WAYS OF CREATING EFFECTIVE AND SAFE ANTIMICROBIAL LIQUID AGENTS AND EVOLUTION OF PUBLIC PERCEPTION OF DISINFECTION MEASURES

WAYS OF CREATING EFFECTIVE AND SAFE ANTIMICROBIAL LIQUID AGENTS AND EVOLUTION OF PUBLIC PERCEPTION OF DISINFECTION MEASURES

V.M.Bakhir, B.I.Leonov, S.A.Panicheva, V.I.Prilutsky, N.Yu.Shomovskaya, I.I.Strelnikov, Yu.G.Suchkov

The Russian Scientific and Research Institute for Medical Engineering (VNIIIMT MZ RF), Research Laboratory Center MGCD

Discussed in the article are the questions of a choice of liquid antimicrobial preparations. Theoretically, ANK anolyte has advantages over stable organic disinfectants.

While reflecting on what an ideal liquid agent to combat microbes should be, one can easily fancy the following desirable features:

  • antimicrobial agent should demonstrate a wide scope of antimicrobial action, that is, effectively destroy bacteria, micobacteria, viruses, fungi and spores irrespective of duration and frequency of its application, which suggests the presence of properties preventing development of microorganism resistance to them;
  • antimicrobial agent should be safe for man and animals both during its production and application, and after the end of its employment as intended, that is, in the period of degradational and destructive changes due to the action of environmental factors, or as a result of bio-degradation processes in the human body, in other words, antimicrobial agent and the products of its natural or artificial degradation should not contain xenobiotic substances;
  • antimicrobial agent must be universal in its action, i.e., not only possess antimicrobial properties, but also be a detergent with the minimal damaging and corrosive ability as regards various materials, as well as be as easy to use as possible and at the same time relatively cheap.

Agents based on stable organic compounds, which predominate on the market of disinfectants today, lack most of these characteristics.

Several examples given below can illustrate a considerable breach between ideal and actual qualities of organic disinfectant solutions. The concept of nosocomial infections’ prevention adopted in 1999 by the First Deputy Minister of Health of the Russian Federation [1] indicates that the most promising groups of compounds for decontaminating various types of indoor surfaces and other objects in health institutions are cationic surface active agents (CSAA) – quaternary ammonium compounds (QAC) and some other organic compounds. These compounds are claimed to be non-hazardous and suitable for patient care. In addition to CSAA, the same document also recommends to employ aldehydes for decontamination and pre-sterilization cleansing of medical utensils.

However, papers [2, 3] presented by the Research Institute of Disinfectology in 2002 and devoted to principal tendencies of increasing disinfectant agents’ effectiveness assert that though being stable CSAA at the same time are inactive, or low-active in relation to resistant microorganism species and forms, such as TB micobacteria, fungi, spores and bacilli. The same paper reports about swift and common growth of microorganism resistance against CSAA, pronounced absorptive and irritating action on skin and eye mucous membranes concentrated CSAAs produce, as well as commonly observed allergic reactions to many CSAAs. It also mentions that aldehydes’ high toxicity and sorption ability prevents them from being widely recommended for treating surfaces, linen and crockery.

High toxicity of glutaric aldehyde is commonly known [4]. That is why in May 2002 its application was prohibited by law in England [5]. However, in Russia advertising and sale of agents based on it continue.

Let us carefully analyze the processes occurring during normal disinfection of premises using a stable organic chemical agent, possessing, for instance, membrane-attacking mechanism of microorganism suppression (CSAA, phenols, iodophors and some others).

This type of agents is known to destroy bio-polymers constituting cell membrane. That results in microbial cell lysis. In small doses the same agents upset membrane functions (change osmotic pressure, permeability, rate of trans-membrane molecule and ion transfer, inhibit metabolic processes and biologic oxidation, hamper cell division).

