Table of Contents

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 00:27

Boranes

Uses

Boron and boranes have varied functions in the electronics, metalworking, chemical, pulp and paper, ceramics, textile and construction industries. In the electronics industry, boron, boron tribromide and boron trichloride are used as semiconductors. Boron is an igniter in radio tubes and a degasifying agent in metallurgy. It is also used in pyrotechnic flares. Diborane, pentaborane and decaborane are utilized in high-energy fuel. Boron trichloride, diborane and decaborane are rocket propellants, and triethylboron and boron serve as igniters for jet and rocket engines. ¹⁰Boron is employed in the nuclear industry as a constituent of neutron-shielding material in reactors.

In the metalworking industry, many of the boranes are used in welding and brazing. Other compounds are employed as flame retardants and as bleaching agents in the textile, paper and pulp, and paint and varnish industries. Boron oxide is a fire-resistant additive in paints and varnishes, while sodium tetraborate, borax and trimethyl borate are fireproofing agents for textile goods. Both borax and sodium tetraborate are used for the fireproofing and artificial aging of wood. In the construction industries, they are components of fibreglass insulation. Sodium tetraborate also serves as an algicide in industrial water and as an agent in the tanning industry for curing and preserving skins. Borax is a germicide in cleaning products, a corrosion inhibitor in antifreeze, and a powdered insecticide for crack and crevice treatment of food-handling areas. Decaborane is a rayon delustrant and a mothproofing agent in the textile industry, and sodium borohydride is a bleaching agent for wood pulp.

In the ceramics industry, boron oxide and borax are found in glazes, and sodium tetraborate is a component of porcelain enamels and glazes. Sodium perborate is employed for bleaching textile goods and for electroplating. It is used in soaps, deodorants, detergents, mouthwash and vat dyes. Boron trifluoride is used in food packaging, electronics, and in the nuclear industry’s breeder reactors.

Health Hazards

Boron is a naturally occurring substance that is commonly found in food and drinking water. In trace amounts it is essential to the growth of plants and certain types of algae. Although it is also found in human tissue, its role is unknown. Boron is generally regarded as safe (GRAS) for use as an indirect food additive (e.g., in packaging), but compounds containing boron can be highly toxic. Boron is present in a number of industrially useful compounds, including borates, boranes and boron halides.

Boron toxicity in humans is seen most commonly following chronic use of medicines containing boric acid and in cases of accidental ingestion, especially among young children. Occupational toxicity usually results from exposure of the respiratory system or open skin wounds to dusts, gases or vapours of boron compounds.

Acute irritation of eyes, skin and the respiratory tract can follow contact with almost any of these materials in usual concentrations. Absorption can affect the blood, respiratory tract, digestive tract, kidneys, liver and central nervous system; in severe cases, it can result in death.

Boric acid is the most common of the borates, which are compounds of boron, oxygen and other elements. Acute exposure to boric acid in liquid or solid forms can cause irritation, the severity of which is determined by the concentration and duration of exposure. Inhalation of borate dusts or mists can directly irritate the skin, eyes and respiratory system.

Symptoms of this irritation include eye discomfort, dry mouth, sore throat and productive cough. Workers usually report these symptoms after acute boric acid exposures over
10 mg/m³; however, chronic exposures of less than half this can also cause irritant symptoms.

Workers exposed to borax (sodium borate) dust have reported chronic productive cough, and, in those who have experienced long exposures, obstructive abnormalities have been detected, though it is unclear whether these are related to exposure.

Borates are readily absorbed through open skin wounds and from the respiratory and digestive tracts. After absorption borates exert predominant actions upon the skin, central nervous system and digestive tract. Symptoms generally develop rapidly, but may take hours to evolve following skin exposures. Following absorption, the skin or mucous membranes may develop abnormal redness (erythema), or surface tissue may be shed. Chronic exposure may cause eczema, patchy hair loss and swelling around the eyes. These dermatologic effects may take days to develop after exposure. The individual may experience abdominal pain, nausea, vomiting and diarrhoea. Vomitus and diarrhoea may be blue-green in colour and may contain blood. Headache, excitement or depression, seizures, lethargy and coma may develop.

In instances of acute poisoning, anaemia, acidosis and dehydration develop, accompanied by rapid, weak pulse and low blood pressure. These effects may be followed by irregular heart rhythm, shock, kidney failure and, in rare cases, liver damage. Victims appear pale, sweaty and acutely ill. Most of these severe findings have been present just before death from acute borate toxicity. However, when victims are diagnosed and treated in time, the effects usually are reversible.

The reproductive effects of borates are still unclear. Boric acid exposure inhibited sperm motility in rats and, at higher levels, led to testicular atrophy. Animal and tissue studies of genotoxicity have been negative, but infertility has been demonstrated in both males and females after chronic boric acid feedings. Offspring have shown delayed and abnormal development including abnormal rib development. In humans, there is only suggestive evidence of decreased fertility among the few workers who have been evaluated in uncontrolled studies.

Boron trihalides—boron trifluoride, boron chloride and boron bromide—can react violently with water, liberating hydrogen halides such as hydrochloric and hydrofluoric acids. Boron trifluoride is a severe irritant of the lungs, eyes and skin. Animals studied after lethal exposures showed kidney failure and kidney tubule damage, pulmonary irritation and pneumonia. Examinations of a small number of exposed workers showed some decreases in pulmonary function, but it was unclear whether these were related to exposure.

Boranes (boron hydrides)—diborane, pentaborane and decaborane—are extremely reactive compounds which can explode on contact with oxygen or oxidizing agents. As a group they are severe irritants which can quickly cause chemical pneumonia, pulmonary oedema and other respiratory injuries. In addition, boranes have been reported to cause seizures and neurological damage with long-lasting neurological deficits and psychological symptoms. These compounds must be handled with extreme caution.

There is no evidence of boron or the borates causing cancer in chronic experiments with animals or in studies of exposed humans.

Boranes tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 00:34

Cyano Compounds

This class of compounds is characterized by the presence of a C=N (cyano) group and includes the cyanides and nitriles (R–C=N) as well as related chemicals such as cyanogens, isocyanates and cyanamides. They primarily owe their toxicity to the cyanide ion, which is capable of inhibiting many enzymes, especially cytochrome oxidase, when released in the body. Death, which may be more or less rapid depending on the rate at which the cyanide ion is released, results from chemical asphyxia at the cellular level.

Inorganic Cyanides

Inorganic cyanides are readily hydrolyzed by water and decomposed by carbon dioxide and mineral acids to form hydrogen cyanide, which can also be produced by certain naturally occurring bacteria. Hydrogen cyanide is evolved in coke and steel-making, and can be generated in fires where polyurethane foam is incinerated (e.g., furniture, partitions and so on). It can be generated accidentally by the action of acids on cyanide-containing wastes (lactonitrile evolves hydrocyanic acid when in contact with an alkali, for example.), and intentionally in gas chambers for capital punishment, where cyanide pellets are dropped into bowls of acid to create a lethal atmosphere.

Nitriles

Nitriles (also called organic cyanides) are organic compounds which contain a cyano group
(–C=N) as the characteristic functional group and have the generic formula RCN. They may be regarded as hydrocarbon derivatives wherein three hydrogen atoms attached to a primary carbon are replaced by a nitrilo group, or as derivatives of carboxylic acids (R—COOH) in which the oxo and hydroxyl radicals are replaced by a nitrilo group (R—C=N). Upon hydrolysis, they yield an acid which contains the same number of carbon atoms and which, therefore, is usually named by analogy with the acid rather than as a derivative of hydrogen cyanide. They are very dangerous when heated to decomposition because of the release of hydrogen cyanide.

Saturated aliphatic nitriles up to C₁₄ are liquids having a rather pleasant odour like the ethers. Nitriles of C₁₄ and higher are odourless solids and generally colourless. Most nitriles will boil without decomposition at temperatures lower than those for the corresponding acids. They are extremely reactive compounds and are used extensively as intermediates in organic synthesis. They are widely used starting materials in the synthesis of various fatty acids, pharmaceuticals, vitamins, synthetic resins, plastics and dyes.

Uses

The inorganic cyano compounds have varied uses in the metal, chemical, plastics and rubber industries. They are utilized as chemical intermediates, pesticides, metal cleaners, and as agents for extracting gold and silver from ores.

Acryonitrile (vinyl cyanide, cyanoethylene, propene nitrile), a flammable and explosive colourless liquid, is found in surface coatings and adhesives and is used as a chemical intermediate in the synthesis of antioxidants, pharmaceuticals, pesticides, dyes and surface-active agents.

Calcium cyanamide (nitrolim, calcium carbimide, cyanamide) is a blackish-grey, shiny powder used in agriculture as a fertilizer, herbicide, pesticide and a defoliant for cotton plants. It is also used in steel hardening and as a desulphurizer in the iron and steel industry. In industry, calcium cyanamide is used for the manufacture of calcium cyanide and dicyandiamide, the raw material for melamine.

Cyanogen, cyanogen bromide and cyanogen chloride are used in organic syntheses. Cyanogen is also a fumigant and a fuel gas for welding and cutting heat-resistant metals. It is a rocket or missile propellant in mixtures with ozone or fluorine; and it may also be present in blast furnace emissions. Cyanogen bromide is utilized in textile treatment, as a fumigant and pesticide, and in gold extraction processes. Cyanogen chloride serves as a warning agent in fumigant gases.

Hydrogen cyanide finds use in the manufacture of synthetic fibres and plastics, in metal polishes, electroplating solutions, metallurgical and photographic processes, and in the production of cyanide salts. Sodium cyanide and potassium cyanide are used in electroplating, steel hardening, extraction of gold and silver from ores, and in the manufacture of dyes and pigments. In addition, sodium cyanide functions as a depressant in the froth flotation separation of ores.

Potassium ferricyanide (red prussiate of potash) is used in photography and in blueprints, metal tempering, electroplating and pigments. Potassium ferrocyanide (yellow prussiate of potash) is used in the tempering of steel and in process engraving. It is employed in the manufacture of pigments and as a chemical reagent.

Calcium cyanide, malononitrile, acetone cyanohydrin (2-hydroxy-2-methylproprionitrile), cyanamide and acrylonitrile are other useful compounds in the metal, plastics, rubber and chemical industries. Calcium cyanide and malononitrile are leaching agents for gold. In addition, calcium cyanide is used as a fumigant, a pesticide, a stabilizer for cement, and in the manufacture of stainless steel. Acetone cyanohydrin is a complexing agent for metal refining and separation, and cyanamide is used in metal cleaners, the refining of ores and the production of synthetic rubber. Ammonium thiocyanate is used in the match and photography industries and for double-dyeing fabrics and improving the strength of silks weighted with tin salts. It is a stabilizer for glues, a tracer in oil fields, and an ingredient in pesticides and liquid rocket propellants. Potassium cyanate serves as a chemical intermediate and as a weed killer.

Some of the more important organic nitriles in industrial use include acryonitrile (vinyl cyanamide, cyanethylene, propene nitrile), acetonitrile, (methyl cyanamide, ethanenitrile, cyanomethane), ethylene cyanohydrin, proprionitrile (ethyl cyanide), lactonitrile, glycolonitrile (formaldehyde cyanohydrin, hydroxyacetonitrile, hydroxymethylcyanide, methylene cyanohydrin), 2-methyl-lactonitrile, and adiponitrile.

Hazards

Cyanide compounds are toxic to the extent that they release the cyanide ion. Acute exposure can cause death by asphyxia, as the result of exposure to lethal concentrations of hydrogen cyanide (HCN) whether by inhalation, ingestion or percutaneous absorption; in the last case, however, the dose required is higher. Chronic exposure to cyanides at levels too low to produce such serious symptoms may cause a variety of problems. Dermatitis, often accompanied by itching, an erythematous rash and papules, has been a problem for workers in the electroplating industry. Severe irritation of the nose may lead to obstruction, bleeding, sloughs and, in some cases, perforation of the septum. Among fumigators, mild cyanide poisoning has been recognized as the cause of symptoms of oxygen starvation, headache, rapid heart rate, and nausea, all of which were completely reversed when the exposure ceased.

Chronic systemic cyanide poisoning may occur, but is rarely recognized because of the gradual onset of the disability, and symptoms which are consistent with other diagnoses. It has been suggested that excessive thiocyanate in extracellular fluids might explain chronic illness due to cyanide, since the symptoms reported are similar to those found when thiocyanate is used as a drug. Symptoms of chronic disease have been reported in electroplaters and silver polishers after several years of exposure. The most prominent were motor weakness of arms and legs, headaches and thyroid diseases; these findings have also been reported as complications of thiocyanate therapy.

Toxicity

Cyanides

The cyanide ion of soluble cyanide compounds is rapidly absorbed from all routes of entry—inhalation, ingestion and percutaneous. Its toxic properties result from its ability to form complexes with heavy metal ions which inhibit the enzymes required for cellular respiration, primarily cytochrome oxidase. This prevents the uptake of oxygen by the tissues, causing death by asphyxia. The blood retains its oxygen, producing the characteristic cherry-red colour of the victims of acute cyanide poisoning. Cyanide ions combine with the approximately 2% of methaemoglobin normally present—a fact that has helped to develop the treatment of cyanide poisoning.

If the initial dose is not fatal, part of the cyanide dose is exhaled unchanged, while rhodanase, an enzyme widely distributed in the body, converts the remainder to the much less harmful thiocyanate, which remains in extracellular body fluids until it is excreted in the urine. Urinary levels of thiocyanate have been used to measure the extent of the intoxication, but they are non-specific and are elevated in smokers. There may be an effect on thyroid function due to the affinity of thiocyanate ion for iodine.

There are variations in the biological effects of the compounds in this group. At low concentrations, hydrogen cyanide (hydrocyanic acid, prussic acid) and the halogenated cyanide compounds (i.e., cyanogen chloride and bromide) in vapour form produce irritation of the eyes and the respiratory tract (the respiratory effects, including pulmonary oedema, may be delayed). Systemic effects include weakness, headaches, confusion, nausea and vomiting. In mild cases, the blood pressure remains normal despite increase in the pulse rate. The respiratory rate varies with the intensity of exposure—rapid with mild exposure, or slow and gasping with severe exposure.

Nitriles

The toxicity of nitriles varies greatly with their molecular structure, ranging from comparatively non-toxic compounds (e.g., the saturated fatty acid nitriles) to highly toxic materials, such as α-aminonitriles and α-cyanohydrins, which are considered to be as toxic as hydrocyanic acid itself. The halogenated nitriles are highly toxic and irritant, and cause considerable lacrimation. Nitriles such as acrylonitrile, propionitrile and fumaronitrile are toxic and may cause severe and painful dermatitis in exposed skin.

Exposure to toxic nitriles may rapidly cause death by asphyxiation similar to that resulting from exposure to hydrogen cyanide. Individuals who survived exposure to high concentrations of nitriles were said to have no evidence of residual physiological effects after the recovery from the acute episode; this has led to the opinion that the person either succumbs to the nitrile exposure or recovers completely.

Medical surveillance should include pre-employment and periodic examinations focused on skin disorders and the cardiovascular, pulmonary and central nervous systems. A history of fainting spells or convulsive disorders might present an added risk for nitrile workers.

All nitriles should be handled under carefully controlled conditions and only by personnel having a thorough understanding and knowledge of safe handling techniques. Leather should not be used for protective garments, gloves and footwear, since it may be penetrated by acryonitrile and other similar compounds; rubber protective equipment should be washed and inspected frequently to detect swelling and softening. The eyes should be protected, proper respirators worn, and all splashes immediately and thoroughly washed away.

Acrylonitrile. Acrylonitrile is a chemical asphyxiant like hydrogen cyanide. It is also an irritant, affecting the skin and mucous membranes; it may cause severe corneal damage in the eye if not rapidly washed away by copious irrigation. IARC has classified acrylonitrile as a Group 2A carcinogen: the agent is probably carcinogenic to humans. The classification is based on limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in animals.

Acrylonitrile may be absorbed by inhalation or through the skin. In gradual exposures, victims may have significant levels of cyanide in the blood before symptoms appear. They derive from tissue anoxia and include, roughly in order of onset, limb weakness, dyspnoea, burning sensation in the throat, dizziness and impaired judgement, cyanosis and nausea. In the later stages, collapse, irregular breathing or convulsions and cardiac arrest may occur without warning. Some patients appear hysterical or may even be violent; any such deviations from normal behaviour should suggest acryonitrile poisoning.

Repeated or prolonged skin contact with acrylonitrile may produce irritation after hours of no apparent effect. Since acrylonitrile is readily absorbed into leather or clothing, blistering may appear unless the contaminated articles are removed promptly and the underlying skin washed. Rubber clothing should be inspected and washed frequently because it will soften and swell.

An important hazard is fire and explosion. The low flashpoint indicates that sufficient vapour is evolved at normal temperatures to form a flammable mixture with air. Acrylonitrile has the ability to polymerize spontaneously under the action of light or heat, which may lead to explosion even when it is kept in closed containers. It must therefore never be stored uninhibited. The danger of fire and explosion is intensified by the lethal nature of the fumes and vapours evolved, such as ammonia and hydrogen cyanide.

Calcium cyanamide. Calcium cyanamide is encountered chiefly as a dust. When inhaled, it will cause rhinitis, pharyngitis, laryngitis and bronchitis. Perforation of the nasal septum has been reported after long exposure. In the eyes, it may cause conjunctivitis, keratitis and corneal ulceration. It may cause an itchy dermatitis which, after a time, may present slowly-healing ulcerations on the palms of the hand and between the fingers. Skin sensitization may occur.

