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Wednesday, 03 August 2011 00:17

Aromatic Amino Compounds

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The aromatic amino compounds are a class of chemicals derived from aromatic hydrocarbons, such as benzene, toluene, naphthalene, anthracene and diphenyl by the replacement of at least one hydrogen atom by an amino –NH2 group. A compound with a free amino group is described as a primary amine. When one of the hydrogen atoms of the –NH2 group is replaced by an alkyl or aryl group, the resultant compound is a secondary amine; when both hydrogen atoms are replaced, a tertiary amine results. The hydrocarbon may have one amino group or two, more rarely three. It is thus possible to produce a considerable range of compounds and, in effect, the aromatic amines constitute a large class of chemicals of great technical and commercial value.

Aniline is the simplest aromatic amino compound, consisting of one –NH2 group attached to a benzene ring and its derivatives are most widely used in industry. Other common single-ring compounds include dimethylaniline and diethylaniline, the chloroanilines, nitroanilines, toluidines, the chlorotoluidines, the phenylenediamines and acetanilide. Benzidine, o-tolidine, o-dianisidine, 3,3'-dichlorobenzidine and 4-aminodiphenyl are the most important conjoined ring compounds from the point of view of occupational health. Of compounds with ring structures, the naphthylamines and aminoanthracenes have attracted much attention because of problems of carcinogenicity. Strict precautions necessary for handling carcinogens apply to many members of this family.

Azo and diazo dyes

Azo dye is a comprehensive term applied to a group of dyestuffs that carry the azo (–N=N–) group in the molecular structure. The group may be divided into subgroups of monoazo, diazo and triazo dye and further in accordance with the number of the azo group in the molecule. From a toxicological perspective, it is important to take into account that the commercial grade dyestuffs usually contain impurities up to 20% or even higher. The composition and quantity of the impurities are variable depending on several factors such as the purity of the starting materials for the synthesis, the process of synthesis employed and the requirements of the users.

Production

Azos dyes are synthesized by diazotization or tetrazotization of aromatic monoamine or aromatic diamine compounds with sodium nitrite in the HCl medium, followed by coupling with dye intermediates such as various aromatic compounds or heterocyclic compounds. When the coupling component carries an amino group, it is possible to produce long-chained polyazo dye by the repetition of diazotization and coupling. The generalized structural formulae for the first three members of the family are:

R–N=N–R'                                  monoazo dye

R–N=N–R'–N=N–R"                   diazo dye

R–N=N–R'–N=N–R"–N=N–R"'    triazo dye

Tetrazotization of benzidine and coupling with naphthionic acid yields the very popular dye Congo Red.

Uses

Aromatic amino compounds are primarily used as intermediates in the manufacture of dyes and pigments. The largest class of dyestuffs is that of the azo colours, which are made by diazotization, a process by which a primary aromatic amine reacts with nitrous acid in the presence of excess mineral acid to produce a diazo (–N=N–) compound; this compound is subsequently coupled with a phenol or an amine. Another important class of dyestuffs, the triphenylmethane colours, is also manufactured from aromatic amines. In addition to serving as chemical intermediates in the dyestuffs industry, several compounds are employed as dyes or intermediates in the pharmaceutical, fur, hairdressing, textile and photography industries.

o-Aminophenol is used for dyeing furs and hair. It is also a developer in the photography industry and an intermediate for pharmaceuticals. p-Aminophenol is used in dyeing textiles, hair, furs and feathers. It finds use in photographic developers, pharmaceuticals, antioxidants and oil additives. 2,4-Diaminoanisole provides an oxidation base for dyeing fur. o-Toluidine, p-phenylenediamine, diphenylamine and N-phenyl-2-naphthylamine find additional uses as antioxidants in the rubber industry.

Diphenylamine is also employed in the pharmaceutical and explosives industries and as a pesticide. N-Phenyl-2-naphthylamine serves as a vulcanization accelerator, a stabilizer for silicone enamels and a lubricant. It is a component of rocket fuels, surgical plaster, tin-electroplating baths and dyes. 2,4-Diaminotoluene and 4,4'-diaminodiphenylmethane are useful intermediates in the manufacture of isocyanates, basic raw materials for the production of polyurethanes.

