 4.3 and 45%. Workers employed in sulphur extraction should have at their disposal suitable self-contained respiratory protective apparatus—in particular for rescue operations. Smoking should be prohibited during the transport and handling of sulphur and in sulphur storage areas. Contact of liquid or flowered sulphur with a source of ignition should be avoided, and sulphur stores should not be located in the vicinity of oxidizing agents. The loading and unloading of liquid sulphur necessitate special fire prevention and protection measures. Transport and storage of sulphur require proper grounding (earthing) procedures, exhaust of hydrogen sulphide and regular monitoring of its concentration, and protection of tanks against corrosion by hydrogen sulphide.

Sulphur is a poor conductor of electricity and tends to develop charges of static electricity during transport or processing; static discharges may lead to the ignition of sulphur dust. Pyrophoric deposits of ferrous sulphur which form on the tank wall are also a hazard. Fires in heaps of sulphur are frequent and insidious since they may break out again even after the original conflagration has ostensibly been extinguished.

Carbon disulphide is also highly flammable and explosive.

Sulphur dioxide management efforts should be directed primarily at reducing gas emission and ensuring sufficient ventilation to maintain sulphur dioxide concentrations at the workplace below maximum permissible levels. Total enclosure of processes is an effective and desirable technique. Respiratory protective equipment should be provided where workers may, under exceptional circumstances, be exposed to dangerous concentrations.

Precautions should be taken to prevent the emission of sulphur dust into the atmosphere, and the use of respirators is recommended if the atmospheric dust concentration exceeds the exposure level.

Pre-employment examination should ensure that persons suffering from bronchitis or asthma are not exposed to sulphur. In the periodic examination, clinical examination should be supplemented by chest x ray. These contraindications should also be borne in mind during the periodic medical examinations, which should be carried out at appropriate intervals.

Inorganic sulphur compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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Carbon monoxide (CO) is an odourless, colourless gas that reduces the ability of haemoglobin to transport and deliver oxygen.

Occurrence. Carbon monoxide is produced when organic material, such as coal, wood, paper, oil, gasoline, gas, explosives or any other carbonaceous material, is burned in a limited supply of air or oxygen. When the combustion process takes place in an abundant supply of air without the flame contacting any surface, carbon monoxide emission is not likely to result. CO is produced if the flame contacts a surface which is cooler than the ignition temperature of the gaseous part of the flame. Naturally occurring sources produce 90% of atmospheric CO, and activity some 10%. Motor vehicules account for 55 to 60% of global man-made CO burden. The exhaust gas of gasoline-fuelled combustion engine (spark ignition) is a common source of ambient CO. The diesel engine (compression ignition) exhaust gas contains about 0.1% of CO when the engine is operating properly, but maladjusted, overloaded or badly maintained diesel engines may emit considerable amounts of CO. Thermal or catalytic afterburners in the exhaust pipes considerably reduce the amount of CO emitted. Other major sources of CO are cupolas in foundries, catalytic cracking units in petroleum refineries, distillation of coal and wood, lime kilns and the kraft recovery furnaces in kraft paper mills, manufacture of synthetic methanol and other organic compounds from carbon monoxide, the sintering of blast furnace feed, carbide manufacture, formaldehyde manufacture, carbon black plants, coke works, gas works and refuse plants.

Any process where incomplete burning of organic material may occur is a potential source of carbon monoxide emission.

Carbon monoxide is produced on an industrial scale by the partial oxidation of hydrocarbon gases from natural gas or by the gasification of coal or coke. It is used as a reducing agent in metallurgy, in organic syntheses, and in the manufacture of metal carbonyls. Several industrial gases that are used for heating boilers and furnaces and driving gas engines contain carbon monoxide.

Carbon monoxide is thought to be by far the most common single cause of poisoning both in industry and in homes. Thousands of persons succumb annually as a result of CO intoxication. The number of victims of non-fatal poisoning that suffer from permanent central nervous system damage can be estimated to be even larger. The magnitude of the health hazard due to carbon monoxide, both fatal and non-fatal, is huge, and poisonings are probably more prevalent than is generally recognized.

A sizeable proportion of the workforce in any country has a significant occupational CO exposure. CO is an ever-present hazard in the automotive industry, garages and service stations. Road transport drivers may be endangered if there is a leak of engine exhaust gas into the driving cab. Occupations with potential exposure to CO are numerous—for example, garage mechanics, charcoal burners, coke oven workers, cupola workers, blast furnace workers, blacksmiths, miners, tunnel workers, Mond process workers, gas workers, boiler workers, pottery kiln workers, wood distillers, cooks, bakers, firefighters, formaldehyde workers and many others. Welding in vats, tanks or other enclosures may result in production of dangerous amounts of CO if ventilation is not efficient. The explosions of methane and coal dust in coal mines produce “afterdamp” which contains considerable amounts of CO and carbon dioxide. If ventilation is decreased or CO emission increases owing to leaks or disturbances in process, unexpected CO poisonings may occur in industrial operations that usually do not create CO problems.

Toxic action

Small quantities of CO are produced within the human body from the catabolism of haemoglobin and other haem-containing pigments, leading to an endogenous carboxyhaemoglobin (COHb) saturation of about 0.3 to 0.8% in the blood. Endogenous COHb concentration is increased in haemolytic anaemias and after significant bruises or haematomas, which result in increased haemoglobin catabolism.

CO is easily absorbed through the lungs into the blood. The best understood biological effect of CO is its combination with haemoglobin to form carboxyhaemoglobin. Carbon monoxide competes with oxygen for the binding sites of the haemoglobin molecules. The affinity of human haemoglobin for CO is about 240 times that of its affinity for oxygen. The formation of COHb has two undesirable effects: it blocks oxygen transport by inactivating haemoglobin, and its presence in the blood shifts the dissociation curve of oxyhaemoglobin to the left so that the release of remaining oxygen to tissues is impaired. Because of the latter effect, the presence of COHb in the blood interferes with tissue oxygenation considerably more than an equivalent reduction of haemoglobin concentration, for example, through bleeding. Carbon monoxide also binds with myoglobin to form carboxymyoglobin, which may disturb muscle metabolism, especially in the heart.

The approximate relation of carboxyhaemoglobin (COHb) and oxyhaemoglobin (O₂Hb) in blood can be calculated from the Haldane’s equation. The ratio of COHb and O₂Hb is proportional to the ratio of the partial pressures of CO and oxygen in alveolar air:

The equation is applicable for most practical purposes to approximate the actual relationship in equilibrium state. For any given CO concentration in the ambient air, the COHb concentration increases or decreases towards the equilibrium state according to the equation. The direction of the change in COHb depends on its starting level. For example, continuous exposure to ambient air containing 35 ppm of CO would result in equilibrium state of about 5% COHb in blood. After that, if the air concentration remains unchanged there will be no change in COHb level. If the air concentration increases or decreases, the COHb also changes towards the new equilibrium. A heavy smoker may have a COHb concentration of 8% in his or her blood at the beginning of a work shift. If he or she is continuously exposed to a 35 ppm CO concentration during the shift, but is not allowed to smoke, his or her COHb level gradually decreases towards the 5% COHb equilibrium. At the same time, the COHb level of non-smoking workers gradually increases from the starting level of about 0.8% endogenous COHb towards the 5% level. Thus, absorption of CO and build up of COHb is determined by gas laws, and the solution of Haldane’s equation will give the approximate maximum value of COHb for any ambient air CO concentration. It should be remembered, however, that the equilibrium time for humans is several hours for air concentrations of CO usually encountered at worksites. Therefore, when judging the potential health risk of exposure to CO it is important that the exposure time is taken into account in addition to CO concentration in the air. Alveolar ventilation is also a major variable in the rate of CO absorption. When alveolar ventilation increases—for example, during heavy physical work—the equilibrium state is approached more rapidly than in a situation with normal ventilation.

The biological half-life of COHb concentration in the blood of sedentary adults is about 3 to 4 h. The elimination of CO becomes slower with time and the lower the initial level of COHb, the slower the rate of excretion.

Acute poisoning

The appearance of symptoms depends on the concentration of CO in the air, the exposure time, the degree of exertion and individual susceptibility. If the exposure is massive, loss of consciousness may take place almost instantaneously with few or no premonitory signs and symptoms. Exposure to concentrations of 10,000 to 40,000 ppm leads to death within a few minutes. Levels between 1,000 and 10,000 ppm cause symptoms of headache, dizziness and nausea in 13 to15 min and unconsciousness and death if exposure continues for 10 to 45 min, the rapidity of onset depending on the concentrations. Below these levels the time before the onset of symptoms is longer: levels of 500 ppm cause headache after 20 min and levels of 200 ppm after about 50 min. The relation between carboxyhaemoglobin concentrations and the main signs and symptoms is shown in table 1.

Table 1. Principal signs and symptoms with various concentrations of carboxyhaemoglobin.

¹ There is considerable individual variation in the occurrence of symptoms.

The victim of poisoning is classically described as being cherry red. In the early stages of poisoning, the patient may appear pale. Later, the skin, nailbeds and mucous membranes may become cherry red due to a high concentration of carboxyhaemoglobin and a low concentration of reduced haemoglobin in the blood. This sign may be detectable above 30% COHb concentration, but it is not a reliable and regular sign of CO poisoning. The patient’s pulse is rapid and bounding. Little or no hyperpnoea is noticed unless COHb level is very high.

Where the symptoms or signs described above occur in a person whose work may expose him or her to carbon monoxide, poisoning due to this gas should be immediately suspected. Differential diagnosis from drug poisoning, acute alcohol poisoning, cerebral or cardiac accident, or diabetic or uraemic coma may be difficult, and the possibility of carbon monoxide exposure is often unrecognized or simply overlooked. Diagnosis of carbon monoxide poisoning should not be considered established until it is ascertained that the body contains abnormal quantities of CO. Carbon monoxide is readily detectable from blood samples or, if a person has healthy lungs, an estimate of blood COHb concentration can be rapidly made from samples of exhaled end-alveolar air which is in equilibrium with blood COHb concentration.

Critical organs in respect to CO action are the brain and the heart, both of which are dependent on an uninterrupted supply of oxygen. Carbon monoxide burdens the heart by two mechanisms—the heart’s work is increased in order to provide the peripheral oxygen demand, while its own oxygen supply is reduced by CO. Myocardial infarction may be precipitated by carbon monoxide.

Acute poisoning may result in neurological or cardiovascular complications which are evident as soon as the patient recovers from the initial coma. In severe poisoning, pulmonary oedema (excess fluid in the lung tissues) may emerge. Pneumonia, sometimes due to aspiration, may develop after a few hours or days. Temporary glycosuria or albuminuria may also occur. In rare cases acute renal failure complicates the recovery from poisoning. Various cutaneous manifestations are occasionally encountered.

After severe CO intoxication the patient may suffer from cerebral oedema with irreversible brain damage of varying extent. The primary recovery may be followed by a subsequent neuropsychiatric relapse, days or even weeks after poisoning. Pathology studies of fatal cases show the predominant nervous system lesion in white matter rather than in neurons in those victims who survive a few days after the actual poisoning. The degree of brain damage after CO poisoning is determined by the intensity and duration of exposure. On regaining consciousness after severe CO poisoning, 50% of the victims have been reported as presenting an abnormal mental state manifested as irritability, restlessness, prolonged delirium, depression or anxiety. A three-year follow-up of these patients revealed that 33% had personality deterioration and 43% had persistent memory impairment.

Repeated exposures. Carbon monoxide does not accumulate in the body. It is completely excreted after each exposure if sufficient time in fresh air is allowed. It is possible, however, that repeated mild or moderate poisonings which do not lead to unconsciousness would result in death of brain cells and ultimately lead to central nervous system damage with a multitude of possible symptoms, such as headache, dizziness, irritability, impairment of memory, personality changes and a state of weakness of the limbs.

Individuals repeatedly exposed to moderate concentrations of CO are possibly adapted to some extent against the action of CO. Mechanisms of adaptation are thought to be similar to the development of tolerance against hypoxia in high altitudes. An increase in the haemoglobin concentration and in haematocrit has been found to occur in exposed animals, but neither the time course nor the threshold of similar changes in exposed humans has been accurately quantified.

Altitudes. At high altitudes the possibility of incomplete burning and greater CO production increases because there is less oxygen per unit of air than at sea level. The adverse body responses also increase due to reduced oxygen partial pressures in breathed air. The oxygen deficiency present at high altitudes and the effects of CO apparently are additive.

Methane-derived halogentated hydrocarbons. Dichloromethane (methylene chloride), which is a major component of many paint strippers and other solvents of this group, is metabolized in the liver with the production of CO. Carboxyhaemoglobin concentration may increase up to moderate poisoning level by this mechanism.

Effects of low level exposure to carbon monoxide. In recent years considerable efforts of investigation have been focused on biological effects of COHb concentrations below 10% upon both healthy persons and patients with cardiovascular diseases. Patients with severe cardiovascular disease may lack compensatory reserve at about 3% COHb level, so that the chest pain of angina pectoris patients is provoked by less exertion. Carbon monoxide readily crosses the placenta to expose the foetus, which is sensitive to any extra hypoxic burden in such a way that its normal development may be endangered.

