Surfactants:
The truth behind their toxicity, their ability to cause chemical resistance and their use in cleaning products
By Navid Omidbakhs, Vice President Open Innovation, P.Eng, PhD Candidate, University of Waterloo & NICOLE KENNY, Director of Professional and Technical Services, B.Sc, Assoc. Chem.

Introduction
Surfactants constitute the most important group of detergent components. They are wetting agents that lower the surface tension of a liquid, allowing easier spreading, and lower the interfacial tension between two liquids. The word surfactant derives from the contraction of the terms surface-active-agents and covers a group of molecules which are able to modify the interfacial properties of the liquids (aqueous or non-aqueous) in which they are present(1). Surfactants play an important role in many practical applications and products, including detergents, fabric softeners, vaccine formulations, and drug delivery and medical treatment (2-7), emulsifiers, paints, adhesives, inks, anti-fogging, wetting, ski wax, snowboard wax, foaming and de-foaming agents, biocides (sanitizers), and hair conditioners (after shampoo).

Detergent formulations contain surface active agents (surfactants) which remove dirt, stain and soil from surfaces and fabrics. The first surfactant made by man was soap. Indeed, soap was already know to the Sumerians (Babylonians) as early as 2500 years BC. Vegetable oils were cooked with potassium carbonate from burnt wood. The next step was the use of potassium hydroxide made from potash and calcium oxide. In this way, soap has been produced for millennia, mainly by the reaction of potassium hydroxide and tallow (extracted from fat of sheep and cattle). Surfactants have historically been classified according to the charge they carry when dissociated in water at neutral pH. This results in four categories, as follows:

  1.  Nonionic surfactants – do not ionize in solution.
  2.  Anionic surfactants – carry a negative charge when dissociated in water.
  3.  Cationic surfactants – carry a positive charge when dissociated in water.
  4.  Amphoteric surfactants – can carry both a positive and a negative charge when dissociated in water.

Anionics are the largest class of surfactants in terms of volume, and include the work-horse surfactants, linear alkylbenzene sulfonate (LAS), alcohol sulphate (AS) and alcohol ether (or ethoxy) sulphate (AES). Soap is also considered as anionic surfactant. These surfactants have strong detergent but weak antimicrobial properties, except in high concentrations (8). Cationic surfactants generally include various quaternary salts, used predominantly as antimicrobial agents, fabric conditioners (“fabric softeners”), and anti-static agents. Amphoteric surfactants represent the smallest class of surfactants, and generally are used when solubility, mildness and compatibility issues are important. Amphoteric surfactants are compounds of mixed anionic-cationic character and are not considered as biocides per se (8). Nonionic surfactants do not ionize in aqueous solutions and are comprised of two parts, a hydrophilic portion (water loving) and hydrophobic (water hating) portion. They are considered to have no antimicrobial properties (8).

The Toxicity And Environmental Profile Of Surfactants:
It is not possible to generalize the toxicity profile of surfactants since surfactants have very distinct chemical structures and consequently totally different properties. As an example, chained alkyl linear benzenesulfonic acids are not biodegradable while linear ones are biodegradable. Some surfactants such as alkyl phenol ethoxylates (APE) are very toxic to aquatic life and their degradation products are even more so (9), while others such as linear alkylbenzenesulfonic acids (LAS) and alcohol ethoxylates (AE) are readily biodegradable (10), and the potential for secondary poisoning effects of these surfactants is extremely low (10). According to European Medicines Agency, Veterinary Medicines and Inspections (11), for LAS: 

  •  toxicity has only been seen on high dose levels in all studies available;
  •  non teratogenic effects have been reported;
  •  no positive findings have been reported in mutagenicity studies;
  •  long-term studies have not show carcinogenic effects;
  •  there was no susceptibility of human gut bacteria up to a dose of 128 ug/ml in vitro;
  •  there was no effect on relevant dairy cultures in concentrations up to 4 ug/ml;
  •  systemic bioavailability of linear alkyl benzene sulphonic acids after application to the teat appears to be negligible;
  •  even maximum residue concentrations observed in milk were well below any dose levels or concentration at which toxicological or microbiological effects may be expected.

LAS is a petroleum-based surfactant, however, based on scientific support from comprehensive studies it has been found safe for many applications including teat-dip solutions which residuals end up in milk. This indicates that it is not true to generalize the toxicity of different surfactants.

Relevance For Surface Cleaning And Disinfection:
The effective use of disinfectants constitutes an important factor in preventing hospital-associated infections (HAIs) (12). Based on Spaulding classification (13), environmental surfaces are considered non-critical items because they come in contact with intact skin, and intact skin is an important barrier to disease acquisition. Use of non-critical items or contact with non-critical surfaces while traditionally thought to carry a low risk of transmitting a pathogen to patients have been highlighted recently as being the potential cause for disease transmission. The routine use of disinfectants to disinfect hospital floors and other surfaces (eg. Bedside tables or bed rails) remains controversial. That said, there are a number of reasons to encourage use of disinfecting products to decontaminate environmental surfaces including (12):

  1.  Epidemiologically important microbes (e.g. VRE, MRSA, Clostridium difficile and viruses) can survive on environmental surfaces for long times and the use of a disinfectant can eliminate them or significantly reduce their number while the use of a cleaning agent may result in cross contamination.
  2.    Disinfectants are required in the United States and Canada for decontamination of surfaces contaminated by blood and other potentially infective material.
  3.  Detergents become contaminated and result in seeding or cross-contamination of the patients’ environment with bacteria.
  4.  Disinfectants are more effective than detergents in reducing the microbial load on floors.
  5.  Disinfection of non-critical equipment and surfaces is recommended for patients on isolation precautions by the Centres for Disease Control and Prevention, and Public Health Agency of Canada.