The major use of benzidine is in the manufacture of dyestuffs. It is tetrazotized and coupled with other intermediates to form colours. Its use in the rubber industry has been abandoned. Auramine is used in printing inks and as an antiseptic and a fungicide.

o-Phenylenediamine is a photographic developing agent and a hair dye component while p-phenylenediamine is used as a photographic chemical and a dyeing agent for fur and hair. However, p-phenylenediamine has been banned for use as an oxidation dye for hair in some countries. p-Phenylenediamine is also a vulcanization accelerator, a component of gasoline antioxidants. m-Phenylenediamine has numerous functions in the dyestuffs, rubber, textile, hairdressing and photography industries. It finds use in rubber curing agents, ion exchange and decolorizing resins, urethanes, textile fibers, petroleum additives, corrosion inhibitors and hair dyes. It is used as an promoter for adhering tire cords to rubber.

Xylidine serves as a gasoline additive as well as raw material in the manufacture of dyes and pharmaceuticals. Melamine is used in moulding compounds, textile and paper treating resins, and in adhesive resins for gluing lumber, plywood and flooring. In addition, it is useful in organic synthesis and in leather tanning. o-Tolidine is a reagent for the detection of gold.

Anilines

The anilines are primarily used as intermediates for dyes and pigments. Several compounds are intermediates for pharmaceuticals, herbicides, insecticides and rubber processing chemicals, as well. Aniline itself is widely used in the manufacture of synthetic dyestuffs. It is also used in printing and cloth marking inks and in the manufacture of resins, varnishes, perfumes, shoe blacks, photographic chemicals, explosives, herbicides and fungicides. Aniline is useful in the manufacture of rubber as a vulcanizing agent, as an antioxidant, and as an antiozone agent. A further important function of aniline is in the manufacture of
p,p'-methylenebisphenyldiisocyanate (MDI), which is then used to prepare polyurethane resin and spandex fibers and to bond rubber to rayon and nylon.

Chloroaniline exists in three isomeric forms: ortho, meta and para, of these only the first and the last are important for manufacturing dyes, drugs and pesticides. p-Nitroaniline is a chemical intermediate for antioxidants, dyes, pigments, gasoline gum inhibitors and pharmaceuticals. It is used in diazotized form to retain fastness of dyes after washing. 4,4'-Methylene-bis(2-chloroaniline), MbOCA, is used as a curing agent with isocyanate-containing polymers for the manufacture of solid abrasion-resistant urethane rubbers and moulded semi-rigid polyurethane foam articles with a hardened skin. These materials are used in an extensive range of products, including wheels, rollers, conveyor pulleys, cable connectors and seals, shoe soles, antivibration mounts and acoustic components. p-Nitroso-N,N,-dimethylaniline and 5-chloro-o-toluidine are used as intermediates in the dyestuffs industry. N,N-Diethylaniline and N,N-dimethylaniline are used in the synthesis of dyestuffs and other intermediates. N,N-Dimethylaniline also serves as a catalytic hardener in certain fibreglass resins.

Azo compounds

Azo compounds are among the most popular groups of various dyes including direct dyes, acid dyes, basic dyes, naphthol dyes, acid mordant dyes, disperse dyes, etc., and are extensively used in textiles, fabrics, leather goods, paper products, plastics and many other items.

Hazards

The manufacture and use in industry of certain aromatic amines may constitute a grave and sometimes unexpected hazard. However, since these hazards have become better known, there has, over recent years, been a tendency to substitute other substances or to take precautions which have reduced the hazard. Discussion has also taken place concerning the possibility of aromatic amines having health effects either when they exist as impurities in a finished product, or when they may be restored as the result of a chemical reaction taking place during the use of a derivative, or—and this is a totally different case—as the result of metabolic degradation within the organism of persons who may be absorbing more complex derivatives.