After disinfection moist surfaces get dry, and organic substances are concentrated in the form of porous materials, and on smooth surfaces turn into finest invisible film. Nevertheless, their molecules continue to enter the air in the premises due to sublimation. Invisible “fog” of disinfectant molecules is practically odorless and thus falsely appears harmless. However, one should remember that in conformity with well-known physical laws each liter of indoor air normally contains several billion molecules of substance evaporating naturally or due to sublimation, even when its concentration is not registered by appropriate measuring devices and does not exceed hundredth and thousandth shares of MAC (maximum allowable concentration). In the process of breathing, as well as through skin and mucous membranes these molecules get into human body (patients, personnel) and each of them continues to perform its main function – suppressing cell vital activity, but now in the human body. Chemical stability of disinfectants is a prerequisite for their cumulation in the human body with subsequent migration along the alimentary tract. The situation is illustrated by an example from the middle of the previous century when the insecticide DDT (dichlorodiphenyltrichloroetan), for the invention of which its authors were awarded the Noble Prize, was detected in penguin liver, and that was one of the reasons why its production and application were banned.

Microorganism colonies immediately emerging on dried up and no bactericidal any longer, though previously active organic substance use it as their habitat and nutritive medium, at the same time developing resistance against the given type of disinfectant.

It is absolutely clear that developing ever new chemical agents for microbial eradication, to which the latter in no time adjust, man creates conditions for perfecting the mechanism of microbial mutability, and initiates with his actions the appearance of new and resistant against disinfectant agents microorganism strains.

Very often, a positive trait of agents based on stable (that is, poorly affected by environmental factors) organic compounds is considered to be lack of odor (as opposed to chlorine-containing preparations), or, on the contrary, the presence of agreeable scent of flavoring substances. Actually, such advantages are to be treated with great care. Most organic compounds used as disinfectants or the products of their transformations in natural or artificial decomposition processes are no less, and sometimes more toxic than, for instance, the same content of gaseous chlorine. For the majority of multicellular complex organisms in their usual habitat odor is a source of information. Absence of odor, which gives warning of danger, prevents man from avoiding harmful exposure, and that results in body functional and organic disturbances. These disturbances are normally observed after more or less lengthy period that passed from direct contact with a hazardous substance, therefore their causes very rarely can be adequately identified.

In recent times, harmful effects of chemical agents became widely known only in cases of catastrophic side results of their application, which could not be concealed or explained in some other way. Among such disasters were the consequences of application in the Central Asian republics of the former Soviet Union of a stable organic agent – the defoliant butyphos – with a pleasant odor of new-mown grass. It should be noted that at that time the said agent passed all strict official licensing procedures and received positive conclusions of several toxicological commissions of experts. Such conclusions were absolutely justified since in the process of such tests it is impossible in principle to adequately simulate the factors of an agent’s real-life practical application.

This kind of experience is necessary to keep in mind while developing new disinfectants giving preference to those whose antimicrobial action mechanism cannot be hazardous for man’s health in principle.

It can be concluded that when they are applied for treating surfaces disinfectant solutions of stable organic compounds invariably form an invisible film on the surface of treated articles, and molecules of active ingredient evaporating from it are harmful for a warm-blooded organism, since organic compounds – disinfectants – are xenobiotic substances, that is, substances, foreign to life in any of its forms, be it microbe’s life, or human life.

Are there environmentally friendly disinfectants? Today this question attracts general attention. Progress in social development involves more frequent direct contacts of man with bactericidal, virucidal and fungicidal agents – from buying fruit preserved with the help of biocidal chemical compounds to visiting various institutions (hospitals, outpatient clinics, dentist surgeries), transport vehicles (trains, planes, quite recently – buses and trams) regularly treated with disinfectant agents. Facing a choice, Consumer, unlike Seller (Manufacturer), gives preference to ecologically pristine product or technology. Thus, an apple with a worm-hole proving that it grew and ripened in natural conditions is valued more than a similar fruit with ideal surface texture longer staying fresh. For Consumer, products having no preservatives are more valuable, while Seller (Manufacturer) cannot do without them because he knows no other ways of suppressing microorganism growth and guarantee long-term undamaged state of products.

