Quaternary ammonium compounds nedir
Quaternary ammonium nedir
quaternary ammonium compounds benzyl-c12-16-alkyldimethyl chlorides
Quaternary ammonium salt
quaternary ammonium compounds benzyl-c12-18-alkyldimethyl chlorides
Alkyl dimethyl benzyl ammonium chloride nedir
Quaternary ammonium cations, also known as quats, are positively charged polyatomic ions of the structure NR+4, R being an alkyl group or an aryl group.
Unlike the ammonium ion (NH+4) and the primary, secondary, or tertiary ammonium cations, the quaternary ammonium cations are permanently charged, independent of the pH of their solution.
Quaternary ammonium salts or quaternary ammonium compounds (called quaternary amines in oilfield parlance) are salts of quaternary ammonium cations.
Polyquats are a variety of engineered polymer forms which provide multiple quat molecules within a larger molecule.
Quaternary ammonium compounds are prepared by the alkylation of tertiary amines with a halocarbon.
In older literature this is often called a Menshutkin reaction, however modern chemists usually refer to it simply as quaternization.
The reaction can be used to produce a compound with unequal alkyl chain lengths; for example when making cationic surfactants one of the alkyl groups on the amine is typically longer than the others.
A typical synthesis is for benzalkonium chloride from a long-chain alkyldimethylamine and benzyl chloride
Quaternary ammonium cations are unreactive toward even strong electrophiles, oxidants, and acids.
They also are stable toward most nucleophiles.
The latter is indicated by the stability of the hydroxide salts such as tetramethylammonium hydroxide and tetrabutylammonium hydroxide.
Because of their resilience, many unusual anions have been isolated as the quaternary ammonium salts.
Examples include tetramethylammonium pentafluoroxenate, containing the highly reactive pentafluoroxenate (XeF−5) ion.
Permanganate can be solubilized in organic solvents, when deployed as its NBu+4 salt.
With exceptionally strong bases, quat cations degrade.
They undergo Sommelet–Hauser rearrangement and Stevens rearrangement, as well as dealkylation under harsh conditions or in presence of strong nucleophiles, like thiolates.
Quaternary ammonium cations containing N–C–C–H units can also undergo the Hofmann elimination and Emde degradation.
Quaternary ammonium salts are used as disinfectants, surfactants, fabric softeners, and as antistatic agents (e.g. in shampoos).
In liquid fabric softeners, the chloride salts are often used.
In dryer anticling strips, the sulfate salts are often used.
Older aluminium electrolytic capacitors and spermicidal jellies also contain quaternary ammonium salts.
Quaternary ammonium compounds have also been shown to have antimicrobial activity.
Certain quaternary ammonium compounds, especially those containing long alkyl chains, are used as antimicrobials and disinfectants.
Examples are benzalkonium chloride, benzethonium chloride, methylbenzethonium chloride, cetalkonium chloride, cetylpyridinium chloride, cetrimonium, cetrimide, dofanium chloride, tetraethylammonium bromide, didecyldimethylammonium chloride and domiphen bromide.
Also good against fungi, amoebas, and enveloped viruses, quaternary ammonium compounds are believed to act by disrupting the cell membrane or viral envelope.
Quaternary ammonium compounds are lethal to a wide variety of organisms except endospores, Mycobacterium tuberculosis and non-enveloped viruses.
Quaternary ammonium compounds are cationic detergents, as well as disinfectants, and as such can be used to remove organic material.
They are very effective in combination with phenols. Quaternary ammonium compounds are deactivated by anionic detergents (including common soaps).
Also, they work best in soft waters.
Effective levels are at 200 ppm.
They are effective at temperatures up to 100 °C
Quaternary ammonium salts are commonly used in the foodservice industry as sanitizing agents.
Phase transfer catalysts
In organic chemistry, quaternary ammonium salts are employed as phase transfer catalysts (PTCs).
Such catalysts accelerate reactions between reagents dissolved in immiscible solvents.
The highly reactive reagent dichlorocarbene is generated via PTC by reaction of chloroform and aqueous sodium hydroxide.
Anion exchange resins, in the form of beads, contain quaternary ammonium ions bound to a polymer.
Fabric softeners and hair conditioners
In the 1950s, distearyldimethylammonium chloride (DHTDMAC), was introduced as a fabric softener.
This compound was discontinued because the cation biodegrades too slowly.
Contemporary fabric softeners are based on salts of quaternary ammonium cations where the fatty acid is linked to the quaternary center via ester linkages;
these are commonly referred to as betaine-esters or ester-quats and are susceptible to degradation.
