Isocyanates are also called polyurethanes when they have been compounded into the industrial products known by that name. They form a group of neutral derivatives of primary amines with the general formula R—N=C=O. The isocyanates most used at present are 2,4-toluene diisocyanate (TDI), toluene 2,6-diisocyanate, and diphenylmethane 4,4'-diisocyanate. Hexamethylene diisocyanate and 1,5-naphthylene diisocyanate are less often used.
Isocyanates react spontaneously with compounds containing active hydrogen atoms, which migrate to the nitrogen. Compounds containing hydroxyl groups spontaneously form esters of substituted carbon dioxide or urethanes.
A major use of isocyanates is in the synthesis of polyurethanes in industrial products. Because of its durability and toughness, methylene bis(4-phenylisocyanate) and 2,4-toluene diisocyanate (TDI) are used in coatings for aircraft, tank trucks and truck trailers. Methylene bis(4-phenylisocyanate) is utilized for bonding rubber to rayon and nylon, and for producing polyurethane lacquer coatings that can be applied to certain automobile components and to patent leather. 2,4-Toluene diisocyanate finds use in polyurethane coatings in floor and wood sealers and finishes, paints and concrete sealers. It is also used for the manufacture of polyurethane foams and for polyurethane elastomers in coated fabrics and clay-pipe seals. Hexamethylene diisocyanate is a cross-linking agent in the preparation of dental materials, contact lenses and medical adsorbants. It is also used as an ingredient in automobile paint.
Isocyanates are irritating to the skin and the mucous membranes, the skin conditions ranging from localized itching to more or less widespread eczema. Eye affections are less common, and, although lacrimation is often found, conjunctivitis is rare. The most common and serious troubles, however, are those affecting the respiratory system. The great majority of authorities mention forms of rhinitis or rhinopharyngitis, and various lung conditions have also been described, the first place being taken by asthmatic manifestations, which range from minor difficulty in breathing to acute attacks, sometimes accompanied by sudden loss of consciousness. Individuals may react with severe symptoms of asthma after exposure to very low levels of isocyanates (sometimes below 0.02 ppm) if they have become sensitized. Furthermore, sensitized individuals may become reactive to and affected by environmental stimuli such as exercise and cold air. Sensitized asthma is usually IgE mediated (with high-molecular-weight substances; the mechanism is still unclear with low-molecular-weight substances), while irritant induced asthma is usually secondary to airway inflammation and direct local toxic effects with non-specific hyperresponsiveness. Details of the mechanism of irritant asthma remain unknown. Allergic responses are discussed in more detail elsewhere in this Encyclopaedia.
The isocyanates are often volatile, and the vapour can then be detected by smell at a concentration of 0.1 ppm, but even this very low level is already dangerous for some persons.
2,4-Toluene diisocyanate (TDI). This is the substance that is most widely used in industry and that leads to the greatest number of pathological manifestations, for it is highly volatile and is often used at considerable concentrations. The symptomatology of the troubles due to inhaling it are stereotypic. At the end of a period ranging from a few days to 2 months, symptoms include irritation of the conjunctiva, lacrimation and irritation of the pharynx; later there are respiratory problems, with an unpleasant dry cough in the evening, chest pains, chiefly behind the sternum, difficulty in breathing, and distress. The symptoms become worse during the night and disappear in the morning with a slight expectoration of mucus. After a few days’ rest they diminish, but a return to work is generally accompanied by the reappearance of the symptoms: cough, chest pains, moist wheezing, shortness of breath (dyspnoea) and distress. Radiological and humoural tests are usually negative.
Respiratory dysfunctions that are known to be caused by TDI include bronchitis, occupational asthma, and a worsening of respiratory function both at work and chronically. In other cases there may be recurrent common cold or a particularly pruriginous eczema that may occur on many different parts of the skin. Some victims may suffer from skin and respiratory troubles at the same time.
In addition to these characteristic consequences of the intoxication, there are rather different effects resulting from exposure to very low concentrations over a long period running into years; these combine typical asthma with expiratory bradypnoea and eosinophilia in the sputum.
The physiopathology of the intoxication is still far from being fully understood. Some believe that there is a primary irritation; others think of an immunity mechanism, and it is true that the presence of antibodies has been shown in some cases. Sensitivity could be demonstrable with provocation tests, but great care must be taken in order to avoid further sensitization, and only an experienced medical practitioner should administer these tests. Many allergological tests, however, (with acetylcholine or the standard allergens, for example) are generally negative. With respect to pulmonary function tests, the FEV/FVC ratio seems to be the most convenient way of expressing defective respiration. The usual functional examinations carried out away from a place of exposure to the hazard are normal.
Diphenyl methane 4,4'-diisocyanate (MDI). This substance is less volatile and its fumes become harmful only when the temperature approaches 75 °C, but similar cases of poisoning have nevertheless been described. They occur mainly with aerosols, for MDI is often used in liquid form for atomizing.
Hexamethylene diisocyanate. This substance, which is less widely used, is highly irritating to the skin and eyes. The most common problems attributed to it are forms of blepharoconjunctivitis. Methyl isocyanate is the chemical thought responsible for the Bhopal disaster.
1,5-Naphthylene diisocyanate. This isocyanate is little used in industry. Poisoning after exposure to the vapour heated to over 100 °C has been reported.
Safety and Health Measures
Ventilation, protective equipment and safety and health training for workers, as described elsewhere in this Encyclopaedia, are all required for working with isocyanates. It is important to have local ventilation located as close as possible to the source of isocyanate vapours. The decomposition and release of isocyanates from polyurethane foams and glues must be taken into consideration in the design of any industrial process.
Medical prevention. The pre-employment medical examination must include a questionnaire and a thorough clinical examination in order to prevent exposure of persons with allergic cutaneous or respiratory antecedents to isocyanates. Exposed workers must be kept under regular observation. The sanitary facilities at the disposal of the workers must include showers.
Table 1 - Chemical information.
Table 2 - Health hazards.
Table 3 - Physical and chemical hazards.
Table 4 - Physical and chemical properties.