Its most notable systemic effect is a characteristic vasomotor reaction featuring diffuse erythema of the body, face and arms which may be accompanied by fatigue, nausea, vomiting, diarrhoea, dizziness and sensations of cold. In severe cases, circulatory collapse may ensue. This vasomotor reaction may be triggered or exaggerated by consumption of alcohol.

In addition to adequate exhaust ventilation and personal protective equipment, a waterproof barrier cream may provide added protection for face and exposed skin. Good personal hygiene, including showers and changes of clothing after each shift, is important.

Cyanates. Some of the more important cyanates in industrial use include sodium cyanate, potassium cyanate, ammonium cyanate, lead cyanate and silver cyanate. Cyanates of such elements as barium, boron, cadmium, cobalt, copper, silicon, sulphur and thallium may be prepared by reactions between solutions of a cyanate and the corresponding salt of the metal. They are dangerous because they release hydrogen cyanide when heated to decomposition or when in contact with acid or acid fumes. Personnel handling these materials should be provided with respiratory and skin protection.

Sodium cyanate is used in organic synthesis, the heat treatment of steel, and as an intermediate in the manufacture of pharmaceuticals. It is considered to be moderately toxic, and workers should be protected against dust inhalation and skin contamination.

Cyanate compounds vary in toxicity; therefore, they should be handled under controlled conditions, taking standard precautions to protect personnel against exposure. When heated to decomposition or when placed in contact with acid or acid fumes, the cyanates emit highly toxic fumes. Adequate ventilation must be provided, and air quality at the worksite should be closely monitored. Personnel should not inhale contaminated air nor allow skin contact with these materials. Good personal hygiene is essential for those working in areas where such compounds are handled.

Safety and Health Measures

Scrupulous attention to proper ventilation is necessary. Complete enclosure of the process is recommended, with supplementary exhaust ventilation available. Warning signs should be posted near entrances to areas in which hydrogen cyanide may be released into the air. All shipping and storage containers for hydrogen cyanide or cyanide salts should bear a warning label that included instructions for first aid; they should be in a well-ventilated area and handled with great care.

Those working with cyanide salts should fully understand the hazard. They should be trained to recognize the characteristic odour of hydrogen cyanide and to evacuate the work area immediately if it is detected. Workers entering a contaminated area must be supplied with air-supplied or self-contained respirators with canisters specific for cyanides, goggles if full-face masks are not worn, and impervious protective clothing.

For those who work with acrylonitrile, the usual precautions for carcinogens and for highly flammable liquids are necessary. Steps must be taken to eliminate the risk of ignition from sources such as electrical equipment, static electricity and friction. Because of the toxic, as well as the flammable, nature of the vapour, its escape into the worksite air must be prevented by enclosure of the process and exhaust ventilation. Continuous monitoring of the workplace air is necessary to ensure that these engineering controls remain effective. Personal respiratory protection, preferably of the positive pressure type, and impermeable protective clothing are necessary when there is a possibility of exposure, as from a normal but non-routine operation such as a pump replacement. Leather should not be used for protective clothing since it is readily penetrated by acrylonitrile; rubber and other types of clothing should be inspected and washed frequently.

Acrylonitrile workers should be educated about the chemical’s dangers and trained in rescue, decontamination, life-support procedures and the use of amyl nitrate. Skilled medical attention is required in emergencies; principal requirements are an alarm system and plant personnel trained to support the activities of the health professionals. Supplies of specific antidotes should be available on site and at adjacent hospital centres.

Medical surveillance of workers potentially exposed to cyanides should focus on the respiratory, cardiovascular and central nervous systems; liver, kidney and thyroid function; condition of the skin; and a history of fainting or dizzy spells. Workers with chronic diseases of the kidneys, respiratory tract, skin or thyroid are at greater risk of developing toxic cyanide effects than healthy workers.

Medical control requires training in artificial resuscitation and the use of drugs prescribed for emergency treatment of acute poisoning (e.g., inhalations of amyl nitrite). As soon as possible, contaminated clothing, gloves and footwear should be removed and the skin washed to prevent continuing absorption. First-aid kits with drugs and syringes should be placed appropriately at hand and checked frequently.

Unfortunately, some widely distributed handbooks suggest that methylene blue is useful in cyanide poisoning because, at certain concentrations, it forms methaemoglobin, which, because of its affinity for the cyanide ion, might reduce the toxic effect. The use of methylene blue is not recommended since at other concentrations it has the reverse effect of converting methaemoglobin to haemoglobin, and analyses to verify that its concentration is appropriate are not feasible under the conditions created by the cyanide emergency.

Treatment

Individuals exposed to toxic levels of nitriles should be immediately removed to a safe area and given amyl nitrite by inhalation. Any indications of respiratory problems would indicate oxygen inhalation and, if necessary, cardiopulmonary resuscitation. Contaminated clothing should be removed and the areas of skin copiously washed. Extended flushing of the eyes with neutral solutions or water is advised if there is lacrimation or any evidence of conjunctival irritation. Properly trained physicians, nurses and emergency medical technicians should be summoned to the scene promptly to administer definitive treatment and keep the victim under close observation until recovery is complete.

Cyano compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 00:39

Epoxy Compounds

Epoxy compounds are those that consist of oxirane rings (either one or more). An oxirane ring is essentially one oxygen atom linked to two carbon atoms. These will react with amino, hydroxyl and carboxyl groups as well as inorganic acids to yield relatively stable compounds.

Uses

Epoxy compounds have found wide industrial use as chemical intermediates in the manufacture of solvents, plasticizers, cements, adhesives and synthetic resins. They are commonly used in various industries as protective coatings for metal and wood. The alpha-epoxy compounds, with the epoxy group (C-O-C) in the 1,2 position, are the most reactive of the epoxy compounds and are primarily used in industrial applications. The epoxy resins, when converted by curing agents, yield highly versatile, thermosetting materials used in a variety of applications including surface coatings, electronics (potting compounds), laminating, and bonding together of a wide variety of materials.

Butylene oxides (1,2-epoxybutane and 2,3-epoxybutane) are used for the production of butylene glycols and their derivatives, as well as for the manufacture of surface active agents. Epichlorohydrin is a chemical intermediate, insecticide, fumigant and solvent for paints, varnishes, nail enamels and lacquers. It is also used in polymer coating material in the water supply system and in raw material for high wet-strength resins for the paper industry. Glycidol (or 2,3-epoxypropanol) is a stabilizer for natural oils and vinyl polymers, a dye-leveling agent and an emulsifier.

1,2,3,4-Diepoxybutane. Short-term (4-hour) inhalation studies with rats have caused watering of the eyes, clouding of the cornea, laboured breathing and lung congestion. Experiments in other animal species have demonstrated that diepoxybutane, like many of the other epoxy compounds, can cause eye irritation, burns and blisters of the skin, and irritation of the pulmonary system. In humans, accidental “minor” exposure caused swelling of the eyelids, upper respiratory tract irritation, and painful eye irritation 6 hours after exposure.

Skin application of D,L- and the meso- forms of 1,2,3,4-diepoxybutane have produced skin tumours, including squamous-cell skin carcinomas, in mice. The D- and L- isomers have produced local sarcomas in mice and rats by subcutaneous and intraperitoneal injection respectively.

Several epoxy compounds are employed in the health care and food industries. Ethylene oxide is used to sterilize surgical instruments and hospital equipment, fabric, paper products, sheets and grooming instruments. It is also a fumigant for foodstuffs and textiles, a rocket propellant, and a growth accelerator for tobacco leaves. Ethylene oxide is used as an intermediary in the production of ethylene glycol, polyethylene terephthalate polyester film and fibre, and other organic compounds. Guaiacol is a local anaesthetic agent, antioxidant, stimulant expectorant, and a chemical intermediate for other expectorants. It is used as a flavouring agent for non-alcoholic beverages and food. Propylene oxide, or 1,2-epoxypropane, has been used as a fumigant for the sterilization of packaged food products and other materials. It is a highly reactive intermediary in the production of polyether polyols, which, in turn, are used to make polyurethane foams. The chemical is also used in the production of propylene glycol and its derivatives.

Vinylcyclohexene dioxide is used as a reactive diluent for other diepoxides and for resins derived from epichlorohydrin and bisphenol A. Its use as a monomer for the preparation of polyglycols containing free epoxide groups or for polymerization to a tridimensional resin has been investigated.

Furfural is used in screening tests for urine, solvent refining of petroleum oils, and manufacturing of varnishes. It is a synthetic flavouring agent, a solvent for nitrated cotton, a constituent of rubber cements, and a wetting agent in the manufacture of abrasive wheels and brake linings. Furfuryl alcohol is also a flavouring agent, as well as a liquid propellant and solvent for dyes and resins. It is used in corrosive-resistant sealants and cements, and foundry cores. Tetrahydrofuran is used in histology, chemical synthesis, and in the fabrication of articles for packaging, transporting and storing foods. It is a solvent for fat oils and unvulcanized rubber. Diepoxybutane has been used to prevent spoilage of foodstuffs, as a polymer curing agent, and for cross-linking textile fibres.

Hazards

There are numerous epoxy compounds in use today. Specific commonly used ones are individually discussed below. There are, however, certain characteristic hazards shared by the group. In general, the toxicity of a resin system is a complicated interplay between the individual toxicities of its various component ingredients. The compounds are known sensitizers of the skin, and those with the highest sensitization potential are those of lower relative molecular weight. Low molecular weight is also generally associated with increased volatility. Delayed and immediate allergic epoxy dermatitis and irritant epoxy dermatitis have all been reported. The dermatitis usually first develops on the hands between the digits, and can range in severity from erythema to marked bullous eruption. Other target organs reportedly adversely affected by epoxy compound exposure include the central nervous sysstem (CNS), the lungs, the kidneys, the reproductive organs, the blood and the eyes. There is also evidence that certain epoxy compounds have mutagenic potential. In one study, 39 of the 51 epoxy compounds tested induced a positive response in the Ames/Salmonella assay. Other epoxides have been shown to induce sister-chromatid exchanges in human lymphocytes. Animal studies looking at associated epoxide exposures and cancers are ongoing.

It should be noted that certain of the curing agents, hardeners and other processing agents used in the production of the final compounds have associated toxicities as well. One in particular, 4,4-methylenedianiline (MDA), is associated with hepatotoxicity and with damage to the retina of the eye, and has been known to be an animal carcinogen. Another is trimellitic anhydride (TMA). Both are discussed elsewhere in this chapter.

One epoxy compound, epichlorohydrin, has been reported to cause a significant increase of pulmonary cancer in exposed workers. This chemical is classified as a Group 2A chemical, probably carcinogenic to humans, by the International Agency for Research on Cancer (IARC). One long-term epidemiological study of workers exposed to epichlorohydrin at two US facilities of the Shell Chemical Company was reported to demonstrate a statistically significant (p < .05) increase in deaths due to respiratory cancer. Like the other epoxy compounds, epichlorohydrin is irritating to the eyes, skin and respiratory tract of exposed individuals. Human and animal evidence has demonstrated that epichlorohydrin may induce severe skin damage and systemic poisoning following extended dermal contact. Exposures to epichlorohydrin at 40 ppm for 1 h have been reported to cause eye and throat irritation lasting 48 h, and at 20 ppm caused temporary burning of the eyes and nasal passages. Epichlorohydrin-induced sterility in animals has been reported, as have liver and kidney damage.

Subcutaneous injection of epichlorohydrin has produced tumours in mice at the injection site but has not produced tumours in mice by skin-painting assay. Inhalation studies with rats have shown a statistically significant increase in nasal cancer. Epichlorohydrin has induced mutations (base-pair substitution) in microbial species. Increases in the chromosomal aberrations found in the white blood cells of workers exposed to epichlorohydrin have been reported. As of 1996 the American Conference of Governmental Industrial Hygienists (ACGIH) established a TLV of 0.5 ppm, and it is considered an A3 carcinogen (animal carcinogen).

1,2-Epoxybutane and isomers (butylene oxides). These compounds are less volatile and less toxic than propylene oxide. The major documented adverse effects in humans have been irritation of the eyes, nasal passages and skin. In animals, however, respiratory problems, pulmonary haemorrhage, nephrosis and nasal-cavity lesions were noted in acute exposures to very high concentrations of 1,2-epoxybutane. No consistent teratogenic effects have been demonstrated in animals. IARC has determined that there is limited evidence for the carcinogenicity of 1,2-epoxybutane in experimental animals.

When 1,2-epoxypropane (propylene oxide) is compared to ethylene oxide, another epoxy compound commonly used in sterilization of surgical/hospital supplies, propylene oxide is considered to be far less toxic to humans. Exposure to this chemical has been associated with irritant effects on the eyes and skin, respiratory tract irritation, and CNS depression, ataxia, stupor and coma (the latter effects have thus far been significantly demonstrated only in animals). In addition, 1,2-epoxypropane has been shown to act as a direct alkylating agent in various tissues, and thus the possibility of carcinogenic potential is raised. Several animal studies have strongly implicated the compound’s carcinogenicity as well. The major adverse effects which have thus far been definitively demonstrated in humans involve burning or blistering of the skin when prolonged contact with non-volatilized chemical has occurred. This has been shown to occur even with low concentrations of propylene oxide. Corneal burns attributed to the chemical have also been reported.

Vinylcyclohexene dioxide. The irritation produced by the pure compound after application on rabbit skin resembles the oedema and reddening of first-degree burns. Skin application of vinylcyclohexene dioxide in mice produces a carcinogenic effect (squamous-cell carcinomas or sarcomas); intraperitoneal administration in rats caused analogous effects (sarcomas of the peritoneal cavity). The substance has proved to be mutagenic in Salmonella typhimurium TA 100; it also produced a significant increase in mutations in Chinese hamster cells. It should be treated as a substance with carcinogenic potential, and appropriate engineering and hygienic controls should be in place.

In industrial experience vinylcyclohexene dioxide has been shown to have skin irritant properties and to cause dermatitis: a severe vesiculation of both feet has been observed in a worker who had put on shoes contaminated by the compound. Eye injury is also a definite hazard. Studies on chronic effects are not available.

2,3-Epoxypropanol. Based on experimental studies with mice and rats, glycidol was found to cause eye and lung irritation. The LC50 for a 4-h exposure of mice was found to be 450 ppm, and for an 8-h exposure of rats it was 580 ppm. However, at concentrations of 400 ppm of glycidol, rats exposed for 7 h a day for 50 days showed no evidence of systemic toxicity. After the first few exposures, slight eye irritation and respiratory distress were noted.

Ethylene oxide (ETO) is a highly dangerous and toxic chemical. It reacts exothermically and is potentially explosive when heated or placed in contact with alkali metal hydroxides or highly active catalytic surfaces. Therefore when in use in industrial areas it is best if it is tightly controlled and confined to closed or automated processes. The liquid form of ethylene oxide is relatively stable. The vapour form, in concentrations as low as 3%, is very flammable and potentially explosive in the presence of heat or flame.

A wealth of information exists regarding the possible human health effects of this compound. Ethylene oxide is a respiratory, skin and eye irritant. At high concentrations it is also associated with central nervous system depression. Some individuals exposed to high concentrations of the chemical have described a strange taste in their mouths after the exposure. Delayed effects of high acute exposures include headache, nausea, vomiting, shortness of breath, cyanosis and pulmonary oedema. Additional symptoms that have been reported after acute exposures include drowsiness, fatigue, weakness and incoordination. Ethylene oxide solution can cause a characteristic burn on exposed skin anywhere from 1 to 5 h post-exposure. This burn often progresses from vesicles to coalescent blebs and desquamation. The skin wounds will often spontaneously resolve, with increased pigmentation resulting at the burn site.

Chronic or low-to-moderate prolonged exposures to ethylene oxide are associated with mutagenic activity. It is known to act as an alkylating agent in biological systems, binding to the genetic material and other electron-donating sites, such as haemoglobin, and causing mutations and other functional damage. ETO is associated with chromosomal damage. The ability of damaged DNA to repair itself was adversely affected by low but prolonged exposure to ETO in one study of exposed human subjects. Some studies have linked ETO exposure with increased absolute lymphocyte counts in exposed workers; however, recent studies are not supportive of this association.

The carcinogenic potential of ethylene oxide has been demonstrated in several animal models. IARC has classified ethylene oxide as a Group 1 known human carcinogen. Leukaemia, peritoneal mesothelioma and certain brain tumours have been associated with long-term inhalation of ETO in rats and monkeys. Studies of exposure in mice have linked inhalation exposures to lung cancers and lymphomas. Both the US National Institute for Occupational Safety and Health (NIOSH) and the US Occupational Safety and Health Administration (OSHA) have concluded that ethylene oxide is a human carcinogen. The former conducted a large-scale study of over 18,000 ETO-exposed workers over a 16-year period and determined that the exposed individuals had greater than expected rates of blood and lymph cancers. Subsequent studies have found that no increased rates of these cancers have been associated with exposed workers. One of the major problems with these studies, and a possible reason for their contradictory nature, has been the inability to accurately quantify levels of exposure. For example, much of the available research on human carcinogenic effects of ETO has been done using exposed hospital sterilizer operators. Individuals who worked in these jobs prior to the 1970s most likely experienced higher exposures to ETO gas due to the technology and lack of local control measures in place at that time. (Safeguards in the use of ETO in health care settings are discussed in the Health care facilities and services chapter in this volume.)