Characteristically, the cations contain one or two long alkyl chains derived from fatty acids linked to an ethoxylated ammonium salt.
Other cationic compounds can be derived from imidazolium, guanidinium, substituted amine salts, or quaternary alkoxy ammonium salts.
Quats (quaternary ammonium compounds) are potent disinfectant chemicals commonly found in disinfectant wipes, sprays and other household cleaners that are designed to kill germs.
It is often the stuff that allows a product to claim to be antibacterial, as they are certified by the EPA as pesticides.
Quaternary Ammonium Compounds
Cleaning products that contain QACs and other disinfectants are commonly used in homes, workplaces, and public spaces.
Disinfectants have an important role in preventing the spread of serious infectious diseases.
Health care facilities, day care centers, and restaurants may be centers for transmission of bacterial and viral illnesses where use of disinfectants is important.
On the other hand,use of these disinfectants is not recommended in places such as homes and offices when there is no elevated risk of infection, or where plain detergents would be effective in removing infectious organisms.
QACs are disinfectants used alone or added to cleaning products.
Manufacturers have added them to dishwashing liquids, hand soaps, window cleaners, “all-purpose” cleaners, floor products, baby-care products, disinfectant sprays and wipes, air fresheners, and other cleaning products that advertise anti-microbial activity.
QACs are used extensively in health care settings to clean noncritical patient care items (non-sterile medical equipment that may come into contact with intact skin but not mucous membranes) and environmental surfaces.
Other industries in which they are approved and widely used for their anti-microbial properties include food service and hydraulic fracturing.
QACs are also used in cleaning homes and offices.
In routine cleaning, where surface contamination with pathogenic bacteria and viruses does not present a hazard, QACs and other disinfectants are usually not necessary or recommended.
QACs are solids that are dissolved in liquid solutions.
They do not evaporate into the air.
When solutions of QACs dry they leave behind a solid residue.
QACs can get in the air if they are sprayed or if mixing of solutions results in foaming or splashing.
In theory, surface residue could become another source of airborne QACs if disturbed or attached to dust, but this has not yet been studied.
QACs persist in the environment,both on cleaned surfaces and in waste water, both of which could possibly result in skin exposure.
Many QACs have the chemical structure N-R1R2R3R4+X- where N isnitrogen, the 4 “R” positions are alkyl groups (methyl, ethyl and longer alkyl chains with up to 18 carbons) or an aryl group (such as benzyl) that may be connected to each other, and X- is an anion, usually chloride.
Other anions include bromide and saccharinate.
Commercial products are often mixtures of QACs with different length carbon chains.
Identification of QACs
There are many different QACs found in disinfectants or cleaning products.
The most commonly used QAC disinfectants are the benzalkonium chlorides, also known as alkyl dimethyl benzyl ammonium chlorides.
Abbreviations for benzalkonium chloride include BAC, BZK,BKC, and ADBAC.
The concentration of benzalkonium chloride in disinfectants and cleaning supplies is usually between 0.01 and 1%, but can be as high as 5%.
Concentrated solutions used for mixing can contain 25% or more.
Other QACs found in cleaning supplies and disinfectants have similar concentrations.
Cleaning supplies claiming antimicrobial activity and containing QACs must list the QACs on the label and be registered with the Environmental Protection Agency.
The label does not specify that a substance is a QAC; rather it lists specific ingredients which often end in “ammonium chloride.”
A typical label entry for a benzalkonium chloride, for example, would be: Alkyl (40% C12, 50% C14, 10% C16) dimethyl benzyl ammonium chloride
QACs might not be listed on Safety Data Sheets because they are often less than 1% of the cleaning product and are not required to be listed.
The NIH Household Products Database can be searched to determine if a household cleaning product contains QACs.
Products can be searched by product name or by ingredients (such as quaternary ammonium compounds, quaternium, ammonium chloride, and ammonium saccharinate).
Three types of QACs used as antimicrobials have been reported to cause irritant and/or allergic contact dermatitis.
These QACs are the benzalkonium chlorides, didecyl dimethyl ammonium chloride (DDAC), and N,N-didecyl-N-methyl-poly(oxyethyl) ammonium propionate.
Other QACs used as preservatives, hand lotions, and cosmetics, including quaternium-15, polyquaternium-9, and cetyl pyridinium chloride, have been reported to cause allergic contact dermatitis.
Accidental spillage of liquid cleaning products containing QACs onto skin and clothes is common.
QACs have been reported to cause irritant contact dermatitis through direct injury to the outer skin layers in exposed individuals.
Contact with concentrated solutions of QACs may be especially hazardous.
