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/m³ was 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.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

Back

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.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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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:

1. by replacement of hydrogen atoms with aliphatic hydrocarbon radicals
2. 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
3. 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.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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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.

Table 3 - Physical and chemical hazards.

Table 4 - Physical and chemical properties.

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