Ethylene oxide has also been associated with adverse reproductive effects in both animals and humans. Dominant lethal mutations in reproductive cells have resulted in higher embryonic death rates in the offspring of ETO-exposed male and female mice and rats. Some studies have linked ethylene oxide exposure to increased rates of miscarriage in humans.

Adverse neurological and neuropsychiatric effects resulting from ethylene oxide exposure have been reported in animals and humans. Rats, rabbits and monkeys exposed to 357 ppm of ETO over a period of 48 to 85 days developed impairment of sensory and motor function, and muscle wasting and weakness of the hind limbs. One study found that human workers exposed to ETO demonstrated impaired vibratory sense and hypoactive deep tendon reflexes. The evidence of impaired neuropsychiatric functioning in humans exposed to low but prolonged levels of ethylene oxide is uncertain. Some studies and an increasing body of anecdotal evidence suggest that ETO is linked to CNS dysfunction and cognitive impairment—for example, clouded thinking, memory problems and slowed reaction times on certain types of tests.

One study of individuals exposed to ethylene oxide in a hospital setting suggested an association between that exposure and the development of ocular cataracts.

An additional hazard associated with exposure to ethylene oxide is the potential for the formation of ethylene chlorohydrin (2-chloroethanol), which may be formed in the presence of moisture and chloride ions. Ethylene chlorohydrin is a severe systemic poison, and exposure to the vapour has caused human fatalities.

Tetrahydrofuran (THF) forms explosive peroxides when exposed to air. Explosions may also occur when the compound is brought into contact with lithium-aluminium alloys. Its vapour and peroxides may cause irritation of the mucous membranes and skin, and it is a strong narcotic.

While limited data are available on the industrial experiences with THF, it is interesting to note that investigators that were engaged in animal experiments with this compound complained of severe occipital headaches and dullness after each experiment. Animals subjected to lethal doses of tetrahydrofuran fell into narcosis quickly, which was accompanied by muscular hypotonia and disappearance of corneal reflexes, and followed by coma and death. Single toxic doses caused giddiness, irritation of mucous membranes with copious flow of saliva and mucous, vomiting, a marked fall in blood pressure, and muscular relaxation, followed by prolonged sleep. Generally, the animals recovered from these doses and showed no evidence of biological changes. After repeated exposures, the effects included irritation of the mucous membranes, which may be followed by renal and hepatic alteration. Alcoholic beverages enhance the toxic effect.

Safety and Health Measures

The primary purposes of control measures for the epoxy compounds should be to reduce the potential for inhalation and skin contact. Wherever feasible, control at the source of contamination should be implemented with enclosure of the operation and/or the application 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 sensitization in exposed workers. Preferred respirators include gas masks with organic vapour cannisters and high-efficiency particulate filters or supplied-air respirators. All body surfaces should be protected against contact with epoxy compounds through the use of gloves, aprons, face shields, goggles and other protective equipment and clothing as necessary. Contaminated clothing should be removed as soon as possible and the affected areas of the skin washed with soap and water.

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

The potential fire hazards associated with epoxy compounds suggest that no flames or other sources of ignition, such as smoking, be permitted in areas where the compounds are stored or handled.

Affected workers should, as necessary, be removed from emergency situations, and if the eyes or skin have been contaminated they should be flushed with water. Contaminated clothing should be promptly removed. If exposure is severe, hospitalization and observation for 72 h for delayed onset of severe pulmonary oedema is advisable.

When the epoxy compounds, such as ethylene oxide, are extremely volatile, stringent safeguards should be taken to prevent fire and explosion. These safeguards should include the control of ignition sources, including static electricity; the availability of foam, carbon dioxide or dry chemical fire extinguishers (if water is used on large fires, the hose should be equipped with a fogging nozzle); the use of steam or hot water to heat ethylene oxide or its mixtures; and storage away from heat and strong oxidizers, strong acids, alkalis, anhydrous chlorides or iron, aluminium or tin, iron oxide, and aluminium oxide.

Proper emergency procedures and protective equipment should be available to deal with spills or leaks of ethylene oxide. In case of a spill, the first step is to evacuate all personnel except those involved in the clean-up operations. All ignition sources in the area should be removed or shut down and the area well ventilated. Small quantities of spilled liquid can be absorbed on cloth or paper and allowed to evaporate in a safe place such as a chemical fume hood. Ethylene oxide should not be allowed to enter a confined space such as a sewer. Workers should not enter confined spaces where ethylene oxide has been stored without following proper operating procedures designed to ensure that toxic or explosive concentrations are not present. Whenever possible, ethylene oxide should be stored and used in closed systems or with adequate local exhaust ventilation.

All substances having carcinogenic properties, such as ethylene oxide and vinylcyclohexene dioxide, must be handled with extreme care to avoid contact with the workers’ skin or being inhaled during both production and use. Prevention of contact is also promoted by designing the work premises and process plant so as to preclude any leakage of the product (application of a slight negative pressure, hermetically sealed process and so on). Precautions are discussed more fully elsewhere in this Encyclopaedia.

Epoxy compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Table 3- Physical and chemical hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 00:58

Esters, Acetates

Acetates are derived from a reaction (called esterification) between acetic acid or an anhydrous compound containing an acetate group and the corresponding alcohol, with the elimination of water. Thus methyl acetate is obtained by the esterification of methyl alcohol with acetic acid in the presence of sulphuric acid as a catalyst. The reaction is reversible and must therefore be conducted with heat, eliminating water formed by the reaction. Ethyl acetate is obtained by the direct esterification of ethyl alcohol with acetic acid, a process which involves mixing acetic acid with an excess of ethyl alcohol and adding a small amount of sulphuric acid. The ester is separated and purified by distillation. Ethyl acetate is easily hydrolyzed in water, giving a slightly acid reaction. In another process the molecules of anhydrous acetaldehyde interact in the presence of aluminium ethoxide to produce the ester, which is purified by distillation. Propyl acetate and isopropyl acetate esters are produced by the reaction of acetic acid with the corresponding propyl alcohol in the presence of a catalyst.

Both butyl acetate and amyl acetate consist of mixtures of isomers. Thus butyl acetate comprises n-butyl acetate, sec-butyl acetate and isobutyl acetate. It is made by the esterification of n-butanol with acetic acid in the presence of sulphuric acid. n-Butanol is obtained by the fermentation of starch with Clostridium acetobutylicum. Amyl acetate is primarily a mixture of n-amyl acetate and isoamyl acetate. Its composition and characteristics depend on its grade. The flashpoints of the various grades vary from 17 to 35 °C.

Uses

The acetates are solvents for nitrocellulose, lacquers, leather finishes, paints and plastics. They are also used as flavouring agents and preservatives in the food industry, and fragrances and solvents in the perfume and cosmetics industries. Methyl acetate, generally mixed with acetone and methyl alcohol, is used in the plastics and artificial leather industries, and in the production of perfumes, colouring agents and lacquers. Ethyl acetate is a good solvent for nitrocellulose, fats, varnishes, lacquers, inks and airplane dopes; it is used in the production of smokeless powder, artificial leather, perfumes, photographic films and plates, and artificial silk. It is also a cleaning agent in the textile industry, and a flavouring agent for pharmaceuticals and food.

n-Propyl acetate and isopropyl acetate are solvents for plastics, inks and nitrocellulose in the production of lacquers. They are utilized in the manufacture of perfumes and insecticides, and in organic synthesis. Butyl acetate is a commonly used solvent in the production of nitrocellulose lacquers. It is also used in the manufacture of vinyl resins, artificial leather, photographic film, perfumes, and in the preserving of foodstuffs.

In its commercial form amyl acetate, a mixture of isomers, is used as a solvent for nitrocellulose in the manufacture of lacquers, and, because of its banana-like smell, it is used as a fragrance. Amyl acetate is useful in the manufacture of artificial leather, photographic film, artificial glass, celluloid, artificial silk, and furniture polish. Isoamyl acetate is used for dyeing and finishing textiles, perfuming shoe polish, and manufacturing artificial silk, leather, pearls, photographic films, celluloid cements, waterproof varnish and metallic paints. It is also used in artificial glass manufacturing and in the straw hat industry as a constituent of lacquers and stiffening solutions. Sodium acetate in used in tanning, photography, electroplating and preserving meat, as well as in the manufacture of soaps and pharmaceuticals.

Vinyl acetate primarily functions as an intermediate for the production of polyvinyl alcohol and polyvinyl acetals. It is also used in hair sprays and in the production of emulsion paint substances, finishing and impregnation materials, and glue. 2-Pentyl acetate has many of the same functions as the other acetates and serves as a solvent for chlorinated rubber, metallic paints, cements, linoleum, washable wallpaper, pearls, and coatings on artificial pearls.

Hazards

Methyl acetate is flammable, and its vapour forms explosive mixtures with air at normal temperatures. High concentrations of vapour can cause irritation to the eyes and mucous membranes. Exposure to the vapours can also cause headache, drowsiness, dizziness, burning and tearing of the eyes, heart palpitations, as well as a constricted feeling in the chest and shortness of breath. Blindness arising from eye contact has also been reported.

Ethyl acetate is a flammable liquid and produces a vapour that forms explosive mixtures with air at normal temperatures. Ethyl acetate is an irritant of the conjunctive and mucous membrane of the respiratory tract. Animal experiments have shown that, at very high concentrations, the ester has narcotic and lethal effects; at concentrations of 20,000 to 43,000 ppm, there may be pulmonary oedema with haemorrhages, symptoms of central nervous system depression, secondary anaemia and damage of the liver. Lower concentrations in humans have caused irritation of the nose and pharynx; cases have also been known of irritation of the conjunctiva with temporary opacity of the cornea. In rare cases exposure may cause sensitization of the mucous membrane and eruptions of the skin.

The irritant effect of ethyl acetate is less strong than that of propyl acetate or butyl acetate. These two propyl acetate isomers are flammable, and their vapours form explosive mixtures with air at normal temperatures. Concentrations of 200 ppm can cause irritation of the eyes, and greater concentrations give rise to irritation of the nose and larynx. Amongst workers occupationally exposed to these esters, there have been cases of conjunctival irritation and reports of a feeling of constriction of the chest, and coughing; however, no cases of permanent or systemic effects have been found in exposed workers. Repeated contact of the liquid with the skin may lead to defatting and cracking.

Amyl acetate. All the isomers and grades of amyl acetate are flammable and evolve flammable mixtures of vapour in air. High concentrations (10,000 ppm for 5 h) can be lethal to guinea-pigs. The principal symptoms in cases of occupational exposure are headaches and irritation of the mucous membranes of the nose and of the conjunctiva. Other symptoms mentioned include vertigo, palpitations, gastrointestinal disorders, anaemia, cutaneous lesions, dermatitis and adverse effects on the liver. Amyl acetate is also a defatting agent, and prolonged exposure may produce dermatitis. Butyl acetate is significantly more irritating than ethyl acetate. In addition, it can exert behavioural symptoms similar to amyl acetate.

Hexyl acetate and benzyl acetate are used industrially and are flammable, but their vapour pressures are low and, unless they are heated, they are unlikely to produce flammable concentrations of vapour. Animal experiments indicate that the toxic properties of these acetates are greater than those of amyl acetate; however, in practice, due to their low volatility, their effect on workers is limited to local irritation. There are few data upon which to evaluate hazards.

Cyclohexyl acetate can exert extreme narcotic effects in animals and appears to be a stronger irritant experimentally that is amyl acetate; however, there are insufficient data on human exposure to evaluate. The chemical does not tend to accumulate in the body, and many effects appear to be reversible.

Vinyl acetate is transformed metabolically into acetaldehyde, which raises a question of carcinogenicity. Based on this and on the positive results of animal assays, the International Agency for Research on Cancer (IARC) has classified vinyl acetate as a Group 2B carcinogen, possibly carcinogenic to humans. In addition, the chemical can be irritating to the upper respiratory tract and eyes. It is defatting to the skin.

Acetates tables

Table 1- Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 01:01

Esters, Acrylates

Uses

The acrylate esters are used in the manufacture of leather finish resins and textile, plastic and paper coatings. Methyl acrylate, producing the hardest resin of the acrylate ester series, is used in the manufacture of acrylic fibres as a co-monomer of acrylonitrile because its presence facilitates the spinning of fibres. It is used in dentistry, medicine and pharmaceuticals, and for the polymerization of radioactive waste. Methyl acrylate is also utilized in the purification of industrial effluents and in the timed release and disintegration of pesticides. Ethyl acrylate is a component of emulsion and solution polymers for surface-coating textiles, paper and leather. It is also used in synthetic flavouring and fragrances; as a pulp additive in floor polishes and sealants; in shoe polishes; and in the production of acrylic fibres, adhesives and binders.

More than 50% of the methyl methacrylate produced is utilized for the production of acrylic polymers. In the form of polymethylmethacrylate and other resins, it is used mainly as plastic sheets, moulding and extrusion powders, surface coating resins, emulsion polymers, fibres, inks and films. Methyl methacrylate is also useful in the production of the products known as Plexiglas or Lucite. They are used in plastic dentures, hard contact lenses and cement. n-Butyl methacrylate is a monomer for resins, solvent coatings, adhesives and oil additives, and it is used in emulsions for textiles, leather and paper finishing, and in the manufacture of contact lenses.

Hazards

As with many monomers—that is, chemicals which are polymerized to form plastics and resins—the reactivity of acrylates can pose occupational health and safety hazards if sufficient levels of exposure exist. Methyl acrylate is highly irritating and can cause sensitization. There is some evidence that chronic exposure may damage liver and kidney tissue. Evidence of carcinogencity is inconclusive (Group 3—Unclassifiable, according to the International Agency for Research on Cancer (IARC)). By contrast, ethyl acrylate is rated as a Group 2B carcinogen (possible human carcinogen). Its vapours are highly irritating to the nose, eyes and respiratory tract. It can cause corneal lesions, and inspiration of high concentrations of the vapours can lead to pulmonary oedema. Some skin sensitization following contact with liquid ethyl acrylate has been reported.

Butyl acrylate shares similar biological properties with methyl and ethyl acrylate, but the toxicity appears to decrease with an increase in molecular weight. It too is an irritating substance capable of causing sensitization after skin contact with the liquid.

The methacrylates resemble the acrylates, but are less biologically active. There is some evidence that the substance does not cause cancer in animals. Methyl methacrylate can act as a central nervous system depressant, and there are reports of sensitization among workers exposed to the monomer. Ethyl methacrylate shares properties of methyl methacrylate but is much less irritating. As with the acrylates, the methacrylates decrease in biological potency with increasing molecular weight, and butyl methacrylate, while an irritant, is less irritating than ethyl methacrylate.

Acrylates tables

Table 1- Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 01:07

Esters, Alkanoates (except Acetates)

Uses

Hazards

Acrylates tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 01:21

Ethers

Ethers are organic compounds in which oxygen serves as a link between two organic radicals. Most of the ethers of industrial importance are liquids, although methyl ether is a gas and a number of ethers, for example the cellulose ethers, are solids.

Hazards

The lower-molecular-weight ethers (methyl, diethyl, isopropyl, vinyl and vinyl isopropyl) are highly flammable, with flashpoints below normal room temperatures. Accordingly, measures should be taken to avoid release of vapours into areas where means of ignition may exist. All sources of ignition should be eliminated in areas where appreciable concentrations of ether vapour may be present in normal operations, as in drying ovens, or where there may be accidental release of the ether either as a vapour or as a liquid. Further control measures should be observed.

On prolonged storage in the presence of air or in sunlight, ethers are subject to peroxide formation that involves a possible explosion hazard. In laboratories, amber glass bottles provide protection, except from ultraviolet radiation or direct sunlight. Inhibitors such as copper mesh or a small amount of reducing agent may not be wholly effective. If a dry ether is not required, 10% of the ether volume of water may be added. Agitation with 5% aqueous ferrous sulphate removes peroxides. The primary toxicological characteristics of the non-substituted ethers is their narcotic action, which causes them to produce loss of consciousness on appreciable exposure; and, as good fat solvents, they cause dermatitis on repeated or prolonged skin contact. Enclosure and ventilation are to be employed to avoid excessive exposure. Barrier creams and impervious gloves assist in preventing skin irritation. In the event of loss of consciousness, the person should be removed from the contaminated atmosphere and given artifical respiration and oxygen.

The principal physiological effect of the unhalogenated ethers shown in the accompanying tables is anaesthesia. At high exposures, such as repeated exposures in excess of 400 ppm to ethyl ether, nasal irritation, loss of appetite, headache, dizziness and excitation, followed by sleepiness may result. Repeated contact with the skin may cause it to become dry and cracked. Following long-term exposures, it has been reported that mental disorders may occur.

Halogenated ethers

In contrast to the unhalogenated ethers, the halogenated ethers represent serious industrial hazards. They share the chemical property of being aklylating agents—that is, they can chemically bind alkyl groups, such as ethyl- and methyl- groups to available electron donor sites (e.g., -NH₂ in genetic material and haemoglobin). Such alklyation is believed to be intimately related to the induction of cancer and is discussed more fully elsewhere in this Encyclopaedia.