Patients with leg ulcers, eczema, or skin infections are particularly susceptible to irritant dermatitis from direct contact with broken skin.
Systemic absorption through unbroken skin is low.
QACs can also cause allergic contact dermatitis.
Quaternium-15, a QAC that is used as a preservative in hand moisturizers, was found to be the most frequent allergen in one North American study of hand allergic contact dermatitis, causing a clinically positive reaction in 16.5% of subjects.
Similarly, in a Swiss study, 5.5% of people with contact dermatitis were found to be sensitized to BAC.
Quaternary Ammonium Compounds
Quaternary ammonium compounds (QACs) are sometimes referred to as quats.
These compounds are among the most commonly used disinfectants in the food industry, and there are numerous commercially available products and formulations.
They are cationic surfactants (positively charged surface-active agents) that impact cell walls and membranes after relatively long contact times.
Their permanent positive charge makes them bind readily to the negatively charged surface of most microbes.
QACs are used at concentrations ranging from 200 to 400 ppm for various food-contact surfaces.
QACs are generally very stable, mostly unaffected by pH levels, and remain effective on a food-contact surface for a long time.
Their antimicrobial activity is more selective than that of other disinfectants, they are inactivated by organic soil, and they should not be diluted in hard water.
QACs are, however, generally very effective against bacterial biofilms.
An example of a QAC is benzalkonium chloride, which is often used as a cleaner and sanitizer for various food surfaces, both at home and in industrial applications such as dairy equipment.
Quaternary ammonium compounds
Quaternary ammonium compounds (QACs) were first introduced in 1917 and are probably the best known cationic surface-active agents.
Their general formula is as follows:
X is usually a halide but sometimes a sulfate ion. R1, R2, R3, and R4 may be a variety of alkyl or aryl groups.
QACs are generally poor detergents but good wetting agents.
In solution, they ionize to produce a cation, the substituted nitrogen part of the molecule, which provides the surface-active property.
The length of the carbon chain in the R groups affects the disinfectant ability; usually, C8 to C18 are the most effective.
The surface-active nature of these molecules tends to make them too high-foaming for CIP use, but they can be used for soak and manual cleaning at 200–400 p.p.m. active.
The optimum activity is around neutral pH, but QACs are active between pH 3.0 and 10.0.
Activity may be inhibited by water hardness.
QACs are noncorrosive and are stable at in-use dilution.
Their major disadvantages are that they are affected by organic soil and that they tend to cling to surfaces, so that they may be difficult to rinse off, resulting in possible taint problems.
The antimicrobial range of QACs is less than that of the oxidizing disinfectants.
They are less effective against Gram-negative bacteria than against Gram-positive bacteria.
They also have limited activity against bacterial spores and very little activity against viruses.
To be effective against yeasts and molds, a higher concentration is required.
Quaternary ammonium compounds (commonly known as quats or QACs) are cationic surfactants (surface active agents) that combine bactericidal and virucidal activity with good detergency and, therefore, cleaning ability.
Although other surfactant types, such as anionic, nonionic and, amphoteric surfactants have some antimicrobial activity depending on the specific biocide, the cationic surfactants (and some of the amphoterics) have the greatest antimicrobial activity.
Examples include hexadecyltrimethylammonium (‘cetrimide’), chlorhexidine, and benzalkonium chloride.
As for other biocides, the activity of QAC-based formulations will vary significantly based on the types of biocides used and their respective formulations.
Given that their primary mechanism of action is the structure/function disruption against cell membranes, they generally demonstrate bactericidal and fungicidal activity, with further activity observed against enveloped viruses.
QACs are also potent microstatic (including sporistatic) agents, but only limited formulations have claimed activity against mycobacteria (presumably by combination of other formulation excipients that allow greater penetration of the mycobacterial cell wall structure) and are generally cited as being nonactive against nonenveloped viruses.
Activity can be affected by the presence of water hardness, fat-containing substances, and anionic surfactants.
QACs have a pleasant odor, are not aggressive on surfaces, and have low toxicity.
They are widely used as cleaners/disinfectants on general, noncritical surfaces, including the removal of gross soil.
QACs and other surfactants are also used as preservatives (e.g., in paints and cosmetics).
Some QACs and amphoterics are also used at low concentrations as antiseptics.
The most widely used ones are the biguanides and in particular chlorhexidine (chlorhexidine gluconate, CHG) and polymeric biguanides (e.g., Vantocil).
CHG is used in such products as antimicrobial soaps, mouthwashes, wound dressings, and in contact lens storage solutions.