The oldest environmentally friendly disinfectant is surely flame. Being meta-stable substance flame plasma has no toxic aftereffect, and unlike most organic chemical disinfectants leaves no chances for microorganisms to develop resistance. Another ecologically harmless substance is hydrogen peroxide, which is used in the latest sterilization systems in its meta-stable state turning it into plasma.

Investigations carried out in recent decades indicate that all higher multi-cellular organisms including humans synthesize hypochlorous acid and highly-active meta-stable chlorine-oxygen and hydroperoxide compounds (a meta-stable oxidants’ mixture) in special cellular structures to combat microorganisms and foreign substances [6]. Hypochlorous acid dissociates in aqueous medium forming hypochlorite-anion and hydrogen ion: НСlО СlO- + Н+. When рН values are close to neutral, concentrations of НСlО and hypochlorite-anions СlO- are approximately equal. Lower рН leads to shift of this reaction equilibrium towards higher concentration of НСlО; higher — towards higher concentration of hypochlorite-anions. Sodium hypochlorite demonstrates a considerably lower bactericidal ability than hypochlorous acid. For instance, if anthrax spores В. anthracis in an aqueous solution of active chlorine compounds of 50 mg/l concentration at рН = 8.6 perish after 40 minutes, a solution with active chlorine content as low as 5 mg/l at рН = 7.2 achieves the same result in 20 minutes [7]. Thus, just a slight change of medium рН causes vast differences in antimicrobial ability of the same solution. The highest bactericidal effect of oxygen chlorine compounds is observed with рН varying from 7.0 to 7.6, where concentrations of hypochlorite-ions and hypochlorous acid are comparable. This is due to the fact that the above compounds being conjugated acid and base (НСlО + Н2О ® Н3О+ + СlO-; СlO- + Н2О ® НСlО + ОН-) form in the given range a meta-stable system capable of generating a number of compounds and particles possessing a much higher antimicrobial ability than hypochlorous acid: 1O2 — singlet molecular oxygen; СlO· — hypochlorite-radical; Сl· — chlorine-radical (atomic chlorine); О· — atomic oxygen; ОН· — hydroxyl radical. Catalysts of reactions with chlorine-oxygen compounds are Н+ and ОН- ions present in water also in approximately equal quantity at рН value close to neutral one [8].

Hence a very important conclusion: it is possible to exclude microorganisms’ growing resistance against liquid antimicrobial agents only applying solutions with meta-stable active ingredients, whose spontaneous decomposition during exposure provides plurality and unpredictability (for microorganisms) of reactions’ course disturbing their life activity.

A unique ability of hypochlorous acid to form meta-stable, universal in its scope of antimicrobial action oxidant mixture is widely employed in many disinfectant agents based on cyanuric acid salts (Aquatabs, Deochlor, Chlorsept, Presept, Javelion, Chlor-Clean, Sanival and others) making it possible to decrease active chlorine content in disinfectant working solutions at least 10-fold as compared to sodium hypochlorite solutions, antimicrobial activity of the former being higher. Let us take the mechanism of action of Johnson & Johnson’s Presept tablets as an example. The principal active ingredient in these tablets is considered to be sodium dichloroisocyanurate. In fact, the active ingredient is hypochlorous acid formed in the process of sodium dichloroisocyanurate interaction with water and present in the working solution at рН value = 6.2, maintained by adipic acid contained in the tablets. All other agents of this type work approximately in the same manner.

However, their use is unsafe for human and other warm-blooded organisms since they contain a chlorine organic compound, in particular, sodium dichloroisocyanurate, which, unlike inorganic chlorine-oxygen compounds, does not disappear leaving no traces during desiccation, but accumulates in the environment and human body.