Bis(chloromethyl) ether (BCME) is a known human carcinogen (Group 1 classification by the International Agency for Research on Cancer (IARC)). It is also an extremely irritating substance. The carcinogenic effects of BCME have been observed in workers exposed to the substance for a relatively short period of time. This reduced latency period is probably related to the potency of the agent.

Chloromethyl methyl ether (CMME) is also a known human carcinogen which is intensely irritating as well. Exposure to the vapours of CMME even at levels of 100 ppm can be life threatening. Workers exposed to such levels have experienced serious respiratory effects, including pulmonary oedema.

Unless there is evidence to the contrary, it is prudent to treat all halogenated ethers prudently and to consider all alkylating agents potential carcinogens unless there is evidence to the contrary. The glycidyl ethers are considered in the family entitled “Epoxy compounds” .

Ethers tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Halogenated ethers tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 04:35

Fluorocarbons

The fluorocarbons are derived from hydrocarbons by the substitution of fluorine for some or all of the hydrogen atoms. Hydrocarbons in which some of the hydrogen atoms are replaced by chlorine or bromine in addition to those replaced by fluorine (e.g., chlorofluorohydrocarbons, bromofluorohydrocarbons) are generally included in the classification of fluorocarbons—for example, bromochlorodifluoromethane (CClBrF₂).

The first economically important fluorocarbon was dichlorodifluoromethane (CCl₂F₂), which was introduced in 1931 as a refrigerant of much lower toxicity than sulphur dioxide, ammonia or chloromethane, which were the currently popular refrigerants.

Uses

In the past, fluorocarbons were used as refrigerants, aerosol propellants, solvents, foam-blowing agents, fire extinguishants and polymer intermediates. As discussed below, concerns about the effects of chlorofluorocarbons in depleting the ozone layer in the upper atmosphere have led to bans on these chemicals.

Trichlorofluoromethane and dichloromonofluoromethane were formerly used as aerosol propellants. Trichlorofluoromethane currently functions as a cleaning and degreasing agent, a refrigerant, and a blowing agent for polyurethane foams. It is also used in fire extinguishers and electric insulation, and as a dielectric fluid. Dichloromonofluoromethane is used in glass-bottle manufacture, in heat-exchange fluids, as a refrigerant for centrifugal machines, as a solvent and as a blowing agent.

Dichlorotetrafluoroethane is a solvent, diluent, and cleaning and degreasing agent for printed circuit boards. It is used as a foaming agent in fire extinguishers, a refrigerant in cooling and air-conditioning systems, as well as for magnesium refining, for inhibiting metal erosion in hydraulic fluids, and for strengthening bottles. Dichlorodifluoromethane was also used for manufacturing glass bottles; as an aerosol for cosmetics, paint and insecticides; and for the purification of water, copper and aluminium. Carbon tetrafluoride is a propellant for rockets and for satellite guidance, and tetrafluoroethylene is used in the preparation of propellants for food-product aerosols. Chloropentafluoroethane is a propellant in aerosol food preparations and a refrigerant for home appliances and mobile air conditioners. Chlorotrifluoromethane, chlorodifluoromethane, trifluoromethane, 1,1-difluoroethane and 1,1,-chlorodifluoroethane are also refrigerants.

Many of the fluorocarbons are used as chemical intermediates and solvents in varied industries, such as textiles, drycleaning, photography and plastics. In addition, a few have specific functions as corrosion inhibitors and leak detectors. Teflon is used in the manufacture of high-temperature plastics, protective clothing, tubing and sheets for chemical laboratories, electric insulators, circuit breakers, cables, wires and anti-stick coatings. Chlorotrifluoromethane is used for hardening metals, and 1,1,1,2-tetrachloro-2,2-difluoroethane and dichlorodifluoromethane are used to detect surface cracks and metal defects.

Halothane, isoflurane and enflurane are used as inhalation anaesthetics.

Environmental Hazards

In the 1970s and 1980s, evidence accumulated that stable fluorocarbons and other chemicals such as methyl bromide and 1,1,1-trichloroethane would slowly diffuse upward into the stratosphere once released, where intense ultraviolet radiation could cause the molecules to release free chlorine atoms. These chlorine atoms react with oxygen as follows:

Cl + O₃ = ClO + O₂

ClO + O = Cl + O₂

O + O₃ = 2O₂

Since the chlorine atoms are regenerated in the reaction, they would be free to repeat the cycle; the net result would be a significant depletion of stratospheric ozone, which shields the earth from harmful solar ultraviolet radiation. The increase in ultraviolet radiation would result in an increase in skin cancer, affect crop yields and forest productivity, and affect the marine ecosystem. Studies of the upper atmosphere have shown areas of ozone depletion in the last decade.

As a result of this concern, beginning in 1979 nearly all aerosol products containing chlorofluorocarbons have been banned throughout the world. In 1987, an international agreement, the Montreal Protocol on Substances that Deplete the Ozone Layer, was signed. The Montreal Protocol controls the production and consumption of substances that can cause ozone depletion. It established a deadline of 1996 for totally phasing out the production and consumption of chlorofluorocarbons in developed countries. Developing countries have an additional 10 years to reach compliance. Controls were also established for halons, carbon tetrachloride, 1,1,1-trichloroethane (methyl chloroform), hydrochlorofluorocarbons (HCFCs), hydrobromofluorocarbons (HBFCs) and methyl bromide. Some essential uses for these chemicals are allowed where there are no technically and economically feasible alternatives available.

Hazards

The fluorocarbons are, in general, lower in toxicity than the corresponding chlorinated or brominated hydrocarbons. This lower toxicity may be associated with the greater stability of the CF bond, and perhaps also with the lower lipoid solubility of the more highly fluorinated materials. Because of their lower level of toxicity, it has been possible to select fluorocarbons which are safe for their intended uses. And because of the history of safe use in these applications, there has mistakenly grown up a popular belief that the fluorocarbons are completely safe under all conditions of exposure.

To a certain extent, the volatile fluorocarbons possess narcotic properties similar to, but weaker than, those shown by the chlorinated hydrocarbons. Acute inhalation of 2,500 ppm of trichlorotrifluoroethane induces intoxication and loss of psychomotor coordination in humans; this occurs at 10,000 ppm (1%) with dichlorodifluoromethane. If dichlorodifluoromethane is inhaled at 150,000 ppm (15%) , loss of consciousness results. Over 100 fatalities have been reported from the sniffing of fluorocarbons by spraying aerosol containers containing dichlorodifluoromethane as propellant into a paper bag and inhaling. At the American Conference of Governmental Industrial Hygienists (ACGIH) TLV of 1,000 ppm, narcotic effects are not experienced by humans.

Toxic effects from repeated exposure, such as liver or kidney damage, have not been produced by the fluoromethanes and fluoroethanes. The fluoroalkenes, such as tetrafluoroethylene, hexafluoropropylene or chlorotrifluoroethylene, can produce liver and kidney damage in experimental animals after prolonged and repeated exposure to appropriate concentrations.

Even the acute toxicity of the fluoroalkenes is surprising in some cases. Perfluoroisobutylene is an outstanding example. With an LC₅₀ of 0.76 ppm for 4-hour exposures for rats, it is more toxic than phosgene. Like phosgene, it produces an acute pulmonary oedema. On the other hand, vinyl fluoride and vinylidene fluoride are fluoroalkanes of very low toxicity.

Like many other solvent vapours and surgical anaesthetics, the volatile fluorocarbons may also produce cardiac arrhythmia or arrest under circumstances where an abnormally large amount of adrenaline is secreted endogenously (such as anger, fear, excitement, severe exertion). The concentrations required to produce this effect are well above those normally encountered during the industrial use of these materials.

In dogs and monkeys, both chlorodifluoromethane and dichlorodifluoromethane cause early respiratory depression, bronchoconstriction, tachycardia, myocardial depression and hypotension at concentrations of 5 to 10%. Chlorodifluoromethane, in comparison to dichlorodifluoromethane, does not cause cardiac arrhythmias in monkeys (although it does in mice) and does not decrease pulmonary compliance in monkeys.

Safety and health measures. All fluorocarbons will undergo thermal decomposition when exposed to flame or red-hot metal. Decomposition products of the chlorofluorocarbons will include hydrofluoric and hydrochloric acid along with smaller amounts of phosgene and carbonyl fluoride. The last compound is very unstable to hydrolysis and quickly changes to hydrofluoric acid and carbon dioxide in the presence of moisture.

The three commercially most important fluorocarbons (trichlorofluoromethane, dichlorodifluoromethane and trichlorotrifluoroethane) have been tested for mutagenicity and teratogenicity with negative results. Chlorodifluoromethane, which received some consideration as a possible aerosol propellant, was found to be mutagenic in bacterial mutagenicity tests. Lifetime exposure tests gave some evidence of carcinogenicity in male rats exposed to 50,000 ppm (5%), but not 10,000 ppm (1%). The effect was not seen in female rats or in other species. The International Agency for Research on Cancer (IARC) has classified it in Group 3 (limited evidence of carcinogenicity in animals), There was some evidence of teratogenicity in rats exposed to 50,000 ppm (5%), but not at 10,000 ppm (1%), and there was no evidence in rabbits at up to 50,000 ppm.

Victims of fluorocarbon exposure should be removed from the contaminated environment and treated symptomatically. Adrenaline should not be administered, because of the possibility of inducing cardiac arrhythmias or arrest.

Tetrafluoroethylene

The principal hazards of tetrafluoroethylene monomer are its flammability over a wide range of concentrations (11 to 60%) and potential explosivity. Uninhibited tetrafluoroethylene is liable to spontaneous polymerization and/or dimerization, both of which reactions are exothermic. The consequent pressure rise in a closed container can result in an explosion, and a number of such have been reported. It is thought that these spontaneous reactions are initiated by active impurities such as oxygen.

Tetrafluoroethylene does not present much of an acute toxic hazard per se, the LC₅₀ for 4-hour exposure of rats being 40,000 ppm. Rats dying from lethal exposures show not only damage to the lungs, but also degenerative changes in the kidney, the latter also being exhibited by other fluoroalkenes but not by fluoroalkanes.

Another hazard relates to the toxic impurities formed during the preparation or pyrolysis of tetrafluoroethylene, particularly octafluoroisobutylene, which has an approximate lethal concentration of only 0.76 ppm for 4-hour exposure of rats. A few fatalities have been described from exposure to these “high boilers”. Because of the potential dangers, casual experiments with tetrafluoroethylene should not be undertaken by the unskilled.

Safety and health measures. Tetrafluoroethylene is transported and shipped in steel cylinders under high pressure. Under such conditions the monomer should be inhibited to prevent spontaneous polymerization or dimerization. Cylinders should be fitted with pressure-relief devices, although it should not be overlooked that such devices may become plugged with polymer.

Teflon (polytetrafluoroethylene) is synthesized by the polymerization of tetrafluoroethylene with a redox catalyst. Teflon is not a hazard at room temperature. However, if it is heated to 300 to 500 °C, pyrolysis products include hydrogen fluoride and octafluoroisobutylene. At higher temperatures, 500 to 800 °C, carbonyl fluoride is produced. Above 650 °C, carbon tetrafluoride and carbon dioxide are produced. It can cause polymer fume fever, a flu-like illness. The most common cause of illness is from lit cigarettes contaminated with Teflon dust. Pulmonary oedema has also been reported.

Fluorocarbon anaesthetics. Halothane is an older inhalation anaesthetic, often used in combination with nitrous oxide. Isoflurane and enflurane are becoming more popular because they have fewer reported side-effects than halothane.

Halothane produces anaesthesia at concentrations above 6,000 ppm. Exposure to 1,000 ppm for 30 minutes causes abnormalities in behavioural tests which do not occur at 200 ppm. There are no reports of skin, eye or respiratory irritation or sensitization. Hepatitis has been reported at sub-anaesthetic concentrations, and severe—sometimes fatal—hepatitis has occurred in patients repeatedly exposed to anaesthetic concentrations. Liver toxicity has not been found from occupational exposures to isoflurane or enflurane. Hepatitis has occurred in patients exposed to 6,000 ppm of enflurane or higher; cases have been also been reported from use of isoflurane, but its role has not been proven.

One animal study of liver toxicity found no toxic effects in rats repeatedly exposed to 100 ppm of halothane in air; another study found brain, liver and kidney necrosis at 10 ppm, according to electron microscopy observations. No effects were found in mice exposed to 1,000 ppm of enflurane for 4 hours/day for about 70 days; a slight reduction in body weight gain was the only effect found when they were exposed to 3,000 ppm for 4 hours/day, 5 days/week for up to 78 weeks. In another study, severe weight loss and deaths with liver damage were found in mice exposed continuously to 700 ppm of enflurane for up to 17 days; in the same study, no effects were seen in rats or guinea pigs exposed for 5 weeks. With isoflurane, continuous exposure of mice to 150 ppm and above in air caused reduced body weight gain. Similar effects were seen in guinea pigs, but not rats, at 1,500 ppm. No significant effect was seen in mice exposed 4 hours/day, 5 days/week for 9 weeks at up to 1,500 ppm.

No evidence of mutagenicity or carcinogenicity was found in animal studies of enflurane or isoflurane, or in epidemiological studies of halothane. Early epidemiological studies suggesting adverse reproductive effects from halothane and other inhalation anaesthetics have not been verified for halothane exposure in subsequent studies.

No convincing evidence of foetal effects was found in rats with halothane exposures up to 800 ppm, and no effect on fertility with repeated exposures up to 1,700 ppm. There was some foetotoxicity (but not teratogenicity) at 1,600 ppm and over. In mice, there was foetotoxicity at 1,000 ppm but not 500 ppm. Reproductive studies of enflurane found no effects on fertility in mice at concentrations up to 10,000 ppm, with some evidence of sperm abnormality at 12,000 ppm. There was no evidence of teratogenicity in mice exposed up to 7,500 ppm or in rats at up to 5,000 ppm. There was slight evidence of embryo/foetotoxicity in pregnant rats exposed to 1,500 ppm. With isoflurane, exposure of male mice at up to 4,000 ppm for 4 hours/day for 42 days had no effect on fertility. There were no foetotoxic effects in pregnant mice exposed at 4,000 ppm for 4 hours/day for 2 weeks; exposure of pregnant rats to 10,500 ppm produced minor loss of foetal body weight. In another study, decreased litter size and foetal body weight and developmental effects were found in the foetuses of mice exposed to 6,000 ppm of isoflurane for 4 hours/day on days 6 to 15 of pregnancy; no effects were found at 60 or 600 ppm.

Fluorocarbons tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 04:43

Glycol Ethers

Uses

Glycol ethers are used extensively as solvents because they tend to be quite soluble in both water and organic liquids. General uses include inks and dyes, enamels, paints and as cleaning agents in the dry-cleaning and glass-cleaning industries. The semiconductor industry also uses these compounds extensively as solvents and cleaning agents.

The ethylene glycol ethers are used widely as solvents for resins, lacquers, paints, varnishes, dyes and inks, as well as components of painting pastes, cleaning compounds, liquid soaps, cosmetics and hydraulic fluids. Propylene and butylene glycol ethers are valuable as dispersing agents and as solvents for lacquers, paints, resins, dyes, oils and greases.

Ethylene glycol monoethyl ether is a solvent in the lacquer, printing, metal and chemical industries. It is also used for dyeing and printing in the textile industry and as a leather-finishing agent, an anti-icing additive for aviation fuels, and a component of varnish removers and cleansing solutions. Diethylene glycol monomethyl ether and ethylene glycol monobutyl ether acetate function in industry as high-boiling solvents. Diethylene glycol monomethyl ether is used for non-grain-raising wood stains, for brushing lacquers with mild odours, for stamp pad inks and for leather finishing. In the paint industry, it is a coalescing agent for latex paint; and in the textile industry, it is used for printing, textile soaps and dye pastes, as well as for setting the twist and conditioning yarns and cloth.

The solvents diethylene glycol monomethyl ether, diethylene glycol monoethyl ether and diethylene glycol mono-n-butyl ether serve as diluents in hydraulic brake fluids. 2-Phenoxyethanol is a fixative for perfumes, cosmetics and soaps, a textile dye carrier and a solvent for cleaners, inks, germicides and pharmaceuticals. 2-Methoxyethanol is also a perfume fixative. It is used in the manufacture of photographic film, as a jet fuel anti-icing additive, as a solvent for resins used in the electronics industry, and as a leather-dyeing agent. 2-Methoxyethanol and propylene glycol methyl ether are useful for solvent-sealing of cellophane. Ethylene glycol mono-n-butyl ether is a solvent for protective coatings and for metal cleaners. It is used in the textile industry to prevent spotting in printing or dyeing.

Hazards

Generally speaking, the acute effects of glycol ethers are limited to the central nervous system and are similar to acute solvent toxicity. These effects include dizziness, headache, confusion, fatigue, disorientation, slurred speech and (if severe enough) respiratory depression and loss of consciousness. The effects of long-term exposure include skin irritation, anaemia and bone marrow supression, encephalopathy and reproductive toxicity. 2-Methoxyethanol and 2-ethoxyethanol (and their acetates) are most toxic. Because of their relatively low volatility, exposure most often occurs as a result of skin contact with liquids, or inhalation of vapours in closed spaces.

Most of the ethylene glycol ethers are more volatile than the parent compound and, consequently, less easily controlled with respect to vapour exposure. All of the ethers are more toxic than ethylene glycol and exhibit a similar symptomatological complex.

