4-aminophenol in drugs and not only: in what way it is dangerous?

According to the register of medicines in the Russian Federation, there are 218 drugs containing paracetamol as an active pharmaceutical ingredient. Paracetamol is widely used as an antipyretic and pain reliever among adults and children. The chemical-pharmaceutical synthesis of paracetamol is carried out from 4-aminophenol, the content of which is normalized in all drugs based on paracetamol. What for?

4-aminophenol is an aromatic organic compound, a representative of monoatomic phenols (benzene ring + one -OH group), in the molecule of which one of the hydrogen atoms in the para-position (opposite) is replaced by an amino group.

Due to the fact that 4-aminophenol is a raw material for the production of the medicinal substance of paracetamol, the appearance of impurities of this substance is not excluded, which may adversely affect the safety of the medicinal product.

The thing is that 4-aminophenol is a highly toxic compound. Currently, the following types of toxicity of this substance are known:

1. Hepatotoxicity – toxic effect on the liver;

2. Nephrotoxicity – toxic effect on the kidneys;

3. Initiation of methemoglobinemia – a condition that occurs when the amount of methemoglobin in blood increases. Methemoglobin is not a carrier of oxygen to tissues from the lungs. With the accumulation of a large amount of it, the transport of oxygen by the blood is sharply reduced.

4. Skin toxicity.

It should be noted that p-aminophenol (4-aminophenol) is also one of the metabolites of paracetamol and causes some toxic effects (nephrotoxicity) observed in overdose.

Interestingly, in addition to the pharmaceutical industry, p-aminophenol can be found in the beauty industry. This substance is used in the production of hair dyes (brown, ash and chestnut shades), in particular, there is a lot of information on the net about henna-based dyes, which include para-aminophenol as a dye (urzol brown).

In addition, p-aminophenol is used for dyeing fur, and it is also included in many black-and-white developers, as it has developing properties.


References:

  1. Materials of the SCIENTIFIC-PRACTICAL CONFERENCE “MODERN APPROACHES TO THE EXAMINATION AND REGISTRATION OF MEDICINES” REGLEK — 2022
  2. Garmonov S. Yu., Salakhov I. A., Nurislamova G. R., Ismailova R. N., Sopin V. F. Determination of 4-aminophenol impurities in medicines by high performance liquid chromatography // Man and his health. 2010. No. 4. URL: https://cyberleninka.ru/article/n/opredelenie-primesi-4-aminofenola-v-lekarstvennyh-sredstvah-metodom-vysokoeffektivnoy-zhidkostnoy-hromatografii (date of access: 08/26/2022).
  3. Harmon RC, Terneus MV, Kiningham KK, Valentovic M. Time-dependent effect of p-aminophenol (PAP) toxicity in renal slices and development of oxidative stress. Toxicol Appl Pharmacol. 2005 Nov 15;209(1):86-94. doi: 10.1016/j.taap.2005.03.011. PMID: 16271624.
  4. https://grls.rosminzdrav.ru/