Aromatic Amino Compounds

1. AROMATIC AMINOAROMATIC AMINO
COMPOUNDSCOMPOUNDS

2. AROMATIC AMINOAROMATIC AMINO
COMPOUNDSCOMPOUNDS
 The aromatic amino compounds are a class ofThe aromatic amino compounds are a class of
chemicals derived from aromatic hydrocarbons,chemicals derived from aromatic hydrocarbons,
such as benzene, toluene, naphthalene,such as benzene, toluene, naphthalene,
anthracene and diphenyl by the replacement ofanthracene and diphenyl by the replacement of
at least one hydrogen atom by an amino group.at least one hydrogen atom by an amino group.
 The aromatic amines constitute a large class ofThe aromatic amines constitute a large class of
chemicals of great technical and commercialchemicals of great technical and commercial
value.value.

3.  Aniline is the simplest aromatic aminoAniline is the simplest aromatic amino
compound, consisting of one group attached tocompound, consisting of one group attached to
a benzene ring and its derivatives are mosta benzene ring and its derivatives are most
widely used in industry.widely used in industry.
 Benzidine, o-tolidine, o-dianisidine, 3,3’-Benzidine, o-tolidine, o-dianisidine, 3,3’-
dichlorobenzidine and 4-aminodiphenyl are thedichlorobenzidine and 4-aminodiphenyl are the
most important conjoined ring compounds frommost important conjoined ring compounds from
the point of view of occupational healththe point of view of occupational health..
AROMATIC AMINOAROMATIC AMINO
COMPOUNDSCOMPOUNDS

4. UsesUses
 Aromatic amino compounds are primarily used asAromatic amino compounds are primarily used as
intermediates in the manufacture of dyes andintermediates in the manufacture of dyes and
pigments.pigments.
 The largest class of dyestuffs is that of the azoThe largest class of dyestuffs is that of the azo
colours, which are made by diazotization, a processcolours, which are made by diazotization, a process
by which a primary aromatic amine reacts withby which a primary aromatic amine reacts with
nitrous acid in the presence of excess mineral acidnitrous acid in the presence of excess mineral acid
to produce a diazo (-N=N-) compound; thisto produce a diazo (-N=N-) compound; this
compound is subsequently coupled with a phenolcompound is subsequently coupled with a phenol
or an amine.or an amine.

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6.  Another important class of dyestuffs, theAnother important class of dyestuffs, the
triphenylmethane colours, is also manufacturedtriphenylmethane colours, is also manufactured
from aromatic amines.from aromatic amines.
 In addition to serving as chemical intermediatesIn addition to serving as chemical intermediates
in the dyestuffs industry, several compounds arein the dyestuffs industry, several compounds are
employed as dyes or intermediates in theemployed as dyes or intermediates in the
pharmaceutical, fur, hairdressing, textile andpharmaceutical, fur, hairdressing, textile and
photography industriesphotography industries..
UsesUses

7.  o-Aminophenolo-Aminophenol is used for dyeing furs andis used for dyeing furs and
hair. It is also a developer in the photographyhair. It is also a developer in the photography
industry and an intermediate forindustry and an intermediate for
pharmaceuticals. pharmaceuticals.
 p-Aminophenolp-Aminophenol is used in dyeing textiles, hair,is used in dyeing textiles, hair,
furs and feathers. It finds use in photographicfurs and feathers. It finds use in photographic
developers, pharmaceuticals, antioxidants and oildevelopers, pharmaceuticals, antioxidants and oil
additives.additives.
UsesUses

8. UsesUses
 o-Toluidine, p-phenylenediamineo-Toluidine, p-phenylenediamine,, diphenylaminediphenylamine and and N-N-
phenyl-2-naphthylaminephenyl-2-naphthylamine find additional uses as antioxidants find additional uses as antioxidants
in the rubber industry.in the rubber industry.
 DiphenylamineDiphenylamine is also employed in the pharmaceuticalis also employed in the pharmaceutical
and explosives industries and as a pesticide. and explosives industries and as a pesticide.
 The major use of The major use of benzidinebenzidine is in the manufacture of is in the manufacture of
dyestuffs. It is tetrazotized and coupled with otherdyestuffs. It is tetrazotized and coupled with other
intermediates to form colours. Its use in the rubberintermediates to form colours. Its use in the rubber
industry has been abandonedindustry has been abandoned
UsesUses

