Metal Processing and Metal Working

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 06:11

Isocyanates

Isocyanates are also called polyurethanes when they have been compounded into the industrial products known by that name. They form a group of neutral derivatives of primary amines with the general formula R—N=C=O. The isocyanates most used at present are 2,4-toluene diisocyanate (TDI), toluene 2,6-diisocyanate, and diphenylmethane 4,4'-diisocyanate. Hexamethylene diisocyanate and 1,5-naphthylene diisocyanate are less often used.

Isocyanates react spontaneously with compounds containing active hydrogen atoms, which migrate to the nitrogen. Compounds containing hydroxyl groups spontaneously form esters of substituted carbon dioxide or urethanes.

Uses

A major use of isocyanates is in the synthesis of polyurethanes in industrial products. Because of its durability and toughness, methylene bis(4-phenylisocyanate) and 2,4-toluene diisocyanate (TDI) are used in coatings for aircraft, tank trucks and truck trailers. Methylene bis(4-phenylisocyanate) is utilized for bonding rubber to rayon and nylon, and for producing polyurethane lacquer coatings that can be applied to certain automobile components and to patent leather. 2,4-Toluene diisocyanate finds use in polyurethane coatings in floor and wood sealers and finishes, paints and concrete sealers. It is also used for the manufacture of polyurethane foams and for polyurethane elastomers in coated fabrics and clay-pipe seals. Hexamethylene diisocyanate is a cross-linking agent in the preparation of dental materials, contact lenses and medical adsorbants. It is also used as an ingredient in automobile paint.

Hazards

Isocyanates are irritating to the skin and the mucous membranes, the skin conditions ranging from localized itching to more or less widespread eczema. Eye affections are less common, and, although lacrimation is often found, conjunctivitis is rare. The most common and serious troubles, however, are those affecting the respiratory system. The great majority of authorities mention forms of rhinitis or rhinopharyngitis, and various lung conditions have also been described, the first place being taken by asthmatic manifestations, which range from minor difficulty in breathing to acute attacks, sometimes accompanied by sudden loss of consciousness. Individuals may react with severe symptoms of asthma after exposure to very low levels of isocyanates (sometimes below 0.02 ppm) if they have become sensitized. Furthermore, sensitized individuals may become reactive to and affected by environmental stimuli such as exercise and cold air. Sensitized asthma is usually IgE mediated (with high-molecular-weight substances; the mechanism is still unclear with low-molecular-weight substances), while irritant induced asthma is usually secondary to airway inflammation and direct local toxic effects with non-specific hyperresponsiveness. Details of the mechanism of irritant asthma remain unknown. Allergic responses are discussed in more detail elsewhere in this Encyclopaedia.

The isocyanates are often volatile, and the vapour can then be detected by smell at a concentration of 0.1 ppm, but even this very low level is already dangerous for some persons.

2,4-Toluene diisocyanate (TDI). This is the substance that is most widely used in industry and that leads to the greatest number of pathological manifestations, for it is highly volatile and is often used at considerable concentrations. The symptomatology of the troubles due to inhaling it are stereotypic. At the end of a period ranging from a few days to 2 months, symptoms include irritation of the conjunctiva, lacrimation and irritation of the pharynx; later there are respiratory problems, with an unpleasant dry cough in the evening, chest pains, chiefly behind the sternum, difficulty in breathing, and distress. The symptoms become worse during the night and disappear in the morning with a slight expectoration of mucus. After a few days’ rest they diminish, but a return to work is generally accompanied by the reappearance of the symptoms: cough, chest pains, moist wheezing, shortness of breath (dyspnoea) and distress. Radiological and humoural tests are usually negative.

Respiratory dysfunctions that are known to be caused by TDI include bronchitis, occupational asthma, and a worsening of respiratory function both at work and chronically. In other cases there may be recurrent common cold or a particularly pruriginous eczema that may occur on many different parts of the skin. Some victims may suffer from skin and respiratory troubles at the same time.

In addition to these characteristic consequences of the intoxication, there are rather different effects resulting from exposure to very low concentrations over a long period running into years; these combine typical asthma with expiratory bradypnoea and eosinophilia in the sputum.

The physiopathology of the intoxication is still far from being fully understood. Some believe that there is a primary irritation; others think of an immunity mechanism, and it is true that the presence of antibodies has been shown in some cases. Sensitivity could be demonstrable with provocation tests, but great care must be taken in order to avoid further sensitization, and only an experienced medical practitioner should administer these tests. Many allergological tests, however, (with acetylcholine or the standard allergens, for example) are generally negative. With respect to pulmonary function tests, the FEV/FVC ratio seems to be the most convenient way of expressing defective respiration. The usual functional examinations carried out away from a place of exposure to the hazard are normal.

Diphenyl methane 4,4'-diisocyanate (MDI). This substance is less volatile and its fumes become harmful only when the temperature approaches 75 °C, but similar cases of poisoning have nevertheless been described. They occur mainly with aerosols, for MDI is often used in liquid form for atomizing.

Hexamethylene diisocyanate. This substance, which is less widely used, is highly irritating to the skin and eyes. The most common problems attributed to it are forms of blepharoconjunctivitis. Methyl isocyanate is the chemical thought responsible for the Bhopal disaster.

1,5-Naphthylene diisocyanate. This isocyanate is little used in industry. Poisoning after exposure to the vapour heated to over 100 °C has been reported.

Safety and Health Measures

Ventilation, protective equipment and safety and health training for workers, as described elsewhere in this Encyclopaedia, are all required for working with isocyanates. It is important to have local ventilation located as close as possible to the source of isocyanate vapours. The decomposition and release of isocyanates from polyurethane foams and glues must be taken into consideration in the design of any industrial process.

Medical prevention. The pre-employment medical examination must include a questionnaire and a thorough clinical examination in order to prevent exposure of persons with allergic cutaneous or respiratory antecedents to isocyanates. Exposed workers must be kept under regular observation. The sanitary facilities at the disposal of the workers must include showers.

Isocyanates tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 06:07

Hydrocarbons, Polyaromatic

Polycyclic aromatic hydrocarbons (PAHs) are organic compounds consisting of three or more condensed aromatic rings, where certain carbon atoms are common to two or three rings. Such a structure is also referred to as a fused ring system. The rings can be arranged in a straight line, angled or in a cluster formation. Furthermore, the name hydrocarbon indicates that the molecule contains only carbon and hydrogen. The simplest fused structure, containing only two condensed aromatic rings, is naphthalene. To the aromatic rings, other types of rings can be fused such as five-carbon rings or rings containing other atoms (oxygen, nitrogen or sulphur) substituted for carbon. The latter compounds are referred to as heteroaromatic or heterocyclic compounds and will not be considered here. In the PAH literature many other notations are found: PNA (polynuclear aromatics), PAC (polycyclic aromatic compounds), POM (polycyclic organic matter). The last notation often includes heteroaromatic compounds. PAHs include hundreds of compounds which have attracted much attention because many of them are carcinogenic, especially those PAHs containing four to six aromatic rings.

The nomenclature is not uniform in the literature, which can confuse the reader of papers from different countries and ages. IUPAC (International Union of Pure and Applied Chemistry) has adopted a nomenclature which nowadays is commonly used. A very brief summary of the system follows:

Some parent PAHs are selected and their trivial names are retained. As many rings as possible are drawn in a horizontal line and the greatest number of remaining rings are placed in the upper right quadrant. The numbering starts with the first carbon atom not common to two rings in the ring to the right in the top line. The following carbon atoms binding a hydrogen are numbered clockwise. The outer sides of the rings are given letters in alphabetical order, beginning with the side between C 1 and C 2.

To elucidate the nomenclature of PAHs, the name for benzo(a)pyrene is taken as an example. Benzo(a)— indicates that an aromatic ring is fused to pyrene in the a position. A ring can be fused also in positions b, e, and so on. However, positions a, b, h and i are equivalent, and so are e and l. Accordingly, there are only two isomers, benzo(a)pyrene and benzo(e)pyrene. Only the first letter is used, and the formulas are written according to the rules above. Also in positions cd, fg, and so on, of pyrene a ring can be fused. However, this substance, 2H-benzo(cd)pyrene, is saturated in position 2, which is indicated by an H.

Physico-chemical properties of PAHs. The conjugated II-electron systems of the PAHs account for their chemical stability. They are solids at room temperature and have very low volatility. Depending on their aromatic character, the PAHs absorb ultraviolet light and give characteristic fluorescence spectra. The PAHs are soluble in many organic solvents, but they are very sparingly soluble in water, decreasing with increasing molecular weight. However, detergents and compounds causing emulsions in water, or PAHs adsorbed on suspended particles, can increase the content of PAHs in wastewater or in natural waters. Chemically, the PAHs react by substitution of hydrogen or by addition reactions where saturation occurs. Generally the ring system is retained. Most PAHs are photo-oxidized, a reaction which is important for the removal of PAHs from the atmosphere. The most common photo-oxidation reaction is formation of endoperoxides, which can be converted to quinones. For steric reasons an endoperoxide cannot be formed by photo-oxidation of benzo(a)pyrene; in this case 1,6-dione, 3,6-dione and 6,12-dione are formed. It has been found that the photo-oxidation of adsorbed PAHs can be greater than that of PAHs in solution. This is of importance when analysing PAHs by thin-layer chromatography, especially on layers of silica gel, where many PAHs very rapidly photo-oxidize when illuminated by ultraviolet light. For the elimination of PAHs from the occupational environment the photo-oxidation reactions are of no importance. PAHs rapidly react with nitrogen oxides or HNO₃. For example anthracene can be oxidized to anthraquinone by HNO₃ or give a nitro derivative by a substitution reaction with NO₂. PAHs can react with
SO₂, SO₃ and H₂SO₄ to form sulphinic and sulphonic acids. That carcinogenic PAHs react with other substances does not necessarily mean that they are inactivated as carcinogens; on the contrary, many PAHs containing substituents are more powerful carcinogens than the corresponding parent compound. A few important PAHs are considered individually here.

Formation. PAHs are formed by pyrolysis or incomplete combustion of organic material containing carbon and hydrogen. At high temperatures the pyrolysis of organic compounds yields molecule fragments and radicals which combine to give PAHs. The composition of the resulting products of the pyrosynthesis is dependent on the fuel, the temperature and the residence time in the hot area. Fuels found to yield PAHs include methane, other hydrocarbons, carbohydrates, lignins, peptides, lipids and so on. However, compounds containing chain branching, unsaturation or cyclic structures generally favour the PAH yield. Evidently PAHs are emitted as vapours from the zone of burning. Due to their low vapour pressures most PAHs will immediately condense on soot particles or form very small particles themselves. PAHs entering the atmosphere as vapour will be adsorbed on existing particles. Aerosols containing PAHs are thus spread in the air and may be transported great distances by winds.

Occurrence and Uses

Many PAHs can be prepared from coal tar. The pure substances have no significant technical use, except for naphthalene and anthracene. However, they are used indirectly in coal tar and petroleum, which contain mixtures of various PAHs.

PAHs can be found almost everywhere, in air, soil and water originating from natural and anthropogenic sources. The contribution from natural sources such as forest fires and volcanoes is minute compared to the emissions caused by humans. The burning of fossil fuels causes the main emissions of PAHs. Other contributions come from the combustion of refuse and wood, and from the spillage of raw and refined petroleum which per se contains PAHs. PAHs also occur in tobacco smoke and grilled, smoked and fried food.

The most important source of PAHs in the air of the occupational environment is coal tar. It is formed by pyrolysis of coal in gas and coke works where emissions of fumes from the hot tar occurs. The workers in the vicinity of the ovens are highly exposed to these PAHs. Most investigations of PAHs in work environments have been made in gas and coke works. In most cases only benzo(a)pyrene has been analysed, but there are also some investigations on a number of other PAHs available. Generally, the benzo(a)pyrene content in the air above the ovens shows the highest values. The air above the flues and the tar precipitator is extremely rich in benzo(a)pyrene, up to 500 mg/m³ has been measured. By personal air sampling, the highest exposure has been found for truck drivers, wharf workers, chimney sweeps, lid workers and tar chasers. Naphthalene, phenanthrene, fluoranthene, pyrene and anthracene dominate among the PAHs isolated from air samples taken on the battery top. It is evident that some of the workers in the gas and coke industry are exposed to PAHs at high levels, even in modern installations. Certainly, in these industries, it would not be unusual for a large number of workers to have been exposed for many years. Epidemiological investigations have shown an elevated risk of lung cancer for these workers. Coal tar is used in other industrial processes, where it is heated, and thereby PAHs are liberated to the ambient air.

The poly aryl hydrocarbons are primarily used in the manufacture of dyes and chemical sythesis. Anthracene is used for the production of anthraquinone, an important raw material for the manufacture of fast dyes. It is also used as a diluent for wood preservatives and in the production of synthetic fibres, plastics and monocrystals. Phenanthrene is used in the manufacture of dye-stuffs and explosives, biological research, and the synthesis of drugs.

Benzofuran is employed in the manufacture of coumarone-indene resins. Fluoranthene is a constituent of coal tar and petroleum-derived asphalt used as lining material to protect the interior of steel and ductile-iron potable water pipes and storage tanks.

Aluminium is manufactured in an electrolytic process at a temperature of about 970 °C. There are two types of anodes: the Söderberg anode and the graphite (“prebaked”) anode. The former type, which is the most commonly used, is the main cause of PAH exposure in aluminium works. The anode consists of a mixture of coal-tar pitch and coke. During electrolysis it is graphitized (“baked”) in its lower, hotter part, and finally consumed by electrolytic oxidation to carbon oxides. Fresh anode paste is added from above to keep the electrode running continuously. PAH components are liberated from the pitch at the high temperature, and they escape to the work area in spite of ventilation arrangements. In many different occupations in an aluminium smelter such as stud-pulling, rack-raising, mounting of flaints and adding of anode paste, the exposure can be considerable. Also ramming of cathodes causes exposure to PAHs, as pitch is used in rodding and slot mixes.

Graphite electrodes are used in aluminium reduction plants, in electric steel furnaces and in other metallurgical processes. The raw material for these electrodes is generally petroleum coke with tar or pitch as a binder. The baking is done by heating this mixture in ovens to temperatures above 1,000 °C. In a second heating step up to 2,700 °C the graphitization occurs. During the baking procedure large quantities of PAHs are liberated from the electrode mass. The second step involves rather little PAH exposure, since the volatile components are given off during the first heating.

In iron and steel works and foundries exposure occurs to PAHs originating from coal tar products in contact with molten metal. The tar preparations are used in furnaces, runners and ingot moulds.

The asphalt used for paving streets and roads mainly comes from the distillation residue of petroleum crude oils. The petroleum asphalt in itself is poor in higher PAHs. In some cases, however, it is mixed with coal tar, which increases the possibility of exposure to PAHs when working with hot asphalt. In other operations where tar is melted and spread on a large area, the workers may be heavily exposed to PAHs. Such operations include pipeline coating, wall insulation and roof tarring.

Hazards

In 1775 an English surgeon, Sir Percival Pott, first described occupational cancer. He associated scrotal cancer in chimney sweeps with their prolonged exposure to tar and soot under conditions of bad personal hygiene. One hundred years later, skin cancer was described in workers exposed to coal tar or shale oil. In the 1930s, lung cancer in workers at steel works and coke works was described. Experimentally developed skin cancer in laboratory animals after repeated application of coal tar was described at the end of the 1910s. In 1933 it was shown that a polycyclic aromatic hydrocarbon isolated from coal tar was carcinogenic. The isolated compound was benzo(a)pyrene. Since then hundreds of carcinogenic PAHs have been described. Epidemiological studies have indicated an elevated frequency of lung cancer of workers in the coke, aluminium and steel industries. Approximately a century later, several of the PAHs have been regulated as occupational carcinogens.

The long latency between first exposure and symptoms, and many other factors, have made the establishment of threshold limit values for PAHs in the work atmosphere an arduous and drawn out task. A long latency period also has existed for standards-making. Threshold limit values (TLVs) for PAHs were practically non-existent until 1967, when the American Conference of Governmental Industrial Hygienists (ACGIH) adopted a TLV of 0.2 mg/m³ for coal tar pitch volatiles. It was defined as the weight of the benzene-soluble fraction of the particulates collected on a filter. In the 1970s, the USSR issued a maximum allowable concentration (MAC) for benzo(a)pyrene (BaP) based upon laboratory experiments with animals. In Sweden a TLV of 10 g/m³was introduced for BaP in 1978. As of 1997, the US Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for BaP is 0.2 mg/m³. The ACGIH has no time-weighted average (TWA) since BaP is a suspected human carcinogen. The US National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL) is 0.1 mg/m³ (cyclohexane extractable fraction).

