Thiols (mercaptans, thioalcohols or sulphydrates) are monofunctional organic sulphydryl compounds, either aliphatic or aromatic, and characterized by the presence of sulphydryl (–SH) groups. Generally, the thiols have a strong, unpleasant odour even at very low concentrations. At equal concentrations the strength of the odour appears to vary inversely with the number of carbon atoms in the molecule, and is essentially absent in 1-dodecane thiol and higher thiols. The most important method for the production of thiols involves the reaction of hydrogen sulphide with olefins or alcohols, at various temperatures and pressures, in combination with a variety of catalysts and promoters including acids, bases, peroxides and metal sulphates. The hydrogen of the –SH group can be replaced by mercury (the word mercaptans is derived from the Latin corpus mercurium captans, meaning entity-seizing mercury) and other heavy metals to form mercaptides.
Naturally occurring thiols exist in all living systems. In living cells, most of the thiols are contributed by the amino acid cysteine and the tripeptide glutathione. Also, methanethiol and ethanethiol occur naturally as “sour” gas at room temperature, while the other thiols are liquids. The C1 through C6 alkane thiols and benzenethiol have obnoxious odours at much lower concentrations than do the other thiols.
Organic sulphur compounds can also be formed when a sulphate unit (SO4) is bound to an organic group. Sulphides and sulphonium salts are formed with two organic groups bonded to a sulphur atom.
Organic sulphides and sulphates are used in industry as solvents, chemical intermediates, flavouring agents and accelerants for rubber vulcanization and in plating baths for coating metals.
The mercaptans are primarily used as chemical intermediates in the manufacture of jet fuels, insecticides, fungicides, fumigants, dyes, pharmaceuticals and other chemicals, and as adroitness for odourless, toxic gases. Amyl mercaptan (1-pentanethiol), ethyl mercaptan and tert-butyl mercaptan (2-methyl-2-propanethiol) are used as adroitness for natural gas, while propel mercaptan (propanethiol) and methyl mercaptan function as odourants and warning agents for other odourless, toxic gases. Methyl mercaptan is also used as a synthetic flavouring agent and as an intermediate in the manufacture of pesticides, jet fuels, fungicides and plastics. Phenyl mercaptan is an intermediate for insecticides, fungicides and pharmaceuticals. 1-Dodecanethiol (dodecyl mercaptan) is utilized in the manufacture of synthetic rubber, plastics, pharmaceuticals, insecticides, fungicides and nonionic detergents. It also serves as a complexing agent for the removal of metals from wastes.
Thioglycolic acid is used in the production of permanent creases in textiles and in biological media for growing micro-organisms. It finds use in permanent hair wave solutions, plastics, pharmaceuticals, and as a reagent for the detection of iron and other metal ions.
Dimethyl sulphate (sulphuric acid dimethyl ether), an oily, colourless liquid that is slightly soluble in water but more soluble in organic solvents, is used primarily for its methylating properties. It is used in the manufacture of methyl esters, ethers and amines; in dyes, drugs and perfumes; phenol derivatives; and other chemicals. It is also used as a solvent in the separation of mineral oils.
Tetramethylthiuram disulphide (TTD, TMTD, Thiram, thirad, thiuram, Disulphuram), a white or yellow crystal insoluble in water but soluble in organic solvents, is used as a rubber accelerator and vulcanizer, a disinfectant for fruit, seeds, nuts and mushrooms, a bacteriostat for edible oils and fats, and as an ingredient in sun-tan and antiseptic sprays, soaps and lotions. It is also used as a fungicide, a rodent repellent and wood preservative.
Ethylene thiourea (2-imadazolidin ethione) and thiourea serve as components of electroplating baths. Ethylene thiourea also finds use in the dye-stuff and pharmaceutical industries, while thiourea has numerous applications in the photography, textile, cosmetics and paper industries. Thiourea is used to remove stains from negatives and as a fixing agent in photography, hair preparations, dry-cleaning chemicals, paper whiteners and in treatments for boiler water and wastewater, to prepare non-glare mirrors, to prevent brown stain in hemlock wood, as a weighting agent for silk and as a fire retardant for textiles.
Dimethyl sulphide (methyl sulphide) is used as a gas odourant and a food additive. Allyl propyl disulphide is another food additive, and dimethyl sulphoxide (methyl sulphoxide) (DMSO) is a solvent found in industrial cleaners, pesticides, paint and varnish removers, and antifreeze or hydraulic fluid when mixed with water. 2,4-Diaminoanisole sulphate (m-phenylediamine-4-methoxy-sulphate) is used in dyeing furs, and sodium lauryl sulphate (sulphuric acid monododecyl ester sodium salt) is an emulsifying agent used in metal processing, detergents, shampoos, creams, pharmaceuticals and foods.