Absorption pathways

Generally speaking, the principal risk of absorption lies in skin contact: the aromatic amines are nearly all lipid-soluble. This particular hazard is all the more important because in industrial practice it is one often not sufficiently appreciated. In addition to skin adsorption, there is also a considerable risk of absorption by inhalation. This may be the result of inhaling the vapours, even though most of these amines are of low volatility at normal temperatures; or it may result from breathing in dust from the solid products. This applies particularly in the case of the amine salts such as sulphates and chlorohydrates, which have a very low volatility and lipid solubility: the occupational hazard from the practical point of view is less but their over-all toxicity is about the same as the corresponding amine, and thus the inhalation of their dust and even skin contact must be considered dangerous.

Absorption by way of the digestive tract does represent a potential danger if inadequate eating and sanitary facilities are provided or if workers do not exercise excellent person hygiene practices. Contamination of food and cigarette smoking with dirty hands are two examples of possible ingestion routes.

Many of the aromatic amines are flammable and represent a moderate fire hazard. Combustion products can often be highly toxic. The primary health danger of industrial exposure to aniline arises from the ease with which it can be absorbed, either by inhalation or from skin absorption. Because of these absorptive properties, prevention of aniline poisoning requires high standards of industrial and personal hygiene. The most important specific measure for the prevention of spillage or contamination of the work atmosphere with aniline vapour is proper plant design. Ventilation control of the contaminant should be designed as close to the point of generation as possible. Work clothing should be changed daily and facilities for an obligatory bath or shower at the end of the working period should be provided. Any contamination of skin or clothing should be washed off immediately and the individual kept under medical supervision. Both workers and supervisors should be educated to be aware of the nature and extent of the hazard and to carry out the work in a clean, safe manner. Maintenance work should be preceded with sufficient attention to removal of possible sources of contact with the offending chemicals.

Since many cases of aniline poisoning result from contamination of the skin or clothing that leads to absorption through the skin, contaminated clothing should be removed and laundered. Even when intoxication results from inhalation, the clothing is likely to be contaminated and should be removed. The entire body surface, including hair and fingernails, should be carefully washed with soap and tepid water. Where methaemoglobinemia is present, appropriate emergency precautions should be taken and the occupational health service must be fully equipped and trained to handle such emergencies. Laundry workers should be provided with adequate precautions to avoid contamination from the aniline compounds.

Metabolism

The amines undergo a process of metabolization within the organism. Generally the active agents are the metabolites, some of which induce methaemoglobinaemia, while others are carcinogenic. These metabolites generally take the form of hydroxylamines (R-NHOH), changing to aminophenols (H2N-R-OH) as a form of detoxification; their excretion provides a means of estimating the degree of contamination when the level of exposure has been such that they are detectable.

Health effects

Aromatic amines have various pathological effects, and each member of the family does not share the same toxicological properties. While each chemical must be evaluated independently, certain important characteristics are prominently shared by many of them. These include:

  • cancer of the urinary tract, particularly of the urinary bladder
  • danger of acute poisoning, particularly methaemoglobinaemia, which may ultimately have adverse effects on the red cells
  • sensitization, notably of the skin, but sometimes respiratory.

 

Toxic effects are also related to chemical characteristics. For example, although an aniline salt has a very similar toxicity to aniline itself, it is not water or lipid soluble and hence not readily absorbed through the skin or by inhalation. Thus, poisoning by aniline salts from industrial exposure are rare.

Acute poisoning generally results from the inhibition of haemoglobin function through the formation of methaemoglobin, leading to a condition called methaemoglobinemia, which is discussed more fully in the Blood chapter. Methaemoglobinemia is more often associated with the single-ring aromatic amino compounds. Methaemoglobin is normally present in the blood at a level of about 1 to 2% of the total haemoglobin. Cyanosis at the oral mucosae begins to become apparent at levels of 10 to 15%, though subjective symptoms are normally not experienced until methaemoglobin levels of the order of 30% are reached. With increases above this level, the patient's skin colour deepens; later, headache, weakness, malaise and anoxia occur, to be succeeded, if absorption continues, by coma, cardiac failure and death. Most cases of acute poisoning react favourably to treatment and the methaemoglobin disappears completely after two to three days. The consumption of alcohol is conducive to and aggravates acute methaemoglobin poisoning. Haemolysis of the red blood cells can be detected after severe poisoning, and is followed by a process of regeneration which is demonstrated by the presence of reticulocytes. The presence of Heinz bodies in the red blood corpuscles may sometimes also be detected.