Occupational sources of PAHs other than coal tar and pitch are carbon black, creosote, mineral oils, smoke and soot from various types of burning, and exhaust gases from vehicles. Mineral oils contain low levels of PAHs, but many types of usage cause considerable increase of the PAH content. Some examples are motor oils, cutting oils and oils used for electric discharge machining. However, since the PAHs remain in the oil, the risk of exposure is mainly limited to skin contact. Exhaust gases from vehicles contain low levels of PAHs compared to fumes from coal tar and pitch. In the following list, measurements of benzo(a)pyrene from various types of workplaces has been used to range them according to the degree of exposure:

very high benzo(a)pyrene exposure (more than 10 mg/m³)— gas and coke works; aluminium works; graphite electrode plants; handling of hot tar and pitch

moderate exposure (0.1 to 10 g/m³)—gas and coke works; steel works; graphite electrode plants; aluminium works; foundries

low exposure (less than 0.1 g/m³)—foundries; asphalt manufacturing; aluminium works with prebaked electrodes; automobile repair shops and garages; iron mines and construction of tunnels.

Hazards associated with selected PAHs

Anthracene is a polynuclear aromatic hydrocarbon with condensed rings, which forms anthraquinone by oxidation and 9,10-dihydroanthracene by reduction. The toxic effects of anthracene are similar to those of coal tar and its distillation products, and depend on the proportion of heavy fractions contained in it. Anthracene is photosensitizing. It can cause acute and chronic dermatitis with symptoms of burning, itching and oedema, which are more pronounced in the exposed bare skin regions. Skin damage is associated with irritation of the conjunctiva and upper airways. Other symptoms are lacrimation, photophobia, oedema of the eyelids, and conjunctival hyperaemia. The acute symptoms disappear within several days after cessation of contact. Prolonged exposure gives rise to pigmentation of the bare skin regions, cornification of its surface layers, and telangioectasis. The photodynamic effect of industrial anthracene is more pronounced than that of pure anthracene, which is evidently due to admixtures of acridine, carbazole, phenanthrene and other heavy hydrocarbons. Systemic effects manifest themselves by headache, nausea, loss of appetite, slow reactions and adynamia. Prolonged effects may lead to inflammation of the gastrointestinal tract.

It has not been established that pure anthracene is carcinogenic, but some of its derivatives and industrial anthracene (containing impurities) have carcinogenic effects. 1,2-Benzanthracene and certain monomethyl and dimethyl derivatives of it are carcinogens. The dimethyl and trimethyl derivatives of 1,2-benzanthracene are more powerful carcinogens than the monomethyl ones, especially 9,10-dimethyl-1,2-benzanthracene, which causes skin cancer in mice within 43 days. The 5,9- and 5,10- dimethyl derivatives are also very carcinogenic. The carcinogenicity of 5,9,10- and 6,9,10-trimethyl derivatives are less pronounced. 20-Methylcholanthrene, which has a structure similar to that of 5,6,10-trimethyl-1,2-benzanthracene, is an exceptionally powerful carcinogen. All dimethyl derivatives which have methyl groups substituted on the additional benzene ring (in the 1, 2, 3, 4 positions) are non-carcinogenic. It has been established that the carcinogenicity of certain groups of alkyl derivatives of 1,2-benzanthracene diminishes as their carbon chains lengthen.

Benz(a)anthracene occurs in coal tar, up to 12.5 g/kg; wood and tobacco smoke, 12 to 140 ng in the smoke from one cigarette; mineral oil; outdoor air, 0.6 to 361 ng/m³; gas works, 0.7 to 14 mg/m³. Benz(a)anthracene is a weak carcinogen, but some of its derivatives are very potent carcinogens—for example, 6-, 7-, 8- and 12-methylbenz(a)anthracene and some of the dimethyl derivatives such as 7,12-dimethylbenz(a)anthracene. Introducing a five-membered ring at the 7 to 8 position of benz(a)anthracene results in cholanthrene (benz(j)aceanthrylene), which, together with its 3-methyl derivative, is an extremely powerful carcinogen. Dibenz(a,h)anthracene was the first pure PAH shown to have carcinogenic activity.

Chrysene occurs in coal tar pitch up to 10 g/kg. From 1.8 to 361 ng/m³ has been measured in air and 3 to 17 mg/m³ in diesel engine exhaust. Smoke from a cigarette can contain up to 60 ng of chrysene. Dibenzo(b,d,e,f)-chrysene and dibenzo(d,e,f,p)-chrysene are carcinogenic. Chrysene has weak carcinogenic activity.

Diphenyls. Little information is available about the toxic effects of diphenyl and its derivatives, with the exception of the polychlorinated biphenyl (PCBs). Owing to their low vapour pressure and smell, exposure by inhalation at room temperature does not usually entail a serious risk. However, in one observation, workers engaged in impregnating wrapping paper with a fungicide powder made of diphenyl experienced bouts of coughing, nausea and vomiting. In repeated exposure to a solution of diphenyl in paraffin oil at 90 °C and airborne concentrations well above 1 mg/m³, one man died of acute yellow atrophy of the liver, and eight workers were found suffering from central and peripheral nervous damage and liver injury. They complained of headache, gastrointestinal disturbances, polyneuritic symptoms and general fatigue.

Molten diphenyl can cause serious burns. Skin absorption is also a moderate hazard. Eye contact produces mild to moderate irritation. Processing and handling of diphenyl ether in ordinary use involves little health hazard. The odour may be very unpleasant, and excessive exposure results in eye and throat irritation.

Contact with the substance can produce dermatitis.

The mixture of diphenyl ether and diphenyl at concentrations between 7 and 10 ppm does not seriously affect experimental animals in repeated exposure. However, in humans it can cause eye and airways irritation and nausea. Accidental ingestion of the compound resulted in severe impairment of liver and kidney.

Fluoranthene occurs in coal tar, tobacco smoke and airborne PAHs. It is not a carcinogen whereas the benzo(b)-, benzo(j)- and benzo(k)- isomers are.

Naphthacene occurs in tobacco smoke and coal tar. It causes colouration of other colourless substances isolated from coal tar, such as anthracene.

Naphthalene is readily flammable and, in particulate or vapour form, will form explosive mixtures with air. Its toxic action has been observed primarily as a result of gastrointestinal poisonings in children who mistook mothballs for sweets, and is manifested by acute haemolytic anaemia with hepatic and renal lesions and vesical congestion.

There have been reports of serious intoxication in workers who had inhaled concentrated naphthalene vapours; the most common symptoms were haemolytic anaemia with Heinz bodies, hepatic and renal disorders, and optic neuritis. Prolonged absorption of naphthalene may also give rise to small punctiform opacities in the periphery of the crystalline lens, with no functional impairment. Eye contact with concentrated vapours and condensed micro-crystals may result in punctiform keratitis and even chorioretinitis.

Skin contact has been found to cause erythemato-exudative dermatitis; however, such cases have been attributed to contact with crude naphthalene which still contained phenol, which was the causative agent of the foot dermatitis encountered amongst workers who discharge naphthalene crystallization trays.

Phenanthrene is prepared from coal tar and can be synthesized by passing diphenylethylene through a red-hot tube. It occurs also in tobacco smoke and is found among airborne PAHs. It does not appear to have carcinogenic activity, but some alkyl derivatives of benzo(c)phenanthrene are carcinogenic. Phenanthrene is a recommended exception to systematic numbering; 1 and 2 are indicated in the formula.

Pyrene occurs in coal tar, tobacco smoke and airborne PAHs. From 0.1 to 12 mg/ml is found in petroleum products. Pyrene has no carcinogenic activity; however, its benzo(a) and dibenzo derivatives are very potent carcinogens. Benzo(a)pyrene (BaP) in outdoor air has been measured from 0.1 ng/m³ or lower in unpolluted areas to values several thousand times higher in polluted urban air. BaP occurs in coal tar pitch, coal tar, wood tar, automobile exhaust, tobacco smoke, mineral oil, used motor oil and used oil from electric discharge machining. BaP and many of its alkyl derivatives are very potent carcinogens.

Terphenyl vapours cause conjunctival irritation and some systemic effects. In experimental animals p-terphenyl is poorly absorbed by oral route and appears to be only slightly toxic; meta- and especially ortho-terphenyls are dangerous to the kidney, and the latter can also impair liver functions. Morphologic alterations of mitochondria (the small cellular bodies performing respiratory and other enzymatic functions essential to biological synthesis) have been reported in rats exposed to 50 mg/m³. Heat transfer agents made of hydrogenated terphenyls, terphenyl mixture and isopropyl-meta-terphenyl produced functional changes of nervous system, kidney and blood in experimental animals, with some organic lesions. A carcinogenic risk has been demonstrated for mice exposed to the irradiated coolant, while the non-irradiated mixture appeared to be safe.

Health and Safety Measures

PAHs are found mainly as air contaminations in a great variety of workplaces. Analyses always show the highest content of PAHs in air samples taken where visible smoke or fumes occur. A general method to prevent exposure is to diminish such emissions. In coke works this is done by tightening leaks, increasing ventilation or using cabs with filtered air. In aluminium works similar measures are taken. In some instances, fume and vapor clearance systems will be necessary. Use of prebaked electrodes almost eliminates PAH emissions. In foundries and steel works PAH emissions can be decreased by avoiding preparations containing coal tar. Special arrangements are not needed to remove PAHs from garages, mines and so on, where exhaust gases from automobiles are emitted; ventilation arrangements necessary to remove other more toxic substances simultaneously decrease the PAH exposure. Skin exposure to used oils containing PAHs is avoidable by using gloves and changing contaminated clothes.

Engineering, personal protective, training and sanitary facilties described elsewhere in this Encyclopaedia are to be applied. Since so many members of this family are known or suspected carcinogens, particular care must be given to adherence to the precautions required for the safe handling of carcinogenic substances.

Polyaromatic hydrocarbons tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 06:01

Hydrocarbons, Halogenated Aromatic

The halogenated aromatic hydrocarbons are chemicals which contain one or more atoms of a halogen (chloride, fluoride, bromide, iodide) and a benzene ring.

Uses

Chlorobenzene (and derivatives such as dichlorobenzene; m-dichlorobenzene;
p-dichlorobenzene; 1,2,3-trichlorobenzene; 1,3,5-trichlorobenzene; 1,2,4-trichlorobenzene; hexachlorobenzene; 1-chloro-3-nitrobenzene; 1-bromo-4-chlorobenzene). Monochlorobenzene and dichlorobenzenes have been widely used as solvents and chemical intermediates. Dichlorobenzenes, especially the p-isomer, are employed as fumigants, insecticides and disinfectants. A mixture of trichlorobenzene isomers is applied to combat termites. 1,2,3-Trichlorobenzene and 1,3,5-trichlorobenzene were formerly used as heat transfer media, transformer fluids and solvents.

Hexachlorobenzene is a fungicide and intermediate for dyes and hexafluorobenzene. It is also the raw material for synthetic rubber, a plasticizer for polyvinyl chloride, an additive for the military’s pyrotechnic compositions, and a porosity controlling agent in the manufacture of electrodes.

Benzyl chloride serves as an intermediate in the manufacture of benzyl compounds. It is used in the manufacture of quaternary ammonium chlorides, dyes, tanning materials, and in pharmaceutical and perfume preparations. Benzoyl chloride is used in the textile and dye industries as a fastness improver for dyed fibre or fabrics.

The chloronaphthalenes in industrial use are mixtures of tri-, tetra-, penta- and hexachloronaphthalenes. Many of these compounds have been formerly used as heat transfer media, solvents, lubricant additives, dielectric fluids and electric insulating material (pentachloronaphthalene, octachloronaphthalene, trichloronaphthalene, hexachloronaphthalene and tetrachloronaphthalene). In most cases, plastics have been substituted for chlorinated naphthalenes.

DDT was extensively used for the control of insects, which are parasites or vectors of organisms causing disease in humans. Among such diseases are malaria, yellow fever, dengue, filariasis, louse-borne typhus and louse-borne relapsing fever, which are transmitted by arthropod vectors vulnerable to DDT. Although the use of DDT has been discontinued in European countries, the United States and Japan, DDT may be used by public health officials and the military for the control of vector diseases, for health quarantine, and in drugs for controlling body lice.

Hexachlorophene is a topical anti-infective agent, a detergent and an antibacterial agent for soaps, surgical scrubs, hospital equipment and cosmetics. It is used as a fungicide for vegetables and ornamentals. Benzethonium chloride is also used as a topical anti-infective in medicine as well as a germicide for cleansing food and dairy utensils, and as a controlling agent for swimming pool algae. It is also an additive in deodorants and hairdressing preparations.

Polychlorinated biphenyls (PCBs). The commercial production of technical PCBs increased in 1929, when PCBs began to be used as non-flammable oils in electrical transformers and condensers. It has been estimated that 1.4 billion pounds of PCBs were produced in the United States from the late 1920s to the mid-1970s, for example. The main properties of PCBs that accounted for their use in the production of a variety of items are: low solubility in water, miscibility with organic solvents and polymers, high dielectric constant, chemical stability (very slow breakdown), high boiling points, low vapour pressure, thermostability and flame resistance. PCBs are also bacteriostatics, fungistatics and pesticide synergists.

PCBs had been used in “closed” or “semiclosed” systems, such as electrical transformers, capacitors, heat transfer systems, fluorescent light ballasts, hydraulic fluids, lubricating oils, insulated electric wires and cables, and so on, and in “open end” applications, such as: plasticizers for plastic materials; adhesives for waterproof wall coatings; surface treatment for textiles; surface coating of wood, metal and concrete; caulking material; paints; printing inks; paper, carbonless copy paper, impregnated citrus fruit wrapping paper; cutting oils; microscopic mounting medium, microscope immersion oil; vapour suppressants; fire retardants; and in insecticide and bactericide formulations.

Hazards

There are numerous hazards associated with exposure to halogenated aromatic hydrocarbons. The effects can vary considerably, depending on the type of compound. As a group, toxicity of the halogenated aromatic hydorcarbons has been associated with acute irritation of the eyes, mucous membranes and lungs, as well as gastrointestinal and neurological symptoms (nausea, headaches and central nervous system depression). Acne (chloracne) and liver dysfunction (hepatitis, jaundice, porphyria) can also occur. Reproductive disorders ( including abortions, stillbirths and low birthweight babies) have been reported, as have certain malignancies. What follows is a closer look at the particular effects associated with selected chemicals from this group.

The chlorinated toluenes as a group (benzyl chloride, benzal chloride and benzotrichloride) are classified by the International Agency for Research on Cancer (IARC) as Group 2A carcinogens. As a result of its strong irritant properties benzyl chloride concentrations of 6 to 8 mg/m³ cause a light conjunctivitis after 5 minutes of exposure. Airborne concentrations of 50 to 100 mg/m³ immediately cause weeping and twitching of the eyelids, and in concentrations of 160 mg/m³ it is unbearably irritating to the eyes and mucous membrane of the nose. The complaints of workers exposed to 10 mg/m³ and more of benzyl chloride included weakness, rapid fatigue, persistent headaches, increased irritability, feeling hot, loss of sleep and appetite, and, in some, itching of the skin. Medical examinations of workers revealed asthenia, dystonia of the autonomic nervous system (hyperhidrosis, tremors in the eyelids and fingers, unsteadiness in Romberg’s test, dermatographic changes, and so on). There may also be disturbances of liver function, such as increased bilirubin content of the blood and positive Takata-Ara and Weltmann tests, a decrease in the number of leucocytes, and a tendency to illness similar to colds and allergic rhinitis. Cases of acute poisoning have not been reported. Benzyl chloride can cause dermatitis, and if it enters the eyes, the result is intense burning, weeping and conjunctivitis.

Chlorobenzene and its derivatives can cause acute irritation of the eyes, nose and skin. At higher concentrations, headache and respiratory depression occur. Of this group, hexachlorobenzene deserves special mention. Between 1955 and 1958, a severe outbreak took place in Turkey after ingestion of wheat that had been contaminated with the fungicide hexachlorobenzene. Thousands of people developed porphyria, which began with bullous lesions progressing to ulceration, healing with pigmented scars. In children the initial lesions resembled comedones and milia. Ten per cent of those affected died. Infants who ingested breast milk contaminated with hexachlorobenzene had a 95% mortality rate. Massive discharges of porphyrins were detected in urine and faeces of the patients. Even 20 to 25 years later, between 70 and 85% of survivors had hyperpigmentation and residual scarring on their skin. Arthritis and muscle disorders have also persisted. Hexachlorobenzene is classified as a Group 2B carcinogen (possibly carcinogenic to humans) by IARC.

The toxicity of chloronaphthalenes increases with a higher degree of chlorination. Chloracne and toxic hepatitis are the primary problem caused by exposure to this substance. The higher chlorinated naphthalenes may cause severe injury to the liver, characterized by acute yellow atrophy or by subacute necrosis. Chloronaphthalenes also have a photosensitizing effect on the skin.

During manufacture and/or handling of PCBs, these compounds may penetrate into the human body following cutaneous, respiratory or digestive exposure. PCBs are very lipophilic and hence distribute readily into fat. Metabolism occurs in the liver, and the higher the chlorine content of the isomer the slower it is metabolized. Hence these compounds are very persistent, and are detectable in fatty tissue years after exposure. The highly chlorinated biphenyl isomers undergo a very slow metabolism in the animal body and are consequently excreted in very low percentages (less than 20% of 2,4,5,2',4',5'-hexachlorobiphenyl was excreted within the lifetime of rats that received a single intravenous dose of this compound).