Ethylene glycol monomethyl ether (methyl cellosolve; Dowanol EM; 2-methoxyethanol). The oral LD₅₀ for ethylene glycol monomethyl ether in rats is associated with delayed deaths involving lung oedema, slight liver injury, and extensive kidney damage. Renal failure is the probable cause of death in response to repeated oral exposures. This glycol ether is moderately irritating to the eye, producing acute pain, inflammation of the membranes, and corneal clouding which persists for several hours. Although ethylene glycol monomethyl ether is not appreciably irritating to skin, it can be absorbed in toxic amounts. Experience with human exposure to ethylene glycol monomethyl ether has indicated that it can result in the appearance of immature leucocytes, monocytic anaemia, and neurological and behavioural changes. Studies have also shown that inhalation exposure in humans can lead to forgetfullness, personality changes, weakness, lethargy and headaches. In animals, inhalation of higher concentrations can result in testicular degeneration, damage to the spleen, and blood in the urine. Animal studies have shown anaemia, thymus and marrow damage at 300 ppm. At 50 ppm during pregnancy in animals, major foetal abnormalities were reported. The most important health effect seems to be the effect on the human reproductive system, with diminished spermatogenesis. Thus, it is evident that the monomethyl ether of ethylene glycol is a moderate toxic compound and that repeated skin contact or inhalation of vapour must be prevented.

Ethylene glycol monoethyl ether (cellosolve solvent; Dowanol EE; 2-ethoxyethanol). Ethylene glycol monoethyl ether is less toxic than the methyl ether (above). The most significant toxic action is on the blood, and neurological symptoms are not expected. In other respects it is similar in toxic action to ethylene glycol monomethyl ether. Excessive exposure can result in moderate irritation to the respiratory system, lung oedema, central nervous system depression and marked glomerulitis. In animal studies, foetotoxicity and teratogenicity were seen at levels above 160 ppm, and behavioural changes in offspring were obvious after maternal exposure at 100 ppm.

Other ethylene glycol ethers. Mention of ethylene glycol monobutyl ether is also in order because of its extensive use in industry. In rats, deaths in response to single oral exposures are attributable to narcosis, whereas delayed deaths result from lung congestion and renal failure. Direct contact of the eye with this ether produces intense pain, marked conjunctival irritation and corneal clouding, which may persist for several days. As with monomethyl ether, skin contact does not cause much skin irritation, but toxic amounts can be absorbed. Inhalation studies have shown that rats can tolerate 30 7-hour exposures to 54 ppm, but some injury occurs at a concentration of 100 ppm. At higher concentrations, rats exhibited haemorrhaging in the lungs, congestion of the viscera, liver damage, haemoglobinuria and marked erythrocyte fragility. Foetotoxicity has been seen in rats exposed to 100 ppm, but not at 50 ppm. Enhanced erythrocyte fragility was evident at all exposure concentrations above 50 ppm of ethylene glycol monobutyl ether vapours. Humans appear to be somewhat less susceptible than laboratory animals because of apparent resistance to its haemolytic action. While headache and eye and nasal irritation was seen in humans above 100 ppm, red blood cell damage was not found.

Both the isopropyl and n-propyl ethers of ethylene glycol present particular hazards. These glycol ethers have low single-dose oral LD₅₀ values and they cause severe kidney and liver damage. Bloody urine is an early sign of severe kidney damage. Death usually occurs within a few days. Eye contact results in rapid conjunctival irritation and partial corneal opacity in the rabbit, with recovery requiring about 1 week. Like most other ethylene glycol ethers, the propyl derivatives are only mildly irritating to the skin but can be absorbed in toxic amounts. Furthermore, they are highly toxic via inhalation. Fortunately, ethylene glycol monoisopropyl ether is not a prominent commercial compound.

Diethylene glycol ethers. The ethers of diethylene glycol are lower in toxicity than the ethers of ethylene glycol, but they have similar characteristics.

Polyethylene glycols. Triethylene, tetraethylene, and the higher polyethylene glycols appear to be innocuous compounds of low vapour pressure.

Propylene glycol ethers. Propylene glycol monomethyl ether is relatively low in toxicity. In rats, the single oral dose LD₅₀ caused death by generalized central nervous system depression, probably respiratory arrest. Repeated oral doses (3 g/kg) over a 35-day period induced in rats only mild histopathological changes in the liver and kidneys. Eye contact resulted in only a mild transitory irritation. It is not appreciably irritating to the skin, but confinement of large amounts of the ether to rabbit skin causes central nervous system depression. The vapour does not present a substantial health hazard if inhaled. Deep narcosis appears to be the cause of death in animals subjected to severe inhalation exposures. This ether is irritating to the eyes and upper respiratory tract of humans at concentrations that are not hazardous to health; hence it does have some warning properties.

Di- and tripropylene glycol ethers exhibit toxicological properties similar to the monopropylene derivatives, but present essentially no hazard with respect to vapour inhalation or skin contact.

Polybutylene glycols. Those that have been examined can cause kidney damage in excessive doses, but they are not injurious to the eyes or skin and are not absorbed in toxic amounts.

Acetic esters, diesters, ether esters. These derivatives of the common glycols are of particular importance since they are employed as solvents for plastics and resins in diverse products. Many explosives contain ester of ethylene glycol as a freezing-point depressant. With respect to toxicity, the glycol ether fatty acid esters are considerably more irritating to mucous membranes than the parent compounds discussed previously. However, the fatty acid esters have toxicity properties essentially identical to the parent materials once the former are absorbed, because the esters are saponified in biological environments to yield fatty acid and the corresponding glycol or glycol ether.

Safety and Health Measures

Measures used to control and limit the exposure to glycol ethers are essentially the same as those used to control solvent exposure as discussed elsewhere in this Encyclopaedia. Substitution of one material for another less toxic one, if possible, is always a good starting point. Adequate ventilation systems that can effectively minimize the concentration of material in the breathing zone is important. Where explosive and fire hazards are in issue, care must be taken to avoid open flames or sparks and to store materials in “explosion safe” containers. Personal protective equipment, such as respirators, gloves and clothing, while important, should not be relied upon exclusively. Protective eyewear should always be worn if splash exposure is a risk. When using ethylene glycol monomethyl ether, workers should wear chemical safety goggles, and adequate ventilation is necessary. Eye protection is also recommended whenever the possibility of such contact exists with ethylene glycol monobutyl ether. Inhalation of its vapours and skin contact should be avoided. Particularly when working with 2-methoxyethanol or 2-ethoxyethanol, all skin contact should be strictly avoided.

Glycol ethers tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

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Wednesday, 03 August 2011 04:47

Glycerols and Glycols

Uses

Glycols and glycerols have numerous applications in industry because they are completely water-soluble organic solvents. Many of these compounds are used as solvents for dyes, paints, resins, inks, insecticides and pharmaceuticals. In addition, their two chemically reactive hydroxyl groups make the glycols important chemical intermediates. Among the many uses of glycols and polyglycols, major ones include being an additive for freezing-point depression, for lubrication and for solubilization. The glycols also serve as indirect and direct additives to foods and as ingredients in explosive and alkyd resin formulations, theatrical fogs and cosmetics.

Propylene glycol is used widely in pharmaceuticals, cosmetics, as a humectant in certain foods and as a lubricant. It is also used as a heat-transfer fluid in uses where leakage might lead to food contact, such as in coolants for dairy refrigeration equipment. It is also used as a solvent in food colours and flavours, an antifreeze in breweries and establishments, and an additive to latex paint to provide freeze-thaw stability. Propylene glycol, ethylene glycol and 1,3-butanediol are components of aircraft de-icing fluids. Tripropylene glycol and 2,3-butanediol are solvents for dye-stuffs. The butanediols (butylene glycols) are used in the production of polyester resins.

Ethylene glycol is an antifreeze in cooling and heating systems, a solvent in the paint and plastics industries, and an ingredient of de-icing fluid used for airport runways. It is used in hydraulic brake fluids, low-freezing dynamite, wood stains, adhesives, leather dyeing, and tobacco. It is also serves as a dehydrating agent for natural gas, a solvent for inks and pesticides, and an ingredient in electrolytic condensers. Diethylene glycol is a humectant for tobacco, casein, synthetic sponges, and paper products. It is also found in cork compositions, book-binding adhesives, brake fluids, lacquers, cosmetics and antifreeze solutions for sprinkler systems. Diethylene glycol is used for water seals for gas tanks, as a lubricating and finishing agent for textiles, a solvent for vat dyes, and a natural-gas dehydrating agent. Triethylene glycol is a solvent and lubricant in textile dyeing and printing. It is also used in air disinfection and in various plastics to increase pliability. Triethylene glycol is a humectant in the tobacco industry and an intermediate for the manufacture of plasticizers, resins, emulsifiers, lubricants and explosives.

Some measure of the versatility of glycerol can be gained from the fact that some 1,700 uses for the compound and its derivatives have been claimed. Glycerol is used in food, pharmaceuticals, toiletries and cosmetics. It is a solvent and a humectant in such products as tobacco, confectionery icing, skin creams and toothpaste, which would otherwise deteriorate on storage by drying out. In addition, glycerol is a lubricant added to chewing gum as a processing aid; a plasticizing agent for moist, shredded coconut; and an additive for maintaining the smoothness and moisture in drugs. It serves to keep frost from windshields and is an antifreeze in automobiles, gas meters and hydraulic jacks. The largest single use of glycerol, however, is in the production of alkyd resins for surface coatings. These are prepared by condensing glycerol with a dicarboxylic acid or anhydride (usually phthalic anhydride) and fatty acids. A further major use of glycerol is in the production of explosives, including nitroglycerine and dynamite.

Glycerol

Glycerol is a trihydric alcohol and undergoes reactions characteristic of alcohols. The hydroxyl groups have varying degrees of reactivity, and those in the 1- and 3- positions are more reactive than that in the 2- position. By using these differences in reactivity and by varying the proportions of reactants, it is possible to make mono-, di- or tri- derivatives. Glycerol is prepared either by the hydrolysis of fats, or synthetically from propylene. The chief constituents of virtually all animal and vegetable oils and fats are triglycerides of fatty acids.

Hydrolysis of such glycerides yields free fatty acids and glycerol. Two hydrolysis techniques are used—alkaline hydrolysis (saponification) and neutral hydrolysis (splitting). In saponification, fat is boiled with sodium hydroxide and sodium chloride, resulting in the formation of glycerol and the sodium salts of fatty acids (soaps).

In neutral hydrolysis, the fats are hydrolyzed by a batch or semi-continuous process in a high-pressure autoclave, or by a continuous countercurrent technique in a high-pressure column. There are two main processes for the synthesis of glycerol from propylene. In one process, propylene is treated with chlorine to give allyl chloride; this reacts with sodium hypochlorite solution to give glycerol dichlorohydrin, from which glycerol is obtained by alkaline hydrolysis. In the other process, propylene is oxidized to acrolein, which is reduced to allyl alcohol. This compound may be hydroxylated with aqueous hydrogen peroxide to give glycerol directly, or treated with sodium hypochlorite to give glycerol monochlorohydrin, which, upon alkaline hydrolysis, yields glycerol.

Hazards

Glycerol has a very low toxicity (oral LD₅₀ (mouse) 31.5 g/kg) and is generally considered harmless under all normal conditions of use. Glycerin produces only very slight diuresis in healthy individuals receiving a single oral dose of 1.5 g/kg or less. Adverse effects following oral administration of glycerin include mild headache, dizziness, nausea, vomiting, thirst and diarrhoea.

When present as a mist, it is classified by the American Conference of Governmental Industrial Hygienists (ACGIH) as a “particulate nuisance”, and as such a TLV of 10 mg/m³ has been assigned. In addition, the reactivity of glycerol makes it dangerous, and liable to explode in contact with strong oxidizing agents such as potassium permanganate, potassium chlorate and so on. Consequently it should not be stored near such materials.

Glycols and derivatives

The commercially important glycols are aliphatic compounds possessing two hydroxyl groups, and are colourless, viscous liquids that are essentially odourless. Ethylene glycol and diethylene glycol are of major importance among the glycols and their derivatives. The toxicity and hazard of certain important compounds and groups are discussed in the final section of this article. None of the glycols or their derivatives that have been studied have been found to be mutagenic, carcinogenic or teratogenic.

The glycols and their derivatives are combustible liquids. since their flashpoints are above normal room temperature, the vapours are liable to be present in concentrations within the flammable or explosive range only when heated (e.g., ovens). For this reason they present no more than a moderate fire risk.

Synthesis. Ethylene glycol is produced commercially by the air oxidation of ethylene, followed by hydration of the resulting ethylene oxide. Diethylene glycol is produced as a by-product of the production of ethylene glycol. Similarly, propylene glycol and 1,2-butanediol are produced by the hydration of propylene oxide and butylene oxide, respectively. 2,3-Butanediol is produced by the hydration of 2,3-epoxybutane; 1,3-butanediol is produced by the catalytic hydrogenation of aldol using Raney nickel; and 1,4-butanediol is produced by the reaction of acetylene with formaldehyde, followed by hydrogenation of the resulting 2-butyne-1,4-diol.

Hazards of Common Glycols

Ethylene glycol. The oral toxicity of ethylene glycol in animals is quite low. However, from clinical experience it has been estimated that the lethal dose for an adult human is about 100 cm³or about 1.6 g/kg, thus indicating a greater toxic potency for humans than for laboratory animals. The toxicity is due to the metabolites, which vary for different species. Typical effects of excessive oral intake of ethylene glycol are narcosis, depression of the respiratory centre, and progressive kidney damage.

Monkeys have been maintained for 3 years on diets containing 0.2 to 0.5% of ethylene glycol without apparent adverse effects; no tumours were found in the bladder, but there were oxalate crystals and stones. Primary eye and skin irritation are generally mild in response to ethylene glycol, but the material can be absorbed through the skin in toxic amounts. Exposure of rats and mice for 8 hours/day for 16 weeks to concentrations ranging from 0.35 to 3.49 mg/l failed to induce organic injury. At the higher concentrations, mist and droplets were present. Consequently, repeated exposures of humans to vapours at room temperature should not present a significant hazard. Ethylene glycol does not seem to present a significant hazard from the inhalation of vapours at room temperatures or from skin or oral contact under reasonable industrial conditions. However, an industrial inhalation hazard could be generated if ethylene glycol were heated or vigorously agitated (generating a mist), or if appreciable skin contact or ingestion occurred over an extended period of time. The primary health hazard of ethylene glycol is related to the ingestion of large quantities.

Diethylene glycol. Diethylene glycol is quite similar to ethylene glycol in toxicity, although without production of oxalic acid. It is more directly toxic to the kidneys than ethylene glycol. When excessive doses are ingested, the typical effects to be expected are diuresis, thirst, loss of appetite, narcosis, hypothermia, kidney failure and death, depending on the severity of exposure. Mice and rats exposed to diethylene glycol at levels of 5 mg/m³ for 3 to 7 months experienced changes in central nervous and endocrine systems and internal organs, and other pathological changes. While not of practical concern, when fed at high doses to animals, diethylene glycol has produced bladder stones and tumours, probably secondary to the stones. These may have been due to monoethylene glycol present in the sample. As with ethylene glycol, diethylene glycol does not seem to present a significant hazard from the inhalation of vapours at room temperatures or from skin or oral contact under reasonable industrial conditions.

Propylene glycol. Propylene glycol presents a low toxicity hazard. It is hygroscopic, and in a study of 866 human subjects, was found to be a primary irritant in some people, probably due to dehydration. It might also cause allergic skin reactions in over 2% of people with eczema. Long-term exposures of animals to atmospheres saturated with propylene glycol are without measurable effect. As a result of its low toxicity, propylene glycol is used widely in pharmaceutical formulations, cosmetics and, with certain limitations, in food products.

Dipropylene glycol is of very low toxicity. It is essentially non-irritating to the skin and eyes and, because of its low vapour pressure and toxicity, is not an inhalation problem unless large quantities are heated in a confined space.

Butanediols. Four isomers exist; all are soluble in water, ethyl alcohol and ether. They have low volatility so inhalation is not a concern under normal industrial conditions. With the exception of the 1,4- isomer, the butanediols create no significant industrial hazard.

In rats, massive oral exposures of 1,2-butanediol induced deep narcosis and irritation of the digestive system. Congestive necrosis of the kidney may also occur. Delayed deaths are believed to be the result of progressive renal failure, while acute fatalities are probably attributable to narcosis. Eye contact with 1,2-butanediol may result in corneal injury, but even prolonged skin contact is usually innocuous with respect to primary irritation and absorption toxicity. No adverse effects of vapour inhalation have been reported.

1,3-Butanediol is essentially non-toxic except in overwhelming oral doses, in which case narcosis may occur.

Little is known abut the toxicity of 2,3-butanediol, but from the few animal studies published, it appears to lie between 1,2- and 1,3-butanediols in toxicity.

1,4-Butanediol is about eight times as toxic as the 1,2-isomer in acute toxicity tests. Acute ingestion results in severe narcosis and possibly renal injury. Death probably results from collapse of the sympathetic and parasympathetic nervous systems. It is not a primary irritant, nor is it easily absorbed percutaneously.

Glycols and glycerols tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 04:54

Halogens and Their Compounds

Fluorine, chlorine, bromine, iodine and the more recently discovered radioactive element astatine, make up the family of elements known as the halogens. Except for astatine, the physical and chemical properties of these elements have been exhaustively studied. They occupy group VII in the periodic table, and they display an almost perfect gradation in physical properties.