Susceptible groups. Particularly sensitive to the action of CO are individuals whose oxygen transport capacity is decreased due to anaemia or haemoglobinopathias; those with increased oxygen needs due to fever, hyperthyroidism or pregnancy; patients with systemic hypoxia due to respiratory insufficiency; and patients with ischemic heart disease and cerebral or generalized arteriosclerosis. Children and young individuals whose ventilation is more rapid than that of adults attain the intoxication level of COHb sooner than healthy adults. Also, smokers whose starting COHb level is higher than that of non-smokers would more rapidly approach dangerous COHb concentrations at high exposures.

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Phthalates are esters of phthalic acid and various alcohols. A number of diesters are of special practical importance. These are mainly the diesters of methanol, ethanol, butanol, isobutanol, iso-octanol, 2-ethylhexanol, isononanol, isodecanol and alfols with linear chains. The synthesis of the phthalates is generally carried out by combining phthalic anhydride and two molecules of the corresponding alcohol.

Uses

Phthalate esters are used in nonplasticizer products such as perfumes and cosmetics, and plasticized products such as vinyl swimming pools, plasticized vinyl seats on furniture and in cars, and clothing including jackets, raincoats and boots. The main uses of these compounds are found in the plastics industry, which consumes about 87% of all phthalate esters for producing “soft-PVC”. The remaining 13% is used for the production of lacquers, dispersion, cellulose, polystyrole, colours, synthetic and natural rubber, lubricants, polyamides, insect repellents, fixatives for perfumes, congealing agents for explosives and working fluids for high-vacuum pumps. Among the phthalates, di-sec-octyl phthalate (DOP) and diisononylphthalate are the most important standard softeners.

Dimethyl phthalate and dibutyl phthalate (DBP) have additional uses in numerous industries, including textiles, dyestuffs, cosmetics and glass. Dimethyl phthalate is a dye carrier and a plasticizer in hair spray and in safety glass. Dibutyl phthalate is useful as an insect repellent for the impregnation of clothing and as a plasticizer in nitrocellulose lacquers, elastomers, explosives, nail polish and solid rocket propellants. It functions as a solvent for perfume oils, a perfume fixative and a textile lubricating agent. In addition, dibutyl phthalate is used in safety glass, printing inks, paper coatings, dental impression materials, and as a component of PVC plastisol for carpet backcoating.

Many diallyl phthalate compounds are sold under military specification and are utilized for reliable electrical and electronic applications in long-term, adverse environmental conditions. These compounds are used in electronic connectors for communications, computer and aerospace systems, as well as in circuit boards, insulators and potentiometers.

Hazards

The first step of biotransformation of the esters of phthalic acid is their scission to monoesters. The next step in mammals is oxidation of the remaining alcohol of the monoester. The corresponding excretion products are detected in the urine.

Phthalates, especially those with a short alcohol chain, can be absorbed through the skin. Twenty-four hours after dermal application of radioactive diethyl phthalate (DEP), 9% of the radioactivity was found in the urine, and after 3 days the radioactive material was evident in various organs. There seems to be a certain connection between metabolism and toxicity of the phthalates, because the phthalates with a short alcohol chain, which have a higher toxicity, are split particularly fast to monoesters, and many of the toxic effects of phthalates are provoked by the monoesters in the animal experiments.

Acute toxicity. The acute toxicity of phthalates is very slight and decreases generally with increasing molecular weight. In the literature the oral LD₅₀ (rat) for DBP is indicated as 8 to 23 g/kg, and for DOP as 30.6 to 34 g/kg. Phthalates do not cause inflammation of the skin or eyes in rabbits. Cases of skin sensitization have not been described, but phthalates are said to cause light irritation of the mucosa of the respiratory tract. The combination of low toxicity and low vapour pressure implies in general only a slight inhalation risk.

Chronic toxicity. In subchronic and chronic feeding experiments, phthalates had in general a relatively low toxicity. Daily feeding of DOP to rats at 65 mg/kg body weight showed no adverse effects after 2 years. No adverse effect levels are reported for other phthalates after feeding experiments over 1 or 2 years in rats or dogs, with a dose ranging from 14 to 1,250 mg/kg weight/day. Nevertheless recently observed testicle changes and weight increases in the liver of rats after application of 0.2% DOP with food over 17 weeks may require a correction of the “no adverse effect level”.

DOP and DBP exceeding the “no adverse effect levels” led to retardation of weight increase, liver and kidney changes, changes of enzyme activities in liver tissue, and degeneration of testicles. The last effect may be attributed to an interference with zinc metabolism. However, it could be provoked not only by DBP but also by the monoester and by DOP. Both DOP and the monoester led to similar changes of liver tissue.

According to this study DOP and the linear chain isomer di-n-octylphthalate are the compounds with the highest cumulative toxicity among the eight substances tested. Two other esters of phthalic acid, bis (2-methoxyethyl)phthalate and butylcarbutoxymethylphthalate, had a relatively low cumulative toxicity (factor 2.53 and 2.06 respectively). It is uncertain, however, whether the observed cumulative effects are important even for low dosage or merely under the condition that the capacities of the enzymes engaged in the biotransformation are insufficient to provide an adequate rate of elimination after high-dose parenteral administration.

Local irritation. Undiluted DOP did not produce inflammation of the skin or the eye of the rabbit, nor necrosis of the cornea. Calley and co-workers found distinct inflammation after intradermal injection. These results were not confirmed by other authors and are probably due to the use of inappropriate solvents. The absence of irritation of the rabbit’s eye was, however, replicated. Experiments with humans (23 volunteers) did not give any hint of irritation of the skin of the back after contact over 7 days, or support for the assumption of sensitization after repeated application at the same site. Both absorption of the compound through the intact skin, and local irritation are obviously slight.

Inhalation toxicity. In inhalation experiments rats tolerated air saturated with DOP vapour over 2 h without fatalities. When the exposure time was extended, all animals died within the following 2 h. In another experiment, air at 50 °C was led through a DOP solution and the vapour was cooled and delivered to an inhalation chamber. In this chamber mice were exposed to the vapour three times per week for 1 h over 12 weeks. All animals survived. Histologic evidence for diffuse chronic pneumonia in these animals, sacrificed after 12 weeks, could not be affirmed when 20 animals were examined in a detailed check-up.

Embryotoxicity and teratogenicity. Several phthalates are embryotoxic and teratogenic for chicken embryos and pregnant rats in high doses (one-tenth of the acute LD₅₀ or 10 ml/kg DOP intraperitoneal). The harmful effect to the embryo increases with the solubility of the phthalates. DEP and DOP can reach the embryo through the placenta of the female rat. In contrast to six other phthalates, DOP and di-n-octylphthalate with linear chains did not produce anomalies of the skeleton in the offspring of Sprague-Dawley rats.

Mutagenicity. DOP exceeded the mutagenicity of dimethoxyethyl phthalate in the dominant-lethal test with the mouse and showed a clear mutagenic effect when one-third, one-half and two-thirds of the acute LD₅₀ was given. Teratogenic experiments had shown a contrary rank of adverse effects. Although Ames tests indicating mutagenic activity in vitro showed differing results, a weak mutagenic activity can be assumed proven by this test procedure. This effect could depend, among other things, on the extent of the splitting of the ester in vitro.

Carcinogenicity. Animal feeding experiments with rats and mice have produced increase rates of of hepatocellular changes in both sexes. The human data are insufficient for evaluating risk; however, the International Agency for Research on Cancer (IARC) has classified DOP as a probable human carcinogen.

Human data. After an oral uptake of 10 g DOP, mild gastric disorders and diarrhoea appeared in one volunteer. A second volunteer tolerated the uptake of 5 g without any symptoms. Some authors report an absence of irritation or only slight irritation of the skin after local application of DOP in volunteers. A second application at the site of former application gave no indication of sensitization.

An average exposure time of 12 years (range from 4 months to 35 years) to workroom concentrations between 0.0006 and 0.001 ppm DOP neither provoked health disorders nor an augmented rate of chromosome aberrations in the exposed personnel. Plastics containing esters of phthalic acid—especially DOP as a softener—are widely used as medical equipment, for example as blood containers for haemodialysis. The problem of possible direct intravenous uptake of phthalates in humans has thus been thoroughly studied. Stocks of blood stored in plastic containers at 4 °C showed a DOP concentration of 5 to 20 mg/100 ml blood after 21 days. This could lead to a DOP uptake of 300 mg or 4.3 mg/kg after a whole-body blood exchange transfusion in a human of 70 kg. Theoretical considerations show a possible uptake of 150 mg DOP during a haemodialysis of 5 h.

Phthalates tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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Occurrence and Uses

Phosphorus does not occur in a free state in nature, but it is found in combination in many plant and animal compounds. In addition, it is found in phosphate rock formations such as apatite (a form of calcium phosphate). Large deposits of phosphate rocks are located in the United States (Tennessee and Florida), in parts of North Africa, and on some Pacific Islands.

Inorganic and organic phosphates are widely used in industry as lubricant additives, fire retardants, plasticizers and chemical intermediates. They are found in the rubber, plastics, paper, varnish and metal industries, and as ingredients in pesticides and cleaning compounds.

Dibutyl phenyl phosphate and tributyl phosphate are components of hydraulic fluid in aircraft engines, and hexamethylphosphoramide is a de-icing additive for jet fuels. Dibutyl phosphate is used in metal separation and extraction, and as a catalyst in the manufacture of phenol and urea resins. Trimethyl phosphate is found in the automobile industry as an antifoulant for spark plugs and as a gasoline additive for the control of surface ignition and rumbling.

Phosphoric acid is found in dental cement, rubber latex, fire-control agents and drilling muds for oil-well operations. It is used for flavouring non-alcoholic beverages, dyeing cotton, water treatment, refractory bricks, in the manufacture of superphosphate fertilizer, cleaning of metals before painting, and as an additive in gasoline and a binder in ceramics.

Tricresyl phosphate (TCP) is used as a solvent for nitrocellulose esters and numerous natural resins. It is a plasticizer for chlorinated rubber, vinyl plastics, polystyrene and polyacrylic and polymethacrylic esters. Tricresyl phosphate also acts as a binder for resins and nitrocellulose to improve toughness, elasticity and polishing properties of coatings. Alone or associated with hydrocarbons, it is used as an antiwear and antifriction additive in numerous synthetic lubricants, incorrectly termed “oils” by reason of their appearance. It is also employed as a hydraulic fluid. When incorporated in gasoline, tricresyl phosphate counteracts the harmful effects of lead deposits. In addition, it is an excellent fire retardant in many industries.

Tetrasodium pyrophosphate has a wide range of applications in the paper, food, textile and rubber industries. It is also used in oil-well drilling, water treatment, cheese emulsification, laundry detergents, and in the electrodeposition of metals. Tetrasodium pyrophosphate is useful for textile dyeing, scouring of wool, and clay and paper processing. Tributyl phosphate functions as a plasticizer for cellulose esters, lacquers, plastics and vinyl resins. It is also a complexing agent in the extraction of heavy metals and an antifoam agent in ore separation processes. Triphenyl phosphate is a flame-retardant plasticizer for cellulosics and a plasticizer for hot-melt adhesives. It is useful in the upholstery and roofing paper industries.

Several of the organic phosphates are used for the production of pyrotechnics, explosives and pesticides. Calcium phosphide is used for signal fires, torpedoes, pyrotechnics, and as a rodenticide. Phosphorus sulphide finds use in the manufacture of safety matches, ignition compounds, lube oil additives and pesticides. Phosphine is used for rodent control and as an insecticide applied for the fumigation of animal feed, leaf-stored tobacco and box cars.

White phosphorus is utilized for the manufacture of rat poisons; red phosphorus is used in pyrotechnics, safety matches, chemical synthesis, pesticides, incendiary shells, tracer bullets and smoke bombs. Tetraphosphorus trisulphide is used for making match heads and friction strips for boxes of “safety” matches.

Phosphorus pentoxide is added to asphalt in the air blowing process to increase the melting point and is used in the development of specialty glasses for vacuum tubes. Phosphorus trichloride is a component of textile finishing agents and an intermediate or reagent in the manufacture of many industrial chemicals, including insecticides, synthetic surfactants and ingredients for silver polish. Phosphorus oxychloride and phosphorus pentachloride serve as chlorinating agents for organic compounds.

Phosphorus

Phosphorus (P) exists in three allotropic forms: white (or yellow), red and black, the last being of no industrial importance. White phosphorus is a colourless or waxlike solid that darkens when exposed to light and glows in the dark (phosphoresces). It ignites spontaneously in the presence of air and burns with a blue flame, producing a characteristically disagreeable odour that is somewhat reminiscent of garlic. The red form is more stable.

Historical importance

Elemental phosphorus was first extracted from animal matter, especially from bone, in the early part of the nineteenth century. Its usefulness in “strike-anywhere” matches was quickly seen and much demand for this element developed as a result. Shortly thereafter, a serious disease appeared in people handling it; the first cases were recognized in 1845, when jaw-bone necrosis occurred in phosphorus-processing workers. This severe and face-disfiguring malady, which terminated fatally in about 20% of the cases during the nineteenth century, was soon recognized and measures sought for its alleviation. This became possible with the development of effective substitutes in the form of red phosphorus and the relatively safe phosphorus sesquisulphide. The European countries also entered into an agreement (the Berne Convention of 1906) in which it was stipulated that the signatories would not manufacture or import matches that were made with white phosphorus.