Although PCB manufacture, distribution and use was banned in the United States in 1977, and later elsewhere, accidental exposure (such as leakages or environmental contamination) is still a concern. It is not uncommon for transformers containing PCBs to catch fire or explode, leading to widespread contamination of the environment with PCBs and toxic decomposition products. In some occupational exposures, the gas-chromatographic pattern of PCB residues differs from that of the general population. Diet, concomitant exposure to other xenobiotics and features of biochemical individuality may also influence the PCB gas-chromatogram pattern. The decrease of plasma PCB levels after withdrawal from occupational exposure was relatively fast in workers exposed for short periods and very slow in those exposed for more than 10 years and/or in those exposed to highly chlorinated PCB mixtures.

In people occupationally exposed to PCBs a broad spectrum of adverse health effects have been reported. Effects include skin and mucous membrane changes; swelling of the eyelids, burning of the eye, and excessive eye discharge. Burning sensation and oedema of the face and hands, simple erythematous eruptions with pruritus, acute eczematous contact dermatitis (vesiculo-erythematous eruptions), chloracne (an extremely refractory form of acne), hyperpigmentation of skin and mucous membranes (palpebral conjunctiva, gingiva), discolouration of fingernails and thickening of the skin can also occur. Irritation of the upper respiratory airways is frequently seen. A decrease in forced vital capacity, without radiological changes, was reported in a relatively high percentage of the workers exposed in a capacitor factory.

Digestive symptoms such as abdominal pain, anorexia, nausea, vomiting and jaundice, with rare cases of coma and death, may occur. At autopsy, acute yellow atrophy of the liver was found in lethal cases. Sporadic cases of acute yellow atrophy of the liver were reported.

Neurological symptoms such as headache, dizziness, depression, nervousness and so on, and other symptoms such as fatigue, loss of weight, loss of libido and muscle and joint pains were found in various percentages of exposed people.

PCBs are Group 2A carcinogens (probably carcinogenic to humans) according to the IARC evaluation. After the environmental disaster in Yusho, Japan, where PCBs contaminated cooking oils, an excess of malignant tumours was observed. Pathological pregnancies (toxaemia of pregnancy, abortions, stillbirths, underweight births and so on) were frequently associated with increased PCB serum levels in Yusho patients and in the general population.

PBBs (polybrominated biphenyls) are chemical analogues of PCBs with bromine rather than chlorine substituents of the biphenyl rings. Like PCBs, there are numerous isomers, although commercial PBBs are predominantly hexabrominated and have been used mainly as fire retardants. They are lipophilic, and accumulate in adipose tissue; being poorly metabolized they are excreted only slowly. Human health effects are known largely because of a 1973 episode in which about 900 kg were inadvertently mixed into livestock feed in Michigan, after which numerous farm families were exposed to dairy and meat products. Adverse health effects noted included acne, drying and darkening of skin, nausea, headache, blurred vision, dizziness, depression, unusual fatigue, nervousness, sleepiness, weakness, paresthesia, loss of balance, joint pain, back and leg pain, elevated liver enzymes SGPT and SGOT, and decreased immune function. PBB has been reported in serum and adipose tissue of PBB production workers and in breast milk, umbilical cord blood, biliary fluid, and faeces of women and infants exposed via diet.

IARC has classified PBBs as possible human carcinogens (Group 2B).

Dioxin

Dioxin—2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—is not manufactured commercially but is present as an impurity in 2,4,5-trichlorophenol (TCP). Minute traces may be present in the herbicide 2,4,5-T and in the antibacterial agent hexachlorophene, which are produced from trichlorophenol.

TCDD is formed as a by-product during the synthesis of 2,4,5-trichlorophenol from 1,2,4,5-tetrachlorobenzene under alkaline conditions by the condensation of two molecules of sodium trichlorophenate. When temperature and pressure keeping the reaction in progress are observed carefully, the crude 2,4,5-trichlorophenol contains less than 1 mg/kg up to a maximum of 5 mg/kg TCDD (1 to 5 ppm). Greater amounts are formed at higher temperatures (230 to 260 °C).

The chemical structure of TCDD was identified in 1956 by Sandermann et al., who first synthetized it. The laboratory technician working on the synthesis was hospitalized with very severe chloracne.

There are 22 possible isomers of tetrachlorodibenzo-p-dioxin. TCDD is commonly used to mean 2,3,7,8-tetrachlorodibenzo-p-dioxin, without excluding the existence of the other 21 tetraisomers. TCDD can be prepared for chemical and toxicological standard by catalytic condensation of potassium 2,4,5-trichlorophenate.

TCDD is a solid substance with very low solubility in common solvents and water (0.2 ppb) and is very stable to thermal degradation. In the presence of a hydrogen donor it is rapidly degraded by light. When incorporated in the soil and aquatic systems, it is practically immobile.

Occurrence

The major source of TCDD formation in the environment is thermal reaction either in the chemical production of 2,4,5-trichlorophenol or in the combustion of chemicals which may contain precursors of the dioxins in general.

Occupational exposure to TCDD may occur during the production of trichlorophenol and its derivatives (2,4,5-T and hexachlorophene), during their incineration, and during the use and handling of these chemicals and their wastes and residues.

General exposure of the public may occur in relation to a herbicide spraying programme; bioaccumulation of TCDD in the food chain; inhalation of fly ashes or flue gases from municipal incinerators and industrial heating facilities, during combustion of carbon-containing material in the presence of chlorine; unearthing of chemical wastes; and contact with people wearing contaminated clothes.

Toxicity

TCDD is extremely toxic in experimental animals. The mechanism by which death occurs is not yet understood. Sensitivity to the toxic effect varies with the species. The lethal dose ranges from 0.5 mg/kg for the guinea-pig to over 1,000 mg/kg for the hamster by the oral route. The lethal effect is slow and ensues several days or weeks after a single dose.

Chloracne and hyperkeratosis are a distinctive feature of TCDD toxicity which is observed in rabbits, monkeys and hairless mice, as well as in the human being. TCDD has teratogenic and/or embryotoxic effects in the rodent. In the rabbit the major site of the toxic action appears to be the liver. In the monkey the first sign of toxicity is in the skin, whereas the liver remains relatively normal. Several species develop disturbance of the hepatic porphyrin metabolism. Immunosuppression, carcinogenicity, enzyme induction and mutagenicity have also been observed under experimental conditions. The half-life in the rat and guinea-pig is approximately 31 days, and the major route of excretion is the faeces.

The identification of TCDD as the toxic agent responsible for the lesions and symptoms observed in humans after exposure to trichlorophenol or 2,4,5-trichlorophenoxyacetic acid was made in 1957 by K.H. Schulz in Hamburg, who eventually determined in tests with rabbits its chloracnegenic and hepatotoxic properties. In a self-administered skin test (10 mg applied two times), he also demonstrated the effect on human skin. A human experiment was repeated by Klingmann in 1970: in humans, application of 70 mg/kg produced definite chloracne.

Toxic effects produced by TCDD in humans have been reported as a consequence of repetitive occupational exposure during the industrial production of trichlorophenol and 2,4,5-T, and of acute exposure in factories and their environment from accidents during the manufacture of the same products.

Industrial exposure

The annual world production of 2,4,5-trichlorophenol was estimated to be about 7,000 tonnes in 1979, the major part of which was used for the production of the herbicide 2,4,5-T and its salts. The herbicide is applied annually to regulate plant growth of forests, ranges and industrial, urban and aquatic sites. The general use of 2,4,5-T has been partially suspended in the United States. It is prohibited in some countries (Italy, Netherlands, Sweden); in others such as the United Kingdom, Germany, Canada, Australia and New Zealand, the herbicide is still in use. The normal application of 2,4,5-T and its salts (0.9kg/acre) would disperse no more than 90 mg TCDD on each treated acre at the highest allowed concentration of 0.1 ppm TCDD in technical 2,4,5-T. In the period since the first commercial production of 2,4,5-T (1946–1947) there have been several industrial episodes involving exposure to TCDD. This exposure usually occurred during the handling of contaminated intermediate products (i.e., trichlorophenol). On eight occasions explosions occurred during the production of sodium trichlorophenate and workers were exposed to TCDD at the time of the accident, during the clean-up or from subsequent contamination from the workshop environment. Four other episodes are mentioned in the literature, but no precise data about the humans involved are available.

Clinical features

About 1,000 people have been involved in these episodes. A wide variety of lesions and symptoms has been described in connection with the exposure, and a causal association has been assumed for some of them. Symptoms include:

dermatological: chloracne, porphyria cutanea tarda, hyperpigmentation and hirsutism

internal: liver damage (mild fibrosis, fatty changes, haemofuscin deposition and parenchymal-cell degeneration), raised serum hepatic enzyme levels, disorders of fat metabolism, disorders of carbohydrate metabolism, cardiovascular disorders, urinary tract disorders, respiratory tract disorders, pancreatic disorders

neurological: (a) peripheral: polyneuropathies, sensory impairments (sight, hearing, smell, taste); (b) central: lassitude, weakness, impotence, loss of libido

Actually only very few cases have been exposed to TCDD on its own. In almost all cases the chemicals utilized for manufacturing TCP and its derivatives (i.e., tetrachlorobenzene, sodium or potassium hydroxide, ethylene glycol or methanol, sodium trichlorophenate, sodium monochloracetate and a few others depending upon the manufacturing procedure) participated in the contamination and might have been the cause of many of these symptoms independently from TCDD. Four clinical signs are probably related to TCDD toxicity, because the toxic effects were predicted by animal testing or they have been consistent in several episodes. These symptoms are:

chloracne, which was present in the great majority of recorded cases

enlarged liver and impairment of liver function, occasionally

neuromuscular symptoms, occasionally

deranged porphyrin metabolism in some cases.

Chloracne. Clinically chloracne is an eruption of blackheads, usually accompanied by small, pale-yellow cysts which in all but the worst cases vary from pin-head to lentil size. In severe cases there may be papules (red spots) or even pustules (pus-filled spots). The disease has a predilection for the skin of the face, especially on the malar crescent under the eyes and behind the ears in the very mild cases. With increasing severity the rest of the face and neck soon follow, whilst the outer upper arms, chest, back, abdomen, outer thighs and genitalia may be involved in varying degrees in the worst cases. The disease is otherwise symptomless and is simply a disfigurement. Its duration depends to a great extent upon its severity, and the worst cases may still have active lesions 15 and more years after the contact has ceased. In human subjects within 10 days after beginning the application there was redness of the skin and a mild increase in keratin in the sebaceous gland duct, which was followed during the second week by plugging of the infundibula. Subsequently sebaceous cells disappeared and were replaced by a keratin cyst and comedones which persisted for many weeks.

Chloracne is frequently produced by skin contact with the causative chemical, but it appears also after its ingestion or inhalation. In these cases it is almost always severe and may be accompanied by signs of systemic lesions. Chloracne in itself is harmless but is a marker indicating that the affected person has been exposed, however minimally, to a choracnegenic toxin. It is therefore the most sensitive indicator we have in the human subject of overexposure to TCDD. However, the absence of chloracne does not indicate absence of exposure.

Enlarged liver and impairment of liver functions. Increased transaminase values in serum over the borderline may be found in cases after exposure. These usually subside within a few weeks or months. However, liver function tests can stay normal even in cases exposed to TCDD concentration in the environment of 1,000 ppm and suffering from severe chloracne. Clinical signs of liver dysfunction such as abdominal disturbances, gastric pressure, loss of appetite, intolerance to certain foods, and enlarged liver have also been observed in up to 50% of cases.

Laparoscopy and biopsy of the liver showed slight fibrous changes, haemofucsin deposition, fatty changes and slight parenchymal cell degeneration in some of these cases. Liver damage caused by TCDD is not necessarily characterized by hyperbilirubinaemia.

Follow-up studies in those cases which still have acneform manifestations after 20 years and more, report that enlargement of the liver and pathological liver function tests have disappeared. In almost all experimental animals the liver damage is not sufficient to cause death.

Neuromuscular effects. Severe muscle pains aggravated by exertion, especially in the calves and thighs and in the chest area, fatigue, and weakness of the lower limbs with sensory changes have been reported to be the most disabling manifestations in some cases.

In the animals, central and peripheral nervous systems are not target organs of TCDD toxicity, and there are no animal studies to substantiate the claims of muscular weakness or impaired skeletomuscular function in humans exposed to TCDD. The effect can therefore be related to the concurrent exposure to other chemicals.

Disturbed porphyrin metabolism. TCDD exposure has been associated with disturbance of the intermediary metabolism of lipids, carbohydrates and porphyrins. In animals TCDD has produced an accumulation of uroporphyrin in the liver with increase of d-amino-laevulinic acid (ALA) and of uroporphyrin excretion in the urine. In cases of occupational exposure to TCDD an increased excretion of uroporphyrins has been observed. The abnormality is disclosed by a quantitative increase in the urinary excretion of uroporphyrins and a change in the proportion with coproporphyrin.

Chronic effects

TCDD produces a variety of adverse health effects in animals and humans, including immunotoxicity, teratogenicity, carcinogenicity, and lethality. Acute effects in animals include death due to wasting, often accompanied by atrophy of the thymus, a gland that plays an active role in immune function in adult animals (but not adult humans). TCDD causes chloracne, a severe skin condition, in animals and humans, and alters immune function in many species. Dioxins cause birth defects and other reproductive problems in rodents, including cleft palate and deformed kidneys.

Effects reported in heavily exposed workers include chloracne and other skin conditions, porphyria cutanea tarda, elevated serum hepatic levels, disorders of fat and carbohydrate metabolism, polyneuropathies, weakness, loss of libido, and impotence.

Teratogenicity and embryotoxicity. TCDD is an extremely potent teratogen in rodents, especially mice, in which it induces cleft palate and hydronephrosis. TCDD causes reproductive toxicity such as decreased sperm production in mammals. In large doses TCDD is embryotoxic (lethal to the developing fetus) in many species. However, few studies of human reproductive outcomes are available. Limited data from the population exposed to TCDD from the 1976 Seveso accident showed no increase in birth defects, although the number of cases was too small to detect an increase in very rare malformations. Lack of historical data and possible reporting bias make it difficult to evaluate spontaneous abortion rates in this population.

Carcinogenicity. TCDD induces cancer at a number of sites in laboratory animals, including lung, oral/nasal cavities, thyroid and adrenal glands, and liver in the rat and lung, liver, subcutaneous tissue, thyroid gland, and lymphatic system in the mouse. Consequently, many studies of dioxin-exposed workers have focussed on cancer outcomes. Definitive studies have been more difficult in humans because workers are ordinarily exposed to dioxin-contaminated mixtures (such as phenoxy herbicides) rather than pure dioxin. For example, in case-control studies, herbicide-exposed agricultural and forestry workers were found to be at increased risk of soft-tissue sarcoma and non-Hodgkins lymphoma.

Many cohort studies have been carried out, but few have furnished definitive results because of the relatively small numbers of workers in any given manufacturing plant. In 1980 the International Agency for Research on Cancer (IARC) established a multinational cohort mortality study that now includes over 30,000 male and female workers in 12 countries, whose employment spans 1939 to the present. A 1997 report noted a two-fold increase in soft-tissue sarcoma, and a small but significant increase in total cancer mortality (710 deaths, SMR=1.12, 95% confidence interval=1.04-1.21). Non-Hodgkins lymphoma and lung cancer rates were also slightly elevated, especially in workers exposed to TCDD contaminated herbicides. In a nested case-control study in this cohort, a ten-fold risk of soft tissue sarcoma was associated with exposure to phenoxy herbicides.

Diagnosis

The diagnosis of TCDD contamination is actually based on the history of logical opportunity (chronological and geographical correlation) of exposure to substances which are known to contain TCDD as a contaminant, and on the demonstration of TCDD contamination of the surroundings by chemical analysis.

The clinical features and symptoms of the toxicity are not sufficiently distinctive to permit clinical recognition. Chloracne, an indicator of TCDD exposure, is known to have been produced in the human subject by the following chemicals:

chlornaphthalenes (CNs)

polychlorinated biphenyls (PCBs)

polybrominated biphenyls (PBBs)

polychlorinated dibenzo-p-dioxins (PCDDs)

polychlorinated dibenzofurans (PCDFs)

3,4,3,4-tetrachlorazobenzene (TCAB)

3,4,3,4-tetrachlorazoxybenzene (TCAOB).

Laboratory determination of TCDD in the human organism (blood, organs, systems, tissues and fat) has only just provided evidence of actual deposition of TCDD in the body, but the level which is liable to produce toxicity in humans is not known.

Safety and Health Measures

Safety and health measures are similar to those for solvents. In general, skin contact and vapour inhalation should be minimized. The manufacturing process should be enclosed as completely as possible. Effective ventilation should be provided together with local exhaust equipment at the main sources of exposure. Personal protective equipment should include industrial filter respirators, eye and face protection as well as hand and arm protection. Work clothes should be frequently inspected and laundered. Good personal hygiene, including a daily shower, is important for workers handling chloronaphthalenes. For some of the agents, such as benzyl chloride, periodic medical examinations should be carried out. Particular safety and health issues surrounding PCBs will be discussed below.