Cancer. The potent carcinogenic effects of the aromatic amines were first discovered in the workplace as a result of the abnormally high incidence of cancer employees in a dye factory. The cancers were described as "dye cancer", but further analysis very soon pointed to their origin being in the raw materials, of which the most important was aniline. They then became known as "aniline cancers". Later, further definition was possible and β-naphthylamine and benzidine were considered to be the “culprit” chemicals. Experimental confirmation of this was long in coming and difficult. Experimental work on many members of this family has found a number to be animal carcinogens. Since insufficient human evidence is available, they have been classified by the International Agency for Research on Cancer (IARC) for the most part as 2B, probable human carcinogens, that is, having sufficient evidence for animal carcinogenicity but insufficient for human carcinogenicity. In some cases, laboratory work has lead to the discovery of human cancer, as in the case of 4-aminodiphenyl, which was first shown to be carcinogenic for animals (in the liver), after which a number of cases of bladder cancer in humans were brought to light.

Dermatitis. Because of their alkaline nature, certain amines, particularly the primary ones, constitute a direct risk of dermatitis. Many aromatic amines can cause allergic dermatitis, such as that due to sensitivity to the "para-amines" (p-aminophenol and particularly p-phenylenediamine). Cross-sensitivity is also possible.

Respiratory allergy. A number of cases of asthma due to sensitization to p-phenylenediamine, for example, have been reported.

Haemorrhagic cystitis can result from heavy exposure to o- and p-toluidine, particularly the chlorine derivatives, of which chloro-5-o-toluidine is the best example. These haematuria appear to be short-lived and the relationship to development of bladder tumours is not established.

Liver injuries. Certain diamines, such as toluenediamine and diaminodiphenylmethane, have potent hepatotoxic effects in experimental animals but serious liver damage resulting from industrial exposure has not been a widely reported. In 1966, however, 84 cases of toxic jaundice were reported from eating bread baked from flour contaminated with 4,4'-diaminodiphenylmethane, and cases of toxic hepatitis have also been reported after occupational exposure.

Some of the toxicological properties of the aromatic amines are discussed below. Because the members of this chemical family are very numerous, it is not possible to include them all, and there may be others, not included below, which also have toxic properties.

Aminophenols

Neither o- nor p-aminophenol isomers, which are crystalline solids of low volatility, are readily absorbed through the skin, although both may act as skin sensitizers and cause contact dermatitis, which appears to be the greatest hazard arising from their use in industry. Although both isomers can cause serious, even life-threatening methaemoglobinaemia, this seldom arises from industrial exposure, since their physical properties are such that neither compound is readily absorbed into the body. p-Aminophenol is the major metabolite of aniline in humans and is excreted in the urine in conjugated form. Bronchial asthma from the ortho isomer has been reported as well.

p-Aminodiphenyl is considered a confirmed human carcinogen by IARC. It was the first compound in which the demonstration of carcinogenic activity in experimental animals preceded the first reports of bladder tumours in exposed workers, where it was used as an antioxidant in rubber manufacture. The substance is clearly a potent bladder carcinogen since in one plant with 315 workers, 55 developed tumours as did 11% of 171 workers in another plant manufacturing 4-aminodiphenyl. The tumours appeared 5 to 19 years after initial exposure, and survival ranged in duration from 1.25 to 10 years.