Industrial processes involving the use of thiols present several types of potential problems, including fire and explosion, as well as adverse effects on the health of workers.
Fire and explosion. Most of the thiols are flammable substances. With the alkane thiols, the vapour pressure decreases as the molecular weight increases. At normal work room temperatures the lower molecular weight thiols (C2 through C6) may vaporize to form explosive mixtures with air. The mercaptans are typically flammable liquids except for methyl mercaptan, which is a gas. A strong unpleasant odour is their prime characteristic.
Health hazards. Thiols have an intensely disagreeable odour, and contact with the liquid or vapour may cause irritation of the skin, eyes and mucous membranes of the upper respiratory tract. Liquid thiols can also cause contact dermatitis. Benzenethiol appears to have stronger irritating properties than the alkane thiols.
All thiols behave as weak acids, and the predominant biological effect is on the central nervous system. Inhalation is of special concern with the C1 through C6 group of alkane thiols, while skin exposure is of greatest concern with the higher thiols (C7 through C12, C16, C18). Benzenethiol is the most toxic of the thiols normally found in the workplace and has a marked potential for causing eye injury.
Accidental exposure of workers to high concentrations of thiols (greater than 50 ppm) have caused muscular weakness, nausea, dizziness and narcosis. Systemically, methanethiol acts like hydrogen sulphide and may depress the central nervous system, resulting in respiratory paralysis and death. Because hydrogen sulphide is a raw material used or generated in thiol manufacturing plants, special precautions are necessary to prevent its release in hazardous concentrations. After an acute exposure, if death is not immediate, irritation of the lower respiratory tract may result in pulmonary oedema which may be delayed and, if not treated promptly, fatal. Victims who survive may have liver and kidney damage and may suffer from headache, dizziness, staggering gait, nausea and vomiting.
Thioglycolic acid. Pure thioglycolic acid has a pronounced irritant effect on the skin and mucous membranes; in dilute form its irritant action is less pronounced. The salts (ammonium, sodium) of the acid have been reported to cause skin lesions including discreet pruriginous, papulopustular and vesicular eruptions of the neck, ears and shoulders of persons having undergone permanent waving. More rarely, isolated lesions of the deep-burn type and contact eczema of the hands, lower arms, face and neck have been seen in hairdressers.
The thioglycolates widely found in trade have a very low sensitizing action and cause dermatitis by primary irritation. It has been reported, however, that the hydrazide and glycolics esters of thioglycolic acid have a pronounced sensitizing action and have resulted in numerous cases of contact eczema amongst hairdressers. As a consequence, the sale of preparations containing the hydrazide was stopped in Germany. Thioglycolic acid derivatives have also, on rare occasions, caused perionyxis and dry skin of the hands in hairdressers. When dermatitis is encountered in a hairdresser, however, thought should also be given to the other products used in permanent waving, excessive alkalinity, and sodium hydrosulphide impurities.
Thioglycolic acid has a high degree of acute toxicity. The oral LD50 of the undiluted acid in rats has been reported as less than 50 mg/kg. It is rapidly absorbed through the skin and, in the rabbit, 60% is excreted in the urine within 24 hours in the form of inorganic sulphate or neutral sulphur.
Prevention. Hairdressers should use thioglycolic acid or its derivatives only in dilute solutions with a pH near to neutral. In Switzerland, for example, they are permitted to use only 7.5% solutions with a maximum pH of 7.5 or 9% solutions with a maximum pH of 8. When applying the solution, the hairdresser should protect his or her hands by the use of rubber or plastic gloves, and eye contact should be avoided. The solution should be neutralized as quickly as possible, and flushed away at the first indication of irritation.
Hairdressers using these products should be informed of the hazards involved and should be alert for early signs of trouble (i.e., burning sensations, itching and so on). These preparations should not be used if there is any pre-existing skin irritation. In hairdressing salons, ventilation should be sufficient to prevent the material from accumulating in the atmosphere in the form of mist.