PCBs

In the past, PCB air levels in the workrooms of plants manufacturing or using PCBs, varied generally up to 10 mg/m³ and often exceeded these levels. Because of the toxic effects observed at these levels, a TLV of 1 mg/m³ for the lower chlorinated biphenyls (42%) and of 0.5 mg/m³ for the higher chlorinated biphenyls (54%) in the working environment were adopted in the United States (US Code for Federal Regulations 1974) and in several other countries. These limits are still in effect today.

The PCB concentration in the work environment should be controlled annually in order to check the efficacy of preventive measures in keeping these concentrations at recommended levels. The surveys should be repeated within 30 days of any change in the technological process likely to increase the occupational exposure to PCBs.

If PCBs leak or are spilled, the personnel should be evacuated from the area immediately. Emergency exits should be clearly marked. Instructions with regard to emergency procedures appropriate to the specific features of the plant technology should be implemented. Only personnel trained in emergency procedures and adequately equipped should enter the area. The duties of the emergency personnel are to repair leaks, clean up spills (dry sand or earth should be spread on the leak or spill area) and fight fires.

Employees should be informed of the adverse health effects caused by occupational exposure to PCBs, as well as on the carcinogenic effects in animals exposed experimentally to PCBs and the reproductive impairment observed in mammals and humans with relatively high PCB residue levels. Pregnant women should be aware that PCBs may endanger the health of woman and foetus, due to the placental transfer of PCBs and their foetotoxicity and provided options for other work during pregnancy and lactation. Nursing by these women should be discouraged because of the high amount of PCBs excreted with milk (the quantity of PCBs transferred to the infant by milk is higher than that transferred by the placenta). A significant correlation was found between plasma levels of PCBs in mothers occupationally exposed to these compounds and the PCB milk levels. It has been observed that if these mothers nursed their babies for more than 3 months, the PCB levels in the infants exceeded that of their mothers.These compounds were subsequently retained in the childrens’ bodies for many years. Extraction and discarding of the milk may, however, help in decreasing the mothers’ PCB body burden.

Access to PCB work areas should be limited to authorized personnel. These workers should be provided with suitable protective clothing: long-sleeved overalls, boots, overshoes and bib-type aprons that cover the boot tops. Gloves are needed to reduce skin absorption during special tasks. The bare-handed handling of cold or heated PCB materials should be forbidden. (The quantity of PCBs absorbed through the intact skin may equal or exceed that absorbed by inhalation.) Clean working clothes should be provided daily (they should be periodically inspected for defects). Safety glasses with side shields should be worn for eye protection. Respirators (meeting legal requirements) should be used in areas with PCB vapours and during installation and repair of containers and emergency activities, when the air concentration of PCBs is unknown or exceeds the TLV. Ventilation will prevent accumulation of vapours. (The respirators must be cleaned after use and stored.)

The employees should wash their hands before eating, drinking, smoking and so on, and refrain from such activities in the polluted rooms. Street clothes should be stored during the work shift in separate lockers. These clothes should be put on at the end of the working day only after a shower bath. Showers, eyewash fountains and washroom facilities should be readily accessible to the workers.

Periodic clinical examination of employees (at least annually) with special emphasis upon skin disorders, liver function and reproductive history is required.

Dioxin

The experience of occupational exposure to TCDD, either from an accident during the production of trichlorophenol and its derivatives or originating from regular industrial operations, has shown that the injuries sustained may completely incapacitate workers for several weeks or even months. Resolution of the lesions and healing can occur, but in several cases skin and visceral lesions can linger on and reduce working capacity to 20 to 50% for more than 20 years. TCDD toxic exposures can be prevented if the chemical processes concerned are carefully controlled. By good manufacturing practice it is possible to eliminate the risk of exposure of workers and applicators handling the products or for the population at large. In case of an accident (i.e., if the process of synthesis of 2,4,5-trichlorophenol is running out of control and high levels of TCDD are present), contaminated clothing should immediately be removed, avoiding contamination of the skin or other parts of the body. Exposed parts should be washed immediately and repeatedly until medical attention is obtained. For workers engaged in the decontamination process after an accident, it is recommended that they wear complete throw-away equipment to protect the skin and prevent exposure to dust and vapours from the contaminated materials. A gas mask should be used if any procedure that may produce inhalation of airborne contaminated material cannot be avoided.

All workers should be obliged to take a shower daily following the work shift. Street clothes and shoes should never come in contact with work clothes and shoes. Experience has shown that several spouses of workers affected by chloracne developed chloracne too, although they had never been in a plant producing trichlorophenol. Some of the children had the same experience. The same rules about safety for workers in case of accident have to be borne in mind for laboratory staff working with TCDD or contaminated chemicals, and for medical staff such as nurses and assistants who treat injured workers or contaminated persons. Animal keepers or other technical personnel coming in contact with contaminated material or with instruments and glassware used for TCDD analysis must be aware of its toxicity and handle the material accordingly. Waste disposal including carcasses of experimental animals requires special incineration procedures. Glassware, benchtops, instruments and tools should be regularly monitored with wipe tests (wipe with filter paper and measure amount of TCDD). TCDD containers as well as all glassware and tools should be segregated, and the whole working area should be isolated.

For the protection of the general public and especially of those categories (applicators of herbicides, hospital staff and so on) more exposed to potential risk, the regulatory agencies throughout the world enforced in 1971 a maximum manufacturing specification of 0.1 ppm TCDD. Under constantly improving manufacturing practice, commercial grades of the products in 1980 contained 0.01 ppm of TCDD or less.

This specification is intended to prevent any exposure to and any accumulation in the human food chain of amounts which would pose a substantial risk for the individual. Furthermore, to prevent contamination of the human food chain of even the extremely low concentration of TCDD which might be present on range or pasture grasses immediately following 2,4,5-T application, grazing of dairy animals on treated areas has to be prevented for 1 to 6 weeks following application.

Halogenated aromatic hydrocarbons tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 05:52

Hydrocarbons, Aromatic

Aromatic hydrocarbons are those hydrocarbons that possess the special properties associated with the benzene nucleus or ring, in which six carbon-hydrogen groups are arranged at the corners of a hexagon. The bonds joining the six groups in the ring exhibit characteristics intermediate in behaviour between single and double bonds. Thus, although benzene can react to form addition products such as cyclohexane, the characteristic reaction of benzene is not an addition reaction but a substitution reaction in which a hydrogen is replaced by a substituent, univalent element or group.

Aromatic hydrocarbons and their derivatives are compounds whose molecules are composed of one or more stable ring structures of the type described and can be considered as derivatives of benzene according to three basic processes:

by replacement of hydrogen atoms with aliphatic hydrocarbon radicals
by linking of two or more benzene rings, either directly or by intermediate aliphatic chains or other radicals, or by intermediate aliphatic chains or other radicals
by condensation of benzene rings.

Each of the ring structures can form the basis of homologous series of hydrocarbons in which a succession of alkyl groups, saturated or non-saturated, replaces one or more of the hydrogen atoms of the carbon-hydrogen groups.

The main sources of the aromatic hydrocarbons are the distillation of coal and a number of petrochemical operations—in particular, catalytic reforming, distillation of crude oil, and alkylation of lower aromatic hydrocarbons. Essential oils, containing terpenes and p-cymene, can also be obtained from pines, eucalyptus and aromatic plants, and are a by-product in the papermaking industry using the pulp of pines. Polycyclic hydrocarbons occur in the smoke of urban atmospheres.

Uses

The economic importance of the aromatic hydrocarbons has been significant since coal tar naphtha was used as a rubber solvent early in the nineteenth century. The current uses of the aromatic compounds as pure products include the chemical synthesis of plastics, synthetic rubber, paints, dyes, explosives, pesticides, detergents, perfumes and drugs. These compounds are used mainly as mixtures in solvents and constitute a variable fraction of gasoline.

Cumene is used as a high-octane blending component in aviation fuel, as a thinner for cellulose paints and lacquers, as an important starting material for the synthesis of phenol and acetone, and for the production of styrene by cracking. It serves as a constituent of many commercial petroleum solvents in the boiling range of 150 to 160 °C. It is a good solvent for fats and resins and has, therefore, been used as a replacement for benzene in many of its industrial uses. p-Cymene occurs in several essential oils and can be made from monocyclic terpenes by hydrogenation. It is a by-product in the manufacture of sulphite paper pulp and is used chiefly with other solvents and aromatic hydrocarbons as a thinner for lacquers and varnishes.

Coumarin is used as a deodorizing and odour-enhancing agent in soaps, tobacco, rubber products and perfumes. It is also used in pharmaceutical preparations.

Benzene has been banned as an ingredient in products intended for use in the home, and its uses as a solvent and component of dry-cleaning liquid have been discontinued in many countries.

Benzene has been used extensively in the manufacture of styrene, phenols, maleic anhydride and a number of detergents, explosives, pharmaceuticals and dye-stuffs. It has been used as a fuel, chemical reagent and extracting agent for seeds and nuts. The mono-, di- and trialkyl derivatives of benzene are used primarily as solvents and thinners in and in the manufacture of perfumes and dye-stuff intermediates. These substances are present in certain petroleums and in distillates of coal tar. Pseudocumene is used in the manufacture of perfumes, and 1,3,5-trimethylbenzene and pseudocumene are used also as dye-stuffs intermediates, but the chief industrial use of these substances is as solvents and paint thinners.

Toluene is a solvent for oils, resins, natural rubber (mixed with cyclohexane) and synthetic rubber, coal tar, asphalt, pitch and acetyl celluloses (hot-mixed with ethyl alcohol). It is also a solvent and diluent for cellulose paint and varnishes, and a diluent for photogravure inks. When mixed with water, it forms azeotropic mixtures that have a depolishing effect. Toluene is found in mixtures that are used as cleaning products in a number of industries and in handicrafts. It is used in the manufacture of detergent and artificial leather, and as an important raw material for organic syntheses, especially those of benzoyl and benzilidene chlorides, saccharine, chloramine T, trinitrotoluene and many dye-stuffs. Toluene is a constituent of aviation fuel and automobile gasoline. This substance was to be withdrawn from these uses in the European Union as a result of EC Council Regulation 594/91.

Naphthalene is used as the starting product in the organic synthesis of a wide range of chemicals, as a pesticide in mothballs, and in wood preservatives. It is also employed in the manufacture of indigo and is applied externally on livestock or poultry to control lice.

Styrene is used in the manufacture of a wide range of polymers (e.g., polystyrene) and copolymer elastomers, such as butadiene-styrene rubber or acrylonitrile-butadiene-styrene (ABS), that are obtained by the copolymerization of styrene with 1,3-butadiene and acrylonitrile. Styrene is widely used in the production of transparent plastics. Ethylbenzene is an intermediate in organic synthesis, particularly in the production of styrene and synthetic rubber. It is employed as a solvent or diluent, a component of automative and aviation fuels, and in the manufacture of cellulose acetate.

There are three isomers of xylene: ortho- (o-), para- (p-) and meta- (m-). The commercial product is a blend of the isomers, the largest proportion consisting of the meta- compound (up to 60 to 70%) and the smallest percentage of the para- compound (up to 5%). Xylene is used commercially as a thinner for paints, for varnishes, in pharmaceuticals, as a high-octane additive to aviation fuels, in the synthesis of dyes and for the production of phthalic acids. Since xylene is a good solvent for paraffin, Canada balsam and polystyrene, it is used in histology.

Terphenyls are used as chemical intermediates in the manufacture of non-spreading lubricants and as nuclear reactor coolants. Terphenyls and biphenyls are used as heat transfer agents, in organic synthesis and in perfume manufacture. Diphenylmethane, for instance, is used as a perfume in the soap industry and as a solvent for cellulose lacquers. It also has some applications as a pesticide.

Hazards

Absorption takes place by inhalation, ingestion and in small quantities through the intact skin. In general the monoalkyl derivatives of benzene are more toxic than the dialkyl derivatives, and the derivatives with branched chains are more toxic than those with straight chains. Aromatic hydrocarbons are metabolized through the bio-oxidation of the ring; if there are side chains, preferably of the methyl group, these are oxidized and the ring is left unchanged. They are, in large part, converted into water-soluble compounds, then conjugated with glycine, glucuronic or sulphuric acid, and eliminated in the urine.

Aromatic hydrocarbons are capable of causing acute and chronic central nervous system effects. Acutely, they can cause headaches, nausea, dizziness, disorientation, confusion and listlessness. High acute doses can even result in loss of consciousness and respiratory depression. Respiratory irritation (cough and sore throat) is a well-known acute effect. Cardiovascular symptoms can include palpitations and light-headedness. Neurological symptoms of chronic exposure can include behavioural changes, depression, mood alterations, and changes in personality and intellectual function. Chronic exposure has also been known to cause or contribute to distal neuropathy in some patients. Toluene has also been associated with a persistent syndrome of cerebellar ataxia. Chronic effects can also include dry, irritated, cracked skin, and dermatitis. Hepatotoxicity has also been associated with exposure, in particular to the chlorinated group. Benzene is a confirmed carcinogen in humans, having been known to cause all types of leukaemia but primarily acute nonlymphocytic leukaemia. It can also cause aplastic anaemia and (reversible) pancytopenia.

Aromatic hydrocarbons as a group pose a significant flammability hazard. The US National Fire Prevention Association (NFPA) has classified most compounds in this group with a flammability code of 3 (where 4 is severe hazard). Measures must be in place to prevent accumulation of vapours in the work environment and to deal with leakages and spills promptly. Extremes of heat must be avoided in the presence of vapours.

Benzene

Benzene is often referred to as “benzol” in its commercial form (which is a mixture of benzene and its homologues) and should not be confused with benzine, a commercial solvent which consists of a mixture of aliphatic hydrocarbons.

Mechanism. Absorption of benzene usually occurs through the lungs and gastrointestinal tract. It tends not to be well absorbed through the skin unless exceptionally high exposures occur. A small amount of benzene is exhaled unchanged. Benzene is widely distributed throughout the body and is metabolized mainly to phenol, which is excreted in the urine after conjugation. After exposure ceases, body tissue levels decline quickly.

From the biological point of view, it seems that the bone marrow and blood disorders found in chronic benzene poisoning can be attributed to the conversion of benzene to benzene epoxide. It has been suggested that benzene might be oxidized to epoxide directly in bone marrow cells, such as erythroblasts. As far as the toxic mechanism is concerned, benzene metabolites seem to interfere with nucleic acids. Increased rates of chromosome aberrations have been observed both in humans and in animals exposed to benzene. Any condition likely to inhibit further metabolism of benzene epoxide and conjugation reactions, especially hepatic disorders, tends to potentiate the toxic action of benzene. These factors are of importance when considering differences in individual susceptibility to this toxic agent. Benzene is discussed in more detail elsewhere in this Encyclopaedia.

Fire and explosion. Benzene is a flammable liquid, the vapour of which forms flammable or explosive mixtures in air over a large range of concentrations; the liquid will evolve vapour concentrations in this range at temperatures as low as -11 °C. In the absence of precautions, therefore, at all normal working temperatures flammable concentrations are liable to be present where the liquid is being stored, handled or used. The risk becomes more pronounced when accidental spillage or escape of liquid occurs.

Toluene and derivatives

Metabolism. Toluene is absorbed into the body mainly through the respiratory tract and, to a lesser extent, through the skin. It penetrates the alveolar barrier, the blood/air mixture being in the proportion of 11.2 to 15.6 at 37 °C, and then spreads through the different tissues in amounts depending upon their perfusion and solubility characteristics respectively.

The tissue-to-blood proportion is 1:3 except in the case of those tissues rich in fat, which have a coefficient of 80:100. The toluene then becomes oxidized to its lateral chain in the liver microsomes (microsomal mono-oxygenation). The most important product of this transformation, which represents about 68% of the absorbed toluene, is hippuric acid (AH), which appears in the urine through renal excretion mainly by being excreted in the proximal tubules. Small quantities of o-cresol (0.1%) and p-cresol (1%), which are the result of oxidation in the aromatic nucleus, can also be detected in the urine, as discussed in the Biological monitoring chapter of this Encyclopaedia.

The biological half-life of AH is very short, being of the order of 1 to 2 hours. The level of toluene in the expired air at rest is of the order of 18 ppm during an exposure rate of 100 ppm, and this drops very rapidly after exposure has terminated. The amount of toluene retained in the body is a function of the percentage of fat present. Obese subjects will retain more toluene in their body.

In the liver the same enzymatic system oxidizes toluene, styrene and benzene. These three substances therefore tend to inhibit each other competitively. Thus, if rats are heavily dosed with toluene and benzene, a reduction in the concentration of benzene metabolites will be seen in the tissue and in the urine, and similarly an increase of benzene in the expired air. In the case of trichloroethylene, the inhibition is not competitive since the two substances are not oxidized by the same enzymatic system. Simultaneous exposure will result in a reduction of AH and the appearance of trichlor compounds in the urine. There will be higher absorption of toluene under effort than at rest. With an output of 50 watts, the values detected in the arterial blood and in the alveolar air are doubled in comparison with those obtained at rest.