A major phosphorus hazard in some countries, however, continued to exist from the use of white phosphorus in the pyrotechnics industry until agreement for its exclusion was reached with these manufacturers. At the present, health hazards from white phosphorus still endanger people who are involved with the various stages of production and in the manufacture of its compounds.

The mechanism involved in this jaw-bone damage has not been fully explained. It is believed by some that the action is due to the local effect of the phosphorus in the oral cavity, and that the infection occurs in the constant presence of infective organisms in the mouth and about the teeth. In fact, it is found that exposed persons with carious teeth are more likely to be affected by the condition, although it is difficult to explain the disease in workers with no teeth at all.

A second, possibly more plausible, explanation is that phosphorus necrosis of the jaw is a manifestation of a systemic disease, one that involves many organs and tissues and, principally, the bones. Supporting this concept are the following significant facts:

• As mentioned previously, edentulous individuals have been known to develop jaw necrosis when exposed to phosphorus in their work, even though their “dental hygiene” may be said to be good.

• Young, growing, experimental animals, given appropriate doses of white phosphorus, develop bone changes in the “growing” areas of their bones, the metaphyses.

• On occasion, injured bones in adults exposed to phosphorus have been found to heal exceedingly slowly.

Hazards

Health hazards. Acute exposure to yellow phosphorus vapour released by spontaneous combustion causes severe irritation of the eye, with photophobia, lacrimation and blepharospasm; severe respiratory tract irritation; and deep, penetrating burns of the skin. Direct skin contact with phosphorus, which occurs both in production and during wartime, leads to deeply penetrating second- and third-degree burns, similar to hydrogen fluoride burns. Massive haemolysis with subsequent haematuria, oliguria and renal failure have been described, although this constellation of events is most likely due to previously advocated treatment with copper sulphate.

Upon ingestion, phosphorus induces burns of the mouth and gastrointestinal (GI) tract, with oral sensations of burning, vomiting, diarrhoea and severe abdominal pain. Burns progress to second and third degree. Oliguria may occur secondary to fluid loss and poor perfusion of the kidney; in less severe cases, the proximal renal tubule is transiently damaged. Absence of sugar in otherwise normal cerebrospinal fluid (CSF) is reportedly pathognomonic.

Following absorption from the GI tract, yellow phosphorus has direct effects on the myocardium, circulatory system in the limbs (peripheral vasculature), liver, kidneys and brain. Hypotension and dilated cardiomyopathy have been reported; interstitial myocardial oedema without cellular infiltration has been observed on autopsy. Intracellular protein synthesis appears to be depressed in heart and liver.

Three clinical stages have been described following ingestion. In Stage I, immediately after ingestion, there is nausea and vomiting, abdominal pain, jaundice and garlic odour of the breath. Phosphorescent vomitus may be hazardous to attending medical staff. Stage II is characterized by a 2- to 3-day latent period where the patient is asymptomatic. During this time, cardiac dilatation as well as fatty infiltration of the liver and kidney may occur. Severe, bloody vomiting, bleeding into many tissues, uremia and marked anaemia precede death, defined as Stage III.

Prolonged intake (10 months to 18 years) may cause necrosis of the mandible and maxilla with sequestration of bone; release of sequestra leads to facial deformity (“phossy jaw”). Toothache and excessive salivation may be the first symptoms. Additionally, anaemia, cachexia and liver toxicity may occur. With chronic exposure, necrosis of the mandible with facial deformity was frequently described in the literature until the early 1900s. There are rare reports of this phenomenon among production workers and rodenticide manufacturers.

Reproductive and carcinogenic effects have not been reported.

Phosphine (PH₃) gas is generated by the reaction of phosphoric acid heated with metals which are being treated for cleaning (similar to phosgene), from heating of phosphorus trichloride, from wetting of aluminium phosphate, from flare manufacture using calcium phosphide, and from acetylene gas production. Inhalation causes severe mucous membrane irritation, leading to coughing, shortness of breath, and pulmonary oedema up to 3 days following exposure. The pathophysiologic effect involves inhibition of mitochondrial respiration as well as direct cytotoxicity.

Phosphine is also liberated from accidentally or intentionally ingested aluminium phosphide by chemical interaction with hydrochloric acid in the stomach. There is a large body of literature from India describing cases of suicidal ingestion of this rodenticide. Phosphine is also used as a fumigant, and there are many case reports which describe accidental death from inhalation when in proximity to grain fumigated during storage. Toxic systemic effects which have been described include nausea, vomiting, abdominal pain, central nervous system excitation (restlessness), pulmonary oedema, cardiogenic shock, acute pericarditis, atrial infarction, renal damage, hepatic failure and hypoglycemia. A silver nitrate test was positive in gastric aspirate and in the breath (the latter with a lower sensitivity). Measurement of blood aluminium may serve as a surrogate for toxin identification. Treatment includes gastric lavage, vasopressive agents, respiratory support, administration of anti-arrhythmics, and high-dose magnesium sulphate infusion.

Zinc phosphide, a commonly used rodenticide, has been associated with severe intoxication of animals that ingest treated bait or the carcasses of poisoned animals. Phosphine gas is liberated in the stomach by stomach acid.

Organophosphorus Compounds

The tricresyl phosphates (TCPs) are part of a series of organophosphorus compounds which have been shown to cause delayed neurotoxicity. The 1930 outbreak of “ginger jake” paralysis was caused by the contamination of ginger extract by cresyl phosphates, used in the processing of the spice. Since that time, there have been several incidents reported of accidental poisoning of food by tri-o-cresyl phosphate (TOCP). There are few case series reports of occupational exposure in the literature. Acute occupational exposures have been described as causing gastrointestinal symptoms followed by a latent period of days to 4 weeks, after which extremity pain and tingling progress to motor paralysis of the lower extremities up to the thighs, and of the upper extremities to the elbow. There is rarely sensory loss. Partial to total recovery may take years. Fatalities have occurred in high-dose ingestion. The anterior horn cells and pyramidal tracts are affected, with autopsy finding of demyelination and anterior horn cell damage. In humans the oral lethal dose is 1.0 g/kg; 6 to 7 mg/kg produces severe paralysis. There is no reported skin or eye irritation, though TOCP is absorbed through the skin. Inhibition of cholinesterase activities does not appear to correlate with symptoms or quantity of exposure. Exposed cats and hens developed damage in the spinal cord and sciatic nerves, with damage to the Schwann cells and myelin sheath resulting from dying back of the longer axons. There was no evidence of teratogenicity in rats dosed up to 350 mg/kg/day.

Three molecules of o-, m- or p-cresol esterify one molecule of phosphoric acid, and, since commercial cresol is normally a mixture of the three isomers with an ortho isomer content varying between 25 and 40% according to the source, the resultant TCP is a mixture of the three symmetrical isomers, which are very difficult to separate. However, since the toxicity of commercial TCP derives from the presence of the ortho isomer, many countries stipulate that the esterified phenolic fraction should contain no more than 3% o-cresol. Consequently, the difficulty lies in the selection of a cresol free of the ortho isomer. A TCP prepared from m- or p-cresol has the same properties as the technical product, but the cost of separating and purifying these isomers is prohibitive.

Two related phosphate-containing esters, cresyldiphenyl phosphate and o-isopropylphenyldiphenyl phosphate, are also neurotoxic to several species, including humans, chickens and cats. Adult animals are generally more susceptible than the young. After a single, large exposure to these neurotoxic organophosphorus compounds, axonal damage becomes apparent after 8 to 10 days. Chronic low-level exposures can also lead to neurotoxicity. Axons of the peripheral nerves and the ascending and descending tracts of the spinal cord are affected through a mechanism other than cholinesterase inhibition. While a few of the organophosphate anticholinesterase insecticides cause this effect (diisopropyl fluorophosphate, leptofos and mipafox), the delayed neuropathy apparently occurs through a mechanism other than cholinesterase inhibition. There is a poor correlation between the inhibition of pseudo- or true cholinesterase and the neurotoxic effect.

Triphenyl phosphate may cause a slight reduction in cholinesterase activity, but is otherwise of low toxicity in humans. This compound sometimes occurs in combination with tri-o-cresyl phosphate (TOCP). No teratogenicity was found in rats fed up to 1% in their diet. Intraperitoneal injection of 0.1 to 0.5 g/kg in cats caused paralysis after 16 to 18 days. Skin irritation has not been demonstrated, and eye effects have not been reported.

Triphenyl phosphite (TPP) has been shown to cause neurotoxicity in laboratory animals which is similar to that described for TOCP. Studies of rats showed early hyperexcitability and tremors followed by flaccid paralysis, with the lower extremities more affected than the upper extremities. The pathologic lesion showed spinal cord damage with mild cholinesterase inhibition. A study of cats receiving injections showed virtually the same clinical findings. TPP has also been demonstrated to be a skin irritant and sensitizer.

Tributyl phosphate causes eye, skin and mucous membrane irritation, as well as pulmonary oedema in laboratory animals. Rats exposed to a commercial formulation (bapros) of 123 ppm for 6 hours developed respiratory irritation. When ingested, the LD₅₀ was 3 g/kg, with weakness, dyspnea, pulmonary oedema and muscle twitching observed. It weakly inhibits plasma and red blood cell cholinesterase.

Hexamethyl phosphoramide has been shown to cause cancer of the nasal cavity when administered to rats at levels between 50 and 4,000 ppb over 6 to 24 months. Squamous metaplasia was seen in the nasal cavity and trachea, the latter at the highest dose. Other findings included dose-dependent increases in tracheal inflammation and desquamation, bone marrow erythropoietic hyperplasia, testicular atrophy, and degeneration of the convoluted tubules of the kidney.

Other Inorganic Phosphorus Compounds

Phosphorus pentoxide (phosphorus anhydride), phosphorus pentachloride, phosphorus oxychloride, and phosphorus trichloride have irritant properties, causing a spectrum of mild effects such as eye corrosion, skin and mucous membrane burns, and pulmonary oedema. Chronic or systemic exposure generally is not as important because of the low tolerance to direct contact with these chemicals.

The mist of phosphoric acid is mildly irritating to the skin, the eyes, and the upper respiratory tract. In groups of workers, phosphorus pentoxide (the anhydride of phosphoric acid) fumes were shown to be perceptible but not uncomfortable at concentrations of 0.8 to 5.4 mg/m³, to produce cough at concentrations between 3.6 and 11.3 mg/m³, and to be intolerable to unacclimated workers at a concentration of 100 mg/m³. There is a small risk of pulmonary oedema with inhalation of the mist. Skin contact with the mist leads to mild irritation, but no systemic toxicity. A 75% solution of phosphoric acid dropped on the skin causes severe burns. A study of a cohort of phosphate workers who were occupationally exposed to phosphoric acid showed no increase in cause-specific mortality.

The median lethal concentration for phosphorus oxychloride and its ammonia neutralization products were found to be 48.4 and 44.4 micromoles per mole of air for rats, and 52.5 and 41.3 for guinea-pigs. Fifteen per cent of phosphorus oxychloride was hydrolyzed. Most case series reports of health effects from phosphorus oxychloride also include exposure to other phosphorus-containing compounds. Alone, it is described as causing stomach necrosis when ingested, necrosis of the respiratory tract on inhalation, skin ulceration from direct application, and eye ulceration with loss of vision in rabbits. Chronic exposure of animals showed abnormalities in mineral metabolism, and osteoporosis with elimination of excessive amounts of inorganic phosphorus, calcium salts and chlorides from the body. In combination with other phosphorus compounds, phosphorus oxychloride has been shown to cause asthma and bronchitis in case series reports.

Phosphorus pentasulphide is hydrolyzed to hydrogen sulphide gas and phosphoric acid, exerting effects of these substances on contact with mucus membranes (see phosphoric acid, above, and also hydrogen sulphide elsewhere in this Encyclopaedia). The oral LD₅₀ was 389 mg/kg in rats. Twenty milligrams instilled in rabbit eyes was severely irritating after 24 hours. After 24 hours, 500 mg applied to rabbit skin was found to be moderately irritating.

The vapour of phosphorus trichloride is a severe irritant of the mucous membranes, eyes and skin. Similar to phosphorus pentasulphide, hydrolysis to hydrochloric acid and phosphoric acid on contact with mucous membranes accounts for much of this effect. Inhalation of the vapour can cause throat irritation, bronchospasm and/or pulmonary oedema for up to 24 hours after exposure, depending on the dose. Reactive airways disease syndrome (RADS), with prolonged symptoms of wheezing and cough, can occur from acute or repeated exposure to the vapour. On contact, phosphorus trichloride causes severe burns of the eyes, skin and mucous membranes. Ingestion, inadvertent or suicidal, causes burns of the gastrointestinal tract. Seventeen people who were exposed to phosphorus trichloride and its hydrolysis products following a tanker accident were medically evaluated. Dyspnea, cough, nausea, vomiting, eye burning and lacrimation were experienced by those closest to the spill. Lactate dehydrogenase was transiently elevated in six. While chest radiographs were normal, pulmonary function tests showed a significant drop in forced vital capacity and FEV₁. Improvement in these parameters was seen in the 17 patients re-tested after 1 month. The LC₅₀ was 104 ppm for 4 hours in rats. Nephrosis was the chief finding at autopsy, with negligible pulmonary damage.

