4 – Nitroaniline
INTRODUCTION
4-Nitroaniline is an organic nitro aromatic compound. It is a yellow powder with a pungent odor and is highly soluble in hot water, methanol, ethanol, acetone etc (Lide 1994). Its chemical formula is C6H6N2O2. It has the following chemical structure:
(Courtesy: PubChem 2016)
It is also known as P-Amino nitrobenzene, P-Nitraniline or Benzene amine (PubChem 2016). It explodes on decomposition to emit toxic nitrogen oxides (Lewis 1996). 4-Nitroaniline is used in the manufacture of textile dyes such as the red azo dyes. It is also used in preparation of antioxidants, fuel additives, pesticides, pharmaceuticals and poultry medicines (Chem Industry 2016). 4-Nitroaniline is widely used in the manufacture of several organic compounds. It has been classified as a hazardous chemical by the GHS (Globally Harmonized System of Classification and Labeling of Chemicals). It is toxic for the human skin to be in contact with 4-Nitroaniline (Clayton 1981). Inhalation of its vapors is also toxic (International Labour Office 1983). If 4- Nitroaniline is swallowed, its effects can be life-threatening. Short term and long term exposure to 4-Nitroaniline may cause difficulty in breathing, nausea, vomiting, diarrhea, convulsions, anemia etc. It may also lead to a blood disorder called methemoglobinemia. It is a life-threatening condition in which oxygen is depleted in the tissues.
4- Nitroaniline greatly harms the aquatic environment when factory wastes containing 4-Nitroaniline, are dumped in natural environments. Care must be taken while handling such toxic compounds. Contact with skin and inhalation of its vapors must be avoided. Protective clothing must be used to avoid direct contact with the chemical. Contaminated clothing must be washed away immediately. Immediate medical attention needs to be given to a person who has been exposed to 4-Nitroaniline as otherwise they may lead to disorders related to the heart, liver or the kidney. Experimental results have found that 4-Nitroaniline induced mortality in rats and rabbits (U.S National Library of Medicine 2016). Storage instructions also need to be followed sternly. 4-nitroaniline must be stored in a cool place and in air-tight containers. It must be kept away from highly reactive chemicals (Fire Protection Guide to Hazardous Materials 2002).
4-Nitroaniline is an organic, nitro aromatic compound which is made up of hard molecules. Such molecules are not easily biodegradable. Not, but recently, research and studies have revealed that the Rhodococcus sp. strain JS360, was capable of biodegrading 4-Nitroaniline by utilizing it as, a carbon and nitrogen source (Nishino 2012). Its biodegradation pathway can be represented using the following diagram:
(Courtesy: Metabolic Diversity for Degradation, Detection and Synthesis of Nitro Compounds and Toxins 2012)
It was found that the Rhodococcus strain utilized 4-Nitroaniline as a carbon and nitrogen source and released nitrite and ammonia. It can be represented as follows:
(Courtesy: Metabolic Diversity for Degradation, Detection and Synthesis of Nitro Compounds and Toxins 2012)
Such studies were also used as precursors to study biotransformation pathways of explosives as they had common chemical structures.
BIOTRANSFORMATION IN HUMANS
In human, 4-Nitroaniline are not carcinogenic (causing cancer). However, being toxic in nature, follow biotransformation pathways in which they are detoxified by the liver. Liver, the main organ of detoxification in the human body, consists of a superfamily of enzymes called Cytochrome (CYP) P450. There are 14 kinds of isoenzymes of the P450 family with 26 subfamilies (Badyal 2001) in mammals. For example, CYP 1A2, 3A4, 2C19, 3A4, 3A5 etc. These enzymes are present largely in the endoplasmic reticulum of the liver cells and also in other parts of the body. The vital function of these enzymes is to eliminate the xenobiotics (foreign bodies) from the body. The mechanism involves hydroxylation of the toxic compounds to make them more hydrophilic so that they may be easily excreted by the kidneys. This hydroxylation is achieved in 4-Nitroaniline by unmasking the amine group present in it. This comprises of Phase I mechanism. The Phase II mechanism is for the detoxification of those metabolites which have not been completely converted to an excretable form. This mechanism consists of sulfate conjugation in which the hydrolyzed amines are conjugated with sulfates and readily excreted in the urine. However, formation of DNA adducts in the metabolic pathway which are carcinogenic in nature have also been found to occur.
Research studies (Mathews 2012) have shown several biotransformation pathways in the metabolism of toxic compounds such as 4-Nitroaniline. The structure of 4-Nitroaniline is similar to rodent carcinogens.
Experiments have been carried out on B6C3F1/N mice, Harlan Sprague Dawley rats and male and female humans. Oral and intravenous doses had been given and the urine and feces samples were tested. The presence of a nitro group in 4-Nitroaniline indicated that it would be metabolized through a hepatic pathway as it is a toxic substance which needs to be detoxified by the liver. Tissue analysis revealed that radioactivity levels were increased in the liver which was 98-106%. It was also high in red blood cells, kidney, stomach and the intestine. Analysis of data showed that clearance of the toxic compound was higher in mice, compared to rats and humans. Females cleared the toxic substances faster than the males.
SUMMARY
4- Nitroaniline is a toxic organic compound which finds its use in various fields.
It is a vital component of several important chemicals such as dyes, fertilizers, antioxidant, medicines, pharmaceuticals etc.
It has to be used with discretion as its effects can be life-threatening.
Proper precautions while handling and all safety standards need to be followed while handling them.
Early studies have shown that when 4-Nitroaniline remains in the soil, it gets converted into nitro amines.
Nitro amines are highly toxic and mutagenic in nature.
In humans, they follow a biotransformation pathway in which they are transformed by P450 enzymes to be changed into an excretable form.
Much research needs to be done on the toxicity of nitro aromatic compounds.
It has also been found that the toxicity of such compounds is not due to the compound itself but due to the products formed on its reduction.
Studies have shown that 4-Nitroaniline was detoxified in the liver where they showed high radioactivity.
Clearances of toxic compounds were faster in mice than in rats and humans.
The action of drugs on the substrates of their biotransformation pathways give us a major hint to study its uses and applications.
Drugs and their disposition with regard to their biotransformation pathways is an area of vital importance to study behavior of toxic compounds and their effects on the human body.
It also gives room for future research on the basis of microbial gene technology which is so easily able to biodegrade such toxic chemicals.
These mechanisms can make us use such toxic chemicals to our advantage without the adverse effects.
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