Acute and chronic health hazards. Toluene has an acute toxicity somewhat more intense than that of benzene. At a concentration of about 200 or 240 ppm, it gives rise after 3 to 7 h to vertigo, dizziness, difficulty in maintaining equilibrium, and headache. Stronger concentrations may result in a narcotic coma.

The symptoms of chronic toxicity are those habitually encountered with exposure to the commonly used solvents, and include: irritation of the mucous membrane, euphoria, headaches, vertigo, nausea, loss of appetite, and alcohol intolerance. These symptoms generally appear at the end of the day, are more severe at the end of the week, and become less or disappear during the weekend or on holiday.

Toluene has no action on the bone marrow. Those cases that have been reported relate either to an exposure to toluene together with benzene or are not clear on this subject. In theory it is possible that toluene can give rise to a hepatotoxic attack, but this has never been proved. Certain authors have suggested the possibility of its causing an autoimmune illness similar to the Goodpasture syndrome (autoimmune glomerulonephritis).

Several cases of sudden death are to be noted, especially in the case of children or adolescents given to glue sniffing (inhaling fumes from adhesives containing toluene among other solvents), resulting from cardiac arrest due to ventricular fibrillation with loss of catecholamines. Animal studies have shown toluene to be teratogenic only at high doses.

Fire and explosion. At all normal working temperatures, toluene evolves dangerously flammable vapours. Open lights or other agencies liable to ignite the vapour should be excluded from areas where the liquid is liable to be exposed in use or by accident. Appropriate facilities for storage and shipment are required.

Other monoalkyl derivatives of benzene. Propylbenzene is a depressant of the central nervous system with slow but prolonged effects. Sodium dodecylbenzene sulphonate is produced by catalytic reaction of tetrapropylene with benzene, acidification with sulphuric acid, and treatment with caustic soda. Repeated contact with the skin may cause dermatitis; in prolonged exposure it might act as a bland irritant of mucous membranes.

p-tert-Butyltoluene. The presence of the vapour is detectable by odour at 5 ppm. Slight conjunctival irritation occurs after exposure to 5 to 8 ppm. Exposure to the vapour gives rise to headaches, nausea, malaise and signs of neurovegetative dystonia. The metabolism of this substance is probably similar to that of toluene. The same fire and health precautions should be taken in the use of p-tert-butyltoluene as those described for toluene.

Xylene

Like benzene, xylene is a narcotic, prolonged exposure to which results in impairment of the haemopoietic organs and disturbances of the nervous system. The clinical picture of acute poisoning is similar to that of benzene poisoning. The symptoms are fatigue, dizziness, drunkenness, shivering, dyspnoea and sometimes nausea and vomiting; in more serious cases there may be unconsciousness. Irritation of the mucous membranes of the eyes, the upper airways and the kidneys are also observed.

Chronic exposure results in complaints about general weakness, excessive fatigue, dizziness, headache, irritability, sleeplessness, loss of memory, and ringing noises in the ear. Typical symptoms are cardiovascular disorders, sweetish taste in the mouth, nausea, sometimes vomiting, loss of appetite, strong thirst, burning in the eyes, and bleeding from the nose. Functional disorders of the central nervous system associated with pronouned neurological effects (e.g., dystonia), impairment of protein-forming function and reduced immunobiological reactivity may be observed in certain cases.

Women are liable to suffer from menstrual disorders (menorrhagia, metrorrhagia). It has been reported that female workers exposed to toluene and xylene in concentrations which periodically exceeded the exposure limits were also affected by pathological pregnancy conditions (toxicosis, danger of miscarriage, haemorrhage during childbirth) and infertility.

The blood changes manifest themselves as anaemia, poikilocytosis, anisocytosis, leukopenia (sometimes leukocytosis) with relative lymphocytosis, and in certain cases strongly pronounced thrombocytopenia. There are data on differences in individual susceptibility to xylene. No chronic intoxication has been observed in certain workers exposed for a few decades to xylene, whereas a third of the personnel working under the same conditions of exposure presented symptoms of chronic xylene poisoning and were disabled. Prolonged exposure to xylene may reduce the resistance of the organism and render it more susceptible to various kinds of pathogenic factors. Urinalysis reveals proteins, blood, urobilin and urobilinogen in the urine.

Fatal cases of chronic poisoning are known, in particular among workers of the intaglio printing industry but also in other branches. Cases of serious and fatal poisoning among pregnant women with haemophilia and bone-marrow aplasia have been reported. Xylene also causes skin changes, in particular eczema.

Chronic poisoning is associated with the presence of xylene traces in all organs, especially the suprarenal glands, bone marrow, spleen and nerve tissue. Xylene oxidizes in the organism to form toluic acids (o-, m-, p-methylbenzoic acids), which later react with glycine and glucuronic acid.

During the production or use of xylene there may be high concentrations in the workplace air if the equipment is not tight and open processes are used, sometimes involving large surfaces of evaporation. Large amounts are also released into the air during repair work and when cleaning the equipment.

Contact with xylene, which may have contaminated the surfaces of premises and equipment or also protective clothing, may result in its absorption through the skin. The rate of skin absorption in humans is 4 to 10 mg/cm² per hour.

Levels of 100 ppm for up to 30 minutes have been associated with mild upper respiratory tract irritation. At 300 ppm, balance, vision and reaction times are affected. Exposure to 700 ppm for 60 minutes can result in headache, dizziness and nausea.

Other dialkyl benzene derivatives. Fire risks are associated with the use of p-cymene, which is also a primary skin irritant. Contact with the liquid can cause dryness, defatting and erythema. There is no conclusive evidence that it can affect the blood marrow. Acute exposure to p-tert-butyltoluene in concentrations of 20 ppm and above may cause nausea, metallic taste, eye irritation and giddiness. Repeated exposure has been found to be responsible for decreased blood pressure, increased pulse rate, anxiety and tremor, slight anaemia with leukopenia and eosinophilia. In repeated exposure it is also a mild skin irritant because of fat removal. Animal toxicity studies show effects on the central nervous sytem (CNS), with lesions in the corpus callosum and spinal cord.

Styrene and ethylbenzene. Styrene and ethylbenzene poisoning are very similar and are consequently dealt with together here. Styrene may enter the body by both vapour inhalation and, being lipid soluble, by absorption through intact skin. It rapidly saturates the body (in 30 to 40 min), is distributed throughout the organs and is rapidly eliminated (85% in 24 h) either in the urine (71% in the form of oxidation products of the vinyl group—hippuric and mandelic acids) or in the expired air (10%). As regards ethylbenzene, 70% of it is eliminated with the urine in the form of various metabolites—phenylacetic acid, α-phenylethyl alcohol, mandelic acid and benzoic acid.

The presence of the double bond in the side chain of styrene significantly increases the irritant properties of the benzene ring; however, the general toxic action of styrene is less pronounced than that of ethylbenzene. Liquid styrene has a local effect on the skin. Animal experiments have shown that liquid styrene irritates the skin and causes blistering and tissue necrosis. Exposure to styrene vapours may also give rise to skin irritation.

Vapours of ethylbenzene and styrene in concentrations of over 2 mg/ml may cause acute poisoning in laboratory animals; the initial symptoms are irritation of the mucous membranes of the upper respiratory tract, the eyes and mouth. These symptoms are followed by narcosis, cramps and death due to respiratory-centre paralysis. The main pathological findings are oedema of the brain and lungs, epithelial necrosis of the renal tubules, and hepatic dystrophy.

Ethylbenzene is more volatile than styrene, and its production is associated with a greater hazard of acute poisoning; both substances are toxic by ingestion. Animal experiments have shown that digestive absorption of styrene causes symptoms of poisoning similar to those resulting from inhalation. Lethal doses are as follows: 8 g/kg body weight for styrene and 6 g/kg for ethylbenzene; lethal inhalation concentrations are between 45 and 55 mg/l.

In industry acute styrene or ethylbenzene poisoning may occur as the result of a breakdown or faulty plant operation. A polymerization reaction that gets out of control is accompanied by a rapid release of heat and necessitates prompt purging the reaction vessel. Engineering controls that avoid a sudden rise of the styrene and ethylbenzene concentrations in the workplace atmosphere are essential or workers involved can be exposed to the dangerous levels with sequelae such as encephalopathy and toxic hepatitis unless they are protected by suitable respirators.

Chronic toxicity. Both styrene and ethylbenzene may also cause chronic poisoning. Prolonged exposure to styrene or ethylbenzene vapours in concentrations above permitted levels may result in functional disorders of the nervous system, irritation of the upper airways, haematological changes (in particular leukopenia and lymphocytosis) and also in hepatic and biliary tract conditions. Medical examination of workers employed for more than 5 years in polystyrene and synthetic rubber plants in which the atmospheric styrene and ethylbenzene concentrations were around 50 mg/m³ revealed cases of toxic hepatitis. Prolonged exposure to styrene concentrations of less than 50 mg/m³ caused disorders of certain liver functions (protein, pigment, glycogen). Polystyrene production workers have also been found to suffer from asthenia and nasal mucosa disorders; ovulation and menstruation disorders have also been observed.

Experimental research in rats has revealed that styrene exerts embryotoxic effects at a concentration of 1.5 mg/m³; its metabolite styrene oxide is mutagenic and reacts with microsomes, proteins and the nucleic acid of the liver cells. Styrene oxide is chemically active and several times more toxic for rats than styrene itself. Styrene oxide is classified as a Group 2A probable carcinogen by IARC. Styrene itself is considered a Group 2B possible human carcinogen.

Animal experiments on the chronic toxicity of ethylbenzene have shown that high concentrations (1,000 and 100 mg/m³) may be harmful and cause functional and organic disturbances (nervous system disorders, toxic hepatitis and upper respiratory tract complaints). Concentrations as low as 10 mg/m³ may lead to catarrhal inflammation of the upper respiratory tract mucosae. Concentrations of 1 mg/m³ give rise to disorders of liver function.

Trialkyl derivatives of benzene. In the trimethylbenzenes three hydrogen atoms in the benzene nucleus have been replaced by three methyl groups to form a further group of aromatic hydrocarbons.The risk of injury to health and a fire risk are associated with the use of these liquids. All three isomers are flammable. The flashpoint of pseudocumene is 45.5 °C, but the liquids are commonly used industrially as constituents of coal tar solvent naphtha, which may have a flashpoint anywhere in a range from 32 °C to below 23 °C. In the absence of precautions, a flammable concentration of vapour may be present where the liquids are used in solvent and thinner operations.

Health hazards. The main information as to the toxic effects of the trimethylbenzenes 1,3,5-trimethylbenzene and pseudocumene, both on animals and also on human beings, has been derived from studies of a solvent and paint thinner which contains 80% of these substances as constituents. They act as depressants of the central nervous system and can affect the blood coagulation. Bronchitis of an asthmatic type, headache, fatigue and drowsiness were also complained of by 70% of the workers exposed to high concentrations. A large proportion of 1,3,5-trimethylbenzene is oxidized in the body into mesitylenic acid, conjugated with glycine and excreted in the urine. Pseudocumene is oxidized into p-xylic acid, then excreted as well in the urine.

Cumene. Regard must be paid to certain health and fire hazards when cumene is used in an industrial process. Cumene is a skin irritant and can be slowly absorbed through the skin. It also has a potent narcotic effect in animals, and the narcosis develops more slowly and lasts longer than with benzene or toluene. It also has a tendency to cause injury to the lungs, liver and kidneys, but no such injuries have been recorded in human beings.

Liquid cumene does not evolve vapours in flammable concentrations until its temperature reaches 43.9 °C. Thus flammable mixtures of vapour and air will be formed only in the course of uncontrolled operations that involve hotter temperatures. If solutions or coatings containing cumene are heated in the course of a process (in a drying oven, for instance), fire and, under certain conditions, explosion readily occur.

Health and Safety Measures

Given that the major route of entry is the lungs, it becomes important to prevent these agents from entering the breathing zone. Effective exhaust ventilation systems to prevent accumulation of toxins is one of the most important methods of preventing excessive inhalation. Open containers should be kept covered or closed when not in use. The above precautions to ensure that a harmful concentration of vapour is not present in the working atmosphere are fully adequate to avoid flammable mixtures in the air in normal circumstances. To cover the risk of accidental leakage or overflow of liquid from storage or process vessels, additional precautions are needed such as mounds round storage tanks, sills at doorways or specially designed floors to limit the spread of escaping liquid. Open flames and other sources of ignition should be excluded where these agents are stored or used. Efficient means of dealing with leakage and spills must be available.

Respirators, while effective, should be used only as backup (or in emergencies) and are entirely user-dependent. Protection from the second major route of exposure, the skin, can be provided by protective clothing such as gloves, facial protectors/shields, and gowns. Furthermore, protective eyeware should be given to workers at risk of splashing these substances in their eyes. Workers should avoid wearing contact lenses when working in areas where exposure (especially to the face and eyes) is a possibility; contact lenses can potentiate the harmful effect of these substances and often make eyewashes less effective unless the lenses are removed immediately.

If skin contact with these substances occurs, wash the skin immediately with soap and water. If clothing has been contaminated, remove it promptly. Aromatic hydrocarbons in the eyes should be removed by irrigating with water for at least 15 minutes. Burns from splashes of liquefied compounds require prompt medical attention. In case of severe exposure, the patient should be taken into the fresh air for rest until the arrival of a physician. Give oxygen if the patient appears to have difficulty in breathing. The majority of persons quickly recover in fresh air, and symptomatic therapy is rarely required.

Substitution for benzene. It is now recognized that the use of benzene should be abandoned for any industrial or commercial purpose where an effective, less harmful substitute is available, although often a substitute may be unavailable when the benzene is being used as a reactant in a chemical synthesis. On the other hand it has proved possible to adopt substitutes in almost all the very numerous operations where benzene has been used as a solvent. The substitute is not always as good a solvent as benzene, but it may still prove the preferable solvent because less onerous precautions are required. Such substitutes include benzene
homologues (especially toluene and xylene), cyclohexane, aliphatic hydrocarbons (either pure, as is the case with hexane, or as mixtures as is the case with the wide range of petroleum solvents), solvent naphthas (which are relatively complex mixtures of variable composition obtained from coal) or certain petroleum products. They contain virtually no benzene and very little toluene; the main constituents are homologues of these two hydrocarbons in proportions that vary depending on the origin of the mixture. Various other solvents may be chosen to suit the material to be dissolved and the relevant industrial processes. They include alcohols, ketones, esters and chlorinated derivatives of ethylene.

Aromatic hydrocarbons tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 05:47

Hydrocarbons, Aliphatic Unsaturated

Uses

The unsaturated hydrocarbons are commercially important as starting materials for the manufacture of numerous chemicals and polymers, such as plastics, rubbers and resins. The vast production of the petrochemicals industry is based on the reactivity of these substances.

1-Pentene is a blending agent for high-octane motor fuel, and isoprene is used in the manufacture of synthetic natural rubber and butyl rubber. Propylene is also used in synthetic rubber manufacture and in the polymerized form as polypropylene plastic. Isobutylene is an antioxidant in the food and food-packaging industries. 1-Hexene is used in the synthesis of flavours, perfumes and dyes. Ethylene, cis-2-butene and trans-2-butene are solvents, and propadiene is a component of fuel gas for metalworking.

The principal industrial use of ethylene is as a building block for chemical raw materials which, in turn, are used to manufacture a large variety of substances and products. Ethylene is used also in oxyethylene welding and cutting of metals, and in mustard gas. It acts as a refrigerant, an inhalation anaesthetic, and as a plant growth accelerator and fruit ripener. However, the amounts used for these purposes are minor in comparison with the quantities used in the manufacture of other chemicals. One of the major chemicals derived from ethylene is polyethylene, which is made by catalytic polymerization of ethylene and is used for the manufacture of a variety of moulded plastic products. Ethylene oxide is produced by catalytic oxidation and in turn is used to make ethylene glycol and ethanolamines. Most of the industrial ethyl alcohol is produced by the hydration of ethylene. Chlorination yields vinyl chloride monomer or 1,2-dichloroethane. When reacted with benzene, styrene monomer is obtained. Acetaldehyde is also made by oxidation of ethylene.

Hazards

Health hazards

Like their saturated counterparts, the lower unsaturated aliphatic hydrocarbons, or olefins, are simple asphyxiants, but as the molecular weight increases the narcotic and irritant properties become more pronounced than those of their saturated analogues. Ethylene, propylene and amylene have, for example, been used as surgical anaesthetics, but they require large concentrations (60%) and for that reason are administered with oxygen. The diolefins are more narcotic than the mono-olefins and are also more irritating to the mucous membranes and the eyes.

1,3-Butadiene. Physico-chemical hazards associated with butadiene result from its high flammability and extreme reactivity. Since a flammable mixture of 2 to 11.5% butadiene in air is easily reached, it constitutes a dangerous fire and explosion hazard when exposed to heat, sparks, flame or oxidizers. On exposure to air or oxygen, butadiene readily forms peroxides, which may undergo spontaneous combustion.