Phosphorus pentachloride fume inhalation causes severe irritation of the respiratory tract, leading to documented bronchitis. Delayed onset of pulmonary oedema could occur, although it has not been reported. Exposure of the eyes to fumes also leads to severe irritation, and skin contact would be expected to cause contact dermatitis. The LC₅₀ for 4 hours of inhalation is 205 mg/m^3..

Phosphates and superphosphates. The principal problem with phosphates in the environment is the causation of eutrophication of lakes and ponds. Phosphates enter bodies of water from run-off of agriculture (sources include phosphorus-containing compounds used as fertilizer and pesticides, and plant and animal decay) and from detergents used in homes and industry. Excessive growth of blue-green algae occurs because phosphorus is generally the limiting nutrient essential for growth. Rapid algae growth affects use of lakes for fishing and recreational activities. It also complicates purification of drinking water.

Toxicity of Phosphates

Phosphate mining has been associated with physical trauma. Pneumoconiosis is not of concern in this setting because of the small amount of dust that is generated. Phosphate dust is created in the drying process, and is of concern in causation of pneumoconiosis in the handling and transport of the material. Fluorides may be present in the dust and lead to toxicity.

In addition, phosphate dust is created in the creation of superphosphates, which are used for fertilization. A study of women employed in the manufacture of superphosphates found abnormalities of menstrual function. Severe eye damage and blindness have been described in humans and animals from direct contact with superphosphates.

Safety and Health Measures

Fire hazard. Phosphorus can ignite spontaneously when exposed to air and start fires and cause explosions. Severe burns can be caused when chips and bits of white phosphorus contact the skin and ignite after drying.

Owing to its flammability in air, white phosphorus should be kept covered with water at all times. In addition, scattered pieces should be doused with water, even before they dry and begin to burn; phosphorus fires may be controlled with water (fog or spray), by covering with sand or earth, or with carbon dioxide extinguishers. The substance should be stored in a cool, ventilated, isolated area and away from powerful oxidizing agents, acute fire hazards, and the direct rays of the sun.

In case of skin contact by burning phosphorus slivers, dousing them with a 1 to 5% solution of aqueous copper sulphate will put out the fire and at the same time form a non-flammable compound on the surface of the phosphorus. Following this treatment, the slivers may be removed with more large quantities of water. A soft-soap solution containing a similar concentration of copper sulphate may be more effective than the simple aqueous solution.

Inorganic and organic phosphates tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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Phenols are derivatives of benzene and have a hydroxyl group (-OH) attached to the benzene ring.

Uses

Phenols find use in industry as antioxidants, chemical intermediates, disinfectants, tanning agents, photographic developers, and additives to lubricants and gasoline. They are widely used in the photography, petroleum, paint, explosive, rubber, plastics, pharmaceutical and agricultural industries. The three major uses for phenols are found in the manufacture of phenolic resins, bisphenol A and caprolactam.

Phenol is used in the manufacture of a variety of compounds, including drugs, dyes and colourless or light-coloured artificial resins. It is a general disinfectant for toilets, stables, cesspools, floors and drains, as well as an extractive solvent for petroleum refining. Phenol is found in germicidal paints, slimicides and glue. Catechol is used particularly as an antioxidant in the rubber, chemical, photography, dye, fat and oil industries. It is also employed in cosmetics and in some pharmaceuticals.

Resorcinol is used in the tanning, cosmetics, rubber, pharmaceutical and photography industries, and in the manufacture of explosives, dyes, organic chemicals and antiseptics. It is found in adhesives for tyres, rubber and wood. Resorcinol is also an indirect food additive polymer for use as a basic component of single and repeated use food contact surfaces. Hydroquinone is a reducing agent and is used extensively as a photographic developer, an antioxidant, and a stabilizer in paints, varnishes, motor fuels and oils. Many derivatives of hydroquinone have been used as bacteriostatic agents. Pyrogallic acid also serves as a developer in photography as well as a mordant for wool, a dyeing agent for furs and hair, an antioxidant in lubricating oils, and a reducing agent for gold, silver and mercury salts. It is used for staining leather, preparing synthetic drugs, and for maintaining anaerobic conditions for bacterial growth. Its use is based primarily on its property of being easily oxidized in alkaline solutions (even by atmospheric oxygen).

2,4-Dimethyl phenol is used to manufacture pharmaceuticals, plastics, insecticides, fungicides, rubber chemicals, wetting agents and dye-stuffs. It acts as a solvent, disinfectant, germicide and sanitizer in commercial mixtures used in all hospital areas, instruments and equipment. o-Phenyl phenol has numerous functions as a fungicide, germicide and household disinfectant. It is used in the rubber and food-storage industries and serves as a dye-stuff carrier for polyester fibres and a disinfectant for cutting oils, timber and paper.

The cresols have wide applications in the phenolic resin, explosive, petroleum, photographic, paint and agricultural industries. They are ingredients of many household disinfecting solutions. Cresol is also an additive to lubricating oils and a component of degreasing compounds and paintbrush cleaners. m-Cresol is a textile scouring agent; o-cresol is used in tanning, fibre treatment and metal degreasing; p-cresol is a solvent for wire enamels and an agent used in metal cleaning, ore flotation, synthetic flavouring and perfumes.

The chlorophenols are intermediates in the synthesis of dyes, pigments and phenolic resins. Certain chlorophenols are used directly as mould inhibitors, antiseptics, disinfectants and anti-gumming agents for gasoline. 

Pentachlorophenol and its sodium salt are used to protect various industrial products from microbiological attack. These include wood and other cellulosic products, starches, adhesives, proteins, leather, finished yarn and cloth, photographic solutions, oils, paints, latex and rubber. Pentachlorophenol is used in the construction of boats and buildings, for mould control in petroleum drilling and production, and as an antibacterial agent in disinfectants and cleaners. It is also useful in the treatment of cable coverings, canvas belting, nets, poles and cooling-tower water. Pentachlorophenol is equally important in controlling termites in wood and insulating board, powder post beetles and other wood-boring insects, and slime and algae. It is also used in manufacturing herbicides, and as an agent to inhibit fermentation in various materials.

Some chlorophenols are used as intermediates and preservatives in the paint, textile, cosmetics and leather industries. 2-Chlorophenol and 2,4-dichlorophenol are used in organic synthesis. 2-Chlorophenol is utilized in the manufacture of dye-stuffs and in the process for extracting sulphur and nitrogen compounds from coal. 2,4,5-Trichlorophenol is a preservative for adhesives, synthetic textiles, rubber, wood, paints and paper; and 2,4,6-trichlorophenol is a wood and glue preservative. The tetrachlorophenols (and their sodium salts) have been used as fungicides and wood preservatives.

Hazards

Phenol

Phenol is readily absorbed through the skin and from the gastroenteric tract, while phenol vapours are readily absorbed into the pulmonary circulation. After absorption of a sublethal dose, most of the phenol is oxidized or conjugated with sulphuric, glucuronic and other acids, and excreted with the urine as “conjugated” phenol. A small portion is excreted as “free” phenol. The toxic effects of phenol are related directly to the concentration of free phenol in the blood.

In humans, acute phenol poisoning results in vasodilation, cardiac depression, hypothermia, coma and respiratiory arrest. Ingested phenol causes intense abdominal pain, and mouth burning occurs. Acute renal failure may also result. In animals, the signs of an acute intoxication are very similar, regardless of the site or the mode of administration of this compound. The predominant effects are exerted upon the motor centres in the spinal cord, resulting in tremors and severe convulsions. Chronic phenol poisoning is reported comparatively infrequently today. Severe cases are characterized by systemic disorders such as digestive disturbances, including vomiting, difficulty in swallowing, ptyalism, diarrhoea and anorexia; by nervous disorders, with headache, fainting, vertigo and mental disturbances; and possibly by ochronosis and an eruption on the skin. The prognosis is grave when there is extensive damage to the liver and kidneys. Ingestion of a dose of 1 g of phenol has been lethal to humans. Approximately every second reported case of acute phenol poisoning has resulted in death.

Generally speaking, the signs and symptoms of intoxication by di- and trihydroxy phenols (resorcinol, hydroquinone, pyrogallol) resemble that of phenol toxicity. The antipyretic action of resorcinol is more marked than that of phenol. The cutaneous application of solutions or salves containing 3 to 5% of resorcinol has resulted in local hyperaemia, itching dermatitis, oedema and loss of the superficial layers of the skin. The approximate lethal dose of resorcinol, in aqueous solution, for rabbits is 0.75 g/kg, and for rats and guinea-pigs, 0.37 g/kg. Hydroquinone is more toxic than phenol. Lethal doses have been reported as 0.2 g/kg (rabbit) and 0.08 g/kg (cat). Skin breakdown and irritation has been reported with dermal application of pyrogallol. Eventually with repeated contact, skin sensitization can occur. The symptoms observed in acute intoxications in humans resemble closely the signs displayed by experimental animals. These may include vomiting, hypothermia, fine tremors, weakness, muscular incoordination, diarrhoea, loss of reflexes, coma, asphyxia, and death by respiratory failure. Estimated lethal doses of aqueous pyrogallol are 1.1 g/kg (orally) for the rabbit, 0.35 g/kg (subcutaneously) for a cat or dog , and 0.09 g/kg (intravenously) in dogs.

Pentachlorophenol and its sodium salt are capable of inducing discomfort and local or systemic effects. Skin irritation is likely to result from a relatively brief, single exposure to a solution containing approximately 10% of the material. A 1% solution may cause irritation if contact is repeated. A solution containing 0.1% or less may result in adverse effects after prolonged contact. The symptoms of severe systemic intoxication include loss of appetite, respiratory difficulties, anaesthesia, hyperpyrexia, sweating, dyspnoea and a rapidly progressive coma.

Fine dusts and sprays of pentachlorophenol or sodium pentachlorophenate will cause painful irritation to the eyes and upper respiratory tract, respiratory tract and the nose. Atmospheric concentrations appreciably greater than 1 mg/m³ of air will cause this pain in the uninitiated person. Pentachlorophenol is classified by IARC as a Group 2B possible human carcinogen.

Other chlorophenols. Dermatoses in humans caused by tetrachlorophenol and its sodium salt have been reported; these included papulofollicular lesions, sebaceous cysts and marked hyperkeratosis. Occupational exposure to chlorophenols increases the risk of soft-tissue sarcomas. Chlorophenoxy derivatives including 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid, 2,4,5-trichlorophenoxypropionic acid, and 2,4-D salts and esters are discussed elsewhere in this chapter and Encyclopaedia.

Signs of intoxication due to o-, m- and p-chlorophenol in rats include restlessness, increased rate of respiration, rapidly developing motor weakness, tremors, clonic convulsions, dyspnoea and coma. The 2,4- and 2,6-dichlorophenols and 2,4,6- and 2,4,5-trichlorophenols also produce these signs, but decreased activity and motor weakness do not appear quite so promptly. The tremors are much less severe, but, in this case also, they continue until a few minutes before death. Tetrachlorophenols take an intermediate place between the lower homologues and pentachlorophenol. These compounds also produce signs similar to those caused by the mono-, di- and trichlorophenols; however, they do not as a rule cause hyperpyrexia.

Dermatoses, including photoallergic contact dermatitis, have been reported in humans after exposure to 2,4,5-trichlorophenol, chloro-2-phenylphenol and tetrachlorophenols; these included papulofollicular lesions, comedones, sebaceous cysts and marked hyperkeratosis (chloracne).

Bromo- and iodophenols. The bromo- and iodophenols are rapidly absorbed from the gastroenteric tract. The approximate lethal oral dose of pentabromophenol is 200 mg/kg rat; of 2,4,6-tribromophenol, 2.0 g/kg rat; and of 2,4,6-triiodophenol, from 2.0 to 2.5 g/kg rat. In rats and guinea-pigs the subcutaneous LD₅₀ of o-bromophenol are 1.5 and 1.8 g/kg, respectively. Generally, the symptoms are similar to those of pentachlorophenol. Pentabromophenol also caused tremors and convulsions.

On the basis of the results of animal experiments, the halogenated phenols, pentabromophenol and sodium and copper pentachlorophenate are considered safe for use as molluscicides in the field, if reasonable precautions are taken in their application.

Catechol (pyrocatechol). Contact with the skin has been known to cause an eczematous dermatitis, while in a few instances absorption through the skin has resulted in symptoms of illness closely resembling those induced by phenol, with the exception of certain marked central effects (convulsions). Toxic or lethal doses induced phenol-like signs of illness in experimental animals. However, unlike phenol, large doses of pyrocatechol cause a predominant depression of the central nervous system and a prolonged rise of blood pressure. The rise of blood pressure appears to be due to peripheral vasoconstriction.

The repeated absorption of sublethal doses by animals has induced methaemoglobinaemia, leucopenia and anaemia. Death is apparently initiated by respiratory failure.

Pyrocatechol is more acutely toxic than phenol. The approximate lethal oral dose is 0.3 g/kg for the dog, and 0.16 g/kg for the guinea-pig. Pyrocatechol is readily absorbed from the gastroenteric tract and through the intact skin. After absorption, part of the catechol is oxidized with polyphenol oxidase to o-benzoquinone. Another fraction conjugates in the body with hexuronic, sulphuric and other acids, while a small amount is excreted in the urine as free pyrocatechol. The conjugated fraction hydrolyzes in the urine with the liberation of the free compound; this is oxidized with the formation of dark-coloured substances which are responsible for the smoky appearance of the urine. Apparently, pyrocatechol acts by mechanisms similar to those reported for phenol.