The most efficient antimicrobial agents among all generally known liquid sterilizing and disinfectant means, which demonstrate very low toxicity or no toxicity at all for warm-blooded animals, are electrochemically activated solutions, in particular ANK neutral anolyte produced in STEL devices from diluted sodium chloride aqueous solution. Very often these solutions are identified with hypochlorite solutions. This is due to inadequate awareness and natural tendency to simplify comprehension by attributing electrochemically activated solutions to well-known hypochlorite ones on the basis of their formal resemblance.

ANK anolyte, unlike 0.5-5.0% hypochlorite solutions possessing only disinfectant ability, is a sterilizing solution at oxidant concentration varying from 0.005 to 0.05%.

The main technological principle of activated solutions’ production is unipolar mutual electrophysical and electrochemical action on treated medium, in the process of which there occurs either electron withdrawal or electron introduction, due to which there takes place aimed alteration of physicochemical (including structural, energetic and catalytic) properties of this medium.

Active ingredients of ANK anolyte are mixed peroxide compounds (НО· — hydroxyl radical; НО2- — peroxide anion; 1О2 — singlet molecular oxygen; О2- — superoxide-anion; О3 — ozone; О· - atomic oxygen) and chlorine-oxygen compounds (НСlО — hypochlorous acid; СlO- — hypochlorite-ion; СlO· - hypochlorite-radical; СlО2 — chlorine dioxide).

Such combination of active ingredients ensures absence of microorganism adaptation to biocidal action of ANK anolyte, while low total concentration of active oxygen and chlorine compounds guarаntees absolute safety for man and the environment in the process of its long-term application.

ANK anolyte is a multi-purpose solution, therefore it is used both for disinfection, presterilization cleansing and sterilization, and for general cleaning of premises, disinfection of equipment in health institutions, clothes, surgeon’s hands and so on.

Total content of active oxygen and chlorine compounds in ANK anolyte (total oxidant content) varies from 100 to 500 mg/l, which is dozens of times lower than in most working solutions of disinfectants routinely used today. ANK anolyte causes no coagulation of protein protecting microorganisms and thanks to its loose structure easily penetrates into micro-channels of living and nonliving matter. ANK anolyte is non-toxic due to low content of active ingredients, therefore there is no need to remove it from treated surfaces after treatment.

To sum up, it can be concluded that the most effective in terms of their functional properties and simultaneously very low-toxic or no toxic are meta-stable low-mineralized chlorine-oxygen antimicrobial solutions (electrochemically activated solutions), which have no alternative as long as life on Earth is represented by various forms of protein bodies existing in electrolyte of aqueous solutions of mainly sodium and chlorine ions.

References

  1. Concept of nosocomial infections’ prevention /V.I.Pokrovsky et al. MZ RF, 1999.
  2. M.G. Shandala. Methodological problems of today’s disinfection / Ibid., pp. 9-16.
  3. L.S. Fyodorova. The main tendencies of elevating the efficiency of disinfectant agents. // Proceedings of All-Russian Research Conference dedicated to 100th Anniversary of V.I.Vashkov Burning issues of disinfectology in prevention of communicable and invasive diseases. Moscow: ITAR-TASS, 2002. – pp. 26-30.
  4. Glass В. Exposure to Glutaraldehyde Alone or in a Fume Mix: a Review of 26 cases//Journal of the NZMRT, 1997. – V. 40. – N 2, June. – pp .13-17.
  5. Richards J. Withdrawal of Disinfectant Hit by Safety Fears // BBC News on Line: Health. January 22, 2002.
  6. Archakov A.I., Karuzina I.I. Oxidation of foreign compounds and toxicology problems // Bulletin of USSR Academy of Medical Sciences, 1988. – N 1. – pp. 14-28.
  7. Faust S.D., Aly O.M. Chemistry of water treatment // 2nd Edition, Lewis Publishers, L., NY, W. D.C., 1998. – 582 p.
  8. Krasnoborodko I.G. Destructive purification of sewage liquids from dyes. Leningrad: Chemistry, 1988. — 193 p.

Published in the journal “Dezinfektsionnoye delo”, N 3, 2004.