Aniline and its derivatives

It has been demonstrated experimentally that aniline vapour can be absorbed via the skin and respiratory tract in approximately equal amounts; however, the rate of absorption of the liquid through the skin is about 1,000 times greater than that of the vapour. The most frequent cause of industrial poisoning is accidental skin contamination, either directly through accidental contact, or indirectly through contact with soiled clothing or footwear. The use of clean and suitable protective clothing and rapid washing in case of accidental contact constitute the best protection. While the US National Institute for Occupational Health and Safety (NIOSH) recommends that aniline be treated as a suspected human carcinogen, IARC has rated it as a Group 3 chemical, meaning insufficient evidence of animal or human carcinogenicity.

p-Chloroaniline is a potent methaemoglobin-former and eye irritant. Animal experiments have provided no evidence of carcinogenicity. 4,4'-Methylene bis(2-chloroaniline), or MbOCA, can be absorbed from contact with dust or from fume inhalation, and in industry, skin absorption may also be an important route for uptake. Laboratory studies showed MbOCA or its metabolites may cause genetic damage in a variety of organisms. In, addition, long-term subcutaneous administration in rats resulted in liver and lung tumours. Thus, MbOCA is regarded as an animal carcinogen and a probable human carcinogen.

N,N-Diethylaniline and N,N-dimethylaniline are readily absorbed through the skin, but poisoning may also occur through inhalation of vapours. Their hazards may be considered as similar to those of aniline. They are, in particular, potent methaemoglobin-formers.

Nitroanilines. Of the three mono-nitroanilines, the most important is p-nitroaniline. All are used as dye intermediates, but the o- and m- isomers only on a small scale. p-Nitroaniline is readily absorbed through the skin and also by inhalation of dust or vapour. It is a powerful methaemoglobin-former, and is alleged, in serious cases, also to bring about haemolysis, or even liver damage. Cases of poisoning and cyanosis have been reported following exposure while cleaning up spills. The chloronitroanilines are also potent methaemoglobin-formers, leading to haemolysis, and are hepatotoxic. They may give rise to dermatitis by sensitization.

p-Nitroso-N,N-dimethylaniline possesses both primary irritant and skin sensitizing properties, and it is a common cause of contact dermatitis. Although, occasionally, workers who develop dermatitis may subsequently work with this compound without further trouble, most will suffer a severe recurrence of the skin lesions on re-exposure, and, in general, it is wise to transfer them to other work to avoid further contact.

5-Chloro-o-toluidine is readily absorbed through the skin or by inhalation. Although it (and some of its isomers) may cause methaemoglobin formation, the most striking feature is its irritant effect on the urinary tract, resulting in haemorrhagic cystitis characterized by painful haematuria and frequency of micturition. Microscopic haematuria may be present in men exposed to this compound before the cystitis is manifest, but there is no carcinoenic hazard to humans. However, laboratory experiments have cast doubts on the carcinogenicity of other isomers for certain species of animals.

Benzidine and derivatives

Benzidine is a confirmed carcinogen, the manufacture and industrial use of which has caused many cases of papilloma and carcinoma of the urinary tract. Among some working populations, more than 20% of all workers have developed the disease. Recent studies indicate that benzidine may raise the rate of cancer at other sites but there is not agreement on this as yet. Benzidine is a crystalline solid with a significant vapour pressure (that is, it forms vapours readily). Penetration through the skin seems to be the most important pathway for the absorption of benzidine, but there is also a hazard from the inhalation of vapour or fine particles. The carcinogenic activity of benzidine has been established by the many reported cases of bladder tumour in exposed workers and by experimental induction in animals. It is a Group1 confirmed human carcinogen according to IARC ratings. The use of benzidine has been discontinued in most places.

3,3'-Dichlorobenzidine is a probable human carcinogen (IARC Class 2B). This conclusion is based on a statistically significantly increased tumor incidence in rats, mice and dogs and positive data on its genotoxicity. The structural relationship to benzidine, a known, powerful human bladder carcinogen, lends further weight to the probability that it is a human carcinogen.

Diamino-4,4'-diaminodiphenylmethane. The most striking example of the toxicity of this compound was when 84 persons contracted toxic hepatitis as a result of eating bread baked from flour that was contaminated with the substance. Other cases of hepatitis were noted after occupational exposure through skin absorption. It may also give rise to allergic dermatitis. Animal experiments have led to its being a suspected potential carcinogen, but conclusive results have not been obtained. Diaminodiphenylmethane derivatives have been shown to be carcinogens for laboratory animals.