9. AnilinesAnilines
 The anilines are primarily used as intermediates for dyes andThe anilines are primarily used as intermediates for dyes and
pigments.pigments.
 Several compounds are intermediates for pharmaceuticals,Several compounds are intermediates for pharmaceuticals,
herbicides, insecticides and rubber processing chemicals, asherbicides, insecticides and rubber processing chemicals, as
well. well.
 AnilineAniline itself is widely used in the manufacture of synthetic itself is widely used in the manufacture of synthetic
dyestuffs. It is also used in printing and cloth marking inksdyestuffs. It is also used in printing and cloth marking inks
and in the manufacture of resins, varnishes, perfumes, shoeand in the manufacture of resins, varnishes, perfumes, shoe
blacks, photographic chemicals, explosives, herbicides andblacks, photographic chemicals, explosives, herbicides and
fungicides. Aniline is useful in the manufacture of rubber asfungicides. Aniline is useful in the manufacture of rubber as
a vulcanizing agent, as an antioxidant, and as an antiozonea vulcanizing agent, as an antioxidant, and as an antiozone
agent.agent.

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

11. Absorption pathwaysAbsorption pathways
 The principal risk of absorption lies in skin contact: theThe principal risk of absorption lies in skin contact: the
aromatic amines are nearly all lipid-soluble.aromatic amines are nearly all lipid-soluble.
 There is also a considerable risk of absorption byThere is also a considerable risk of absorption by
inhalation. This may be the result of inhaling theinhalation. This may be the result of inhaling the
vapours, even though most of these amines are of lowvapours, even though most of these amines are of low
volatility at normal temperatures; or it may result fromvolatility at normal temperatures; or it may result from
breathing in dust from the solid products. This appliesbreathing in dust from the solid products. This applies
particularly in the case of the amine salts such asparticularly in the case of the amine salts such as
sulphates and chlorohydrates, which have a very lowsulphates and chlorohydrates, which have a very low
volatility and lipid solubility:volatility and lipid solubility:

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

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

14. Health effectsHealth effects
 Aromatic amines have variousAromatic amines have various
pathological effects, and each memberpathological effects, and each member
of the family does not share the sameof the family does not share the same
toxicological properties. While eachtoxicological properties. While each
chemical must be evaluatedchemical must be evaluated
independently, certain importantindependently, certain important
characteristics are prominently sharedcharacteristics are prominently shared
by many of them.by many of them.

15. Health effectsHealth effects
These include: These include:
 cancer of the urinary tract, particularly of thecancer of the urinary tract, particularly of the
urinary bladderurinary bladder
 danger of acute poisoning, particularlydanger of acute poisoning, particularly
methaemoglobinaemia, which may ultimatelymethaemoglobinaemia, which may ultimately
have adverse effects on the red cellshave adverse effects on the red cells
 sensitization, notably of the skin, but sometimessensitization, notably of the skin, but sometimes
respiratory.respiratory.

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

17. Acute poisoningAcute poisoning
Acute poisoningAcute poisoning generally results from the inhibition ofgenerally results from the inhibition of
haemoglobin function through the formation ofhaemoglobin function through the formation of
methaemoglobin, leading to a condition calledmethaemoglobin, leading to a condition called
methaemoglobinemia, which is discussed more fully in themethaemoglobinemia, which is discussed more fully in the
BloodBlood chapter. Methaemoglobinemia is more oftenchapter. Methaemoglobinemia is more often
associated with the single-ring aromatic aminoassociated with the single-ring aromatic amino
compounds. Methaemoglobin is normally present in thecompounds. Methaemoglobin is normally present in the
blood at a level of about 1 to 2% of the total haemoglobin.blood at a level of about 1 to 2% of the total haemoglobin.
Cyanosis at the oral mucosae begins to become apparentCyanosis at the oral mucosae begins to become apparent
at levels of 10 to 15%, though subjective symptoms areat levels of 10 to 15%, though subjective symptoms are
normally not experienced until methaemoglobin levels ofnormally not experienced until methaemoglobin levels of
the order of 30% are reached. With increases above thisthe order of 30% are reached. With increases above this
level, the patient’s skin colour deepens; later, headache,level, the patient’s skin colour deepens; later, headache,
weakness, malaise and anoxia occur, to be succeeded, ifweakness, malaise and anoxia occur, to be succeeded, if
absorption continues, by coma, cardiac failure and death.absorption continues, by coma, cardiac failure and death.

18. Acute poisoningAcute poisoning
Most cases ofMost cases of acute poisoningacute poisoning react favourably toreact favourably to
treatment and the methaemoglobin disappearstreatment and the methaemoglobin disappears
completely after two to three days. The consumption ofcompletely after two to three days. The consumption of
alcohol is conducive to and aggravates acutealcohol is conducive to and aggravates acute
methaemoglobin poisoning. Haemolysis of the redmethaemoglobin poisoning. Haemolysis of the red
blood cells can be detected after severe poisoning, andblood cells can be detected after severe poisoning, and
is followed by a process of regeneration which isis followed by a process of regeneration which is
demonstrated by the presence of reticulocytes. Thedemonstrated by the presence of reticulocytes. The
presence of Heinz bodies in the red blood corpusclespresence of Heinz bodies in the red blood corpuscles
may sometimes also be detected.may sometimes also be detected.

