Aniline, known as phenylamine or aminobenzene, is an organic compound with the formula C6H5NH2. Consisting of a phenyl group attached to an amino group, aniline is an aromatic amine. Like most volatile amines, it possesses the unpleasant odor of rotten fish. It ignites readily, burning with a smoky flame characteristic of aromatic compounds. Aniline is colorless and is slightly soluble in water and mixes readily with most organic solvents.
Figura 1. Aniline's structure
- Aniline is produced in industry in two steps from benzene
- First, benzene is using a concentrated mixture of nitric acid and sulfuric acid which gives nitrobenzene.
- In the second step, the nitrobenzene is
C6H5NO2 + 3 H2 → C6H5NH2 + 2 H2O
Synthesis of Nitrobenzene and Aniline, 2004
- As an alternative, aniline is also prepared from phenol and ammonia.
In commerce, three brands of aniline are distinguished: , which is pure aniline; , a mixture of equimolecular quantities of aniline and ortho- and para-toluidines; and , which contains aniline and ortho-toluidine.
Many derivatives of aniline can be prepared from nitrated aromatic compounds. Nitration followed by reduction of toluene affords toluidines.
There are three isomers of toluidine , which are o-toluidine, m-toluidine, and p-toluidine. The o- stands for ortho-, m- stands for meta- , and p- stands for para- . All three are aryl amines whose chemical structures are similar to aniline except that a methyl group is substituted into the benzene ring. The difference between these three isomers is the position where the methyl group (-CH3) is bonded to the ring relative to the amino functional group (-NH2).
Figura 2. Isomers of Toluidine
Ortho- and meta-toluidines are usually viscous liquids, but para-toluidine is a solid. Toluidines are used in the production of dyes. In the occupational environment, there is the potential for significant carcinogenic and genotoxic effects.
The principal signs of toxicity following acute short term exposure to this chemical are methemaglobinemia and related effects on the spleen or bladder.
Increased bladder cancer risk among workers exposed to o-toluidine and aniline, 2010
Continued epidemic of bladder cancer in workers exposed to ortho-toluidine in a chemical factory, 2004.
The related compound o-toluidine, used as a presumptive test for blood in forensic science, is two o-toluidine molecules linked together.
"Exposition and Metabolism"
The general population may be exposed to aniline by eating food or drinking water containing aniline, but these amounts are usually very small.
‘ If you work in a place that makes products like dyes, varnishes, herbicides, and explosives, you may be exposed to aniline. ‘
Aniline has also been detected in tobacco smoke, so people who smoke or breath in second-hand smoke may also be exposed to aniline. ‘
People living near uncontrolled hazardous waste sites may be exposed to higher than normal levels of aniline.
It enters the body when people or consume food or water contaminated with aniline.It can also be absorbed through . It does not remain in the body due to its breakdown and removal.
Aniline can evaporate when exposed to air. It dissolves when mixed with water. In air, aniline breaks down to other chemicals.
Sunlight also breaks down aniline in surface water and in soil.
Microorganisms that live in water andin soil can also break down aniline.
Aniline is oxidized by cyt p450 to P AMINO PHENOL and is excreted in urine as SULFO and GLUCURONIC CONJUGATED after 24 hours from the exposure.
Sometimes aniline is hydroxilated on amino group to FENILIDROSSILAMINA which is considered one of the most toxic metabolite causing damages in organs.
Figura 3. Metabolism
- In industry
- aniline is used for the preparation of methylene diphenyl diisocyanate used for the production of rigid polyurethane . These rigid polyurethane foams are good thermal insulators and used in nearly all freezers and refrigerators worldwide, as well as buildings.
Toxic dusts, fumes and gases in industry
- herbicides (2%) and agricultural chemicals, 1968
- dyes and pigments (2%)as a precursor to indigo, the blue of blue jeans and also as ink for tattoo. Other aniline dyes followed, such as fuchsine, safranine, and induline.
- solvent and rubber.
Signs and Symptoms
The effects of aniline on human health and the environment depend on how much aniline is present and the length and frequency of exposure.
- Lips, tongue and mucous membranes navy blue to black (CYANOSIS) ; skin slate gray, all without signs of cardiac or pulmonary insufficiency.
