Chemical Teratogens, Carcinogens, Mutagens
There is sufficient evidence for the carcinogenicity of some soot extracts, coal tars and coal tar pitches, creosotes, and untreated and mildly treated mineral oils in experimental animals. There is inadequate evidence for the carcinogenicity of soots and highly refined mineral oils in experimental animals (IARC V.3, 1973; IARC S.4, 1982; IARC V.33, 1984; IARC V.34, 1984; IARC V.35, 1985; IARC S.7, 1987). In two studies, when administered topically, an extract of a coal-derived soot induced skin carcinomas and papillomas in mice of both sexes. Coal-derived soot was tested in two experiments in mice by whole-body exposure, but the studies were inadequate for evaluation. A wood-soot extract applied to the skin of mice was inadequately tested. In limited studies, subcutaneous implants of wood soot in female rats produced a few local sarcomas; similar implants in the scrotal sac of rats did not. An extract of fuel oil soot was inadequately tested by application to the skin of mice. Extracts of soot from the combustion of oil shale produced skin papillomas and carcinomas in mice after dermal application and lung carcinomas in rats after intratracheal instillation. Extracts of soot from the combustion of a heating oil produced from shale oil produced skin papillomas and carcinomas in mice in two experiments when applied to the skin (IARC S.7, 1987). Analyses of various soots reveal the presence of a number of known carcinogens and potentially carcinogenic chemicals that are in the Eighth Report on Carcinogens, including arsenic, cadmium, chromium, nickel, benz[a]anthracene, benzo[a]pyrene, dibenz[a,h]anthracene, and indeno[1,2,3-cd]pyrene (see Arsenic and Chromium in Section III.A and Cadmium, Nickel, and Polycyclic Aromatic Hydrocarbons, 15 Listings, in Section III.B).
When administered topically coal tars (8007-45-2), coal tar extracts, and high-temperature coal tars (65996-89-6) induced skin papillomas and carcinomas. Pharmaceutical coal tars and tar ointments caused skin papillomas, squamous cell carcinomas, and/or carcinomas when applied to the skin of mice of both sexes. When applied to the skin, coal tar induced epidermoid lung carcinomas in rats, and when applied to the ears of rabbits, coal tar caused skin papillomas. When administered intramuscularly, coal tar fume condensate induced injection site sarcomas in mice of both sexes. Analyses of coal tars indicate the presence of a number of known carcinogens and potentially carcinogenic chemicals which are in the Eighth Report on Carcinogens, including benz[a]anthracene, benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, dibenzo[a,i]pyrene, and indeno[1,2,3-cd]pyrene (see Polycyclic Aromatic Hydrocarbons, 15 Listings, Section III.B).
When administered topically creosote (8001-58-9), a coal tar distillate, induced skin papillomas and carcinomas in male and female mice and lung adenomas in mice. When applied topically, creosote oils induced skin papillomas and carcinomas in mice of both sexes. Creosote contains several carcinogenic polycyclic aromatic hydrocarbons which are in the Eighth Report on Carcinogens, including benz[a]anthracene, benzo[a]pyrene, and dibenz[a,h]anthracene (see Polycyclic Aromatic Hydrocarbons, 15 Listings, Section III.B).
When administered topically or by whole-body exposure, coal tar pitch, a coal tar distillate, induced skin papillomas and carcinomas in mice. When applied topically, coal tar pitch extracts induced skin papillomas and carcinomas in mice; these extracts also had both initiating and promoting activities (in separate studies) in mouse skin. In one study, an extract of a hard residue from a coke oven tar induced lung tumors but no skin tumors in mice (IARC V.7, 1974). Analyses of coal tar pitches reveal the presence of several carcinogenic polycyclic aromatic hydrocarbons which are in the Eighth Report on Carcinogens, including benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, and indeno[1,2,3-cd]pyrene (see Polycyclic Aromatic Hydrocarbons, 15 Listings, Section III.B) (IARC V.35, 1985).