Dimethylaminoazobenzene. The metabolism of DAB has been extensively studied and it has been found that it involves reduction and cleavage of the azo group, demethylation, ring hydroxylation, N-hydroxylation, N-acetylation, protein binding and binding of nucleic acids. DAB shows mutagenic properties after activation. It has carcinogenic power by various routes in the rat and mouse (liver carcinoma), and by oral route it causes carcinoma of the bladder in the dog. The only occupational health observation in humans was of contact dermatitis in factory workers handling DAB.

Technical measures should prevent any contact with the skin and mucous membranes. Workers exposed to DAB should wear personal protective equipment and their work should be carried out only in restricted areas. Clothing and equipment after use should be placed in an impervious container for decontamination or disposal. Pre-employment and periodical examinations should focus on liver function. In the US, DAB has been included by OSHA among the cancer suspect agents for humans.

Diphenylamine. This chemical can be mildly irritating. It appears that under ordinary industrial conditions it offers little hazard, but the potent carcinogen 4-aminodiphenyl may be present as an impurity during the manufacturing process. This may be concentrated to significant proportions in the tars produced at the distillation stage and will constitute a hazard of bladder cancer. While modern manufacturing procedures have enabled the amount of impurities in this compound to be considerably reduced in the commercial product, appropriate prevention must be taken to prevent unnecessary contact.

Naphthylamines

The naphthylamines occur in two isomeric forms, a-naphthylamine and b-naphthylamine.
α-Naphthylamine is absorbed through the skin and by inhalation. Contact may cause burns to the skin and eyes. Acute poisoning does not arise from its industrial use, but exposure to commercial grades of this compound in the past has resulted in many cases of papilloma and carcinoma of the bladder. It is possible that these tumours were attributable to the substantial β-naphthylamine impurity. This matter is not merely of academic interest, as α-naphthylamine with greatly reduced levels of β-naphthylamine impurity is now available.

β-Naphthylamine is a known human bladder carcinogen. Acute poisoning results in methaemoglobinemia or acute haemorrhagic cystitis. Although at one time extensively used as an intermediate in the manufacture of dyestuffs and antioxidants, its manufacture and use has been almost entirely abandoned throughout the world, and it has been condemned as too dangerous to make and handle without prohibitive precautions. It is readily absorbed through the skin and by inhalation. The question of its acute toxic effects does not arise because of its high carcinogenic potency.

Phenylenediamines

Various isomeric forms of the phenylenediamines exist but only the m- and p-isomers are of industrial importance. While p-phenylenediamine can act as a methaemoglobin-former in vitro, methaemoglobinaemia arising from industrial exposure is unknown. p-Phenylenediamine is notorious for its sensitizing properties of the skin and respiratory tract. Regular skin contact readily causes contact dermatitis. Acne and leukoderma have also been reported. The former problem of "fur dermatitis" is much less frequent now owing to improvements in the dyeing process having the effect of removing all traces of p-phenylenediamine. Similarly, asthma, at one time common among fur dyers using this substance, is now relatively rare after improvements in the control of airborne dust. Even with controls, a preliminary skin test is useful prior to possible occupational exposure. m-Phenylenediamine is a strong irritant to the skin and causes eye and respiratory irritation. Conclusions drawn from experiments conducted on the phenylenediamines and their derivatives (e.g. N-phenyl or 4- or 2-nitro) relating to their carcinogenic potential are, up to the present time, either insufficient, inconclusive or negative. Chlorine derivatives that have been tested seem to have a carcinogenic potential in animal tests.

The carcinogenic potential of commercial mixtures in the past was of great concern because of the presence of β-naphthylamine, which had been found to exist as an impurity in considerable quantities (running into tens or even hundreds of ppm) in some of the older preparations, and by the discovery, in the case of N-phenyl-2-naphthylamine, PBNA, of β-naphthylamine as a metabolic excretion, though in infinitesimal quantities. The experiments point to a carcinogenic potential for the animals tested but do not permit a conclusive judgment to be made, and the degree of significance of the metabolic findings is not yet known. Epidemiological investigations on a large number of persons working under different conditions have not shown any significant increase in the incidence of cancer among workers exposed to these compounds. The amount of β-naphthylamine that is present in the marketed products today is very low—less than 1 ppm and frequently 0.5 ppm. At the present time it is not possible to draw any conclusions as to the true cancer hazard, and for this reason every precaution should be taken, including the elimination of impurities that may be suspect, and technical protective measures in the manufacture and use of these compounds.