Sulphates and sulphides
Dimethyl sulphate is an extremely hazardous poison. Its toxicity is derived from its alkylating properties and its hydrolysis to sulphuric acid and methyl alcohol. The liquid is highly irritating to skin and mucous membranes. In the skin it causes blisters which are typically slow-healing and may result in scars, and numbness which may persist for months. Irritation of the eye may result in tearing (lacrimation), light sensitivity (photophobia), conjunctivitis and keratitis; in severe cases, corneal opacities and permanent impairment of vision have occurred. In addition to acute irritation of the respiratory tract, it may cause delayed pulmonary oedema, bronchitis and pneumonitis. The effect of the vapour on trigeminal, laryngeal and vagal nerve endings may result in bradycardia or tachycardia and pulmonary vasodilatation.
Long-term effects are seen only rarely and are usually limited to respiratory and ocular difficulties.
Dimethyl sulphate has been shown to be carcinogenic in the rat both directly and following prenatal exposure. The inhalation of 1 ppm was followed by urinary excretion of methylpurines showing a non-specific alkylation of DNA. The International Agency for Research on Cancer (IARC) classifies dimethyl sulphate as a Group 2A chemical, probably carcinogenic to humans.
Tetramethylthiuram disulphide (TTD). Exposure to TTD is by inhalation of its dust, spray or mist. Local effects result from irritation of mucous membranes: conjunctivitis, rhinitis, sneezing, cough. TTD ranges high among substances giving rise to contact hypersensitivity, perhaps reflecting the frequent use of rubber in domestic, medical and industrial utensils. It may produce contact dermatitis, erythema and urticaria; skin sensitivity is confirmed by patch testing.
Workers exposed to TTD have shown an intolerance to alcohol, manifested by flushing of the face, palpitation, rapid pulse, hypotension and dizziness. These effects are thought to be due to the blocking of the oxidation of acetaldehyde. (The diethyl homologue of TTD is marketed under the name of Antabuse as a drug to be administered to chronic alcoholics in the hope that the severely disagreeable symptoms that follow their ingestion of alcohol will condition them against breaking their abstinence.)
Intoxication due to inhalation or ingestion of TTD results in nausea, vomiting, diarrhoea, ataxia, hypothermia, hypotonia and, finally, ascending paralysis with death from respiratory failure. Toxicity is greater in the presence of fats, oils and fat solvents. TTD is metabolically converted to carbon disulphide, to which the neurologic and cardiovascular effects are attributed.
Safety and Health Measures
Open flames and other ignition sources should be excluded from areas where flammable sulphur compounds (e.g., thiols), especially the more volatile ones, are used. Emergency procedures and routine work practices should emphasize proper handling, containment of spills, and the use of proper protective equipment, such as respirators and eye goggles. Spills of thiols should be neutralized with a household bleach solution and flushed with an abundant flow of water. The primary purpose of control measures is to reduce the potential for inhalation or skin contact with thiols, with special emphasis on the eyes. Whenever feasible, control at the source of exposure should be implemented; this may involve enclosure of the operation and/or the use of local exhaust ventilation. Where such engineering controls are not sufficient to reduce airborne concentrations to acceptable levels, respirators may be necessary to prevent pulmonary irritation and systemic effects. At low concentrations (less than 5 ppm) a chemical cartridge respirator with a half-mask facepiece and organic vapour cartridges can be used. At high concentrations, supplied air respirators, with a full facepiece, are necessary.
Safety showers, eyewash fountains and fire extinguishers should be located in areas where appreciable amounts of thiols are used. Handwashing facilities, soap and ample amounts of water should be made available to involved employees.
Treatment. Affected employees should, as necessary, be removed from emergency situations and if the eyes or skin have been contaminated they should be lavaged with water. Contaminated clothing should be promptly removed. If high concentrations are inhaled, hospitalization and observation should be continued for at least 72 hours because of the potential delayed onset of severe pulmonary oedema. Therapeutic measures should follow those suggested for respiratory irritants.
Protective measures are similar to those for sulphur dioxide. They include the wearing of impervious clothing, aprons, gloves, goggles and boots by those working where liquid thiols are likely to be spilled or splashed.
All industrial operations involving the use of dimethyl sulphate should be carried out in fully enclosed systems, and established procedures for the handling of human carcinogens should be followed. Arrangements should be made for proper disposal of any spillage, and workers should be strictly forbidden to attempt to clean up massive spillages such as may occur in the event of container breakage until the area has been thoroughly washed down. Many accidents with dimethyl sulphate have been the result of hasty and uninformed clean-up attempts.
Organic sulphur compounds tables
Table 1 - Chemical information.
Table 2 - Health hazards.
Table 3 - Physical and chemical hazards.
Table 4 - Physical and chemical properties.