Vacuum-distillate fractions, acid-treated oils, mildly treated solvent-refined oils, mildly treated hydrotreated oils, solvent extracts (aromatic oils), and some cutting oils produced skin tumors after repeated skin applications to mice. Similar treatment with high-boiling, catalytically cracked oils produced skin tumors in rabbits and Rhesus monkeys. Some severely solvent-refined oils did not produce skin tumors in mice. Highly-refined food-grade mineral oils did not produce skin tumors when applied to the skin of mice, although after intraperitoneal injection they produced plasma cell neoplasms and reticulum cell sarcomas in certain strains of female mice. An IARC Working Group concluded that the latter finding was difficult to interpret (IARC S.7, 1987). Analyses of mineral oils used for medicinal and cosmetic purposes reveal the presence of several carcinogenic polycyclic aromatic hydrocarbons which are in the Eighth Report on Carcinogens, including benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene (see Polycyclic Aromatic Hydrocarbons, 15 Listings, Section III.B) (IARC V. 33, 1984).
An IARC Working Group reported that there is sufficient evidence for the carcinogenicity of soots, coal tars, coal tar pitches, and untreated and mildly refined mineral oils in humans; there is limited evidence for the carcinogenicity of creosotes in humans; and there were no adequate data available to evaluate the carcinogenicity of highly refined mineral oils (IARC S.7, 1987).
The carcinogenicity of soot is demonstrated by numerous case reports, dating back over 200 years, of skin cancer, particularly of the scrotum, among chimney sweeps. More recent cohort studies of mortality among chimney sweeps have shown a significantly increased risk of lung cancer. Supporting evidence for an association with lung cancer was provided by two earlier epidemiological studies. The potentially confounding and interactive effects of smoking could not be evaluated; however, cigarette smoking is not believed to have seriously biased these estimates. In addition to lung cancer, statistically significant excess mortality from esophageal cancer, primary liver cancer, and leukemia was found among chimney sweeps in one study (IARC S.7, 1987).
There have been a number of case reports of skin cancer in patients who used tar ointments for a variety of skin diseases. A mortality analysis in the United Kingdom from 1946 showed a greatly increased scrotal cancer risk for patent-fuel workers. Furthermore, a large number of case reports describe the development of skin (including the scrotum) cancer in workers exposed to coal tars or coal-tar pitches. Several epidemiological studies have shown an excess of lung cancer among workers exposed to coal tar fumes in coal gasification and coke production. A cohort study of U.S. roofers indicated an increased risk for cancer of the lung and suggested increased risks for cancers of the oral cavity, larynx, esophagus, stomach, skin, and bladder and for leukemia. Some support for excess risks of lung, laryngeal, and oral cavity cancer is provided by other studies of roofers. Several epidemiological studies have shown excesses of lung and urinary bladder cancer among workers exposed to pitch fumes in aluminum production plants. A slight excess of lung cancer was found among furnace and maintenance workers exposed to coal tar pitch fumes in a calcium carbide production plan. One study showed a small excess of bladder cancer in tar distillers and in patent-fuel workers. An elevated risk of cancer of the renal pelvis was seen in workers exposed to "petroleum or tar or pitch." One study of millwrights and welders exposed to coal tars and coal tar pitch in a stamping plant showed significant excesses of leukemia and of cancers of the lung and digestive organs (IARC S.7, 1987).
In a number of case reports, the development of skin cancer in workers exposed to creosotes is described. One study involved a review of 3,753 cases of cutaneous epithelioma and showed that 35 cases (12 of which were of the scrotum) involved exposure to creosotes. Most cases occurred in workers handling creosotes or creosoted wood during timber treatment. A mortality analysis of workers in many occupations indicated an increased risk of scrotal cancer for creosote-exposed brickmakers (IARC S.7, 1987).
Exposure to mineral oils that have been used in a variety of occupations, including mulespinning, metal machining and jute processing, has been associated strongly and consistently with the occurrence of squamous cell cancers of the skin, and especially of the scrotum. Among 682 turners with 5 or more years of exposure to mineral oils, five cases of squamous cell carcinoma of the skin (four of the scrotum) occurred, with 0.3 expected. In a case-control study, an excess of sinonasal cancers was seen in toolsetters, set-up men, and toolmakers.