The family relationship of the halogens is illustrated also by the similarity in the chemical properties of the elements, a similarity which is associated with the arrangement of seven electrons in the outer shell of the atomic structure of each of the elements in the group. All the members form compounds with hydrogen, and the readiness with which union occurs decreases as the atomic weight increases. In like manner, the heats of formation of the various salts decrease with the increasing atomic weights of the halogens. The properties of the halogen acids and their salts show as striking a relationship; the similarity is apparent in organic halogen compounds, but, as the compound becomes chemically more complex, the characteristics and influences of other components of the molecule may mask or modify the gradation of properties.

Uses

Halogens are used in the chemical, water and sanitation, plastics, pharmaceutical, pulp and paper, textile, military and oil industries. Bromine, chlorine, fluorine and iodine are chemical intermediates, bleaching agents and disinfectants. Both bromine and chlorine are used in the textile industry for bleaching and shrink-proofing wool. Bromine is also used in gold mining extraction processes and in oil- and gas-well drilling. It is a fire retardant in the plastics industry and an intermediate in the manufacture of hydraulic fluids, refrigerating and dehumidifying agents, and hair-waving preparations. Bromine is also a component of military gas and fire-extinguishing fluids.

Chlorine is used as a disinfectant for refuse and in the purification and treatment of drinking water and swimming pools. It is a bleaching agent in laundries and in the pulp and paper industry. Chlorine is used in the manufacture of special batteries and chlorinated hydrocarbons, and in the processing of meat, vegetables, fish and fruit. In addition, it acts as a flame retardant. Chlorine dioxide is utilized in the water and sanitation and swimming pool industries for water purification, taste and odour control. It is a bleaching agent in the food, leather, textile, and pulp and paper industries, as well as an oxidizing agent, bactericide and antiseptic. It is used in cleaning and detanning leather and in bleaching cellulose, oils and beeswax. Nitrogen trichloride was formerly used as a bleach and “improver” for flour. Iodine is also a disinfectant in the water and sanitation industry, and acts as a chemical intermediate for inorganic iodides, potassium iodide, and organic iodine compounds.

Fluorine, fluorine monoxide, bromine pentafluoride and chlorine trifluoride are oxidizers for rocket fuel systems. Fluorine is also used in the conversion of uranium tetrafluoride to uranium hexafluoride, and chlorine trifluoride is used in nuclear reactor fuel and for cutting oil-well tubes.

Calcium fluoride, found in the mineral fluorspar, is the primary source of fluorine and its compounds. It is used in ferrous metallurgy as a flux to increase fluidity of the slag. Calcium fluoride is also found in the optical, glass and electronics industries.

Hydrogen bromide and its aqueous solutions are useful for manufacturing organic and inorganic bromides and as reducing agents and catalysts. They are also used in the alkylation of aromatic compounds. Potassium bromide is used to manufacture photographic papers and plates. Large quantities of phosgene gas are required for numerous industrial syntheses, including the manufacture of dye-stuffs. Phosgene is also used in military gas and in pharmaceuticals. Phosgene is found in insecticides and fumigants.

Hazards

The similarity which these elements exhibit in chemical properties is apparent in the physiological effects associated with the group. The gases (fluorine and chlorine) and the vapours of bromine and iodine are irritants of the respiratory system; inhalation of relatively low concentrations of these gases and vapours gives an unpleasant, pungent sensation, which is followed by a feeling of suffocation, coughing and a sensation of constriction in the chest. The damage to the lung tissue which is associated with these conditions may cause the lungs to become overloaded with fluid, resulting in a condition of pulmonary oedema which may well prove fatal.

Fluorine and its compounds

Sources

The majority of fluorine and its compounds is obtained directly or indirectly from calcium fluoride (fluorspar) and phosphate rock (fluorapatite), or chemicals derived from them. The fluoride in phosphate rock limits the usefulness of this ore and, therefore, the fluoride must be removed almost completely in the preparation of elemental phosphorus or food-grade calcium phosphate, and partially in the conversion of fluorapatite to fertilizer. These fluorides are recovered in some cases as aqueous acid or as calcium or sodium salts of the liberated fluoride (probably a mixture of hydrogen fluoride and silicon tetrafluoride), or released to the atmosphere.

Fire and explosion hazards

Many of the fluorine compounds present a fire and explosion hazard. Fluorine reacts with nearly all materials, including metal containers and piping if the passivating film is broken. The reaction with metals can produce hydrogen gas. Absolute cleanliness is required in conveying systems to prevent localized reactions and subsequent fire hazards. Special lubricant-free valves are used to prevent reactions with lubricants. Oxygen difluoride is explosive in gaseous mixtures with water, hydrogen sulphide or hydrocarbons. When heated, many fluorine compounds produce poisonous gases and corrosive fluoride fumes.

Health hazards

Hydrofluoric acid. Skin contact with anhydrous hydrofluoric acid produces severe burns that are felt immediately. Concentrated aqueous solutions of hydrofluoric acid also cause early sensation of pain, but dilute solutions may give no warning of injury. External contact with liquid or vapour causes severe irritation of eyes and eyelids that may result in prolonged or permanent visual defects or total destruction of eyes. Fatalities have been reported from skin exposure to as little as 2.5% of total body surface.

Quick treatment is essential, and should include washing copiously with water on the way to the hospital, then soaking in an iced solution of 25% magnesium sulphate if possible. Standard treatment for mild to moderate burns involves application of a calcium gluconate gel; more severe burns may require injection in and around the affected area with 10% calcium gluconate or magnesium sulphate solution. Sometimes local anaesthesia may be needed for pain.

Inhalation of concentrated hydrofluoric acid mists or anhydrous hydrogen fluoride may cause severe respiratory irritation, and as little as 5 minutes’ exposure is usually fatal within 2 to 10 hours from haemorrhagic pulmonary oedema. Inhalation may also be involved in skin exposures.

Fluorine and other fluorinated gases. Elemental fluorine, chlorine trifluoride and oxygen difluoride are strong oxidizers and may be highly destructive. At very high concentrations, these gases may have an extremely corrosive effect on animal tissue. However, nitrogen trifluoride is strikingly less irritating. Gaseous fluorine in contact with water forms hydrofluoric acid, which will produce severe skin burns and ulceration.

Acute exposure to fluorine at 10 ppm causes slight skin, eye and nasal irritation; exposure above 25 ppm is intolerable, although repeated exposures may cause acclimatization. High exposures may cause delayed pulmonary oedema, haemorrhage and kidney damage, and possibly be fatal. Oxygen difluoride has similar effects.

In an acute rat inhalation study with chlorine trifluoride, 800 ppm for 15 minutes and 400 ppm for 25 minutes were fatal. The acute toxicity is comparable to that of hydrogen fluoride. In a long-term study in two species, 1.17 ppm caused respiratory and eye irritation, and in some animals, death.

In long-term repeated inhalation animal studies with fluorine, toxic effects on the lungs, liver and testicles were observed at 16 ppm, and irritation of mucous membranes and lungs observed at 2 ppm. Fluorine at 1 ppm was tolerated. In a subsequent multi-species study, no effects were observed from 60-minute exposures at concentrations up to 40 ppm.

There are sparse data available on industrial exposure of workers to fluorine. There is even less experience of long-term exposure to chlorine trifluoride and oxygen difluoride.

Fluorides

Ingestion of quantities of soluble fluorides in the range of 5 to 10 grams is almost certainly fatal to human adults. Human fatalities have been reported in connection with the ingestion of hydrogen fluoride, sodium fluoride and fluosilicates. Non-fatal illnesses have been reported due to ingesting these and other fluorides, including the sparingly soluble salt, cryolite (sodium aluminium fluoride).

In industry, fluoride-bearing dusts play a part in a considerable proportion of cases of actual or potential fluoride exposure, and dust ingestion may be a significant factor. Occupational fluoride exposure may be largely due to gaseous fluorides, but, even in these cases, ingestion can rarely be ruled out completely, either because of contamination of food or beverages consumed in the workplace or because of fluorides coughed up and swallowed. In exposure to a mixture of gaseous and particulate fluorides, both inhalation and ingestion may be significant factors in fluoride absorption.

Fluorosis or chronic fluorine intoxication has been widely reported to produce fluoride deposition in skeletal tissues of both animals and humans. The symptoms included increased radiographic bone opacity, formation of blunt excrescences on the ribs, and calcification of intervertebral ligaments. Dental mottling is also found in cases of fluorosis. The exact relationship between fluoride levels in urine and the concurrent rates of osseous fluoride deposition is not fully understood. However, provided urinary fluoride levels in workers are consistently no higher than 4 ppm, there appears to be little need for concern; at a urinary fluoride level of 6 ppm more elaborate monitoring and/or controls should be considered; at a level of 8 ppm and above, it is to be expected that skeletal deposition of fluoride will, if exposure is allowed to continue for many years, lead to increased osseous radio-opacity.

The fluoborates are unique in that absorbed fluoborate ion is excreted almost completely in the urine. This implies that there is little or no dissociation of fluoride from the fluoborate ion, and hence virtually no skeletal deposition of that fluoride would be expected.

In one study of cryolite workers, about half complained of lack of appetite, and shortness of breath; a smaller proportion mentioned constipation, localized pain in the region of the liver, and other symptoms. A slight degree of fluorosis was found in cryolite workers exposed for 2 to 2.5 years; more definite signs were found in those exposed nearly 5 years, and signs of moderate fluorosis appeared in those with more than 11 years of exposure.

Fluoride levels have been associated with occupational asthma among workers in aluminium reduction potrooms.

Calcium fluoride. The hazards of fluorspar are due primarily to the harmful effects of the fluorine content, and chronic effects include diseases of teeth, bones and other organs. Pulmonary lesions have been reported among persons inhaling dust containing 92 to 96% calcium fluoride and 3.5% silica. It was concluded that calcium fluoride intensifies the fibrogenic action of silica in the lungs. Cases of bronchitis and silicosis have been reported amongst fluorspar miners.

Environmental Hazards

Industrial plants using quantities of fluorine compounds, such as iron and steelworks, aluminium smelters, superphosphate factories and so on, may emit fluorine-containing gases, smokes or dusts into the atmosphere. Cases of environmental damage have been reported in animals grazing on contaminated grass, including fluorosis with dental mottling, bone deposition and wasting; etching of window glass in neighbouring houses has also occurred.

Bromine and its compounds

Bromine is widely distributed in nature in the form of inorganic compounds such as minerals, in seawater and in salt lakes. Small amounts of bromine are also contained in animal and vegetable tissues. It is obtained from salt lakes or boreholes, from seawater and from the mother liquor remaining after the treatment of potassium salts (sylnite, carnallite).

Bromine is a highly corrosive liquid, the vapours of which are extremely irritating to the eyes, skin and mucous membranes. On prolonged contact with tissue, bromine may cause deep burns which are long in healing and subject to ulceration; bromine is also toxic by ingestion, inhalation and skin absorption.

A bromine concentration of 0.5 mg/m³ should not be exceeded in case of prolonged exposure; in a bromine concentration of 3 to 4 mg/m³, work without a respirator is impossible. A concentration of 11 to 23 mg/m³ produces severe choking, and it is widely considered that 30 to 60 mg/m³ is extremely dangerous for humans and that 200 mg/m³ would prove fatal in a very short time.

Bromine has cumulative properties, being deposited in the tissues as bromides and displacing other halogens (iodine and chlorine). Long-term effects include disorders of the nervous system.

Persons exposed regularly to concentrations three to six times higher than the exposure limit for 1 year complain of headache, pain in the region of the heart, increasing irritability, loss of appetite, joint pains and dyspepsia. During the fifth or sixth year of work there may be loss of corneal reflexes, pharyngitis, vegetative disorders and thyroid hyperplasia accompanied by thyroid dysfunction. Cardiovascular disorders also occur in the form of myocardial degeneration and hypotension; functional and secretory disorders of the digestive tract may also occur. Signs of inhibition of leucopoiesis and leucocytosis are seen in the blood. The blood concentration of bromine varies between 0.15 mg/100 cm³ to 1.5 mg/100 cm³ independently of the degree of intoxication.

Hydrogen bromide gas is detectable without irritation at 2 ppm. Hydrobromic acid, its 47% solution in water, is a corrosive, faintly yellow liquid with a pungent smell, which darkens on exposure to air and light.

The toxic action of hydrobromic acid is two to three times weaker than that of bromine, but more acutely toxic than hydrogen chloride. Both the gaseous and aqueous forms irritate the mucous membranes of the upper respiratory tract at 5 ppm. Chronic poisoning is characterized by upper respiratory inflammation and digestive problems, slight reflex modifications and diminished erythrocyte counts. Olfactory sensitivity may be reduced. Contact with the skin or mucous membranes may cause burns.

Bromic acid and hypobromous acid. The oxygenated acids of bromine are found only in solutions or as salts. Their action on the body is similar to that of hydrobromic acid.

Ferroso-ferric bromide. Ferroso-ferric bromides are solid substances used in the chemical and pharmaceutical industries and in the manufacture of photographic products. They are produced by passing a mixture of bromine and steam over iron filings. The resultant hot, syrupy brome salt is tipped into iron containers, where is solidifies. Wet bromine (that is, bromine containing more than about 20 ppm of water) is corrosive to most metals, and elemental bromine has to be transported dry in hermetically sealed monel, nickel or lead containers. To overcome the corrosion problem, bromine is frequently transported in the form of ferroso-ferric salt.

Bromophosgene. This is a decomposition product of bromochloromethane and is encountered in the production of gentian violet. It results from the combination of carbon monoxide with bromine in the presence of anhydrous ammonium chloride.

The toxic action of bromophosgene is similar to that of phosgene (see Phosgene in this article).

Cyanogen bromide. Cyanogen bromide is a solid used for gold extraction and as a pesticide. It reacts with water to produce hydrocyanic acid and hydrogen bromide. Its toxic action resembles that of hydrocyanic acid, and it probably has similar toxicity.

Cyanogen bromide also has a pronounced irritant effect, and high concentrations may cause pulmonary oedema and lung haemorrhages. Twenty ppm for 1 minute and 8 ppm for 10 minutes is intolerable. In mice and cats, 70 ppm causes paralysis in 3 minutes, and 230 ppm is fatal.

Chlorine and its inorganic compounds

Chlorine compounds are widely found in nature, comprising about 2% of the earth’s surface materials, especially in the form of sodium chloride in sea water and in natural deposits as carnallite and sylvite.

Chlorine gas is primarily a respiratory irritant. In sufficient concentration, the gas irritates the mucous membranes, the respiratory tract and the eyes. In extreme cases difficulty in breathing may increase to the point where death can occur from respiratory collapse or lung failure. The characteristic, penetrating odour of chlorine gas usually gives warning of its presence in the air. Also, at high concentrations, it is visible as a greenish-yellow gas. Liquid chlorine in contact with skin or eyes will cause chemical burns and/or frostbite.

The effects of chlorine may become more severe for up to 36 hours after exposure. Close observation of exposed individuals should be a part of the medical response programme.

Chronic exposure. Most studies indicate no significant connection between adverse health effects and chronic exposure to low concentrations of chlorine. A 1983 Finnish study did show an increase in chronic coughs and a tendency for hypersecretion of mucous among workers. However, these workers showed no abnormal pulmonary function in tests or chest x rays.

A 1993 Chemical Industry Institute of Toxicology study on the chronic inhalation of chlorine exposed rats and mice to chlorine gas at 0.4, 1.0 or 2.5 ppm for up to 6 hours a day and 3 to 5 days/week for up to 2 years. There was no evidence of cancer. Exposure to chlorine at all levels produced nasal lesions. Because rodents are obligatory nasal breathers, how these results should be interpreted for humans is not clear.

Chlorine concentrations considerably higher than current threshold values may occur without being immediately noticeable; people rapidly lose their ability to detect the odour of chlorine in small concentrations. It has been observed that prolonged exposure to atmospheric chlorine concentrations of 5 ppm results in disease of the bronchi and a predisposition to tuberculosis, while lung studies have indicated that concentrations of 0.8 to 1.0 ppm cause permanent, although moderate, reduction in pulmonary function. Acne is not unusual in persons exposed for long periods of time to low concentrations of chlorine, and is commonly known as “chloracne”. Tooth enamel damage may also occur.

Oxides

In all, there are five oxides of chlorine. They are dichlorine monoxide, chlorine monoxide, chlorine dioxide, chlorine hexoxide and chlorine heptoxide; they have mainly the same effect on the human organism and require the same safety measures as chlorine. The one most used in industry is chlorine dioxide. Chlorine dioxide is a respiratory and eye irritant similar to chlorine but more severe in degree. Acute exposures by inhalation cause bronchitis and pulmonary oedema, the symptoms observed in affected workers being coughing, wheezing, respiratory distress, nasal discharge, and eye and throat irritation.

Nitrogen trichloride is a powerful irritant to the skin and mucous membranes of the eyes and respiratory tract. The vapours are as corrosive as chlorine. It is highly toxic when ingested.

The mean lethal concentration (LC₅₀) of nitrogen trichloride in rats is 12 ppm according to one study involving exposing the rats at concentrations from 0 to 157 ppm for 1 hour. Dogs fed on flour bleached with nitrogen trichloride rapidly develop ataxia and epileptiform convulsions. Histological examination of experimental animals has shown cerebral cortex necrosis and Purkinje cell disorders in the cerebellum. The red cell nucleus may also be affected.