Despite the fact that over the years, the experience of workers with occupational exposure to butadiene, and laboratory experiments on humans and animals, had appeared to indicate that its toxicity is of a low order, epidemiological studies have shown that 1,3-butadiene is a probable human carcinogen (Group 2A rating by the International Agency for Research on Cancer (IARC)). Exposure to very high levels of gas may result in primary irritant and anaesthetic effects. Human subjects could tolerate concentrations up to 8,000 ppm for 8 hours with no ill effects other than slight irritation of the eyes, nose and throat. It was found that dermatitis (including frostbite due to cold injury) may result from exposure to liquid butadiene and its evaporating gas. Inhalation of excessive levels—which might produce anaesthesia, respiratory paralysis and death—can occur from spills and leaks from pressure vessels, valves and pumps in areas with inadequate ventilation. Butadiene is discussed in more detail in the Rubber industry chapter in this volume.

Similarly isoprene, which had not been associated with toxicity except at very high concentrations, is now considered a possible human carcinogen (Group 2B) by IARC.

Ethylene. The major hazard of ethylene is that of fire or explosion. Ethylene spontaneously explodes in sunlight with chlorine and can react vigorously with carbon tetrachloride, nitrogen dioxide, aluminium chloride and oxidizing substances in general. Ethylene-air mixtures will burn when exposed to any source of ignition such as static, friction or electrical sparks, open flames or excess heat. When confined, certain mixtures will explode violently from these sources of ignition. Ethylene is often handled and transported in liquefied form under pressure. Skin contact with the liquid can cause a “freezing burn”. There is little opportunity of exposure to ethylene during its manufacture because the process takes place in a closed system. Exposures may occur as a result of leaks, spills or other accidents that lead to release of the gas into the air. Empty tanks and vessels that have contained ethylene are another potential source of exposure.

In air, ethylene acts primarily as an asphyxiant. Concentrations of ethylene required to produce any marked physiological effect will reduce the oxygen content to such a low level that life cannot be supported. For example, air containing 50% of ethylene will contain only about 10% oxygen.

Loss of consciousness results when the air contains about 11% of oxygen. Death occurs quickly when the oxygen content falls to 8% or less. There is no evidence to indicate that prolonged exposure to low concentrations of ethylene can result in chronic effects. Prolonged exposure to high concentrations may cause permanent effects because of oxygen deprivation.

Ethylene has a very low order of systemic toxicity. When used as a surgical anaesthetic, it is always administered with oxygen. In such cases, its action is that of a simple anaesthetic having a rapid action and an equally rapid recovery. Prolonged inhalation of about 85% in oxygen is slightly toxic, resulting in a slow fall in the blood pressure; at about 94% in oxygen, ethylene is acutely fatal.

Safety and Health Measures

For those chemicals with which no carcinogenicity or similar toxic effects have been observed, adequate ventilation should be maintained to prevent exposure of workers to a concentration above the recommended safe limits. Workers should be instructed that smarting of the eyes, respiratory irritation, headache and vertigo may indicate that the concentration in the atmosphere is unsafe. Cylinders of butadiene should be stored upright in a cool, dry, well-ventilated location away from sources of heat, open flames and sparks.

The storage area should be segregated from supplies of oxygen, chlorine, other oxidizing chemicals and gases, and combustible materials. Since butadiene is heavier than air and any leaking gas will tend to collect in the depressions, storage in pits and basements should be avoided. Containers of butadiene should be clearly labelled and coded appropriately as an explosive gas. Cylinders should be suitably constructed to withstand pressure and minimize leaks, and should be handled so as to avoid shock. A safety relief valve is usually incorporated in the cylinder valve. A cylinder should not be subjected to temperatures above 55 °C. Leaks are best detected by painting the suspected area with a soap solution, so that any escaping gas will form visible bubbles; under no circumstances should a match or flame be used to check for leaks.

For possible or probable carcinogens, all appropriate handling precautions required for carcinogens should be instituted.

Both in its manufacture and usage, butadiene should be handled in a properly designed, closed system. Antioxidants and inhibitors (such as tert-butylcatechol at about 0.02 weight per cent) are commonly added to prevent the formation of dangerous polymers and peroxides. Butadiene fires are difficult and dangerous to extinguish. Small fires may be extinguished by carbon dioxide or dry chemical fire extinguishers. Water may be sprayed over large fires and adjacent areas. Wherever possible, a fire should be controlled by shutting off all sources of fuel. No specific preplacement or periodic examinations are needed for employees working with butadiene.

The lower members of the series (ethylene, propylene and butylene) are gases at room temperature and highly flammable or explosive when mixed with air or oxygen. The other members are volatile, flammable liquids capable of giving rise to explosive concentrations of vapour in air at normal working temperatures. When exposed to air, the diolefins can form organic peroxides which, upon concentration or heating, can detonate violently. Most commercially produced diolefins are generally inhibited against peroxide formation.

All sources of ignition should be avoided. All electrical installations and equipment should be explosion-proof. Good ventilation should be provided in all rooms or areas where ethylene is handled. Entry into confined spaces that have contained ethylene should not be permitted until gas tests indicate that they are safe and entry permits have been signed by an authorized person.

Persons who may be exposed to ethylene should be carefully instructed about and trained in its safe and proper handling methods. Emphasis should be given to the fire hazard, the “freezing burns” due to contact with the liquid material, use of protective equipment, and emergency measures.

Hydrocarbons, aliphatic unsaturated, tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Published in 104. Guide to Chemicals

Wednesday, 03 August 2011 05:37

Hydrocarbons, Aliphatic and Halogenated

Halogenated aliphatic hydrocarbons are organic chemicals in which one or more hydrogen atoms has been replaced by a halogen (i.e., fluorinated, chlorinated, brominated or iodized). Aliphatic chemicals do not contain a benzene ring.

The chlorinated aliphatic hydrocarbons are produced by chlorination of hydrocarbons, by the addition of chlorine or hydrogen chloride to unsaturated compounds, by the reaction between hydrogen chloride or chlorinated lime and alcohols, aldehydes or ketones, and exceptionally by chlorination of carbon disulphide or in some other way. In some cases more steps are necessary (e.g., chlorination with subsequent elimination of hydrogen chloride) to obtain the derivative needed, and usually a mixture arises from which the desired substance has to be separated. Brominated aliphatic hydrocarbons are prepared in a similar manner, while for iodized and particularly for fluorinated hydrocarbons, other methods such as electrolytic production of iodoform are preferred.

The boiling point of substances generally increases with molecular mass, and is then further raised by halogenation. Amongst the halogenated aliphatics, only not very highly fluorinated compounds (i.e., up to and including decafluorobutane), chloromethane, dichloromethane, chloroethane, chloroethylene and bromomethane are gaseous at normal temperatures. Most other compounds in this group are liquids. The very heavily chlorinated compounds, as well as tetrabromomethane and triodomethane, are solids. The odour of hydrocarbons is often strongly enhanced by halogenation, and several volatile members of the group have not merely an unpleasant odour but also have a pronounced sweet taste (e.g., chloroform and heavily halogenated derivatives of ethane and propane).

Uses

The unsaturated halogenated aliphatic and alicyclic hydrocarbons are used in industry as solvents, chemical intermediates, fumigants and insecticides. They are found in the chemical, paint and varnish, textile, rubber, plastics, dye-stuff, pharmaceutical and dry-cleaning industries.

Industrial uses of the saturated halogenated aliphatic and alicyclic hydrocarbons are numerous, but their primary importance is their application as solvents, chemical intermediates, fire-extinguishing compounds, and metal-cleaning agents. These compounds are found in the the rubber, plastics, metalworking, paint and varnish, healthcare and textile industries. Some are components of soil fumigants and insecticides, and others are rubber-vulcanizing agents.

1,2,3-Trichloropropane and 1,1-dichloroethane are solvents and ingredients in paint and varnish removers, while methyl bromide is a solvent in aniline dyes. Methyl bromide is also used for degreasing wool, sterilizing food for pest control, and for extracting oils from flowers. Methyl chloride is a solvent and diluent for butyl rubber, a component of thermometric and thermostatic equipment fluid, and a foaming agent for plastics. 1,1,1-Trichloroethane is used primarily for cold type metal cleaning and as a coolant and lubricant for cutting oils. It is a cleaning agent for instruments in precision mechanics, a solvent for dyes, and a component of spotting fluid in the textile industry; in plastics, 1,1,1-trichloroethane is a cleaning agent for plastic moulds. 1,1-Dichloroethane is a solvent, cleaning agent and degreaser used in rubber cement, insecticide spray, fire extinguishers and gasoline, as well as for high-vacuum rubber, ore flotation, plastics and fabric spreading in the textile industry. Thermal cracking of 1,1-dichloroethane produces vinyl chloride. 1,1,2,2-Tetrachloroethane has varied functions as a non-flammable solvent in the rubber, paint and varnish, metal and fur industries. It is also a moth-proofing agent for textiles and is used in photographic film, the manufacture of artificial silk and pearls, and for estimating the water content of tobacco.

Ethylene dichloride has limited uses as a solvent and as a chemical intermediate. It is found in paint, varnish and finishing removers, and has been used as a gasoline additive to reduce lead content. Dichloromethane or methylene chloride is primarily used as a solvent in industrial and paint-stripping formulations, and in certain aerosols, including pesticides and cosmetic products. It serves as a process solvent in the pharmaceutical, plastics and foodstuff industries. Methylene chloride is also used as a solvent in adhesives and in laboratory analysis. The major use of 1,2-dibromoethane is in the formulation of lead-based antiknock agents for blending with gasoline. It is also used in the synthesis of other products and as a component of refractive-index fluids.

Chloroform is also a chemical intermediate, a dry-cleaning agent and a rubber solvent. Hexachloroethane is a degassing agent for aluminium and magnesium metals. It is used to remove impurities from molten metals and to inhibit the explosiveness of methane and the combustion of ammonium perchlorate. It is used in pyrotechnics, explosives and the military.

Bromoform is a solvent, fire retardant and flotation agent. It is used for mineral separation, rubber vulcanization and chemical synthesis. Carbon tetrachloride was formerly used as a degreasing solvent and in dry-cleaning, fabric spotting, and fire-extinguishing fluid, but its toxicity has led to discontinuing its use in consumer products and as a fumigant. Since a large part of its use is in the manufacture of chlorofluorocarbons, which in turn are eliminated from the great majority of commercial uses, the use of carbon tetrachloride will decrease still further. It is now used in semiconductor manufacture, cables, metal recovery and as a catalyst, an azeotropic drying agent for wet spark plugs, soap fragrance and for extracting oil from flowers.

Although replaced by tetrachloroethylene in most areas, trichloroethylene functions as a degreasing agent, solvent and paint diluent. It serves as an agent for removing basting threads in textiles, an anaesthetic for dental services and a swelling agent for dyeing polyester. Trichloroethylene is also used in vapour degreasing for metal work. It has been used in typewriter correction fluid and as an extraction solvent for caffeine. Trichloroethylene, 3-chloro-2-methyl-1-propene and allyl bromide are found in fumigants and in insecticides. 2-Chloro-1,3-butadiene is used as a chemical intermediate in the manufacture of artificial rubber. Hexachloro-1,3-butadiene is used as a solvent, as an intermediate in lubricant and rubber production, and as a pesticide for fumigation.

Vinyl chloride has been mainly used in the plastics industry and for the synthesis of polyvinyl chloride (PVC). However, it was formerly widely used as a refrigerant, extraction solvent and aerosol propellant. It is a component of vinyl-asbestos floor tiles. Other unsaturated hydrocarbons are primarily used as solvents, flame retardants, heat exchange fluids, and as cleaning agents in a wide variety of industries. Tetrachloroethylene is used in chemical synthesis and in textile finishing, sizing and desizing. It is also used for dry-cleaning and in the insulating fluid and cooling gas of transformers. cis-1,2-Dichloroethylene is a solvent for perfumes, dyes, lacquers, thermoplastics and rubber. Vinyl bromide is a flame retardant for carpet backing material, sleepwear and home furnishings. Allyl chloride is used for thermosetting resins for varnishes and plastics, and as a chemical intermediate. 1,1-Dichloroethylene is used in food packaging, and 1,2-dichloroethylene is a low-temperature extracting agent for heat-sensitive substances, such as perfume oils and caffeine in coffee.

Hazards

The production and use of halogenated aliphatic hydrocarbons involves serious potential health problems. They possess many local as well as systemic toxic effects; the most serious include carcinogenicity and mutagenicity, effects on the nervous system, and injury of vital organs, particularly the liver. Despite the relative chemical simplicity of the group, the toxic effects vary greatly, and the relation between structure and effect is not automatic.

Cancer. For several halogenated aliphatic hydrocarbons (e.g., chloroform and carbon tetrachloride) experimental evidence of carcinogenicity was observed rather a long time ago. The carcinogenicity classifications of of the International Agency for Research on Cancer (IARC) are given in the appendix to the Toxicology chapter of this Encyclopaedia. Some halogenated aliphatic hydrocarbons also exhibit mutagenic and teratogenic properties.

Depression of the central nervous system (CNS) is the most outstanding acute effect of many of the halogenated aliphatic hydrocarbons. Inebriation (drunkenness) and excitation passing into narcosis is the typical reaction, and for that reason many of chemicals in this group have been used as anaesthetics or even abused as a recreational drug. The narcotic effect varies: one compound may have very pronounced narcotic effects while another is only weakly narcotic. In severe acute exposure there is always the danger of death from respiratory failure or cardiac arrest, for the halogenated aliphatic hydrocarbons make the heart more susceptible to catecholamines.

The neurological effects of some compounds, such as methyl chloride and methyl bromide, as well as other brominated or iodized compounds in this group, are much more severe, particularly when there is repeated or chronic exposure. These central nervous system effects cannot simply be described as depression of the nervous system, since the symptoms can be extreme and include headache, nausea, ataxia, tremors, difficulty in speech, visual disturbances, convulsions, paralysis, delirium, mania or apathy. The effects may be long lasting, with only a very slow recovery, or there may be permanent neurological damage. The effects associated with different chemicals can go by a variety of names such as “methyl chloride encephalopathy” and “chloroprene encephalomyelitis”. The peripheral nerves may also be affected, such as is observed with tetrachloroethane and dichloroacetylene polyneuritis.

Systemic. Harmful effects on the liver, the kidney and other organs are common to virtually all the halogenated aliphatic hydrocarbons, though the extent of damage varies substantially from one member of the group to another. Since the signs of injury do not appear immediately, these effects have sometimes been referred to as delayed effects. The course of acute intoxication has often been described as biphasic: the signs of a reversible effect at an early stage of the intoxication (narcosis) as the first phase, with signs of other systemic injury not becoming apparent until later as the second phase. Other effects, such as cancer, may have extremely long latency periods. It is not always possible, however, to make a sharp distinction between the toxic effects of chronic or repeated exposure and the delayed effects of acute intoxication. There is no simple relation between the intensity of the immediate and the delayed effects of particular halogenated aliphatic hydrocarbons. It is possible to find substances in the group with a rather strong narcotic potency and weak delayed effects, and substances that are very dangerous because they may cause irreversible organ injuries without showing very strong immediate effects. Almost never is only a single organ or system involved; in particular, injury is rarely caused to the liver or kidneys alone, even by compounds which used to be regarded as typically hepatotoxic (e.g., carbon tetrachloride) or nephrotoxic (e.g., methyl bromide).

The local irritant properties of these substances are particularly pronounced in the case of some of the unsaturated members; surprising differences exist, however, even between very similar compounds (e.g., octafluoroisobutylene is enormously more irritating than the isomeric octafluoro-2-butene). Lung irritation may be a major danger in acute inhalation exposure to some compounds belonging to this group (e.g., allyl chloride), and a few of them are lacrimators (e.g., carbon tetrabromide). High concentrations of vapours or liquid splashes may be dangerous for the eyes in some instances; the injury caused by the most used members, however, recovers spontaneously, and only prolonged exposure of the cornea gives rise to persistent injury. Several of these substances, such as 1,2-dibromoethane and 1,3-dichloropropane, are definitely irritating and injurious to the skin, causing reddening, blistering and necrosis even on brief contact.

Being good solvents, all of these chemicals can damage the skin by degreasing it and making it dry, vulnerable, cracked and chapped, particularly on repeated contact.

Hazards of specific compounds

Carbon tetrachloride is an extremely hazardous chemical which has been responsible for deaths from poisoning of workers acutely exposed to it. It is classified as a Group 2B possible human carcinogen by IARC, and many authorities, such as British Health and Safety Executive, require the phasing out of its use in industry. Since a large part of the carbon tetrachloride use was in the production of chlorofluorocarbons, the virtual elimination of these chemicals further drastically limits the commercial uses of this solvent.

Most carbon tetrachloride intoxications have resulted from the inhalation of the vapour; however, the substance is also readily absorbed from the gastrointestinal tract. Being a good fat solvent, carbon tetrachloride removes fat from the skin on contact, which may lead to development of a secondary septic dermatitis. Since it is absorbed through the skin, care should be taken to avoid prolonged and repeated skin contact. Contact with the eyes may cause a transient irritation, but does not lead to serious injury.