One of three mortality studies on manual workers in the printing industry, not specifically addressing printing pressmen, did not shown an increased lung cancer risk, whereas the other two studies found a statistically significant excess. One of two mortality studies of printing pressmen indicated a statistically significant increase of deaths from rectal cancer, and the other showed a statistically nonsignificant increase of deaths from colon cancer. One mortality study among newspaper and other commercial printing pressmen showed a statistically significant excess of mortality from cancers of the buccal cavity and pharynx, whereas no such excess was observed in a cohort study. One case-control study indicted a statistically significant excess of cancers of the buccal cavity and pharynx (IARC S.7, 1987).
Soots are generally lusterless, black substances that are by-products of the incomplete combustion or pyrolysis of carbon-containing materials. Soots consist of variable quantities of carbonaceous and inorganic solids with absorbed and occluded organic tars and resins. Most soots contain inorganic matter such as oxides, salts, metals, absorbed liquids and gases, sulfur, and nitrogen compounds; organic compounds, such as polycyclic aromatic hydrocarbons, their derivatives, and their heterocyclic analogues, that can be extracted with organic solvents (methylene chloride or benzene); and insoluble carbonaceous matter consisting of resins and/or incompletely carbonized fuel fragments.
Coal tars are by-products of the destructive distillation (carbonization) of coal to produce coke and/or gas. The composition and properties of a coal tar depend mainly on the temperature of the carbonization and, to a lesser extent, on the nature of the coal used as feedstock. Coal tars are usually viscous liquids or semisolids that are black or almost black in color. Coal tars have a characteristic naphthalene-like odor. Coal tars are soluble in benzene and nitrobenzene and partially soluble in acetone, carbon disulfide, chloroform, diethyl ether, ethanol, methanol, petroleum ether, and sodium hydroxide. Coal tars are slightly soluble in water. In general, coal tars are complex combinations of hydrocarbons, phenols, heterocyclic oxygen, sulfur, and nitrogen compounds. Over 400 compounds have been identified in coal tars and as many as 10,000 may actually be present. The content of polycyclic aromatic hydrocarbons in coal tars increases as the carbonization temperature increases. Low-temperature coal tars (< 700% C) are black, viscous liquids that are more dense than water. Low-temperature coal tars are less aromatic than high-temperature coal tars (> 700% C) containing only 40-50% aromatic hydrocarbons.
Creosote, a distillation product of coal tars, is a yellowish dark green to brown oily liquid. It consists of aromatic hydrocarbons, anthracene, naphthalene, and phenanthrene derivatives; some tar acids; and tar bases. Polycyclic aromatic hydrocarbons make up at least 75% of creosote.
Coal tar pitch is a shiny, dark brown to black residue produced during the distillation of coal tars. Pitch contains various polycyclic aromatic hydrocarbons and their methyl and polymethyl derivatives, as well as heteronuclear compounds.
Mineral oils, refined from petroleum crude oils, are complex mixtures of straight- and branched-chain paraffinic, naphthenic, and aromatic hydrocarbons with 15 or more carbons and boiling points in the range of 300%-600% C. Paraffinic crude oils are characterized by high wax content, high natural viscosity index (the rate of change of viscosity over a given temperature range), and relatively low aromatic hydrocarbon content. Naphthenic crude oils are generally low in wax content and relatively high in cycloparaffins and aromatic hydrocarbons. All crude oils contain some polycyclic aromatic compounds, and the proportions and types of these compounds in finished base oils are determined mainly by the refining processes. Medicinal white mineral oils are clear, tasteless, and odorless at room temperature with little odor after heating. Some medicinal and technical-grade white mineral oils may contain up to 10 mg/kg _-tocopherol as an antioxidant. Polycyclic aromatic hydrocarbons have been detected in white mineral oils.
The primary use of soots is in the recovery of trace metals in the metallurgical industry. Soots have also been used as fertilizers after weathering to allow acid to leach away or be neutralized by the ammonium compounds and other bases (IARC V.35, 1985). The fertilizing action is probably due to its nitrogen and trace metals content.