The advantage of using a single product for decontamination of non-critical surfaces (including floors and equipment) simplifies both training and practice. Even though there is a debate on using either a cleaning or disinfecting agent to decontaminate the environmental surfaces, there is a consensus that at least one of them should be used. Even if a cleaner is intended to be used, it should have good cleaning performance, since all studies to support the contribution of cleaning agents have been generated using detergent with decent cleaning performance. Cleaning performance of a cleaner mostly comes from the contribution of surfactants used in the formulation. If surfactants are removed from a detergent formulation, the wetting capability and consequently cleaning performance decrease significantly. This will result in ineffectiveness of product for using as a detergent.

Microbial Resistance:
Recently, studying bacterial adaptation and resistance to antiseptics and disinfectants has had considerable interest (14). This is due to the fact that there is not enough knowledge in this field where as the resistance to antibiotics has been well studied (15). Understanding the microbial resistance to different types of biocides and potential cross-resistance can be very helpful in reducing usage of potential resistance developers, and consequently to decrease the risk for developing more resistance bacteria in our environment. In general, the mechanism of bacterial resistance to biocides is essentially of two types, via Intrinsic and Acquired (15).

  •  Intrinsic resistance is the natural, chromosomally controlled property of a bacterial cell that enables it to circumvent the action of a biocide. It is most commonly found in gram-negative bacteria, in mycobacteria and in bacterial spores. Additionally, physiological (phenotypic) adaptation is considered to alter the intrinsic resistance of bacteria – e.g. of cells contained within a biofilm (16).
  •  Acquired resistance to biocides results from genetic changes in a cell and arises either by mutation or by acquisition of genetic material from another cell (15). Acquired, resistance to biocides can result when bacteria are exposed to gradually increasing concentrations of a biocide. Examples are provided by highly QAC resistance Serratia marcescens , and chlorhexidine-resistant E.coli, P.mirabilis, P.aeruginosa and S. marcescens (17,18).

Resistance Development To Biocides:
The association between chronic sublethal exposure to bacterial monocultures to biocides and changes in susceptibility to both the biocides and antibiotics has been demonstrated unequivocally in the laboratory (19). Such phenomenon has not yet been demonstrated any relevance to the real world (19). If the increasing use of antibacterial agents within consumer products is likely to impact antibiotic resistance within the home, similar effects should already be apparent in clinical and hospital settings (19).

Minimum inhibitory concentrations (MICs) have been used to evaluate the emergence of biocide resistance in bacteria. However, the possibility of failure to achieve disinfection standard because of the elevated MICs is debatable since significantly higher concentrations are used in practice (20). Studies carried out with biocides in their use level, demonstrate that there isn’t less susceptibility to use dilutions of biocides against the bacteria with elevated susceptibility in MIC level (21-23).

Arguably, such studies support the view that antiseptic use in hospitals does not contribute to the biocide susceptibilities of enterococcal isolates. Additionally, studies conducted on the susceptibility of antiobiotic-resistant bacteria showed that there was no correlation between resistance to antibiotics and a decreased susceptibility to antiseptics or disinfectants (24). This seems to be due to the biocidal concentration factor. Biocidal concentration is a key factor in biocidal activity (20). Most biocide formulations contain high concentrations of active agents to achieve an optimal, broad-spectrum activity for direct use on an inanimate surface, skin and in water (25). The mechanism of action for biocides in their MIC and in their disinfection concentrations is different (26). It is generally accepted that most biocides, at high concentrations is different (26). It is generally accepted that most biocides, at high concentrations act in a non-specific way (25). This seems to be very relevant especially for oxidizers. Since selection or transfer of determinants for reduced susceptibility will only apply to biocides which have selective target sites, it seems unlikely (although not impossible) that is could occur with chemically reactive agents such as oxygen-releasing agents (19), or with solvent molecules such as alcohols (27). This likelihood is further reduced by the fact that these agents are unstable or volatile, and do not persist in the environment in an active form (19).

Non-ionic surfactants have no antimicrobial activity (8) and therefore no acquired microbial resistance would be developed for them. Anionic surfactants have very low antimicrobial activity only in acidic solution, and do not have any residual activity, and therefore microorganisms would not develop any resistance against them. As per the authors’ knowledge, there is no study available to support the hypothesis that non-ionic or anionic surfactants cause microbial resistance.

In summary, the mechanism of resistance to chemical germicides is often dependent on the concentration of the germicide. At high concentrations multiple structural and metabolic targets are involved, and at low concentrations fewer targets are entailed (8). On the other hand, some of these disinfectants, such as chlorine, have been around for a long time. Based on the current evidence, it seems that intrinsic and acquired antimicrobial resistance occurring in response to biocide exposure is not a significant problem, per se (19).

Concluding Remarks
Surfactants are a large class of chemicals and have different physical, chemical and toxicity properties. Some, like quaternary ammonium compounds (cationic surfactants), have microbial activity where as nonionics do not provide microbial activity. Some including alkyl phenol ethoxylates are toxic to aquatic life, and not environmentally favourable while others, such as LAS and AE, are readily biodegradable and do not accumulate in the environment.

That said, the responsibility remains on the shoulders of the product manufacturers to develop products which have a balance in their performance and environmental profile.

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