19. Cancer.Cancer.
The potent carcinogenic effects of the aromaticThe potent carcinogenic effects of the aromatic
amines were first discovered in the workplace asamines were first discovered in the workplace as
a result of the abnormally high incidence ofa result of the abnormally high incidence of
cancer employees in a dye factory. The cancerscancer employees in a dye factory. The cancers
were described as "dye cancer", but furtherwere described as "dye cancer", but further
analysis very soon pointed to their origin beinganalysis very soon pointed to their origin being
in the raw materials, of which the mostin the raw materials, of which the most
important was aniline. They then became knownimportant was aniline. They then became known
as "aniline cancers". Later, further definition wasas "aniline cancers". Later, further definition was
possible and b-naphthylamine and benzidinepossible and b-naphthylamine and benzidine
were considered to be the “culprit” chemicals.were considered to be the “culprit” chemicals.

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

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

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

23. AminophenolsAminophenols
Neither Neither oo-- nor nor pp-aminophenol-aminophenol isomers, which areisomers, which are
crystalline solids of low volatility, are readily absorbedcrystalline solids of low volatility, are readily absorbed
through the skin, although both may act as skinthrough the skin, although both may act as skin
sensitizers and cause contact dermatitis, which appears tosensitizers and cause contact dermatitis, which appears to
be the greatest hazard arising from their use in industry.be the greatest hazard arising from their use in industry.
Although both isomers can cause serious, even life-Although both isomers can cause serious, even life-
threatening methaemoglobinaemia, this seldom arisesthreatening methaemoglobinaemia, this seldom arises
from industrial exposure, since their physical propertiesfrom industrial exposure, since their physical properties
are such that neither compound is readily absorbed intoare such that neither compound is readily absorbed into
the body. the body. p-Aminophenolp-Aminophenol is the major metabolite ofis the major metabolite of
aniline in humans and is excreted in the urine inaniline in humans and is excreted in the urine in
conjugated form. Bronchial asthma from the orthoconjugated form. Bronchial asthma from the ortho

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

25. N,N-DiethylanilineN,N-Diethylaniline
 N,N-DiethylanilineN,N-Diethylaniline and and N,N-N,N-
dimethylanilinedimethylaniline are readily absorbed through are readily absorbed through
the skin, but poisoning may also occurthe skin, but poisoning may also occur
through inhalation of vapours. Theirthrough inhalation of vapours. Their
hazards may be considered as similar tohazards may be considered as similar to
those of aniline. They are, in particular,those of aniline. They are, in particular,
potent methaemoglobin-formers.potent methaemoglobin-formers. N,N-N,N-
DiethylanilineDiethylaniline

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

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

28. Benzidine and derivativesBenzidine and derivatives
 Benzidine is a confirmed carcinogen, the manufactureBenzidine is a confirmed carcinogen, the manufacture
and industrial use of which has caused many cases ofand industrial use of which has caused many cases of
papilloma and carcinoma of the urinary tract.papilloma and carcinoma of the urinary tract.
 Penetration through the skin seems to be the mostPenetration through the skin seems to be the most
important pathway for the absorption of benzidine, butimportant pathway for the absorption of benzidine, but
there is also a hazard from the inhalation of vapour orthere is also a hazard from the inhalation of vapour or
fine particles.fine particles.
 The carcinogenic activity of benzidine has beenThe carcinogenic activity of benzidine has been
established by the many reported cases of bladderestablished by the many reported cases of bladder
tumour in exposed workerstumour in exposed workers

29. NaphthylaminesNaphthylamines
 The naphthylamines occur in two isomericThe naphthylamines occur in two isomeric
forms, forms,
 αα--naphthylaminenaphthylamine
 ββ--naphthylaminenaphthylamine..

30. NaphthylaminesNaphthylamines
 αα -naphthylamine-naphthylamine is absorbed through the skinis absorbed through the skin
and by inhalation. Contact may cause burns toand by inhalation. Contact may cause burns to
the skin and eyes. Acute poisoning does notthe skin and eyes. Acute poisoning does not
arise from its industrial use, but exposure toarise from its industrial use, but exposure to
commercial grades of this compound in the pastcommercial grades of this compound in the past
has resulted in many cases of papilloma andhas resulted in many cases of papilloma and
carcinoma of the bladder. It is possible thatcarcinoma of the bladder. It is possible that
these tumours were attributable to thethese tumours were attributable to the
substantialsubstantial

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

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