The primary use of coal tar is for the production of refined chemicals and coal tar products such as creosote, coal tar pitch, and crude naphthalene and anthracene oils from the distillation of crude coal tar. It is also used as a fuel in open-hearth furnaces and blast furnaces in the steel industry. Coal tar is suitable as a fuel because of its availability, its low sulfur content, and its high heating value. Both high-temperature and low-temperature coal tars are used to treat psoriasis and other chronic skin diseases. Coal tar products are also used in numerous pharmaceutical products including creams, ointments, pastes, lotions, bath and body oils, shampoos, soaps, and gels. The coal tar products present in these formulations include coal tars (0.18-10%), coal tar solution (2-48.5%), coal tar extract (5%), tar distillate (3-25%), coal tar fraction (1.25%), and a cetyl alcohol coal tar (4%). Coal tar extract is also used in neomycin sulfate-hydrocortisone ointment. USP-grade coal tar is approved for use in denatured alcohol. Coal tar is also used as a binder and filler in surface-coating formulations and as a modifier for epoxy-resin surface coatings (IARC V.35, 1985).
The primary use of creosote is for the preservation of wood (IARC V.35, 1985). Creosote is used to treat railway sleepers, poles, pilings, lumber and timber, railway-switch sleepers, fence posts, and other wood products. Creosote is registered for use as an animal and bird repellent, animal dip, miticide, fungicide, herbicide, and insecticide; however, it is currently used in only limited quantities as an animal and bird repellent, as an insecticide (ovicide), and as an animal dip. Creosote is also used in a tap-hole refractory cement which is used to close openings in furnaces or ovens after material has been withdrawn. Creosote has also been used as a frothing agent in mineral flotation and as a feedstock for the production of carbon blacks (IARC V.35, 1985).
The primary use of coal tar pitch is as the binder for aluminum smelting electrodes (IARC V.34, 1984). Pitches are also used in roofing materials, surface coatings, black varnishes, and pipe-coating enamels. Coal tar pitch is used to impregnate and strengthen the walls of brick refractories. Hard pitch is used as a binder for foundry cores. Coke oven pitch is used to produce pitch coke which is used as the carbon component of electrodes, carbon brushes, and carbon and graphite articles (IARC V.35, 1985). Distillation fractions and residues from high-temperature coal tars are used in the production of naphthalene, recovery of benzene, production of anthracene paste, briquetting of smokeless solid fuel, impregnation of electrodes and fibers, manufacture of electrodes and graphite, and for road paving and construction (IARC V.35, 1985).
The primary use of mineral oils is as lubricant base oils to produce further refined oil products. These products include: engine oils, automotive and industrial gear oils, transmission fluids, hydraulic fluids, circulating and hydraulic oils, bearing oils, machine oils, machine-tool oils, compressor and refrigerator oils, steam-engine oils, textile machine oils, air-tool oils, metalworking oils (cutting oils, roll oils, can-forming oils, drawing oils), rust preventative oils, heat-treating oils, transformer oils, greases, medicinal and technical-grade white oils, and processing oils (product extenders, processing aids, carriers and diluents, water repellents, surface-active agents, batching oils, mold-release oils, wash oils). These oils are used in manufacturing (78.5% of the oils produced), mining (5.0%), construction (1.8%), and miscellaneous industries (14.7%). Approximately 57% of the lubricating oils produced are used by the automotive industry and the remaining 43% by other industries. In the automotive industry, lubricating oils are used as multigrade engine oils (23% of the lubricating oils produced), monograde engine oils (22%), transmission and hydraulic fluids (8%), gear oils (2%), and aviation oils (1%). Other industrial uses for lubricating oils include general industrial diesel engine oils (19%), process oils (13%), metalworking oils (4%), railroad diesel engine oils (3%), and marine diesel engine oils (2%). Technical-grade white oils are used in cosmetics (hair oils, creams), textile-machine lubricants, horticultural sprays, wrapping paper, for corrosion protection in the meat-packing industry, and as lubricants for watches, bicycles, and spindles. Medicinal white oils are used in pharmaceutical preparations (processing aids, intestinal lubricants), food additives (release agents, binders, flotation sealants, defoamants, protective coatings), food packaging and processing, and animal feed products. Medicinal white oils are also used in the chemical and plastics industry as processing media, extenders, and plasticizers (IARC V.33, 1984).
For detasils See Coal Tar