Carbon tetrachloride has anaesthetic properties, and exposures to high vapour concentrations can lead to the rapid loss of consciousness. Individuals exposed to less than anaesthetic concentrations of carbon tetrachloride vapour frequently exhibit other nervous system effects such as dizziness, vertigo, headache, depression, mental confusion, and incoordination. It may cause cardiac arrhythmias and ventricular fibrillation at higher concentrations. At surprisingly low vapour concentrations, gastrointestinal disturbances such as nausea, vomiting, abdominal pain and diarrhoea are manifested by some individuals.

The effects of carbon tetrachloride on the liver and kidney must be given primary consideration in evaluating the potential hazard incurred by individuals working with this compound. It should be noted that the consumption of alcohol augments the injurious effects of this substance. Anuria or oliguria is the initial response, which is followed in a few days by a diuresis. The urine obtained during the period of diuresis has a low specific gravity, and usually contains protein, albumin, pigmented casts and red blood cells. Renal clearance of inulin, diodrast and p-aminohippuric acid are reduced, indicating a decrease in blood flow through the kidney as well as glomerular and tubular damage. The function of the kidney gradually returns to normal, and within 100 to 200 days after exposure, the kidney function is in the low-normal range. Histopathological examination of the kidneys reveals varying degrees of damage to the tubular epithelium.

Chloroform. Chloroform is also a dangerous volatile chlorinated hydrocarbon. It may be harmful by inhalation, ingestion and skin contact, and can cause narcosis, respiratory paralysis, cardiac arrest or delayed death due to liver and kidney damage. It may be misused by sniffers. Liquid chloroform may cause defatting of the skin, and chemical burns. It is teratogenic and carcinogenic for mice and rats. Phosgene is also formed by the action of strong oxidants on chloroform.

Chloroform is a ubiquitous chemical, used in many commercial products and formed spontaneously through the chlorination of organic compounds, such as in chlorinated drinking water. Chloroform in air may result at least partly from photochemical degradation of trichloroethylene. In sunlight it decomposes slowly to phosgene, chlorine and hydrogen chloride.

Chloroform is classified by IARC as a Group 2B possible human carcinogen, based on experimental evidence. The oral LD₅₀ for dogs and rats is about 1 g/kg; 14-day-old rats are twice as susceptible as adult rats. Mice are more susceptible than rats. Liver damage is the cause of death. Histopathological changes in the liver and kidney were observed in rats, guinea-pigs and dogs exposed for 6 months (7 h/day, 5 days/week) to 25 ppm in air. Fatty infiltration, granular centrilobular degeneration with necrotic areas in the liver, and changes in serum enzyme activities, as well as swelling of tubular epithelium, proteinuria, glucosuria and decreased phenolsulphonephtalein excretion, were reported. It appears that chloroform has little potential for causing chromosomal abnormalities in various test systems, so it is believed that its carcinogenicity arises from non-genotoxic mechanisms. Chloroform also causes various foetal abnormalities in test animals and a no-effect level has not yet been established.

Persons acutely exposed to chloroform vapour in air may develop different symptoms depending on the concentration and duration of exposure: headache, drowsiness, feeling of drunkenness, lassitude, dizziness, nausea, excitation, unconsciousness, respiratory depression, coma and death in narcosis. Death may occur due to respiratory paralysis or as a result of cardiac arrest. Chloroform sensitizes the myocardium to catecholamines. A concentration of 10,000 to 15,000 ppm of chloroform in inhaled air causes anaesthesia, and 15,000 to 18,000 ppm may be lethal. Narcotic concentrations in blood are 30 to 50 mg/100 ml; levels of 50 to 70 mg/100 ml blood are lethal. After transient recovery from heavy exposure, failure of liver functions and kidney damage may cause death. Effects on heart muscle have been described. Inhalation of very high concentrations may cause sudden arrest of the heart’s action (shock death).

Workers exposed to low concentrations in air for long periods and persons with developed dependance on chloroform may suffer from neurological and gastrointestinal symptoms resembling chronic alcoholism. Cases of various forms of liver disorders (hepatomegaly, toxic hepatitis and fatty liver degeneration) have been reported.

2-Chloropropane is a potent anaesthetic; it has not been widely used, however, because vomiting and cardiac arrhythmia have been reported in humans, and injury to liver and kidneys has been found in animal experiments. Splashes on the skin or into the eyes can result in serious but transient effects. It is a severe fire hazard.

Dichloromethane (methylene chloride) is highly volatile, and high atmospheric concentrations may develop in poorly ventilated areas, producing loss of consciousness in exposed workers. The substance does, however, have a sweetish odour at concentrations above 300 ppm, and consequently it may be detected at levels lower than those having acute effects. It has been classified by IARC as a possible human carcinogen. There is insufficient data on humans, but the animal data which are available are considered sufficient.

Cases of fatal poisoning have been reported in workers entering confined spaces in which high dichloromethane concentrations were present. In one fatal case, an oleoresin was being extracted by a process in which most of the operations were conducted in a closed system; however, the worker was intoxicated by vapour escaping from vents in the indoor supply tank and from the percolators. It was found that the actual loss of dichloromethane from the system amounted to 3,750 l per week.

The principal acute toxic action of dichloromethane is exerted on the central nervous system—a narcotic or, in high concentrations, an anaesthetic effect; this latter effect has been described as ranging from severe fatigue to light-headedness, drowsiness and even unconsciousness. The margin of safety between these severe effects and those of a less serious character is narrow. The narcotic effects cause loss of appetite, headache, giddiness, irritability, stupor, numbness and tingling of the limbs. Prolonged exposure to the lower narcotic concentrations may produce, after a latent period of several hours, shortness of breath, a dry, non-productive cough with substantial pain and possibly pulmonary oedema. Some authorities have also reported haematological disturbance in the form of reduction of the erythrocyte and haemoglobin levels as well as engorgement of the brain blood vessels and dilation of the heart.

However, mild intoxication does not seem to produce any permanent disability, and the potential toxicity of dichloromethane to the liver is much less than that of other halogenated hydrocarbons (in particular, carbon tetrachloride), although the results of animal experiments are not consistent in this respect. Nevertheless, it has been pointed out that dichloromethane is seldom used in a pure state but is often mixed with other compounds which do exert a toxic effect on the liver. Since 1972 it has been shown that persons exposed to dichloromethane have elevated carboxyhaemoglobin levels (such as 10% an hour after two hours’ exposure to 1,000 ppm of dichloromethane, and 3.9% 17 hours later) because of the in vivo conversion of dichloromethane to carbon monoxide. At that time exposure to dichloromethane concentrations not exceeding a time-weighted average (TWA) of 500 ppm could result in a carboxyhaemoglobin level in excess of that allowed for carbon monoxide (7.9% COHb is the saturation level corresponding to 50 ppm CO exposure); 100 ppm of dichloromethane would produce the same COHb level or concentration of CO in the alveolar air as 50 ppm of CO.

Irritation of the skin and eyes may be caused by direct contact, yet the chief industrial health problems resulting from excessive exposure are the symptoms of drunkenness and incoordination that result from dichloromethane intoxication and the unsafe acts and consequent accidents to which these symptoms may lead.

Dichloromethane is absorbed through the placenta and can be found in the embryonic tissues following exposure of the mother; it is also excreted via milk. Inadequate data on reproductive toxicity are available to date.

Ethylene dichloride is flammable and a dangerous fire hazard. It is classified in Group 2B—a possible human carcinogen—by IARC. Ethylene dichloride can be absorbed through the airways, the skin and the gastrointestinal tract. It is metabolized into 2-chloroethanol and monochloroacetic acid, both more toxic than the original compound. It has an odour threshold in humans that varies from 2 to 6 ppm as determined under controlled laboratory conditions. However, adaptation appears to occur relatively early, and after 1 or 2 minutes the odour at 50 ppm is barely detectable. Ethylene dichloride is appreciably toxic to humans. Eighty to 100 ml are enough to produce death within 24 to 48 hours. Inhalation of 4,000 ppm will cause serious illness. In high concentrations it is immediately irritating to the eyes, nose, throat and skin.

A major use of the chemical is in the manufacture of vinyl chloride, which is primarily a closed process. Leaks from the process can and do occur, however, producing a hazard for the worker so exposed. However, the most likely chance of exposure occurs during the pouring of containers of ethylene dichloride into open vats, where it is subsequently used for the fumigation of grain. Exposures also occur through manufacturing losses, application of paints, solvent extractions and waste-disposal operations. Ethylene dichloride rapidly photo-oxidizes in air and does not accumulate in the environment. It is not known to bioconcentrate in any food chains or to accumulate in human tissues.

The classification of ethylene chloride as a Group 2B carcinogen is based on the significant increases in tumour production found in both sexes in mice and rats. Many of the tumours, such as haemangiosarcoma, are uncommon types of tumours, rarely if ever encountered in control animals. The “time to tumour” in treated animals was less than in controls. Since it has caused progressive malignant disease of various organs in two species of animals, ethylene dichloride must be considered potentially carcinogenic in humans.

Hexachlorobutadiene (HCBD). Observations on occupationally induced disorders are scarce. Agricultural workers fumigating vineyards and simultaneously exposed to 0.8 to 30 mg/m³ HCBD and 0.12 to 6.7 mg/m³ polychlorobutane in the atmosphere exhibited hypotension, heart disorders, chronic bronchitis, chronic liver disease and nervous-function disorders. Skin conditions likely to be due to HCBD were observed in other exposed workers.

Hexachloroethane possesses a narcotic effect; however, since it is a solid and has a rather low vapour pressure under normal conditions, the hazard of a central nervous system depression by inhalation is low. It is irritating to skin and mucous membranes. Irritation has been observed from dust, and exposure of operators to fumes from hot hexachloroethane has been reported to cause blepharospasm, photophobia, lacrimation and reddening of the conjunctivae, but not corneal injury or permanent damage. Hexachloroethane may cause dystrophic changes in the liver and in other organs as demonstrated in animals.

IARC has placed HCBD into Group 3, non-classifiable as to carcinogenicity.

Methyl chloride is an odourless gas and therefore gives no warning. It is thus possible for considerable exposure to occur without those concerned becoming aware of it. There is also the risk of individual susceptibility to even mild exposure. In animals it has shown markedly differing effects in different species, with greater susceptibility in animals with more highly developed central nervous systems, and it has been suggested that human subjects may show an even greater degree of individual susceptibility. A hazard pertaining to mild chronic exposure is the possibility that the “drunkenness”, dizziness and slow recovery from slight intoxication may cause failure to recognize the cause, and that leaks may go unsuspected. This could result in further prolonged exposure and accidents. The majority of fatal cases recorded have been caused by leakage from domestic refrigerators or defects in refrigeration plants. It is also a dangerous fire and explosion hazard.

Severe intoxication is characterized by a latent period of several hours before the onset of symptoms such as headache, fatigue, nausea, vomiting and abdominal pain. Dizziness and drowsiness may have existed for some time before the more acute attack was precipitated by a sudden accident. Chronic intoxication from milder exposure has been less frequently reported, possibly because the symptoms may disappear rapidly with cessation of exposure. The complaints during mild cases include dizziness, difficulty in walking, headache, nausea and vomiting. The most frequent objective symptoms are a staggering gait, nystagmus, speech disorders, arterial hypotension, and reduced and disturbed cerebral electrical activity. Mild prolonged intoxication is liable to cause permanent injury of the heart muscle and the central nervous system, with a change of personality, depression, irritability, and occasionally visual and auditory hallucinations. Increased albumen content in the cerebrospinal fluid, with possible extrapyramidal and pyramidal lesions, may suggest a diagnosis of meningoencephalitis. In fatal cases, autopsy has shown congestion of lungs, liver and kidneys.

Tetrachloroethane is a powerful narcotic, and a central nervous system and liver poison. The slow elimination of tetrachloroethane from the body may be a reason for its toxicity. Inhalation of the vapour is ordinarily the chief source of tetrachloroethane absorption, although there is evidence that absorption through the skin may occur to some extent. It has been speculated that certain nervous-system effects (e.g., tremor) are caused chiefly by skin absorption. It is also a skin irritant and may produce dermatitis.

Most of the occupational exposures to tetrachloroethane have resulted from its use as a solvent. A number of fatal cases occurred between 1915 and 1920 when it was employed in the preparation of aeroplane fabric and in the manufacture of artificial pearls. Other fatal cases of tetrachloroethane intoxication have been reported in the manufacture of safety goggles, the artificial leather industry, the rubber industry and a non-specified war industry. Non-fatal cases have occurred in artificial silk manufacture, wool degreasing, penicillin preparation and the manufacture of jewellery.

Tetrachloroethane is a powerful narcotic, being two to three times as effective as chloroform in this respect for animals. Fatal cases among humans have resulted from the ingestion of tetrachloroethane, with death occurring within 12 hours. Non-fatal cases, involving loss of consciousness but no serious after-effects, have also been reported. In comparison with carbon tetrachloride, the narcotic effects of tetrachloroethane are much more severe, but the nephrotoxic effects are less marked. Chronic intoxication by tetrachloroethane can take two forms: central nervous system effects, such as tremor, vertigo and headache; and gastrointestinal and hepatic symptoms, including nausea, vomiting, gastric pain, jaundice and enlargement of the liver.

1,1,1-Trichloroethane is rapidly absorbed through the lungs and the gastrointestinal tract. It can be absorbed through the skin, but this is seldom of systemic importance unless it is confined to the skin surface beneath an impermeable barrier. The first clinical manifestation of overexposure is a functional depression of the central nervous system, commencing with dizziness, incoordination and impaired Romberg test (subject balances on one foot, with eyes closed and arms at his side), progressing to anaesthesia and respiratory centre arrest. The CNS depression is proportional to the magnitude of exposure and typical of an anaesthetic agent, hence the danger of epinephrine sensitization of the heart with the development of an arrhythmia. Transient liver and kidney injury has been produced following heavy overexposure, and lung injury has been noted at autopsy. Several drops splashed directly on the cornea can result in a mild conjunctivitis, which will resolve spontaneously within a few days. Prolonged or repeated contact with skin results in transient erythema and slight irritation, owing to the defatting action of the solvent.

Following the absorption of 1,1,1-trichloroethane a small percentage is metabolized to carbon dioxide while the remainder appears in the urine as the glucuronide of 2,2,2-trichloroethanol.

Acute exposure. Humans exposed to 900 to 1,000 ppm experienced transient, mild eye irritation and prompt, though minimal, impairment of coordination. Exposures of this magnitude may also induce headache and lassitude. Disturbances of equilibrium have been occasionally observed in “susceptible” individuals exposed to concentrations in the 300 to 500 ppm range. One of the most sensitive clinical tests of mild intoxication during the time of exposure is the inability to perform a normal modified Romberg test. Above 1,700 ppm, obvious disturbances of equilibrium have been observed.

The majority of the few fatalities reported in the literature have occurred in situations in which an individual was exposed to anaesthetic concentrations of the solvent and either succumbed as a result of respiratory centre depression or an arrhythmia resulting from epinephrine sensitization of the heart.

1,1,1-Trichloroethane is unclassifiable (Group 3) as to carcinogenicity accord to IARC.

The 1,1,2-trichloroethane isomer is used as a chemical intermediate and as a solvent. The principal pharmacologic response to this compound is depression of the CNS. It appears to be less acutely toxic than the 1,1,2- form. Although IARC considers it a nonclassifiable carcinogen (Group 3), some government agencies treat it as a possible human carcinogen (e.g., US National Institute of Occupational Safety and Health (NIOSH)).

Trichloroethylene. Although, under ordinary conditions of use, trichloroethylene is non-flammable and non-explosive, it may decompose at high temperatures to hydrochloric acid, phosgene (in the presence of atmosphere oxygen) and other compounds. Such conditions (temperatures above 300 °C) are found on hot metals, in arc welding and open flames. Dichloroacetylene, an explosive, flammable, toxic compound, may be formed in the presence of strong alkali (e.g., sodium hydroxide).

Trichloroethylene has primarily a narcotic effect. In exposure to high concentrations of vapour (above about 1,500 mg/m³) there may be an excitatory or euphoric stage followed by dizziness, confusion, drowsiness, nausea, vomiting and possibly loss of consciousness. In accidental ingestion of trichloroethylene a burning sensation in the throat and gullet precedes these symptoms. In inhalation poisonings, most manifestations clear with the breathing of uncontaminated air and elimination of the solvent and its metabolites. Nevertheless, deaths have occurred as a result of occupational accidents. Prolonged contact of unconscious patients with liquid trichloroethylene may cause blistering of the skin. Another complication in poisoning may be chemical pneumonitis and liver or kidney damage. Trichloroethylene splashed in the eye produces irritation (burning, tearing and other symptoms).

After repeated contact with liquid trichloroethylene, severe dermatitis may develop (drying, reddening, roughening and fissuring of the skin), followed by secondary infection and sensitization.