Quinone. Large doses of quinone which have been absorbed from the subcutaneous tissues or from the gastroenteric tract of animals, induce local changes, crying, clonic convulsions, respiratory difficulties, drop in blood pressure and death by paralysis of the medullary centres. Asphyxia appears to play a major role in causing death because of pulmonary damage resulting from excretion of quinone into the alveoli and because of certain not too well defined effects of quinone upon haemoglobin. The urine of severely poisoned animals may contain protein, blood, casts, and free and conjugated hydroquinone.

In humans, severe local damage to the skin and mucous membranes may follow contact with the crystalline material, solutions of quinone and quinone vapour condensing upon exposed parts of the body (particularly moist surfaces). Local changes may include discolouration, severe irritation with erythema, swelling, and the formation of papules and vesicles. Prolonged skin contact may lead to necrosis. Vapours condensing upon the eyes are capable of inducing serious disturbances of vision. It was reported that the injury usually extends through the entire layer of the conjunctiva and is characterized by a deposit of pigment. The staining, varying from diffuse brown to globules of brownish-black, is located primarily in the zones extending from the canthi medially to the edges of the cornea. All layers of the cornea are involved in the injury, with a resultant discolouration that may be white and opaque or brownish-green and translucent. Alteration of the cornea can occur after the pigment has disappeared. Ulceration of the cornea has resulted from one brief exposure to a high concentration of the vapour of quinone, as well as from repeated exposures to moderately high concentrations.

Cresols and derivatives. Pure cresol is a mixture of ortho- (o-), meta- (m-) and para (p-) isomers, while cresylic acid, sometimes used synonymously for a mixture of cresols, is defined as a mixture of cresols, xylenols and phenol in which 50% of the material boils above 204 °C. The relative concentration of the isomers in pure cresol is determined by the source. The toxic effects of cresol are similar to those of phenol. It can be absorbed through the skin, from the respiratory system, and from the digestive system. The rate of penetration through the skin is more dependent upon the surface area than on the concentration.

Like phenol, it is a general protoplasmic poison and is toxic to all cells. Concentrated solutions are locally corrosive to the skin and mucous membranes, while dilute solutions cause redness, vesiculation and ulceration of the skin. Skin contact has also resulted in facial peripheral neuritis, impairment of renal function, and even necrosis of liver and kidneys. A sensitivity dermatitis may occur in susceptible people from solutions of less than 0.1%. Systemically, it is a severe depressant of the cardiovascular and central nervous systems, particularly the spinal cord and medulla. Oral administration causes a burning sensation in the mouth and oesophagus, and vomiting may result. Concentrations of vapour that can be produced at relatively high temperatures may cause irritation of the upper airways and nasal mucosa. Systemic absorption is followed by vascular collapse, shock, low body temperature, unconsciousness, respiratory failure and death. Pancreatic complications have been described. The oral toxic dose for small animals averages about 1 mg/kg, and specifically 0.6 mg/kg for
p-cresol, 0.9 mg/kg for o-, and 1.0 mg/kg for m-cresol. On the basis of its similarity to phenol, the human fatal dose can be estimated to be about 10 g. In the body, some of it is oxidized to hydroquinone and pyrocatechin, and the remainder and largest proportion is excreted unchanged, or conjugated with glycuronic and sulphuric acids. If urine is passed, it contains blood cells, casts and albumin. Cresol is also a moderate fire hazard.

Safety and Health Measures

These substances must be handled with caution. Inhalation of the vapours, and dust and skin contact with solutions of these materials, must be avoided to prevent local effects and absorption. The ingestion even of traces should be prevented. If exposure to the dust cannot be completely avoided, the nose and mouth should be protected with a respirator or folded gauze, and the eyes with tight-fitting goggles. Protective clothing, including rubber (not cotton) gloves, should be worn. Clothing should be removed immediately if contaminated by spillage. All clothing worn during one spraying operation should be laundered before re-use. Routine precautions include washing hands, arms, and face with soap and water before eating, drinking or smoking. At the end of each day, a worker should shower and change into clean clothing.

Measures that apply to phenol and its derivatives include:

• careful instruction of persons engaged in the manufacture, handling, storage and transport of phenol

• effective ventilation

• proper disposal of phenolic wastes with precautions against the possible pollution of air, streams and underground waters, since aquatic species are particularly susceptible to the effects of chemicals in this family

• special precautions in tank cleaning, which should not be attempted without proper gear, forced-air supply, a rescue harness and lifeline, hose mask, boots, rubber apron and gloves, and a “watcher” stationed at the entrance of the tank

• continuous vigilance on the part of the hygienist or physician for signs and symptoms of acute or chronic (local or systemic) intoxication

• fire prevention precautions.

First aid. In the event of an acute exposure, speed in treatment is essential. The offending agent must be removed from the skin, which is done most efficiently by flooding the affected area with water. After several minutes under the shower, continue decontamination with repeated swabbings or sprayings with polyethyleneglycol-300 until the danger of collapse has passed. If the exposed area is covered by clothing, remove it under the shower. Cover phenol burns lightly with a clean, white cloth. Do not use greases, powders or ointments in the first-aid treatment of such burns. Hospital treatment may include sedation, removal of dead tissue, fluid therapy, and the administration of antibiotics and vitamins. If phenol is splashed into eyes, copious irrigation with water for at least 15 minutes is necessary. All but the most trivial eye injuries should be referred to an ophthalmologist.

Speed is equally essential if a phenol has been ingested. Appropriate first aid must be available, and local medical facilities must be completely informed of the possibility of accidents and be prepared for emergency medical treatment. The treatment of chronic phenol poisoning is symptomatic after the individual has been removed from the site of exposure.

Phenols and phenolic compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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The characteristic chemical structure of peroxides is the presence of two oxygen molecules that are linked together by a single covalent bond (peroxy compounds). This structure is inherently unstable. Peroxides will decompose readily into highly reactive free radicals.The negatively charged peroxide ion serves as an initiatior of many chemical reactions. This reactivity is a key to the usefulness of some peroxides in industry and also to the safety hazards which they may present.

Uses

Organic peroxides are most widely used in the chemical, plastics and rubber industries. They act as initiators for free-radical polymerizations of monomers to thermoplastic polymers and as agents for curing thermoset polyester resins and cross-linking elastomers and polyethylene. Organic peroxides are used as free-radical sources in many organic syntheses.

2-Butanone peroxide is a hardening agent for fibreglass and reinforced plastics, and a curing agent for unsaturated polyester resins. Cyclohexanone peroxide is a catalyst for the hardening of certain fibreglass resins; a bleaching agent for flour, vegetable oils, fats and waxes; as well as a polymerization agent in the plastics industry and a curing agent in the rubber industry. Dilauroyl peroxide finds use in the cosmetics and pharmaceutical industries and as a burn-out agent for acetate yarns. In addition to serving as a polymerization catalyst, tert-butyl peroxide acts as an ignition accelerator for diesel fuels.

Benzoyl peroxide is primarily used in the polymer industry to initiate free-radical polymerizations and copolymerizations of vinyl chloride, styrene, vinyl acetate and acrylics. It is also utilized for curing thermoset polyester resins and silicone rubbers and for hardening certain fibreglass resins. Benzoyl peroxide is used in medicine for the treatment of acne. It is the preferred bleaching agent for flour, and has been used for bleaching cheese, vegetable oils, waxes, fats and so on. Cumene hydroperoxide is used for the manufacture of phenols and acetone. Peracetic acid is a bactericide and a fungicide used especially in food processing. It also functions as a bleaching agent for textiles, paper, oil, waxes and starch, and as a polymerization catalyst.

Hydrogen peroxide has numerous uses, most of which derive from its properties as a strong oxidizing or bleaching agent. It also functions as a reagent in the synthesis of chemical compounds. Various grades of hydrogen peroxides have different uses: 3% and 6% solutions are used for medicinal and cosmetic purposes; the 30% solution is used for laboratory reagent purposes, the 35% and 50% solutions for most industrial applications, the 70% solution for some organic oxidation uses, and the 90% solution for some industrial uses and as a propellant for military and space programmes. Solutions of over 90% are utilized for specialized military purposes.

Hydrogen peroxide is utilized in the production of glycerin, plasticizers, bleaching agents, pharmaceuticals, cosmetics, drying agents for fats, oils and waxes, and amine oxides for home dishwashing detergents. It is used in the textile industry for bleaching textiles, particularly cotton, and in the pulp and paper industry for the bleaching of mechanical wood pulps. In mining, hydrogen peroxide is used to increase the solubility of uranium in leaching solutions. It is also useful for metal etching and oxidizing in the electronics industry and for treating metal surfaces. In addition, hydrogen peroxide is a sterilizing agent in the food industry and a source of oxygen in respiratory protective equipment.

Hazards

The major hazards are fire and explosion. Organic peroxides are fuel-rich compounds that generally ignite easily and burn vigorously. The oxygen-oxygen bond is thermally unstable, decomposing exothermically at an increasing rate as temperature rises. Thermal instability varies widely. The 10-hour half-life temperatures of organic peroxides range from about 25 °C to about 172 °C. Decomposition products generally are flammable vapours which can form explosive mixtures in air; they may be hot enough to auto-ignite on contact with air if decomposition is rapid. Decomposition can be initiated by heat, friction, mechanical shock or contamination, though sensitivity to these stimuli varies greatly. If the heat of decomposition is not carried away quickly enough, a reaction ranging from mild gassing to violent spontaneous decomposition, deflagration or explosion can result. Peroxides formed spontaneously in various low-molecular-weight ethers and aldehydes are extremely sensitive to friction and impact shock. Methyl ethyl ketone peroxide and peroxyacetic acid are extremely shock sensitive, requiring diluents for safe handling. Dry benzoyl peroxide is shock sensitive. Dicumyl peroxide is insensitive to shock and friction. Shock sensitivity may be increased at elevated temperatures. Vigorous decomposition can be stimulated by even trace amounts of a wide variety of contaminants, such as strong acids, bases, metals, metal alloys and salts, sulphur compounds, amines, accelerators or reducing agents. This is particularly true of methyl ethyl ketone and benzoyl peroxides, which are intentionally stimulated to decompose at room temperature using small amounts of accelerators. The violence of decomposition is greatly affected by the quantity and type of peroxide, rate of temperature rise, amount and type of contamination, and degree of confinement.

The safety of many organic peroxides is greatly improved by dispersing them in solvent or non-solvent diluents that absorb the heat of decomposition (e.g., water or plasticizer) or reduce shock sensitivity (e.g., dimethyl phthalate). These formulations are generally much less flammable than the pure peroxide. Some are fire-resistant. However, the toxicity of the diluent may markedly increase the toxicity of the peroxide solution.

The main toxic effect of most of the peroxides is irritation of skin, mucous membranes and eyes. Prolonged or intense skin contact or splashes in the eyes may cause severe injury. Some organic peroxide vapours are irritating and may also cause headaches, intoxication similar to alcohol, and lung oedema if inhaled in high concentrations. Some, such as cumene hydroperoxides, are known skin sensitizers. Dialkyl peroxides are generally not as strongly irritating, and the diacyl peroxides are the least irritating of the peroxides. Hydroperoxides, peroxyacids and particularly methyl ethyl ketone peroxide are much more severe. They are extremely irritating and corrosive to the eyes, with risk of blindness, and may cause serious injury or death if ingested in sufficient quantity.

The carcinogenicity of the peroxides has been under investigation, but the results to date are not conclusive. The International Agency for Research on Cancer (IARC) has assigned a Group 3 rating (non-classifiable as to carcinogenicity) to benzoyl peroxide, benzoyl chloride and hydrogen peroxide

Benzoyl peroxide. The hazards of dry benzoyl peroxide are greatly reduced by dispersing it in non-solvent diluents that absorb any heat of decomposition and provide other benefits. Benzoyl peroxide is commonly produced in hydrated granular form with 20 or 30% water, and in various pastes, usually containing about 50% of a plasticizer or other diluents. These formulations have greatly reduced flammability and shock sensitivity compared to dry benzoyl peroxide. Some are fire-resistant. The hardeners used with plastic resin fillers, such as auto body putty, typically contain 50% benzoyl peroxide in a paste formulation. Flour bleach contains 32% benzoyl peroxide with 68% grain starch and calcium sulphate dihydrate or dicalcium phosphate dihydrate, and is considered non-flammable. Acne creams, also non-flammable, contain 5 or 10% benzoyl peroxide.

Hydrogen peroxide is commercially available in aqueous solutions, usually 35%, 50% (industrial strength), 70% and 90% (high strength) by weight, but also is available in 3%, 6%, 27.5% and 30% solutions. It is also sold by “volume strength” (meaning the amount of oxygen gas which will be liberated per ml of solution). Hydrogen peroxide is stabilized during manufacture to prevent contamination by metals and other impurities; however, if excessive contamination occurs, the additive cannot inhibit decomposition.