Nitrogen trichloride may explode as the result of an impact, exposure to heat, supersonic waves, and even spontaneously. The presence of certain impurities may increase the explosion hazard. It will also explode on contact with traces of certain organic compounds—in particular, turpentine. Decomposition results in highly toxic chlorinated decomposition products.

Phosgene. Commercially, phosgene (COCl₂) is manufactured by the reaction between chlorine and carbon monoxide. Phosgene is also formed as an undesirable by-product when certain chlorinated hydrocarbons (especially dichloromethane, carbon tetrachloride, chloroform, trichloroethylene, perchloroethylene and hexachloroethane) come into contact with an open flame or hot metal, as in welding. The decomposition of chlorinated hydrocarbons in closed rooms can result in the accumulation of harmful concentrations of phosgene, as for example from the use of carbon tetrachloride as a fire-extinguishing material, or tetrachloroethylene as a lubricant in the machining of high-grade steel.

Anhydrous phosgene is not corrosive to metals, but in the presence of water it reacts to from hydrochloric acid, which is corrosive.

Phosgene is one of the most poisonous gases used in industry. The inhalation of 50 ppm for a short time is fatal to test animals. For humans, prolonged inhalation of 2 to 5 ppm is dangerous. An additional hazardous property of phosgene is the lack of all warning symptoms during its inhalation, which may merely cause light irritation of the mucous membranes of the respiratory tract and eye at concentrations of 4 to 10 ppm. Exposure to 1 ppm for extended periods can cause delayed pulmonary oedema.

Light cases of poisoning are followed by temporary bronchitis. In serious cases, delayed pulmonary oedema can occur. This can occur after a latent period of several hours, usually 5 to 8, but seldom more than 12. In most cases, the patient remains conscious until the end; death is caused by asphyxiation or heart failure. If the patient survives the first 2 to 3 days, the prognosis is generally favourable. High concentrations of phosgene cause immediate acid damage to the lung and rapidly cause death by suffocation and termination of circulation through the lungs.

Environmental protection

Free chlorine destroys vegetation and, as it may occur in concentrations causing such damage under unfavourable climatic conditions, its release into the surrounding atmosphere should be prohibited. If it is not possible to utilize the liberated chlorine for the production of hydrochloric acid or the like, every precaution must be taken to bind the chlorine, for instance by means of a lime scrubber. Special technical safety measures with automatic warning systems should be installed, in the factories and in the surroundings, wherever there is a risk that appreciable quantities of chlorine may escape to the surrounding atmosphere.

From the point of view of environmental pollution, particular attention should be paid to cylinders or other vessels used for the transport of chlorine or its compounds, to measures for the control of possible hazards, and to steps to be taken in case of emergency.

Iodine and its compounds

Iodine does not occur free in nature, but iodides and/or iodates are found as trace impurities in deposits of other salts. Chilean saltpetre deposits contain enough iodate (about 0.2% sodium iodate) to make its commercial exploitation feasible. Similarly, some naturally occurring brines, especially in the United States, contain recoverable quantities of iodide. Iodide in ocean water is concentrated by some seaweeds (kelp), the ash of which was formerly a commercially important source in France, the United Kingdom and Japan.

Iodine is a powerful oxidizing agent. An explosion may result if it contacts materials such as acetylene or ammonia.

Iodine vapour, even in low concentrations, is extremely irritating to the respiratory tract, eyes and, to a lesser extent, the skin. Concentrations as low as 0.1 ppm in the air may cause some eye irritation upon prolonged exposure. Concentrations higher than 0.1 ppm cause increasingly severe eye irritation along with irritation of the respiratory tract and, ultimately, pulmonary oedema. Other systemic injury from the inhalation of iodine vapour is unlikely unless the exposed person already has a thyroid disorder. Iodine is absorbed from the lungs, converted to iodide in the body, and then excreted, mainly in urine. Iodine in crystalline form or in strong solutions is a severe skin irritant; it is not easily removed from the skin and, after contact, tends to penetrate and cause continuing injury. Skin lesions caused by iodine resemble thermal burns except that iodine stains the burned areas brown. Ulcers that are slow to heal may develop because of iodine remaining fixed to the tissue.

The probable mean lethal oral dose of iodine is 2 to 3 g in adults, due to its corrosive action on the gastrointestinal system. In general, iodine-containing materials (both organic and inorganic) appear to be more toxic than analogous bromine- or chlorine-containing materials. In addition to “halogen-like” toxicity, iodine is concentrated in the thyroid gland (the basis for treating thyroid cancer with ¹³¹I), and therefore metabolic disturbances are likely to result from overexposure. Chronic absorption of iodine causes “iodism”, a disease characterized by tachycardia, tremor, weight loss, insomnia, diarrhoea, conjunctivitis, rhinitis and bronchitis. In addition, hypersensitivity to iodine may develop, characterized by skin rashes and possibly rhinitis and/or asthma.

Radioactivity. Iodine has an atomic number of 53 and an atomic weight ranging from 117 to 139. Its only stable isotope has a mass of 127 (126.9004); its radioactive isotopes have half-lives from a few seconds (atomic weights of 136 and higher) to millions of years (¹²⁹I). In the reactions that characterize the fission process in a nuclear reactor, ¹³¹I is formed in abundance. This isotope has a half-life of 8.070 days; it emits beta and gamma radiation with principal energies of 0.606 MeV (max) and 0.36449 MeV, respectively.

Upon entering the body by any route, inorganic iodine (iodide) is concentrated in the thyroid gland. This, coupled with the abundant formation of ¹³¹I in nuclear fission, makes it one of the most hazardous materials that can be released from a nuclear reactor either deliberately or by accident.

Halogens and compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 05:26

Heterocyclic Compounds

The heterocyclic compounds are used as chemical intermediates and solvents in the pharmaceutical, chemical, textile, dye-stuffs, petroleum and photography industries. Several compounds also function as vulcanization accelerators in the rubber industry.

Acridine and benzanthrone are used as starting materials and intermediates in the manufacture of dyes. Benzanthrone is also used in the pyrotechnics industry. Propyleneimine is used in flocculants in petroleum refining and as a modifier for rocket propellant fuels. It has been used in oil additives as a modifier for viscosity control, for high-pressure performance, and for oxidation resistance. 3-Methylpyridine and 4-methylpyridine serve as waterproofing agents in the textile industry. 4-Methylpyridine is a solvent in the synthesis of pharmaceuticals, resins, dye-stuffs, rubber accelerators, pesticides and waterproofing agents. 2-Pyrrolidone is also used in pharmaceutical preparations and functions as a high-boiling solvent in petroleum processing. It is found in specialty printing inks and in certain floor polishes. 4,4'-Dithiodimorpholine is used in the rubber industry as a staining protector and a vulcanizing agent. In the rubber industry, 2-vinylpyridine is made into a terpolymer that is used in adhesives for bonding tire cord to rubber.

Several heterocyclic compounds—morpholine, mercaptobenzothiazole, piperazine, 1,2,3-benzotriazole and quinoline—function as corrosion inhibitors for copper and industrial water treatment. Mercaptobenzothiazole is also a corrosion inhibitor in cutting oils and petroleum products, and an extreme-pressure additive in greases. Morpholine is a solvent for resins, waxes, casein and dyes, and a defoaming agent in the paper and paperboard industries. In addition, it is found in insecticides, fungicides, herbicides, local anaesthetics, and antiseptics. 1,2,3-Benzotriazole is a restrainer, developer and antifogging agent in photographic emulsions, a component of military aircraft de-icing fluid, and a stabilizing agent in the plastics industry.

Pyridine is utilized by numerous industries as both a chemical intermediate and a solvent. It is used in the manufacture of vitamins, sulpha drugs, disinfectants, dye-stuffs and explosives, and as a dyeing assistant in the textile industry. Pyridine is also useful in the rubber and paint industries, oil and gas well drilling, and in the food and non-alcoholic beverage industries as a flavouring agent. The vinylpyridines are utilized for the production of polymers. Sulpholane, a solvent and a plasticizer, is used for the extraction of aromatic hydrocarbons from oil refinery streams, for textile finishing, and as a component of hydraulic fluid. Tetrahydrothiophene is a solvent and a fuel gas odorant used in fire safety stench warning systems in underground mines. Piperidine is used in the manufacture of pharmaceuticals, wetting agents and germicides. It is a hardening agent for epoxy resins and a trace constituent of fuel oil.

Hazards

Acridine is a powerful irritant which, in contact with the skin or mucous membrane, causes itching, burning, sneezing, lacrimation and irritation of the conjunctiva. Workers exposed to acridine crystal dust in concentrations of 0.02 to 0.6 mg/m³ complained of headache, disturbed sleep, irritability and photosensitization, and presented oedema of the eyelids, conjunctivitis, skin rashes, leucocytosis and increased red cells sedimentation rates. These symptoms did not appear at an acridine airborne concentration of 1.01 mg/m³. When heated, acridine emits toxic fumes. Acridine, and a large number of its derivatives have been shown to possess mutagenic properties and to inhibit DNA repair and cell growth in several species.

In animals, near-lethal doses of aminopyridines produce increased excitability to sound and touch, and cause tremor, clonic convulsions and tetany. They also cause contraction of skeletal muscle and smooth muscle, producing vasconstriction and increased blood pressure. It has been reported that aminopyridines and some alkyl pyridines exert inotropic and chronotropic action on the heart. Vinyl pyridines cause less dramatic convulsions. Acute poisoning can occur either from inhalation of the dust or vapour at relatively low concentrations, or by skin absorption.

A common hazard of benzanthrone is skin sensitization due to exposure to benzanthrone dust. Sensitivity varies from person to person, but after exposure of between a few months and several years, sensitive persons, especially those who are blond or red-headed, develop an eczema which may be intense in its course and the acute phase of which may leave a hazel or slate-grey pigmentation, especially around the eyes. Microscopically, atrophy of the skin has been found. Skin disorders due to benzanthrone are more frequent in the warm season and are significantly aggravated by heat and light.

Morpholine is a moderately toxic compound by ingestion and by cutaneous application; undiluted morpholine is a strong skin irritant and a potent eye irritant. It does not appear to have chronic toxic effects. It is a moderate fire hazard when exposed to heat, and thermal decomposition results in the release of fumes containing nitrogen oxides.

Phenothiazine has harmful irritant properties, and industrial exposure may produce skin lesions and photosensitization, including photosensitized keratitis. As far as systemic effects are concerned, severe intoxication in therapeutic use has been reported to be characterized by haemolitic anaemia and toxic hepatitis. Because of its low solubility, the rate of its absorption from the gastrointestinal tract is dependent on particle size. A micronized form of the drug is absorbed rapidly. The toxicity of the substance varies a great deal from animal to animal, the oral LD₅₀ in rats being 5 g/kg.

Although phenothiazine oxidizes fairly easily when it is exposed to air, the risk of fire is not high. However, if involved in a fire, phenothiazine produces highly toxic sulphur and nitrogen oxides, which are dangerous lung irritants.

Piperidine is absorbed by inhalation and through the digestive tract and the skin; it produces a toxic response in animals similar to that obtained with the aminopyridines. Large doses block ganglionic conduction. Small doses cause both parasympathetic and sympathetic stimulation due to action on the ganglia. Increased blood pressure and heart rate, nausea, vomiting, salivation, laboured breathing, muscular weakness, paralysis and convulsions are signs of intoxication. This substance is highly flammable and evolves explosive concentrations of vapour at normal room temperatures. The precautions recommended for pyridine should be adopted.

Pyridine and homologues. Some information on pyridine is available from clinical reports of human exposure, primarily through medical treatments or through exposure to the vapour. Pyridine is absorbed through the gastrointestinal tract, through the skin and by inhalation. Clinical symptoms and signs of intoxication include gastrointestinal disturbance with diarrhoea, abdominal pain and nausea, weakness, headache, insomnia and nervousness. Exposures less than those required to produce overt clinical signs may cause varying degrees of liver damage with central lobular fatty degeneration, congestion and cellular infiltration; repeated low-level exposures cause cirrhosis. The kidney appears to be less sensitive to pyridine-induced damage than is the liver. In general, pyridine and its derivatives cause local irritation on contact with the skin, mucous membranes and cornea. The effects on the liver may occur at levels that are too low to elicit a response from the nervous system, and so no warning signs may be available to a potentially exposed worker. Further, although the odour of pyridine is easily detectable at vapour concentrations of less than 1 ppm, odour detection cannot be relied upon because olfactory fatigue occurs quickly.

Pyridine in both the liquid and vapour phase may constitute a severe fire and explosion hazard when exposed to flame; it may also react violently with oxidizing substances. When pyridine is heated to decomposition, cyanide fumes are released.

Pyrrole and pyrrolidine. Pyrrole is a flammable liquid and, when burning, gives off dangerous nitrogen oxides. It has a depressant action on the central nervous system and, in severe intoxication, is injurious to the liver. Few data are available about the degree of occupational risk that this substance presents. Fire protection and prevention measures should be adopted and means of extinguishing fire should be provided. Respiratory protective equipment should be available for persons fighting a fire involving pyrrole.

The human experience with pyrrolidine is not well documented. Prolonged administration in rats caused reduction of diuresis, inhibition of spermatogenesis, decreased haemoglobin content in blood, and nervous excitation. As with many nitrates, the acidity of the stomach can convert pyrrolidine into N-nitrosopyrrolidine, a compound which has been found to be carcinogenic in laboratory animals. Some workers may develop headaches and vomiting from exposure.

The liquid is capable of evolving flammable concentrations of vapour at ordinary working temperatures; consequently, open lights and other agencies liable to ignite the vapour should be excluded from areas in which it is used. When burning, pyrrolidine gives off dangerous nitrogen oxides, and persons exposed to these combustion products should be supplied with suitable respiratory protection. Bunding and sills should be provided to prevent the spread of liquid accidentally escaping from storage and process vessels.

Quinoline is absorbed through the skin (percutaneously). The clinical signs of toxicity include lethargy, respiratory distress, and prostration leading to coma. This substance is irritating to the skin and may cause pronounced permanent corneal damage. It is a carcinogen in several animal species but there are inadequate data available on the human cancer risk. It is moderately flammable but does not evolve a flammable concentration of vapour at a temperature below 99 °C.

Vinylpyridine. Brief exposure to the vapour has caused eye, nose and throat irritation and transient headache, nausea, nervousness and anorexia. Skin contact causes burning pain followed by severe skin burns. Sensitization may develop. The fire hazard is moderate, and decomposition by heat is accompanied by the release of dangerous cyanide fumes.

Safety and Health Measures

The normal safety precautions are required for handling the dusts and vapours of the chemicals in this grouping. Since skin sensitization is associated with a number of them, it is particularly important that adequate sanitary and washing facilities be provided. Care should be taken to assure that workers have access to clean eating areas.

Heterocyclic compounds tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 05:29

Hydrocarbons, Saturated and Alicyclic

Aliphatic hydrocarbons are compounds of carbon and hydrogen. They may be saturated or unsaturated open chain, branched or unbranched molecules, the nomenclature being as follows:

paraffins (or alkanes)—saturated hydrocarbons

olefins (or alkenes)—unsaturated hydrocarbons with one or more double bond linkages

acetylenes (or alkynes)—unsaturated hydrocarbons with one or more triple bond linkages

The general formulae are C_nH_2n+2 for paraffins, C_nH_2n for olefins, and C_nH_2n-2 for acetylenes.

The smaller molecules are gases at room temperature (C₁ to C₄). As the molecule increases in size and structural complexity it becomes a liquid with increasing viscosity (C₅ to C₁₆), and finally the higher molecular weight hydrocarbons are solids at room temperature (above C₁₆).

The aliphatic hydrocarbons of industrial importance are derived mainly from petroleum, which is a complex mixture of hydrocarbons. They are produced by the cracking, distillation and fractionation of crude oil.

Methane, the lowest member of the series, comprises 85% of natural gas, which may be tapped directly from pockets or reservoirs in the vicinity of petroleum deposits. Large amounts of pentane are produced by fractional condensation of natural gas.

Uses

The saturated hydrocarbons are used in industry as fuels, lubricants and solvents. After undergoing processes of alkylation, isomerization and dehydrogenation, they also act as starting materials for the synthesis of paints, protective coatings, plastics, synthetic rubber, resins, pesticides, synthetic detergents and a wide variety of petrochemicals.

The fuels, lubricants and solvents are mixtures which may contain many different hydrocarbons. Natural gas has long been distributed in the gaseous form for use as a town gas. It is now liquefied in large quantities, shipped under refrigeration and stored as a refrigerated liquid until it is introduced unchanged or reformed into a town gas distribution system. Liquefied petroleum gases (LPGs), consisting mainly of propane and butane, are transported and stored under pressure or as refrigerated liquids, and are also used to augment town gas supply. They are used directly as fuels, often in high-grade metallurgical work in which a sulphur-free fuel is essential, in oxypropane welding and cutting, and in circumstances where a heavy industrial demand for gaseous fuels would strain public supply. Storage installations for these purposes vary in size from about 2 tons to several thousands of tons. Liquefied petroleum gases are also used as propellants for many types of aerosols, and the higher members of the series, from heptane upwards, are used as motor fuels and solvents. Isobutane is used to control the volatility of gasoline and is a component of instrument calibration fluid. Isooctane is the standard reference fuel for octane rating of fuels, and octane is used in antiknock engine fuels. In addition to being a component of gasoline, nonane is a component of biodegradable detergent.