- Breathing large amounts of aniline for short periods of time decreases the ability of blood to carry oxygen .Lack of oxygen causes effects ranging from severe headache, nausea, sometimes vomiting, to dryness of throat and loss of appetite
- Central nervous symptoms: confusion, ataxia, vertigo, tinnitus, weakness, disorientation, lethargy, drowsiness, and finally coma. Continued exposure may lead to difficult breathing, dizziness, stupor, unconsciousness, convulsions may occur but appear to be uncommon.
- Cardiac effects: heart blocks, arrhythmias, and shock.
- Death, although uncommon, is usually due to cardiovascular collapse and not resp paralysis.
- Urinary signs and symptoms may include painful micturition, hematuria, hemoglobinuria, and renal insufficiency (usually mild) Exposure to high concentrations may result in damage to kidneys and bladder.
- Formation of methemoglobin .
- Skin: causes irritation. May cause excessive drying of skin and irritation. Absorption is signficant and may increase severity of symptoms listed under inhalation.
- Eyes: causes irritation, redness, and chemical burns.
- : aniline and its derivates involvement in damaging oxidative reactions, especially during the progression of characteristic splenic lesions,is demonstrated in time-dependent sub chronic studies conducted in rats.
Oxidative modification of lipids and proteins in aniline-induced splenic toxicity, 1999
Such oxidative modifications, directly or indirectly, could contribute to the splenic toxicity leading to deleterious consequences, including capsular hyperplasia and fibrosis, as observed in this study, and possibly tumorigenesis in chronic aniline exposure conditions.
Also In this project aniline exposure results in selective splenic toxicity leading to splenomegaly, hemorrhage, capsular hyperplasia, fibrosis and eventually a variety of sarcomas.
Splenic toxicity of aniline, 2010
- : aniline is also known for inducing allergic and autoimmune reactions. In 1981 in Spain, many people succumbed to toxic oil syndrome , a disease caused by ingestion of cooking oil contaminated with aniline. The disease was linked to the consumption of rapeseed oil denatured with aniline and among the aniline derivatives detected in the oil batches generated by an uncontrolled deodorisation procedure during the refining process, fatty acid anilides were first postulated as the causal agents.
T cells ignore aniline, a prohapten, but respond to its reactive metabolites generated by phagocytes, 2001
The toxic oil syndrome: a perspective on immunotoxicological mechanisms, 1994
Potential implication of aniline derivatives in the Toxic Oil Syndrome (TOS), 2011
- Aniline-induced : Hemolytic anemia after aniline and aniline-related drugs such as dapsone and primaquine is thought to be mediated by active/reactive metabolite formed during the hepatic clearance of the parent compounds.
Role of aniline metabolites in aniline-induced hemolytic anemia, 1986
- is a disorder characterized by the presence of a higher than normal level of methemoglobin (metHb, i.e., ferric [Fe3+] rather than ferrous [Fe2+] haemoglobin) in the blood. Methemoglobin is an oxidized form of hemoglobin that has a decreased affinity for oxygen, resulting in an increased affinity of oxygen to other heme sites (that are still ferrous) within the same red blood cell. This leads to an overall reduced ability of the red blood cell to release oxygen to tissues. In this review there is evidence of the contribute of aniline metabolites to aniline-induced methemoglobinemia.
Contribution of aniline metabolites to aniline-induced methemoglobinemia, 1987
- In food or some cooking utensils used in food preparation or in tobacco smoke, Migration of aniline from polyamide cooking utensils was investigated. Aniline was found to originate from the application of black colorant in the polyamide 66 raw materia.
Red Food Coloring Used in Sausage Linked to Cancer, 2007
Migration of aniline from polyamide cooking utensils into food simulants, 2004
- Tattoo pigment in Aniline and its derivatives and coal tar, their natural mother substance, have demonstrated their ability to produce inflammatory and neoplastic reactions in the skin. Intense inflammation and resulting necrosis and fluidification of the involved tissue are the invariable stages which lead to ulceration, extrusion of the foreign dyes via the exudate
Melanoma caused by indelible pencil, 1938
Keratoacanthoma is a cutaneous neoplasm that commonly affects sun-exposed areas of elderly individuals. most consider it a form of squamous cell carcinoma. There are some reports of keratoacanthoma arising over sites of trauma, burn scars. Recently, the association of keratoacanthomas with tattoos has been reported.
Keratoacanthoma in a tattoo, 2009
Figura 4. Keratoacanthoma in a tattoo