Human exposure by inhalation may result in extreme irritation and inflammation of nose, throat and respiratory tract; pulmonary oedema, headache, dizziness, nausea, vomiting, diarrhoea, irritability, insomnia, hyper-reflexia; and tremors and numbness of extremities, convulsions, unconsciousness and shock. The latter symptoms are a result of severe systemic poisoning. Exposure to mist or spray may cause stinging and tearing of the eyes. If hydrogen peroxide is splashed into the eye, severe damage such as ulceration of the cornea may result; sometimes, though rarely, this may appear as long as a week after exposure.

Skin contact with hydrogen peroxide liquid will result in temporary whitening of the skin; if the contamination is not removed, erythema and vesicle formation may occur.

Although ingestion is unlikely to occur, if it does the hydrogen peroxide will cause irritation of the upper gastrointestinal tract. Decomposition results in rapid liberation of O₂, leading to distension of the oesophagus or stomach, and possibly severe damage and internal bleeding.

Decomposition continuously occurs even at a slow rate when the compound is inhibited, and thus it must be stored properly and in vented containers. High-strength hydrogen peroxide is a very high-energy material. When it decomposes to oxygen and water, large amounts of heat are liberated, leading to an increased rate of decomposition, since decomposition is accelerated by increases in temperature. This rate increases about 2.2 times per 10 °C temperature increase between 20 and 100 °C. Although pure hydrogen peroxide solutions are not usually explosive at atmospheric pressure, equilibrium vapour concentrations of hydrogen peroxide above 26 mol per cent (40 weight per cent) become explosive in a temperature range below the boiling point of the liquid.

Since the compound is such a strong oxidizer, when spilled on combustible materials it can set fire to them. Detonation can occur if the peroxide is mixed with incompatible (most) organic compounds. Solutions of less than 45% concentration expand during freezing; those greater than 65% contract. If rapid decomposition takes place near combustible materials, detonation can occur with exposures that lead to severe irritation of skin, eyes, and mucous membranes. Hydrogen peroxide solutions in concentrations greater than 8% are classified as corrosive liquids.

Hydrogen peroxide is not itself flammable but can cause spontaneous combustion of flammable materials and continued support of the combustion because it liberates oxygen as it decomposes. It is not considered to be an explosive; however, when mixed with organic chemicals, hazardous impact-sensitive compounds may result. Materials with metal catalysts can cause explosive decomposition.

Contamination of hydrogen peroxide by such metals as copper, cobalt, manganese, chromium, nickel, iron and lead, and their salts, or by dust, dirt, oils, various enzymes, rust and undistilled water results in an increased rate of decomposition. Decomposition results in the liberation of oxygen and heat. If the solution is dilute, the heat is readily absorbed by the water present. In more concentrated solutions the heat increases the temperature of the solution and its decomposition rate. This may lead to an explosion. Contamination with materials containing metal catalysts can result in immediate decomposition and explosive rupture of the container if it is not properly vented. When an ammonium peroxidisulphate route is used in the production of hydrogen peroxide, a risk of bronchial and skin sensitization may be present.

Safety Precautions

Spills should be cleaned up promptly using non-sparking tools and an inert, moist diluent such as vermiculite or sand. Sweepings may be placed in open containers or polyethylene bags and the area washed with water and detergent. Spilled, contaminated, waste or questionable peroxides should be destroyed. Most peroxides can be hydrolyzed by adding them slowly with stirring to about ten times their weight of cold 10% sodium hydroxide solution. The reaction may require several hours. Rigid containers of uncertain age or condition should not be opened but carefully burned from a safe distance.

Persons handling peroxides should use safety glasses with side shields, goggles or face shields for eye protection. Emergency eyewash facilities should be provided. Gloves, aprons and other protective clothing as necessary should be used to prevent skin contact. Clothing and equipment that generate static electricity should be avoided. Smoking should be prohibited. Peroxides should not be stored in refrigerators containing food or drink. Laboratory reactions should be carried out behind a safety shield.

Storage and handling areas should be protected from fire by a deluge system or sprinklers. (A liquid nitrogen deluge system may be used for protection of peroxides which are stable only below the freezing point of water.) In case of fire, water should be applied by the sprinkler system or by hose from a safe distance, preferably with a fog nozzle. Foam may be necessary instead if the peroxide is diluted in a low density flammable solvent. Portable extinguishers should not be used except for very small fires. Peroxides threatened by fire should be wetted from a safe distance for cooling.

Peroxides should be washed promptly from the skin to prevent irritation. In the case of eye contact, the eyes should be flushed immediately with large amounts of water, and medical attention should be obtained. Delay in the case of corrosive irritants such as methyl ethyl ketone peroxide can result in blindness. Medical attention should also be obtained in case of accidental ingestion. If sensitization occurs, further contact should be avoided.

Organic and inorganic peroxides tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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The aromatic nitrocompounds are a group of organic chemicals headed by nitrobenzene (C₆H₅NO₂) and derived from benzene and its homologues (toluene and xylene), naphthalene and anthracene by replacement of one or more hydrogen atoms by a nitro- group (NO₂). The nitro- group may be replaced along with halogen and certain alkyl radicals at almost any position in the ring.

Nitrocompounds of major industrial importance include nitrobenzene, the mono- and dinitrotoluenes, trinitrotoluene (TNT), tetryl, the mononitrochlorobenzenes, nitroanilines, nitrochlorotoluenes, nitronaphthalene, dinitrophenol, picric acid (trinitrophenol) and dinitrocresol. Sufficient experience has been documented on these compounds to provide an outline of their toxic properties and the exposure control measures required to prevent injury to humans.

A much larger number of compounds in this group is accounted for by those derivatives which in no single case have been manufactured in sufficient quantities to allow complete hazard evaluation; these derivatives include the dinitrochlorobenzenes, dichloronitrobenzenes, nitroxylenes, nitrotoluidines, nitrochloroanilines, nitroanisoles, nitrophenetoles and nitroanisidines.

Uses

Aromatic nitrocompounds have few direct uses other than in the formulation of explosives or as solvents. The major consumption involves reduction to aniline derivatives used in the manufacture of dyes, pigments, insecticides, textiles (heat-resistant polyamide-”Nomex”), plastics, resins, elastomers (polyurethane), pharmaceuticals, plant-growth regulators, fuel additives, and rubber accelerators and antioxidants.

The dinitrotoluenes are used in organic syntheses, dyes, explosives, and as propellant additives. Nitrotoluenes are employed in the manufacture of dyes, explosives, toluidines, and nitrobenzoic acids. They are also used in some detergent formulations, flotation agents, and in the tyre industry. Nitrotoluenes are employed in the synthesis of sunscreening agents and in the production of gasoline inhibitors. 2,4,6-Trinitrotoluene is a military and industrial explosive. Nitrobenzene is utilized in the manufacture of aniline. It acts as a solvent for cellulose ethers and as an ingredient in metal, floor and shoe polishes, and soaps. Nitrobenzene is also used for refining lubricating oils and in the production of isocyanates, pesticides, rubber chemicals and pharmaceuticals.

In the leather industry, m-nitrophenol is a fungicide and p-nitrophenol is a chemical intermediate for leather preservatives. 2,4-Dinitrophenol is useful in the manufacture of photographic developers and serves as a wood preservative and an insecticide. 2-Nitro-p-phenylenediamine and 4-amino-2-nitrophenol are components of permanent hair dye products and fur dyes.

p-Nitrosodiphenylamine acts as an accelerator for rubber vulcanization and as a polymerization inhibitor during the manufacture of vinyl monomers. Picric acid has numerous uses in the leather, textile and glass industries. It is found in explosives, dyes, germicides, fungicides, electric batteries, and in rocket fuel. Picric acid is also used for etching copper and as a chemical intermediate. Tetryl is employed as an intermediary detonating agent for other less sensitive high explosives and as a booster charge for military devices.

Hazards

Health

The most prominent acute health hazard of the aromatic nitro- compounds is cyanosis, and the chronic manifestation is anaemia. The fat-soluble nitrocompounds are very rapidly absorbed through the intact skin. A certain amount is excreted unchanged through the kidneys, but the major portion is reduced to cyanogenic nitroso and hydroxylamine derivatives, which in turn are degraded to the ortho- and para-aminophenol analogues and excreted in the urine. Three out of four cases of cyanosis will exhibit the classical blue or ashen-grey appearance, but only one-third of the victims will complain of anoxia symptoms (headache, fatigue, nausea, vertigo, chest pain, numbness, abdominal pain, aching, palpitation, aphonia, nervousness, air hunger and irrational behaviour). Blood and urine analyses are required for confirmation. Heinz bodies may be detected in the red cells. Methaemoglobinemia is discussed in more detail elsewhere in this Encyclopaedia.

Cyanogenic potential is profoundly altered by both the nature and position of substituent groups in the benzene ring. In addition to cyanogenic potential, the nitrochlorobenzenes as a class are also skin irritants. The dinitrochlorobenzenes produce sensitivity dermatitis in most people even after slight contact. Dichloronitrobenzenes possess intermediate toxicity.

The long-term chronic effects are more insidious and can be detected only from well-documented medical records. Bimonthly blood analyses will disclose the onset of anaemia over several years even in the absence of detectable cyanosis or significantly elevated urinary excretion.

2,4-Dinitrotoluene affects the drug-metabolizing enzymes in liver microsomes, and it has been shown to be a hepatocarcinogen in the rat. No data are available as regards its carcinogenic potential to humans.

1- and 2-Nitronaphthylamine were isolated as urinary metabolites of 1- and 2-nitronaphthalene, respectively, in the rat. This has important implications for possible carcinogencity of the nitronapthalenes.

Dinitrophenol (DNP) is an acute poison disrupting cellular metabolism in all tissues by disturbing the essential process of oxidative phosphorylation. If not fatal, the effects are rapidly and completely reversible. Exposure may occur by the inhalation of the vapour, dusts or sprays of solutions of DNP. It penetrates the intact skin but, as it is a brilliant yellow dye, skin contamination is readily recognized. Systemic poisoning has occurred during both production and use. DNP solid is explosive, and accidents have also occurred during production and use. Care must be exercised when handling it.

Poisoning results first in excessive sweating, a feeling of warmth with weakness and fatigue. In severe cases, there is rapid respiration and tachycardia even at rest, and there may be a rise in body temperature. Death, if it occurs, is sudden, and rigor mortis ensues almost immediately. DNP exerts its toxic effects by a general disturbance of cell metabolism resulting in a need to consume excessive amounts of oxygen in order to synthesize the essential adenine nucleotide required for cell survival in the brain, heart and muscles. If heat production is greater than heat loss, fatal hyperthermia may result. The effects are most severe in hot workplaces.

DNP is readily reduced to the much less toxic, but not innocuous, aminophenol, which is excreted in the urine in this form. Since DNP is rapidly metabolized and excreted and since poisoning does not lead to structural changes in tissues, chronic or cumulative effects from small doses absorbed over long periods do not occur. Poisoning may be confirmed by finding DNP or aminophenol in the urine by Derrien’s test. Methaemoglobinemia does not develop.

Dinitrobenzene is a potent chemical with multisystemic effects (minimally affecting the central nervous system (CNS), blood, liver, cardiovascular system and eyes). It can cause severe anaemia and is a methaemoglinemia inducer.

Nitrobenzene may be absorbed into the body through the respiratory system or the skin (e.g., from shoes dyed black with a dye containing nitrobenzene, or from contamination of clothing worn by workers employed on nitrobenzene production). The outstanding toxic effect of nitrobenzene is its capacity for causing methaemoglobinemia. The onset is insidious, and cyanosis appears only when the methaemoglobin level in the blood reaches 15% or more. At a later stage, hypotension, headache, nausea, vertigo, numbness of the limbs, severe general weakness and cortical disturbances may occur if methaemoglobinemia is severe. Nitrobenzene is also a central nervous poison, causing in some cases, excitement and tremors followed by severe depression, unconsciousness and coma. Examination of the urine of exposed persons reveals the presence of nitro- and aminophenols, the amounts of which run parallel with the level of methaemoglobinemia. Repeated exposure may be followed by liver impairment up to yellow atrophy, haemolitic icterus and anaemia of varying degrees, with the presence of Heinz bodies in the red cells. Nitrobenzene may also produce dermatitis due to primary irritation or sensitization.

Picric acid and derivatives. Picric acid derivatives of industrial importance are the metallic picrates (iron, nickel, barium, chromium, lead and potassium) and the salts of ammonia and guanidine. Some of the metallic salts (barium, lead or potassium) have been used as constituents of detonating and boosting mixtures in bombs, mines and shells. Toxic effects may result from skin contact or inhalation or ingestion of the dust of picric acid or its salts. Skin contact may also produce skin disease. A number of its metallic salts are also dangerous fire and explosion hazards.

Following ingestion of a few grams of picric acid, which has an intensely bitter taste, acute gastroenteritis, toxic hepatitis, nephritis, haematuria and other urinary symptoms may occur. The skin and conjunctivae become yellow, mostly due to the acid but partly due to jaundice. Yellow vision may develop. Death, if it follows, is due to renal lesions and anuria. Rarely, jaundice and coma with convulsions precede death. Headache and vertigo with nausea and vomiting and skin rashes occur after absorption from the body surface.

In industry, particularly in the manufacture of explosives, the main health problem has been the occurrence of skin disease, and systemic poisoning is rare. It has been reported that picric acid is a distinct skin irritant in the solid form, but in aqueous solution it irritates only hypersensitive skin; it causes sensitization dermatitis similar to that produced by ammonium picrate. The face is usually involved, especially around the mouth and sides of the nose. There are oedema, papules, vesicles and finally desquamation. Hardening occurs as with tetryl and trinitrotoluene. Workers handling picric acid or its salts have the skin and hair dyed a yellowish colour.