Other compounds

Toluidine exists in three isomeric forms but only the o- and p- isomers are of industrial importance. o-Toluidine and p-toluidine are readily absorbed through the skin, or inhaled as dust, fume or vapour. They are powerful methaemoglobin-formers, and acute poisoning may be accompanied by microscopic or macroscopic haematuria, but they are much less potent as bladder irritants than 5-chloro-o-toluidine. There is sufficient evidence of carcinogenicity in animals to classify o-toluidine and p-toluidine as suspected human carcinogens.

Toluenediamines. Among the six isomers of toluenediamine the one most frequently encountered is the 2,4- which accounts for 80% of the intermediate product in the manufacture of toluene diisocyanate, a further 20% being the 2,6- isomer, which is one of the basic substances for the polyurethanes. Attention was drawn to this compound following the experimental discovery of a carcinogenic potential in laboratory animals. Data on humans are not available.

Xylidines. Results of animal experiments indicate that they are primarily liver toxins and act secondarily on the blood. However, other experiments have demonstrated that methaemoglobinaemia and Heinz body formation were readily induced in cats, though not in rabbits.

Azo Dyes

In general, azo dyes as a group represent a relatively low order of general toxicity. Many of them have an oral LD50 of more than 1 g/kg when tested in rats and mice, and the rodents can be given lifetime laboratory diets containing more than 1 g of the test chemical per kg of diet. A few may cause contact dermatitis but usually with only mild manifestations; in practice, it is rather difficult to determine whether the dye per se or co-existing material is responsible for the observed skin lesion. In contrast, increasing attention has been focused on the carcinogenic potentials of the azo dyes. Although confirmative epidemiological observations are as yet rare, the data from long-term experiments have accumulated to show that some azo dyes are carcinogenic in laboratory animals. The main target organ under such experimental conditions is the liver, followed by the urinary bladder. The intestine is also involved in some cases. It is, however, very problematic to extrapolate these findings to humans.

Most of the carcinogenic azo dyes are not direct carcinogens, but pre-carcinogens. That is, they require conversion by in vivo metabolic activation through proximate carcinogens to be ultimate carcinogens. For example, methylaminoazobenzene first undergoes N-hydroxylation and N-demethylation at the amino group, and then sulphate conjugation takes place with the N-hydroxy derivative forming the ultimate carcinogen which is reactive with the nucleic acid.

It should be noted that benzidine-derived diazo dyes may be transformed to the highly carcinogenic chemical benzidine by the body’s normal metabolic processes. The body reduces two azo groups in vivo or by the activity of intestinal bacteria, to benizidine. Thus azo dyes should be handled with prudence.

Safety and Health Measures

The most important specific measure for the prevention of spillage or contamination of the work atmosphere by these compounds is proper plant design. Ventilation control of the contaminant should be designed as close to the point of generation as possible. Work clothing should be changed daily and facilities for an obligatory bath or shower at the end of the working period should be provided. Any contamination of skin or clothing should be washed off immediately and the individual kept under medical supervision. Both workers and supervisors should be educated to be aware of the nature and extent of the hazard and to carry out the work in a clean, safe manner. Maintenance work should be preceded with sufficient attention to removal of possible sources of contact with the offending chemicals.

Aromatic amino compounds 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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Preface
Part I. The Body
Part II. Health Care
Part III. Management & Policy
Part IV. Tools and Approaches
Part V. Psychosocial and Organizational Factors
Part VI. General Hazards
Part VII. The Environment
Part VIII. Accidents and Safety Management
Part IX. Chemicals
Part X. Industries Based on Biological Resources
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