The principal use of hexane is as a solvent in glues, cements and adhesives for the production of footwear, whether from hide or from plastics. It has been used as a solvent for glue in the assembling of furniture, in adhesives for wallpaper, as a solvent for glue in the production of handbags and suitcases from hide and artificial hide, in the manufacture of raincoats, in the retreading of car tyres and in the extraction of vegetable oils. In many uses, hexane has been replaced by heptane because of the toxicity of n-hexane.

It is not possible to list all the occasions when hexane may be present in the working environment. It may be advanced as a general rule that its presence is to be suspected in volatile solvents and grease removers based on hydrocarbons derived from petroleum. Hexane is also used as a cleaning agent in the textile, furniture and leather industries.

Aliphatic hydrocarbons used as starting materials of intermediates for synthesis may be individual compounds of high purity or relatively simple mixtures.

Hazards

Fire and explosion

The development of large storage installations first for gaseous methane and later for LPGs has been associated with explosions of great magnitude and catastrophic effect, which have emphasized the danger when a massive leakage of these substances occurs. The flammable mixture of gas and air may extend far beyond the distances that are regarded as adequate for normal safety purposes, with the result that the flammable mixture may become ignited by a household fire or automobile engine well outside the specified danger zone. Vapour may thus be set alight over a very large area, and flame propagation through the mixture may reach explosive violence. Many smaller—but still serious—fires and explosions have occurred during the use of these gaseous hydrocarbons.

The largest fires involving liquid hydrocarbons have occurred when large quantities of liquid have escaped and flowed towards a part of the factory where ignition could take place, or have spread over a large surface and evaporated quickly. The notorious Flixborough (United Kingdom) explosion is attributed to a leak of cyclohexane.

Health hazards

The first two members of the series, methane and ethane, are pharmacologically “inert”, belonging to a group of gases called “simple asphyxiants”. These gases can be tolerated in high concentrations in inspired air without producing systemic effects. If the concentration is high enough to dilute or exclude the oxygen normally present in the air, the effects produced will be due to oxygen deprivation or asphyxia. Methane has no warning odour. Because of its low density, methane may accumulate in poorly ventilated areas to produce an asphyxiating atmosphere. Ethane in concentrations below 50,000 ppm (5%) in the atmosphere produces no systemic effects on the person breathing it.

Pharmacologically, the hydrocarbons above ethane can be grouped with the general anaesthetics in the large class known as the central nervous system depressants. The vapours of these hydrocarbons are mildly irritating to mucous membranes. The irritation potency increases from pentane to octane. In general, alkane toxicity tends to increase as the carbon number of alkanes increases. In addition, straight-chain alkanes are more toxic than the branched isomers.

The liquid paraffin hydrocarbons are fat solvents and primary skin irritants. Repeated or prolonged skin contact will dry and defat the skin, resulting in irritation and dermatitis. Direct contact of liquid hydrocarbons with lung tissue (aspiration) will result in chemical pneumonitis, pulmonary oedema, and haemorrhage. Chronic intoxication by n-hexane or mixtures containing n-hexane may involve polyneuropathy.

Propane causes no symptoms in humans during brief exposures to concentrations of 10,000 ppm (1%). A concentration of 100,000 ppm (10%) is not noticeably irritating to the eyes, nose or respiratory tract, but it will produce slight dizziness in a few minutes. Butane gas causes drowsiness, but no systemic effects during a 10-minute exposure to 10,000 ppm (1%).

Pentane is the lowest member of the series that is liquid at room temperature and pressure. In human studies a 10-min exposure to 5,000 ppm (0.5%) did not cause mucous membrane irritation or other symptoms.

Heptane caused slight vertigo in men exposed for 6 min to 1,000 ppm (0.1%) and for 4 min to 2,000 ppm (0.2%). A 4-min exposure to 5,000 ppm (0.5%) heptane caused marked vertigo, inability to walk a straight line, hilarity and incoordination. These systemic effects were produced in the absence of complaints of mucous membrane irritation. A 15-min exposure to heptane at this concentration produced a state of intoxication characterized by uncontrolled hilarity in some individuals, and in others it produced a stupor lasting for 30 min after the exposure. These symptoms were frequently intensified or first noticed at the moment of entry into an uncontaminated atmosphere. These individuals also complained of loss of appetite, slight nausea, and a taste resembling gasoline for several hours after exposure to heptane.

Octane in concentrations of 6,600 to 13,700 ppm (0.66 to 1.37%) caused narcosis in mice within 30 to 90 min. No deaths or convulsions resulted from these exposures to concentrations below 13,700 ppm (1.37%).

Because it is likely that in an alkane mixture the components have additive toxic effects, the US National Institute for Occupational Safety and Health (NIOSH) has recommended keeping a threshold limit value for total alkanes (C₅ to C₈) of 350 mg/m³ as a time-weighted average, with a 15-min ceiling value of 1,800 mg/m³. n-Hexane is considered separately because of its neurotoxicity.

n-Hexane

n-Hexane is a saturated, straight-chain aliphatic hydrocarbon (or alkane) with the general formula C_nH_2n+2 and one of a series of hydrocarbons with low boiling points (between 40 and
90 °C) obtainable from petroleum by various processes (cracking, reforming). These hydrocarbons are a mixture of alkanes and cycloalkanes with five to seven carbon atoms
(n-pentane, n-hexane, n-heptane, isopentane, cyclopentane, 2-methylpentane,
3-methylpentane, cyclohexane, methylcyclopentane). Their fractional distillation produces single hydrocarbons that may be of varying degrees of purity.

Hexane is sold commercially as a mixture of isomers with six carbon atoms, boiling at 60 to
70 °C. The isomers most commonly accompanying it are 2-methylpentane, 3-methylpentane, 2,3-dimethylbutane and 2,2-dimethylbutane. The term technical hexane in commercial use denotes a mixture in which are to be found not only n-hexane and its isomers but also other aliphatic hydrocarbons with five to seven carbon atoms (pentane, heptane and their isomers).

Hydrocarbons with six carbon atoms, including n-hexane, are contained in the following petroleum derivatives: petroleum ether, petrol (gasoline), naphtha and ligroin, and fuels for jet aircraft.

Exposure to n-hexane may result from occupational or non-occupational causes. In the occupational field it may occur through the use of solvents for glues, cements, adhesives or grease-removing fluids. The n-hexane content of these solvents varies. In glues for footwear and rubber cement, it may be as high as 40 to 50% of the solvent by weight. The uses referred to here are those that have caused occupational disease in the past, and in some instances hexane has been replace with heptane. Occupational exposure to n-hexane may occur also through the inhalation of petrol fumes in fuel depots or workshops for the repair of motor vehicles. The danger of this form of occupational exposure, however, is very slight, because the concentration of n-hexane in petrol for motor vehicles is maintained below 10% owing to the need for a high octane number.

Non-occupational exposure is found mainly among children or drug addicts who practise the sniffing of glue or petrol. Here the n-hexane content varies from the occupational value in glue to 10% or less in petrol.

Hazards

n-Hexane may penetrate the body in either of two ways: by inhalation or through the skin. Absorption is slow by either way. In fact measurements of the concentration of n-hexane in the breath exhaled in conditions of equilibrium have shown the passage from the lungs to the blood of a fraction of the n-hexane inhaled of from 5.6 to 15%. Absorption through the skin is extremely slow.

n-Hexane has the same skin effects previously described for other liquid aliphatic hydrocarbons. Hexane tends to vaporize when swallowed or aspirated into tracheobronchial tree. The result can be rapid dilution of alveolar air and a marked fall in its oxygen content, with asphyxia and consequent brain damage or cardiac arrest. The irritative pulmonary lesions occurring after the aspiration of higher homologues (e.g., octane, nonane, decane and so on) and of mixtures thereof (e.g., kerosene) do not appear to be a problem with hexane. Acute or chronic effects are almost always due to inhalation. Hexane is three times more acutely toxic than pentane. Acute effects occur during exposure to high concentrations of n-hexane vapours and range from dizziness or vertigo after brief exposure to concentrations of about 5,000 ppm, to convulsions and narcosis, observed in animals at concentrations of about 30,000 ppm. In humans, 2,000 ppm (0.2%) produces no symptoms in a 10-min exposure. An exposure of 880 ppm for 15 min can cause eye and upper respiratory tract irritation in humans.

Chronic effects occur after prolonged exposure to doses that do not produce obvious acute symptoms and tend to disappear slowly when the exposure ends. In the late 1960s and early 1970s, attention was drawn to outbreaks of sensorimotor and sensory polyneuropathy among workers exposed to mixtures of solvents containing n-hexane in concentrations mainly ranging between 500 and 1,000 ppm with higher peaks, although concentrations as low as 50 ppm could cause symptoms in some instances. In some cases, muscular atrophy and cranial nerve involvements such as visual disorders and facial numbness were observed. About 50% showed denervation and regeneration of the nerves, Tingling, numbness and weakness of distal extremities were complained of, mainly in the legs. Stumbling was often observed. Achilles tendon reflexes disappeared; touch and heat sensation were diminished. Conduction time was decreased in the motor and sensory nerves of the arms and legs.

The course of the disease is generally very slow. After the appearance of the first symptoms, a deterioration of the clinical picture is often observed through an aggravation of the motor deficiency of the regions originally affected and their extension to those which have hitherto been sound. This deterioration can occur for some months after exposure has ceased. The extension generally takes place from the lower to the upper limbs. In very serious cases ascending motor paralysis appears with a functional deficiency of the respiratory muscles. Recovery may take as long as 1 to 2 years. Recovery is generally complete, but a diminution of the tendon reflexes, particularly that of the Achilles tendon, may persist in conditions of apparent full well-being.

Symptoms in the central nervous system (defects of the visual function or the memory) have been observed in serious cases of intoxication by n-hexane and have been related to degeneration of the visual nuclei and the tracts of hypothalamic structures. These may be permanent.

With regard to laboratory tests, the most usual haematological and haemato-chemical tests do not show characteristic changes. This is also true of urine tests, which show increased creatinuria only in serious cases of paralysis with muscular hypotrophy.

The examination of the spinal fluid does not lead to characteristic findings, either manometric or qualitative, except for rare cases of increased protein content. It appears that only the nervous system shows characteristic changes. The electroencephalograph readings (EEG) are usually normal. In serious cases of disease, however, it is possible to detect dysrhythmias, widespread or subcortical discomfort and irritation. The most useful test is electromyography (EMG). The findings indicate myelinic and axonal lesions of the distal nerves. The motor conduction velocity (MCV) and the sensitive conduction velocity (SCV) are reduced, the distal latency (LD) is modified and the sensory potential (SPA) is diminished.

Differential diagnosis with respect to the other peripheral polyneuropathies is based on the symmetry of the paralysis, on the extreme rareness of sensory loss, on the absence of changes in the cerebrospinal fluid, and, above all, on the knowledge that there has been exposure to solvents containing n-hexane and the occurrence of more than one case with similar symptoms from the same workplace.

Experimentally, technical grade n-hexane has produced peripheral nerve disturbances in mice at 250 ppm and higher concentrations after 1 year of exposure. Metabolic investigations have indicated that in guinea-pigs n-hexane and methyl butyl ketone (MBK) are metabolized to the same neurotoxic compounds (2-hexanediol and 2,5-hexanedione).

The anatomical modifications of the nerves underlying the clinical manifestations described above have been observed, whether in laboratory animals or in sick human beings, through muscular biopsy. The first convincing n-hexane polyneuritis reproduced experimentally is due to Schaumberg and Spencer in 1976. The anatomical modifications of the nerves are represented by axonal degeneration. This axonal degeneration and the resulting demyelination of the fibre start at the periphery, particularly in the longer fibres, and tend to develop towards the centre, though the neuron does not show signs of degeneration. The anatomical picture is not specific to the pathology of n-hexane, for it is common to a series of nervous diseases due to poisons in both industrial and non-industrial use.

A very interesting aspect of n-hexane toxicology lies in the identification of the active metabolites of the substance and its relations with the toxicology of other hydrocarbons. In the first place it seems to be established that the nervous pathology is caused only by n-hexane and not by its isomers referred to above or by pure n-pentane or n-heptane.

Figure 1 shows the metabolic pathway of n-hexane and methyl n-butyl ketone in human beings. It can be seen that the two compounds have a common metabolic pathway and that MBK can be formed from n-hexane. The nervous pathology has been reproduced with 2-hexanol, 2,5-hexanediol and 2,5-hexanedione. It is obvious, as has been shown, moreover, by clinical experience and animal experiment, that MBK is also neurotoxic. The most toxic of the n-hexane metabolites in question is 2,5-hexanedione. Another important aspect of the connection between n-hexane metabolism and toxicity is the synergistic effect that methyl ethyl ketone (MEK) has been shown to have in the neurotoxicity of n-hexane and MBK. MEK is not by itself neurotoxic either for animals or for humans, but it has led to lesions of the peripheral nervous systems in animals treated with n-hexane or MBK that arise more quickly than similar lesions caused by those substances alone. The explanation is most likely to be found in a metabolic interference activity of MEK in the pathway which leads from n-hexane and MBK to the neurotoxic metabolites referred to above.

Figure 1. The metabolic pathway of n-hexane and methyl-n-butyl ketone

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Safety and Health Measures

It is clear from what has been observed above that the association of n-hexane with MBK or MEK in solvents for industrial use is to be avoided. Whenever possible, substitute heptane for hexane.

With regard to TLVs in force for n-hexane, modifications of the EMG pattern have been observed in workers exposed to concentrations of 144 mg/ml (40 ppm) that have not been present in workers not exposed to n-hexane. The medical monitoring of exposed workers is based both on acquaintance with the data concerning the concentration of n-hexane in the atmosphere and on clinical observation, particularly in the neurological field. Biological monitoring for 2,5-hexanedione in the urine is the most useful indicator of exposure, although MBK will be a confounder. If necessary, measurement of n-hexane in exhaled air at the end of shift can confirm exposure.

Cycloparaffins (Cycloalkanes)

The cycloparaffins are alicyclic hydrocarbons in which three or more of the carbon atoms in each molecule are united in a ring structure and each of these ring carbon atoms is joined to two hydrogen atoms, or alkyl groups. The members of this have the general formula C_nH_2n. Derivatives of these cycloparaffins include compounds such as methylcyclohexane (C₆H₁₁CH₃). From the occupational safety and health point of view, the most important of these are cyclohexane, cyclopropane and methylcyclohexane.

Cyclohexane is used in paint and varnish removers; as a solvent for lacquers and resins, synthetic rubber, and fats and waxes in the perfume industry; as a chemical intermediate in the manufacture of adipic acid, benzene, cyclohexyl chloride, nitrocyclohexane, cyclohexanol and cyclohexanone; and for molecular weight determinations in analytical chemistry. Cyclopropane serves as a general anaesthetic.

Hazards

These cycloparaffins and their derivatives are flammable liquids, and their vapours will form explosive concentrations in air at normal room temperature.

They may produce toxic effects by inhalation and ingestion, and they have an irritant and defatting action on the skin. In general, the cycloparaffins are anaesthetics and central nervous system depressants, but their acute toxicity is low and, due to their almost complete elimination from the body, the danger of chronic poisoning is relatively slight.

Cyclohexane. The acute toxicity of cyclohexane is very low. In mice, exposure to 18,000 ppm (61.9 mg/l) cyclohexane vapour in air produced trembling in 5 min, disturbed equilibrium in 15 min, and complete recumbency in 25 min. In rabbits, trembling occurred in 6 min, disturbed equilibrium in 15 min, and complete recumbency in 30 min. No toxic changes were found in the tissues of rabbits after exposure for 50 periods of 6 h to concentrations of 1.46 mg/l (434 ppm). 300 ppm was detectable by odour and somewhat irritating to the eyes and mucous membranes. Cyclohexane vapour causes weak anaesthesia of brief duration but more potent than hexane.

Animal experimentation has shown that cyclohexane is far less harmful than benzene, its six-membered ring aromatic analogue, and, in particular, does not attack the haemopoietic system as does benzene. It is thought that the virtual absence of harmful effects in the blood-forming tissues is due, at least partially, to differences in the metabolism of cyclohexane and benzene. Two metabolites of cyclohexane have been determined—cyclohexanone and cyclohexanol—the former being partially oxidized to adipic acid; none of the phenol derivatives that are a feature of the toxicity of benzene have been found as metabolites in animals exposed to cyclohexane, and this has led to cyclohexane being proposed as a substitute solvent for benzene.

Methylcyclohexane has a toxicity similar to but lower than that of cyclohexane. No effects resulted from repeated exposures of rabbits at 1,160 ppm for 10 weeks, and only slight kidney and liver injury was observed at 3,330 ppm. Prolonged exposure at 370 ppm appeared to be harmless to monkeys. No toxic effects from industrial exposure or intoxication in humans by methylcyclohexane have been reported.

Animal studies show that the majority of this substance entering the bloodstream is conjugated with sulphuric and glucuronic acids and excreted in the urine as sulphates or glucuronides, and in particular the glucuronide of trans-4-methylcyclohexanol.

Saturated and alicyclic hydrocarbons tables

Table 1 - Chemical information.

Table 2 - Health hazards.