Experimental animals severely exposed to ammonium picrate dust for periods up to 12 months revealed lesions that suggested definite injury to certain tissues. Dust of picric acid may cause not only irritation of the skin but also of the nasal mucosa. The inhalation of high concentrations of dust has caused temporary unconsciousness followed by weakness, myalgia, anuria and later polyuria. The effects of picric acid on the eyes include irritation, corneal injury, strange visual effects (e.g., yellow appearance of objects) and yellow colouring of the tissues.

Picric acid and its flammable and explosive derivatives should be stored in small quantities in a cool, ventilated area away from acute fire hazards and powerful oxidizing materials and, preferably, in an isolated or detached building.

Tetryl. The explosion hazards encountered in the production of tetryl are basically the same as those for other products of the explosives industry, although tetryl, being relatively stable, cannot be considered among the most hazardous of explosives.

During the manufacture of tetryl, workers may be exposed to nitrogen oxides and acid vapours should leakage occur from the nitration reactors. There can be exposure to appreciable amounts of tetryl dust during booster manufacture and subsequent handling operations, especially in non-automated mixing, weighing, tablet-pressing, dedusting, and in the loading and assembling of explosive devices. The principal manifestations of exposure are irritation of the mucous membranes, staining and discoloration of the skin and hair, dermatitis and, in cases of prolonged, severe exposure, systemic poisoning due to inhalation and skin absorption.

On initial exposure, tetryl produces acute irritation of the nasal and pharyngeal mucous membranes. Within a few days, the hands, face, scalp and hair of exposed workers are stained a yellowish colour. Under severe exposure, the conjunctivae are affected and nearly always bloodshot; palpebral and periorbital oedema is not uncommon. During the first 2 to 3 weeks of exposure, workers may develop a dermatitis in the form of erythema, particularly in the region of the neck, chest, back and the inside surface of the forearms. After a few days the erythema may regress, leaving moderate desquamation. Workers who can continue to work in spite of the dermatitis develop a tolerance for, or become hardened to, tetryl. However, with severe exposure, or in subjects with poor personal hygiene or very fair skin, the dermatitis may spread to other parts of the body and become papular, vesicular and eczematous.

After only 3 to 4 days of exposure to high dust concentrations, workers may complain of headaches followed by periodic nosebleeding. Upper respiratory tract irritation does not frequently extend to the bronchi because, due to their large size, tetryl crystals do not usually reach this far; however, dry cough and bronchial spasms have been observed. Diarrhoea and menstrual disorders may occur occasionally.

Many of the disorders caused by tetryl are to be attributed to the irritant action of the crystals. In some cases, the dermatitis is allergic; in many cases, mechanisms such as local histamine liberation have been suggested.

Following severe, prolonged exposure, tetryl causes chronic poisoning with digestive disorders (such as loss of appetite, abdominal pain, vomiting), loss of weight, a chronic hepatitis, central nervous system irritation with insomnia, exaggerated reflexes, and mental excitation. Cases of leucocytosis with occasional slight anaemia have been reported. There have been reports of menstrual disturbances as well. Animal experiments indicate renal tubule damage.

Trinitrotoluene, commonly known as TNT, is also a methaemoglobin inducer. During the First World War it was found that workers who were involved in the manufacture of munitions developed severe liver effects and anaemia, with at least 25% of the approximately 500 cases reported ending in fatalities. Adverse effects were also observed during the Second World War. Presumably conditions have improved so that exposure is far more limited and overt poisoning should then not occur. Menstrual irregularities, urinary tract problems and cataracts have also been reported.

Fire and explosion

Aromatic nitrocompounds are flammable and the di- and trinitroderivatives are explosive under favourable conditions (heat and shock). Pumps operating against a closed discharge valve or plugged line have produced sufficient frictional heat with mononitrotoluene and nitrochlorobenzenes to produce explosions. Other than nitrobenzene, aromatic nitro- compounds should not be heated under alkaline conditions. Dinitro- compounds may form shock-sensitive nitrolium salts, and fires have resulted from heating potassium carbonate in
o-nitrotoluene.

Contact with strong reducing agents such as sodium sulphide, zinc powder, sodium hydrosulphite and metallic hydrides, and strong oxidizing agents such as bichromates, peroxides and chlorates, must be avoided in storage and transit. Those derivatives containing reactive chlorine atoms require special care in storage and transit. Chemical reduction processes must provide for addition of the nitro- compound to the reducing system (acidic iron reduction, alkaline sulphide and so on) in small increments at a rate which avoids overheating or accumulation of excess nitro- compound.

Although hazards inherent in concentrated nitric and sulphuric acids are recognized, caution must be observed in the disposal of spent mixed acid which contains organic components which are highly unstable in storage or on heating. The finished product must be washed thoroughly and neutralized to avoid metallic corrosion and spontaneous decomposition.

Safety and Health Measures

An effective health programme to prevent health impairment due to exposure to aromatic nitro- compounds requires exposure control and medical supervision measures. Job analysis to ensure proper handling procedures, adequate equipment design for both operating and maintenance, and appropriate ventilation with air-pollution control are minimum requirements. Totally enclosed systems are preferred. Where appropriate, air analysis can be helpful; but in general, results have been misleading due to the low vapour pressure of nitrobenzene derivatives and contamination of surfaces where skin contact occurs. However, mist from hot charges, leaking lines, steaming operations, hot drainage ditches and so on, cannot be ignored as sources of gross skin exposure and contamination of the work environment.

The necessary protective measures in ascending order of effectiveness are respiratory protection, job rotation, limitation of exposure time, use of protective clothing and whole-body protection. Respiratory protection has limited application, since skin absorption is the major problem. Protective equipment must be selected carefully to assure impermeability to the chemicals in use.

A high standard of personal hygiene—in particular, a warm shower with plenty of soap and water vigorously applied at the end of the shift—will minimize chronic exposure which deprives the worker of limited tolerance to cyanogenic agents. Because of the suspected carcinogenic potential for humans of 1- and 2-nitronaphthalene, occupational exposure to these compounds should be kept at the lowest possible level.

Where possible, picric acid and its hazardous derivatives should be replaced by substances which are innocuous or less harmful. Where this is not possible, the process should be modified, isolated or enclosed; automatic or mechanical handling techniques, local exhaust ventilation and wet methods should be employed to minimize atmospheric concentrations; and direct contact with the chemicals should be avoided.

Aromatic nitrocompounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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Nitrocompounds are characterized by the linkage C–NO₂. They include the mononitroparaffins, polynitroparaffins, nitro-olefins, and the alkyl nitrites and nitrates.

The mononitroparaffins below are obtained by direct nitration of the appropriate paraffins in the vapour phase and are used chiefly as solvents for cellulose esters, other resins, and for oils, fats, waxes and dyes. Among the special groups of mononitroparaffins are the chloronitroparaffins.

Uses

The aliphatic nitrocompounds are used as solvents, explosives, rocket propellants, fumigants and gasoline additives. Several are found in the rubber, textile, and paint and varnish industries.

Pentaerythritol tetranitrate, ethylene glycol dinitrate (EGDN), tetranitromethane, nitroglycerin and 2-nitropropane are ingredients in explosives. Ethylene glycol dinitrate is a high explosive, but it also has the property of lowering the freezing point of nitroglycerin. In most countries with a temperate-to-cold climate, dynamite is made from a mixture of nitroglycerin and EGDN. Nitroglycerin is used in high explosives and in the production of dynamite and other explosives; however, it has gradually been replaced by ammonium nitrate in this application. In addition, nitroglycerin is used to combat fires in oil wells. Nitroglycerine is also used in medicine as a vasodilator in coronary artery spasm.

Nitroglycerin, 2-nitropropane, tetranitromethane and nitromethane serve as rocket propellants. 1-Nitropropane and 2-nitropropane are solvents and gasoline additives, and tetranitromethane is a diesel fuel booster. 2-Nitropropane finds use as a smoke depressant in diesel fuel and as a component of racing-car fuels and paint and varnish removers.

Chloropicrin is a rodenticide and a chemical warfare agent, while nitromethane and nitroethane are utilized as propellants in the military. Nitrilotriacetic acid has numerous uses in water treatment, textiles, rubber, and the pulp and paper industries. It also functions as a boiler feedwater additive and a chelating agent in the cleaning and separation of metals.

The chlorinated nitroparaffins are used most frequently as solvents and intermediates in the chemical and synthetic rubber industries. They have found use as pesticides, especially fumigants, fungicides and mosquito ovicides.

Nitro-olefins may be produced by dehydration of the nitro-alcohols or by immediate addition of nitrogen oxides to olefins. They have no broad industrial use.

Alkyl nitrites are produced by the action of nitrites on alcohols in the presence of dilute sulphuric acid, and also with the mononitroparaffins by the reaction of alkyl halides and nitrites. The major use of alkyl nitrites has been in industrial and military explosives, although these substances are also used in organic synthesis and as therapeutic agents (vasodilators) in medicine. They undergo hydrolysis easily with the release of nitrous acid, as well as exchange reactions when dissolved in alcohols. Alkyl nitrates are formed by the interaction of alcohols and nitric acid. Ethyl nitrate and to some extent methyl nitrate are used in organic synthesis as nitrating agents for aromatic compounds. Methyl nitrate is also used as a rocket fuel.

Hazards

Effects may be produced from absorption by any route (i.e., inhalation, ingestion, skin absorption). Irritation may occur as a result of skin contact. Often the most important industrial hazard is inhalation of vapours, since the vapour pressures are often sufficiently high to produce considerable vapour levels in the workplace. When exposed to high temperatures, flames or impact, certain aliphatic nitro-compounds constitute a fire and explosion hazard. Spontaneous exothermic chemical reactions may also take place. Symptoms of exposure can include mucosal irritation, nausea, vomiting, headaches, shortness of breath (dyspnea) and dizziness. Chronic exposure to these substances can increase the risk of carcinogenicity (in animals), ischemic heart disease and sudden death.

Nitroparaffins

Nitroparaffins have a depressive effect on the central nervous system and also cause lesions in the liver and kidneys. The polynitroparaffins are considerably more toxic than the mononitroparaffins. Industrial exposure to 30 ppm of nitropropane (a mononitroparaffin) caused symptoms such as headache, nausea, vomiting and diarrhoea. No signs were observed at concentrations of 10 to 20 ppm. In workers, the observed effects of tetranitromethane (a polynitroparaffin) included irritation of the respiratory system, dyspnoea, dizziness and, with repeated exposures, anaemia, cyanosis and bradycardia. The carcinogenic potential is discussed below. Under ordinary conditions, nitromethane (a mononitroparaffin) is relatively stable, but it can be detonated by impact or by heat. The damage caused by two separate tank car explosions of nitromethane was very considerable, and, as a result of these experiences, nitromethane is now stored and transported in drums rather than in bulk. Inhalation of nitromethane produces mild irritation and toxicity before narcosis occurs; liver damage can result from repeated exposure. It should be handled under conditions of good ventilation, preferably local exhaust ventilation; personal protective equipment should be worn.

Although nitroethane is less explosive than nitromethane, this substance could explode under appropriate conditions of contamination and confinement, and safe handling methods are necessary. It is a moderate respiratory tract irritant, but no serious industrial injury has been recorded. Well-ventilated conditions should be provided.

Nitro-olefins

Nitro-olefins are considered highly toxic because of the vigorous local irritation that is caused by coming into contact with the liquids or with vapours in concentrations as low as 0.1 to 1 ppm (e.g., nitrobutene, nitrohexene, nitrononene), and to the rapid absorption of these compounds by any route. The toxic effects appear immediately after exposure and include hyperexcitability, convulsions, tachycardia, hyperpnoea, depression, ataxia, cyanosis and asphyxia. Pathologic changes are most pronounced in the lungs, regardless of the route of absorption.

Alkyl nitrites and nitrates

Alkyl nitrites are considered toxic because of their effect on the formation of nitrite ions, which are strong oxidizing agents. The alkyl nitrates and nitrites may cause methaemoglobin formation in the blood. When heated, they may decompose, releasing nitrogen oxides, which are highly toxic. In high concentrations alkyl nitrites are narcotic. Alkyl nitrates are highly toxic and in large doses may cause dizziness, abdominal cramps, vomiting, bloody diarrhoea, weakness, convulsions and collapse. Small, repeated doses may lead to weakness, general depression, headache and mental disorders.

Chloropicrin vapours are highly irritating to the eyes, causing intense lacrimation, and to the skin and respiratory tract. Chloropicrin causes nausea, vomiting, colic and diarrhoea if it enters the stomach.

Data on the effects of chloropicrin are derived mainly from First World War experience with chemical warfare agents. It is a pulmonary irritant with a toxicity greater than chlorine but less than phosgene. Military data indicate that exposure to 4 ppm for a few seconds is sufficient to render a person unfit for action, and 15 ppm for 60 seconds causes marked bronchial or pulmonary lesions. It causes injury particularly to the small and medium bronchi, and oedema is frequently the cause of death. Because of its reaction with sulphydryl groups, it interferes with oxygen transport and can produce weak and irregular heartbeats, recurrent asthmatic attacks and anaemia. A concentration of around 1 ppm causes severe lacrimation and provides good warning of exposure; at higher concentrations, skin irritation is evident. Ingestion may occur due to the swallowing of saliva containing dissolved chloropicrin and produce vomiting and diarrhoea. Chloropicrin is non-combustible; however, when heated it can detonate and can also be shock detonated above a critical volume.

