Active ingredients in biocidal products – Part III – Halogenated compounds, quaternary ammonium compounds

Halogenated compounds

Iodine compounds are among the most widely used antiseptics. Iodine was discovered by chance in 1811 by Bernard Courtois, a pharmacist in the French army.

Iodine tinctures were used for a long time as antiseptics, while iodophors also have disinfectant properties. An iodophor is a combination of iodine and a solubilizing agent (carrier). The complex releases small amounts of free iodine in an aqueous solution. The best known and most widely used is povidone-iodine, a compound of polyvinylpyrrolidone (povidone, PVP) with elemental iodine. This product, as well as other iodophors, retains the antimicrobial efficacy of iodine while reducing its irritant potential.

Povidone-iodine was discovered in 1955 at the Industrial Toxicology Laboratories in Philadelphia by H. A. Shelanski and M. V. Shelanski, and it has been used clinically since 1956, being formulated in various pharmaceutical forms: solution, spray, cream, ointment, etc. The concentration varies between 9% and 12%.

Studies on the in vitro antimicrobial efficacy of iodophors demonstrate that they are bactericidal (even against MRSA – methicillin-resistant Staphylococcus aureus), mycobactericidal, and virucidal, but may require prolonged contact times to kill certain fungi and spores.

They are used for the hygienic and preoperative disinfection of hands, skin disinfection before procedures, wound antisepsis, including skin burns, or as an adjuvant in skin infections. Besides their use as antiseptics, they can be used to disinfect blood culture bottles and medical equipment, such as hydrotherapy tanks, thermometers, and endoscopes. Iodophors formulated as antiseptics contain less free iodine than those formulated as disinfectants. Iodine or iodine-based antiseptics should not be used on silicone catheters because they can adversely affect the silicone tubing.

Mechanism of action: the antimicrobial effect of povidone-iodine is due to free iodine, which acts on -SH or -OH groups in the structure of microbial enzymes or proteins, causing their destruction.

Chlorine compounds

Sodium hypochlorite

Around 1785, the Frenchman Berthollet used sodium hypochlorite to develop liquid bleaching agents. The product was named "Javel water" after it was introduced to the market by the Javel Company. In France, sodium hypochlorite is still known as "Eau de Javel". In the past, it was used for bleaching cotton.

Hypochlorites, the most widely used of chlorine disinfectants, are available in liquid form (e.g., sodium hypochlorite) or solid form (e.g., calcium hypochlorite). They have a broad spectrum of antimicrobial activity, do not leave toxic residues, are unaffected by water hardness, are inexpensive, have a rapid action, and even remove biofilms from surfaces.

Mechanism of action: although not precisely known, it is possible that the oxidation of sulfhydryl enzymes and amino acids, chlorination of the amino acid ring, loss of intracellular content, decreased nutrient uptake, inhibition of protein synthesis, decreased oxygen uptake, oxidation of respiratory components, decreased adenosine triphosphate production, DNA breaks, and decreased DNA synthesis are the causes of microbial inactivation.

Sodium hypochlorite solution is also used for the disinfection of hard surfaces and can even be used to disinfect areas containing blood contaminated with HIV or HBV.

Active chlorine released from sodium hypochlorite was approved in the European Union in 2017 as an active biocidal agent for product types 1 (Human hygiene), 2 (Disinfectants and algaecides not intended for direct application to humans or animals), 3 (Veterinary hygiene), 4 (Food and feed area), and 5 (Drinking water). Ready-to-use products typically contain between 0.05% and 5% sodium hypochlorite.

It is effective against: bacteria, mycobacteria, yeasts, fungi, viruses, spores.

Hypochlorous acid

In the body, hypochlorous acid (HOCl) is produced by neutrophils in response to increased inflammatory markers and immunological stimuli. Myeloperoxidase (neutrophil-peroxidase = verdoperoxidase, due to its green color) is a basic protein that catalyzes the oxidation of H⁺ or electron donor substrates by H₂O₂. Together with hydrogen peroxide (oxidizing agent) and a halogen (Cl or I), it forms hypochlorous acid, a strong oxidant.

Hypochlorous acid is obtained through the electrolysis of a sodium chloride aqueous solution in a specially designed reactor. The process of obtaining hypochlorous acid without elemental chlorine is due to the neutral pH of the process. Sodium hypochlorite solution has a weakly acidic pH, which gives it the character of an oxidizing agent.

The product exhibits a low toxicity profile and is active against a wide spectrum of microbial agents. It is effective against: bacteria, mycobacteria, yeasts, fungi, viruses, spores.

Mechanism of action: by inhibiting the synthesis of adenosine 5ʹ-triphosphate, the structure and replication of nucleic acids, and the synthesis of proteins and the cell wall.

• Products in the Klintensiv portfolio containing halogenated compounds include:
• Klintensiv PVP Iodine Soap
• Betaklin
• Fizzy Tablet
• Disinfectant&Odorizer Hospital Level
• Klintensiv Pure Hypochlourous 4Medical
• Klintensiv Pure Hypochlourous For Air
• Klintensiv Clor

Quaternary ammonium compounds

Quaternary ammonium compounds are chemical substances formed by a central nitrogen atom to which four substituent radicals (R1-R4, alkyl or heterocyclic with different chain lengths) and a halide, sulfate, or other similar radical are attached. Depending on the structure of the groups, the compounds are divided into several generations. This helps ensure that toxicity studies are conducted on one representative from each generation.

The first compounds were developed in 1916 by Jacobs and Heidelberg, and as new generations were developed, efficacy and tolerance to hard water increased while toxicity decreased. They also have cleaning power, with reduced foaming, work effectively in the presence of organic matter (proteins, fats, carbohydrates), and are compatible with most surfaces.

Some of the most used are alkyl dimethyl benzyl ammonium chloride, alkyl didecyl dimethyl ammonium chloride, and dialkyl dimethyl ammonium chloride.

Benzalkonium chloride (alkyl dimethyl benzyl ammonium chloride) belongs to the first generation of quaternary compounds in which the alkyl group has various lengths with an even number of carbon atoms. It was the first product introduced into practice in 1935, being used with good results both as a disinfectant and as a detergent.

Didecyldimethylammonium chloride belongs to the fourth generation of quaternary compounds, having a much-improved biocidal efficacy.

Quaternary ammonium salts exhibit fungicidal, bactericidal, and virucidal efficacy against lipophilic (enveloped) viruses, are mycobacteriostatic, are not sporicidal (they only inhibit spore growth), and generally do not have tuberculocidal or virucidal efficacy against hydrophilic (non-enveloped) viruses.

They are usually used for the disinfection of hard surfaces, such as floors, furniture, and walls, and medical instruments and equipment that come into contact with the skin (e.g., blood pressure cuffs). They can be used as antiseptics and for the hygienic and surgical disinfection of hands.

Mechanism of action: they inactivate energy-producing enzymes, denature proteins in the cell wall composition, and alter the cell membrane. They can also denature phospholipids in the cytoplasmic membrane, resulting in major dysfunctions in membrane transport and the leakage of essential compounds and ions (K⁺) from the cell.