Trichloroethylene is classified as a Group 2A probable human carcinogen by IARC. In addition, the central nervous system is the main target organ for chronic toxicity. Two types of effects are to be distinguished: (a) narcotic effect of trichloroethylene and its metabolite trichloroethanol when still present in the body, and (b) the long-lasting sequellae of repeated over-exposures. The latter may persist for several weeks or even months after the end of the exposure to trichloroethylene. The main symptoms are lassitude, giddiness, irritability, headache, digestive disturbances, intolerance of alcohol (drunkenness after consumption of small quantities of alcohol, skin blotches due to vasodilation—”degreaser’s flush”), mental confusion. The symptoms may be accompanied by dispersed minor neurological signs (mainly of brain and autonomic nervous system, rarely of peripheral nerves) as well as by psychological deterioration. Irregularities of cardiac rhythm and minor liver involvement have rarely been observed. The euphoric effect of trichloroethylene inhalation may lead to craving, habituation and sniffing.

Allyl compounds

The allyl compounds are unsaturated analogues of corresponding propyl compounds, and are represented by the general formula CH₂:CHCH₂X, where X in the present context is usually a halogen, hydroxyl or organic acid radical. As in the case of the closely allied vinyl compounds, the reactive properties associated with the double bond have proved useful for the purposes of chemical synthesis and polymerization.

Certain physiological effects of significance in industrial hygiene are also associated with the presence of the double bond in the allyl compounds. It has been observed that unsaturated aliphatic esters exhibit irritant and lacrimatory properties which are not present (at least to the same extent) in the corresponding saturated esters; and the acute LD₅₀by various routes tends to be lower for the unsaturated ester than for the saturated compound. Striking differences in these respects are found between allyl acetate and propyl acetate. These irritant properties, however, are not confined to the allyl esters; they are found in different classes of allyl compounds.

Allyl chloride (chloroprene) has flammable and toxic properties. It is only weakly narcotic but is otherwise highly toxic. It is very irritating to the eyes and upper respiratory tract. Both acute and chronic exposure can give rise to lung, liver and kidney injury. Chronic exposure has also been associated with decrease in the systolic pressure and in the tonicity of the brain blood vessels. In contact with the skin it causes mild irritation, but absorption through the skin causes deep-seated pain in the contact area. Systemic injury may be associated with skin absorption.

Animal studies give contradictory results with respect to carcinogenicity, mutagencity and reproductive toxicity. IARC has placed allyl chloride into a Group 3 classification—not classifiable.

Vinyl and vinylidene chlorinated compounds

Vinyls are chemical intermediates and are used primarily as monomers in the manufacture of plastics. Many of them can be prepared by the addition of the appropriate compound to acetylene. Examples of vinyl monomers include vinyl bromide, vinyl chloride, vinyl fluoride, vinyl acetate, vinyl ethers and vinyl esters. Polymers are high-molecular-weight products formed by polymerization, which can be defined as a process involving the combination of similar monomers to produce another compound containing the same elements in the same proportions, but with a higher molecular weight and different physical characteristics.

Vinyl chloride. Vinyl chloride (VC) is flammable and forms an explosive mixture with air at proportions between 4 and 22% by volume. When burning it is decomposed into gaseous hydrochloric acid, carbon monoxide and carbon dioxide. It is easily absorbed by the human organism through the respiratory system, from where it passes into the blood circulation and from there to the various organs and tissues. It is also absorbed through the digestive system as a contaminant of food and beverages, and through the skin; however, these two routes of entry are negligible for occupational poisoning.

The absorbed VC is transformed and excreted in various ways depending on the amount accumulated. If it is present in high concentrations, up to 90% of it may be eliminated unchanged by exhalation, accompanied by small amounts of CO₂; the rest undergoes biotransformation and is excreted with the urine. If present in low concentrations, the amount of monomer exhaled unchanged is extremely small, and the proportion reduced to CO₂ represents approximately 12%. The remainder is subjected to further transformation. The principal centre of the metabolic process is the liver, where the monomer undergoes a number of oxidative processes, being catalyzed partly by alcohol dehydrogenase, and partly by a catalase. The main metabolic pathway is the microsomal one, where VC is oxidated to chloroethylene oxide, an unstable epoxide which spontaneously transforms into chloroacetaldehyde.

Whichever the metabolic pathway followed, the final product is always chloroacetaldehyde, which consecutively conjugates with glutathion or cysteine, or is oxidated to monochloroacetic acid, which partly passes into the urine and partly combines with glutathion and cysteine. The main urinary metabolites are: hydroxyethyl cysteine, carboxyethyl cysteine (as such or N-acetylated), and monochloroacetic acid and thiodiglycolic acid in traces. A small proportion of metabolites are excreted with the gall into the intestine.

Acute poisoning. In humans, prolonged exposure to VC brings about a state of intoxication which may have an acute or chronic course. Atmospheric concentrations of about 100 ppm are not perceptible since the odour threshold is 2,000 to 5,000 ppm. If such high monomer concentrations are present, they are perceived as a sweetish, not unpleasant smell. Exposure to high concentrations results in a state of elation followed by asthenia, sensation of heaviness in the legs, and somnolence. Vertigo is observed at concentrations of 8,000 to 10,000 ppm, hearing and vision are impaired at 16,000 ppm, loss of consciousness and narcosis are experienced at 70,000 ppm, and concentrations of more than 120,000 ppm may be fatal to humans.

Carcinogenic action. Vinyl chloride is classified as a Group 1 known human carcinogen by IARC, and it is regulated as a known human carcinogen by numerous authorities throughout the world. In the liver, it may induce the development of an extremely rare malignant tumour known as angiosarcoma or haemangioblastoma or malignant haemangio-endothelioma or angiomatous mesenchymoma. The mean latency period is about 20 years. It evolves asymptomatically and becomes apparent only at a late stage, with symptoms of hepatomegaly, pain and decay of the general state of health, and there may be signs of concomitant liver fibrosis, portal hypertension, oesophageal varicose veins, ascites, haemorrhage of the digestive tract, hypochromic anaemia, cholestasia with an increase in alkaline phosphatasis, hyperbilirubinaemia, increase in BSP retention time, hyperfunction of the spleen characterized essentially by thrombocytopenia and reticulocytosis, and liver-cell involvement with a decrease in serum albumin and in fibrinogen.

Long-term exposure to sufficiently high concentrations gives rise to a syndrome called “vinyl chloride disease”. This condition is characterized by neurotoxic symptoms, modifications of the peripheral microcirculation (Raynaud’s phenomenon), skin changes of the scleroderma type, skeletal changes (acro-osteolysis), modifications in the liver and spleen (hepato-splenic fibrosis), pronounced genotoxic symptoms, as well as cancer. There may be skin involvement, including scleroderma on the back of the hand at the metacarpal and phalangeal joints and on the inside of the forearms. The hands are pale and feel cold, moist and swollen on account of a hard oedema. The skin may lose elasticity, be difficult to lift in folds, or covered by small papules, microvesicles and urticaroid formations. Such changes have been observed on the feet, neck, face and back, as well as the hands and arms.

Acro-osteolysis. This is a skeletal change generally localized at the distal phalanges of the hands. It is due to aseptic bone necrosis of ischaemic origin, induced by stenosing osseous arteriolitis. The radiologic picture shows a process of osteolysis with transverse bands or with thinned ungual phalanges.

Liver changes. In all cases of VC poisoning, liver changes can be observed. They may start with difficult digestion, a sensation of heaviness in the epigastric region, and meteorism. The liver is enlarged, has its normal consistency, and does not give particular pain when palpated. Laboratory tests are rarely positive. The liver enlargement disappears after removal from exposure. Liver fibrosis may develop in persons exposed for longer periods of time—that is, after 2 to 20 years. This fibrosis is sometimes isolated, but more often associated with an enlargement of the spleen, which may be complicated by portal hypertension, varicose veins at the oesophagus and cardia, and consequently by haemorrhages of the digestive tract. Fibrosis of the liver and spleen is not necessarily associated with an enlargement of these two organs. Laboratory tests are of little help, but experience has shown that a BSP test should be made, and the SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase), gamma GT and bilirubinaemia be determined. The only reliable examination is a laparoscopy with biopsy. The liver surface is irregular on account of the presence of granulations and sclerotic zones. The general structure of the liver is rarely changed, and the parenchyma is little affected, although there are liver cells with turbid swellings and liver-cell necrosis; a certain polymorphism of the cell nuclei is evident. The mesenchymal changes are more specific as there is always a fibrosis of the Glisson’s capsule extending into the portal spaces and passing into the liver-cell interstices. When the spleen is involved, it presents a capsular fibrosis with follicular hyperplasia, dilatation of the sinusoids and congestion of the red pulp. A discreet ascites is not infrequent. After removal from exposure the hepatomegaly and splenomegaly diminish, the changes of the liver parenchyma reverse, and the mesenchymal changes may undergo further deterioration or also cease their evolution.

Vinyl bromide. Although the acute toxicity of vinyl bromide is lower than that of many other chemicals in this group, it is considered a probable human carcinogen (Group 2A) by IARC and should be handled as a potential occupational carcinogen in the workplace. In its liquid state vinyl bromide is moderately irritant for the eyes, but not for the skin of rabbits. Rats, rabbits and monkeys exposed to 250 or 500 ppm for 6 hours per day, 5 days per week during 6 months did not reveal any damage. A 1-year experiment on rats exposed to 1,250 or 250 ppm (6 hours per day, 5 days per week) disclosed an increase in mortality, loss of body weight, angiosarcoma of the liver and carcinomas of Zymbal’s glands. The substance proved to be mutagenic in strains of Salmonella typhimurium with and without metabolic activation.

Vinylidene chloride (VDC). If pure vinylidene chloride is kept between -40 °C and +25 °C in the presence of air or oxygen, a violently explosive peroxide compound of undetermined structure is formed, which can detonate from slight mechanical stimuli or from heat. The vapours are moderately irritating to the eyes, and exposure to high concentrations may cause effects similar to drunkenness, which may progress to unconsciousness. The liquid is an irritant to the skin, which may be in part due to the phenolic inhibitor added to prevent uncontrolled polymerization and explosion. It also has sensitizing properties.

The carcinogenic potential of VDC in animals is still controversial. IARC has not classified it as a possible or probable carcinogen (as of 1996), but the US NIOSH has recommended the same exposure limit for VDC as for vinyl chloride monomer—that is, 1 ppm. No case reports or epidemiological studies relevant to the carcinogenicity to humans of VDC-vinyl chloride copolymers are available to date.

VDC has a mutagenic activity, the degree of which varies according to its concentration: at low concentration it has been found higher than that of vinyl chloride monomer; however, such activity seems to decrease at high doses, probably as a result of an inhibitory action on the microsomal enzymes responsible for its metabolic activation.

Aliphatic hydrocarbons containing bromine

Bromoform. Much of the experience in poisoning cases in humans has been from oral administration, and it is difficult to determine the significance of the toxicity of bromoform in industrial use. Bromoform has been used as a sedative and particularly as an antitussive for years, ingestion of quantities above the therapeutic dose (0.1 to 0.5 g) having caused stupor, hypotension and coma. In addition to the narcotic effect, a rather strong irritant and lacrimatory effect occurs. Exposure to bromoform vapours causes a marked irritation of the respiratory passages, lacrimation and salivation. Bromoform may injure the liver and the kidney. In mice, tumours have been elicited by intraperitoneal application. It is absorbed through the skin. On exposure to concentrations of up to 100 mg/m³ (10 ppm), complaints of headache, dizziness and pain in the liver region have been made, and alterations in the liver function have been reported.

Ethylene dibromide (dibromoethane) is a potentially dangerous chemical with an estimated minimum human lethal dose of 50 mg/kg. In fact, the ingestion of 4.5 cm³ of Dow-fume W-85, which contains 83% dibromoethane, proved to be fatal for a 55 kg adult female. It is classified as a Group 2A probable human carcinogen by IARC.

The symptoms induced by this chemical depend on whether there has been direct contact with the skin, inhalation of vapour, or oral ingestion. Since the liquid form is a severe irritant, prolonged contact with the skin leads to redness, oedema and blistering with eventual sloughing ulceration. Inhalation of its vapours results in respiratory system damage with lung congestion, oedema and pneumonia. Central nervous system depression with drowsiness also occurs. When death supervenes, it is usually due to cardiopulmonary failure. Oral ingestion of this material leads to injury of the liver with lesser damage to the kidneys. This has been found in both experimental animals and in humans. Death in these cases is usually attributable to extensive liver damage. Other symptoms which may be encountered following ingestion or inhalation include excitement, headache, tinnitus, generalized weakness, a weak and thready pulse and severe, protracted vomiting.

Oral administration of dibromoethane by stomach tube caused squamous cell carcinomas of the forestomach in rats and mice, lung cancers in mice, haemoangiosarcomas of the spleen in male rats, and liver cancer in female rats. No case reports in humans or definitive epidemiological studies are available.

Recently a serious toxic interaction has been detected in rats between inhaled dibromoethane and disulphiram, resulting in very high mortality levels with a high incidence of tumours, including haemoangiosarcomas of liver, spleen and kidney. Therefore the US NIOSH recommended that (a) workers should not be exposed to dibromoethane during the course of sulphiram therapy (Antabuse, Rosulfiram used as alcohol deterrents), and (b) no worker should be exposed to both dibromoethane and disulphiram (the latter being also used in industry as an accelerator in rubber production, a fungicide and an insecticide).

Fortunately the application of dibromoethane as a soil fumigant is ordinarily under the surface of the ground with an injector, which minimizes the hazard of direct contact with the liquid and vapour. Its low vapour pressure also reduces the possibility of inhalation of appreciable amounts.

The odour of dibromoethane is recognizable at a concentration of 10 ppm. Procedures set forth earlier in this chapter for the handling of carcinogens should be applied to this chemical. Protective clothing and nylon-neoprene gloves will help avoid skin contact and possible absorption. In case of direct contact with the skin surface, treatment consists of removal of covering garments and thorough washing of the skin with soap and water. If this is accomplished within a short time after the exposure, it constitutes adequate protection against development of skin lesions. Involvement of the eyes by either the liquid or vapour can be successfully treated by flushing with copious volumes of water. Since the ingestion of dibromoethane by mouth leads to serious liver injury, it is imperative that the stomach be promptly emptied and thorough gastric lavage be accomplished. Efforts to protect the liver should include such traditional procedures as a high-carbohydrate diet and supplementary vitamins, especially vitamins B, C and K.

Methyl bromide is among the most toxic organic halides and gives no odour warning of its presence. In the atmosphere it disperses slowly. For these reasons it is among the most dangerous materials encountered in industry. Entry to the body is mainly by inhalation, whereas the degree of skin absorption is probably insignificant. Unless severe narcosis results, it is typical for the onset of symptoms to be delayed by hours or even days. A few deaths have resulted from fumigation, where its continued use is problematic. A number have occurred due to leakage from refrigerating plants, or from the use of fire extinguishers. Lengthy skin contact with clothing contaminated by splashes can cause second-degree burns.

Methyl bromide may damage the brain, heart, lungs, spleen, liver, adrenals and kidneys. Both methyl alcohol and formaldehyde have been recovered from these organs, and bromide in amounts varying from 32 to 62 mg/300 g of tissue. The brain may be acutely congested, with oedema and cortical degeneration. Pulmonary congestion may be absent or extreme. Degeneration of the kidney tubules leads to uraemia. Damage to the vascular system is indicated by haemorrhage in the lungs and brain. Methyl bromide is said to be hydrolyzed in the body, with the formation of inorganic bromide. The systemic effects of methyl bromide may be an unusual form of bromidism with intracellular penetration by bromide. Pulmonary involvement in such cases is less severe.

An acneform dermatitis has been observed in persons repeatedly exposed. Cumulative effects, often with disturbances of the central nervous system, have been reported after repeated inhalation of moderate concentrations of methyl bromide.

Safety and Health Measures

The use of the most dangerous compounds of the group should be avoided entirely. Where it is technically feasible, they should be replaced by less harmful substances. For example, as far as practicable, less hazardous substances should be used instead of bromomethane in refrigeration and as fire extinguishers. In addition to the prudent safety and health measures applicable to volatile chemicals of similar toxicity, the following are also recommended:

Fire and explosion. Only the higher members of the series of halogenated aliphatic hydrocarbons are not flammable and not explosive. Some of them do not support combustion and are used as fire extinguishers. In contrast the lower members of the series are flammable, in some instances even highly flammable (for example, 2-chloropropane) and form explosive mixtures with air. Besides, in the presence of oxygen, violently explosive peroxide compounds may arise from some unsaturated members (for example, dichloroethylene) even at very low temperatures. Toxicologically dangerous compounds may be formed by thermal decomposition of halogenated hydrocarbons.

The engineering and hygiene measures of prevention should be completed by periodic health examinations and complementary laboratory tests aimed at the target organs, in particular the liver and kidneys.

Halogenated saturated hydrocarbons tables

Table 1 - Chemical information.

Table 2 - Health hazards.

Halogenated unsaturated hydrocarbons tables

Table 5 - Chemical information.

Table 6 - Health hazards.

Table 7 - Physical and chemical hazards.

Table 8 - Physical and chemical properties.

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

MISSING

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.

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 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.