Ethylene glycol dinitrate (EGDN). When ethylene glycol dinitrate was first introduced into the dynamite industry, the only changes noticed were similar to those affecting workers exposed to nitroglycerin—headache, sweating, face redness, arterial hypotension, heart palpitations and dizziness especially at the beginning of work, on Monday mornings and after an absence. EGDN, which is absorbed through the respiratory tract and the skin, has indeed a significant acute hypotensive action. When cases of sudden death started to occur amongst workers in the explosives industry, no one immediately suspected the occupational origin of these accidents until, in 1952, Symansky attributed numerous cases of fatality already observed by the manufacturers of dynamite in the United States, the United Kingdom and the Federal Republic of Germany to chronic EGDN poisoning. Other cases were then observed, or at least suspected, in a number of countries, such as Japan, Italy, Norway and Canada.

Following a period of exposure which often varies between 6 and 10 years, workers exposed to mixtures of nitroglycerin and EGDN may complain of sudden pain in the chest, resembling that of angina pectoris, and/or die suddenly, usually between 30 and 64 hours after termination of exposure, either during sleep or following the first physical efforts of the day after arriving at work. Death is generally so sudden that it is usually not possible to assess the victims carefully during the attack.

Emergency treatment with coronary dilators and, in particular, nitroglycerin has proved ineffective. In most cases, autopsy proved negative or it did not appear that coronary and myocardial lesions were more prevalent or extensive than in the general population. In general, electrocardiograms have also proved deceptive. From the clinical point of view, observers have noted systolic hypotension, which is more marked during working hours, accompanied by increased diastolic pressure, sometimes with modest signs of hyperexcitability of the pyramidal system; less frequently there have been signs of acrocyanosis—together with some changes in vasomotor reaction. Peripheral paraesthesia, particularly at night, has been reported, and this may be attributed to arteriolar spasms and/or to peripheral neuropathy. Skin sensitization has also been reported.

Nitroglycerin. Nitroglycerin is a highly explosive substance which is very sensitive to mechanical shock; it is also readily detonated by heat or spontaneous chemical reaction. In commercial explosives, its sensitivity is reduced by the addition of an absorbent such as woodpulp and chemicals such as ethylene glycol dinitrate and ammonium nitrate. In the form of straight or ammonia dynamite, the substance presents only a moderate explosion hazard.

Nitroglycerin may be absorbed into the body by ingestion, inhalation or through intact skin. It causes arterial dilation, increased heart rate, and reduced blood and pulse pressure. Cases of sudden death have been reported amongst explosives workers in contact with nitroglycerin; however, death has usually been attributed to the action of the ethylene glycol dinitrate mixed with nitroglycerin in the manufacture of dynamite.

Most workers rapidly adapt to the hypotensive action of nitroglycerin, but discontinuation of exposure (even for a few days, such as at the weekend) may interrupt this adaptation, and some workers may even be subject to a period of nausea when resuming work on Monday mornings; some workers never adapt and have to be removed from exposure after a trial period of 2 to 3 weeks. Prolonged exposure to nitroglycerin may result in neurological disorders, and ingestion of large amounts usually causes fatal collapse.

The initial symptoms of exposure are headache, dullness and reduced blood pressure; these may be followed by nausea, vomiting with consequent fatigue and weight loss, cyanosis and central nervous disorders that may be as intense as acute mania. In cases of severe poisoning, confusion, pugnaciousness, hallucinations and maniacal manifestations have been observed. Alcoholic beverages may precipitate poisoning and increase its severity. In chronic poisoning, there are digestive troubles, tremors and neuralgia.

Nitroglycerin may produce moderate irritation at the site of application; eruptions of the palms and interdigital spaces, and ulcers under the nails have been observed in workers handling nitroglycerin.

Chlorinated nitroparaffins. When exposed to heat or flame, chlorinated nitroparaffins are easily decomposed into dangerous fumes such as phosgene and nitrogen oxides. These highly toxic fumes may result in the irritation of mucous membranes and pulmonary damage with varying degrees of acute oedema and death. However, no information about accidental exposures of humans has been reported.

The toxicity of some of the substances has not been clearly elucidated. In general, however, experimental exposures to high concentrations produced damage not only to the respiratory system but also possibly to the liver, kidneys and cardiovascular system. In addition, ingestion has caused congestion of the gastrointestinal tract, and skin irritation resulted from contact with large amounts. No significant reports about chronic local or systemic cases of poisoning in industrial workers have been recorded.

The chlorinated nitroparaffins include chloronitromethane, dichloronitromethane, 1-chloro-1-nitroethane, 1,1-dichloro-1-nitro-ethane, 1-chloro-1-nitropropane, 1-chloro-2-nitropropane, 2-chloro-1-nitropropane and 2-chloro-2-nitropropane.

2-Nitropropane (2-NP)

Studies of humans who were accidentally exposed to 2-NP show that brief exposure to high concentrations may be harmful. One report attributes the death of one worker and liver damage in another to high-level exposures to 2-NP that occurred while they painted the inside of a tank. They had used a zinc-epoxy paint diluted with 2-NP and ethylglycol (2-ethoxyethanol). Another report describes the deaths of four men who were working in confined spaces with paint, surface coating, and polyester-based resin products containing 2-NP. All four workers had liver damage and destruction of hepatocytes. The authors attributed the deaths to overexposure to 2-NP but admitted that other solvents might have played a role since 2-NP was not identified by toxicological analysis. Continuing exposure to concentrations of 20 to 45 ppm of 2-NP caused nausea, vomiting, diarrhoea, anorexia and severe headaches in workers in one plant. In another instance toxic hepatitis developed in construction workers applying epoxy resins to the walls of a nuclear power plant. Although the hepatitis was attributed to a known hepatoxin, p,p'-methylenedianiline (4,4'-diaminodiphenylmethane), it could also have resulted from the 2-NP that the men used to wash the epoxy resins from their skin.

Workers may not be able to detect 2-NP by its odour, even in the presence of potentially hazardous concentrations. One report states that humans cannot detect 2-NP at 83 ppm by its odour. Another states that 2-NP cannot be detected by odour until the concentration is about 160 ppm. However, in 1984 one study did report odor detection at 3.1 and 5 ppm.

Carcinogenicity studies. 2-NP is carcinogenic in rats. Studies have shown that exposure to 100 ppm of 2-NP for 18 months (7 hours per day, 5 days per week) resulted in destructive liver changes and hepatocellular carcinoma in some males. Increasing the exposure to 2-NP resulted in increased incidence in liver cancer and more rapid liver damage. In 1979 an epidemiological study of 1,481 workers in a chemical company exposed to 2-NP was reported. The authors conclude that “analysis of these data does not suggest any unusual cancer or other disease mortality pattern among this group of workers”. They appropriately note, however, that “both because the cohort is small and because the period of latency is, for most, relatively short, one cannot conclude from these data that 2-NP is non-carcinogenic in humans”.

There are, in addition, a number of unexplained findings with respect to cancer mortality observed among employees whom the company has classified as not exposed to 2-NP. When the mortality figures for all males, regardless of exposure category, are combined, there were four deaths from lymphatic cancer where only one was expected. Among the total of 147 female employees there were eight deaths from all causes compared to 2.9 expected deaths, and four deaths from cancer compared to 0.8 expected. Finally, the authors report that seven deaths from sarcomas, which is a relatively rare form of malignancy, were observed in the small study cohort. This number seems unusually high. However, it was not possible to generate an expected number of deaths for comparison to determine statistically if the sarcomatous cancers were in excess, because as a category they cannot be broken out in the standard method of reporting and classifying deaths. In short, there is no direct evidence to date that 2-NP is carcinogenic in humans. By 1982 the IARC had concluded that there was “sufficient evidence” for 2-NP as a carcinogen in rats; at the same time the ACGIH classified it as a suspected human carcinogen. Currently it is classified as an A3 carcinogen (carcinogenic in animals).

Safety and Health Measures

The most important methods of technical control to prevent hazards are general or local exhaust ventilation. General ventilation entails dilution of contaminated air with fresh air by fans or blowers in the working environment. Local exhaust ventilation usually means removal of the contaminants from the environments where harmful fumes are generated. The working room concentration should be maintained below the exposure limits by using both of these methods.

If it is not possible to reduce excessive amounts of contaminants in the air by only the ventilation methods, enclosure of a process or segregation of personnel is recommended. Apparatus in which aliphatic nitro-compounds are produced or processed should be of the sealed type. Workers should be provided with respiratory protective equipment and skin protection. Measures against fires and explosions are also necessary. General medical supervision, including periodic medical examination of workers, is also recommended.

Where possible, chloropicrin should be replaced by a less toxic chemical. Where there is a risk of exposure (e.g., in soil fumigation), workers should be adequately protected by wearing suitable chemical eye protection, respiratory protective equipment preferably of the supplied-air type and, in the case of high concentrations, protective clothing to prevent skin exposure. Particular care should be taken during mixing and dilution of chloropicrin; greenhouses in which soil has been treated should be clearly labelled and entry of unprotected persons prevented.

The prime consideration in the production and use of EGDN is the prevention of explosions; it is consequently necessary to adopt the same safety measures as those employed in the manufacture of nitroglycerin and in the explosives industry as a whole. Considerable progress in this respect has been achieved by remote control (by optical, mechanical or electronic means) of the most dangerous operations (in particular milling) and by the automation of numerous processes such as nitration, mixing, cartridge filling and so on. Arrangements of this type also have the advantage of reducing to a minimum both the number of workers exposed to direct contact with EGDN and the related exposure times.

In cases where workers are still exposed to EGDN, a variety of safety and health measures are necessary. In particular, the concentration of EGDN in the explosives mixture should be reduced depending on the ambient temperature, and—in temperate-climate countries—it should not exceed 20 to 25% EGDN; during the warm season, it may be appropriate to exclude EGDN completely. However, too frequent changes in the EGDN concentration should be avoided in order to prevent an increased frequency of withdrawals. In order to reduce the inhalation hazard, it is necessary to control the atmospheric concentration at the workplace by means of general ventilation and, if necessary, air induction, since local exhaust ventilation may entail an explosion hazard.

Skin absorption may be reduced by the adoption of suitable working methods and the use of protective clothing, including polyethylene hand protection; neoprene, rubber and leather are easily penetrated by nitroglycol and cannot provide adequate protection. The employer should assure that the equipment is washed at least twice per week. Personal hygiene should be encouraged, and workers should shower at the end of each shift. A sulphite indicator soap could detect any residual traces of nitroglycerin/EGDN mixture on the skin; work clothing should be completely separated from personal clothing. Respiratory protective equipment may be necessary under certain circumstances (such as work in confined areas).

During the production of nitroglycerin it is essential to apply the measures needed for handling explosive materials, as discussed elsewhere in the Encyclopaedia. Special attention should be paid to effective control of the nitration process, which involves a highly exothermic reaction. Nitration vessels should be fitted with cooling coils or similar devices, and it must be possible to drown the charge completely in the event of a dangerous situation developing. No exposed glass or metal should be used in the plant, and electrically operated equipment is normally excluded.

Where possible, the process should be fully automated, with remote control and closed-circuit television supervision. Where persons are required to work with nitroglycerin, local exhaust ventilation backed up by good general ventilation should be installed. Each worker should be provided with at least three complete sets of working clothes, including headwear, which should be laundered by the employer. These clothes should be changed at least at the beginning of each shift; on no account should trouser legs or tunic sleeves be turned back, and only approved shoes in good condition should be worn. Nitroglycerin will penetrate thin rubber; consequently, hand protection should be made from nylon or polyethylene with a sweat-absorbent cotton liner.

Where unduly high atmospheric concentrations of nitroglycerin may be suspected, workers should wear respiratory protective equipment, and workers cleaning tally bowls, hall machines and drag belt pits should be equipped with an airline respirator. Under no circumstances should food, beverages or tobacco products be allowed into the workplace, and careful washing is necessary before meals.

2-Nitropropane should be handled in the workplace as a potential human carcinogen.

Medical prevention. This includes a pre-placement examination dealing with the general state of health, the cardiovascular system (electrocardiographic examination at rest and during exercise is essential), neurological system, urine and blood. Persons with systolic pressure higher than 150 or lower than 100 mm Hg or diastolic pressure higher than 90 or lower than 60 mm Hg should not in principle be considered fit for occupational exposure to nitroglycol. It is inadvisable for pregnant women to be exposed. In addition to periodic examinations, examination of workers returning to work after lengthy absence due to illness is necessary. The electrocardiogram should be repeated at least once a year.

All workers suffering from cardiac diseases, hypertension, hepatic disorders, anaemia or neurological disorders, especially of the vasomotor system, should not be exposed to nitroglycerin/EGDN mixtures. It is also advisable to move to other jobs all workers who have been employed for more than 5 to 6 years on dangerous work, and to avoid too frequent a change in the intensity of exposure.

Aliphatic nitrocompounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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