In these applications, in addition to direct antimicrobial activity, CHG has the further benefits of low irritation and binding to, and remaining on, the skin and mucous membranes at low, bacteristatic concentrations following application (thereby providing longer term or ‘substantive’ antimicrobial protection).
In addition to antiseptic applications, the polymeric bioguanides are also used as general disinfectants and for water sanitization (as chlorine alternatives). Overall, the antimicrobial activity of CHG and the polymerics are similar to other QACs, but have limited fungicidal activity in their own right that can be enhanced in formulation but are fungistatic and sporistatic at low concentrations.
As for the QACs, the cell membrane is the main target for antimicrobial activity and the action of CHG in particular has been well studied.
Being positively charged, they are rapidly attracted to the cell wall surface, with initial surface structure disruption, penetration to the cell membrane, and direct insertion to and interaction with the phospholipids, leading to structure/function disruption (including leakage of cytoplasmic components); these effects culminate in cell death and loss of viability of enveloped viruses.
Quaternary ammonium compounds are surface-active agents.
Some of them precipitate or denature proteins and destroy microorganisms.
The most important disinfectants in this group are cationic surface-active agents, such as benzalkonium chloride, benzethonium chloride and methylbenzethonium chloride, and cetylpyridinium chloride; the problems that they cause are similar.
Benzalkonium chloride is composed of a mixture of alkyldimethylbenzylammonium chlorides.
The hydrophobic alkyl residues are paraffinic chains with 8–18 carbon atoms.
Benzalkonium chloride is used as a preservative in suspensions and solutions for nasal sprays and in eye-drops.
Depending on the concentration of the solution, local irritant effects can occur.
In nasal sprays it can exacerbate rhinitis and in eye-drops it can cause irritation or keratitis.
Quaternary ammonium compounds.
(QACs) were first released commercially circa 1935.
An early example of this class of antimicrobials is BAK, often employed for its antifungal properties.
Anionic (negative) detergents can interact or bind with cationic (positive) preservatives such as BAK (and other QACs, e.g. cetyl-pyridinium chloride) by electrostatic attraction thereby lessening the availability of the active ingredient(s).
If maximum efficacy is to be realised, such combinations need to be avoided.
Quaternary Ammonium Compounds
Disinfectant products utilizing quaternary ammonium compounds as the active ingredient are among the most extensively used.
Among the advantages of quats are good stability and toxicology, surface activity and compatibility with cleaner formulation ingredients, and lack of odor.
These properties make it well suited for consumer products that combine cleaning with disinfection.
The antimicrobial properties of quaternary ammonium compounds were discovered in the early part of the twentieth century.
The enhanced efficacy of substituting long-chain alkyl moieties to quats was reported by Domagk in 1935.
The recognition of the potential to alter antimicrobial and toxicological properties through chemical substitution has led to the development of a range of quat structures.
The two types of quats that are most prevalent in disinfectants are alkyldimethylbenzylammonium chloride (ADBAC) and dialkyldimethylammonium chloride.
The efficacy of quats against specific bacteria vary with their hydrocarbon chain length.
Maximum efficacy for ADBAC quats is obtained with chain lengths between C12 and C16, while for dialkyl quats, this occurs at C8 and C10 chain lengths.
Most of the commercially available quats fall within this range.
Quaternary ammonium compounds are considered low-level disinfectants, as defined by the US Centers for Disease Control and Prevention.
They are effective against most vegetative bacteria and enveloped viruses, and some fungi.
The conditions necessary to attain disinfection with quats depend on concentration and contact time.
Typical end-use concentrations will have from 0.05 to 0.2% quat, and require 10 min to achieve disinfection.
The primary interaction between quaternary ammonium compounds and bacteria is electrostatic in nature.
Cell membranes contain phospholipids which impart an anionic character to bacteria at pH above 3–4.
Quaternary ammonium compounds, being cationic surfactants, show affinity for bacteria and exhibit antibacterial efficacy under these conditions.
It is believed that they interfere with the function of the cell membrane, resulting in leakage of cell components and eventually lysis, or destruction of the cell.
Quaternary ammonium compounds can be readily formulated with nonionic surfactants, builders, dye, and fragrance into a product that cleans and deodorizes in addition to disinfecting.
Anionic surfactants and polymers are to be avoided as they will usually form insoluble precipitates with quaternary ammonium compounds. Builders are useful for maintaining disinfectant activity as well as cleaning, because hard water also impacts on the efficacy of quaternary ammonium compounds. In addition to cleaning performance, the choice and concentration of nonionic surfactant should be made with the goal of maintaining antimicrobial activity. As cationic surfactants, quaternary ammonium compounds form micelles. Nonionic surfactants typically form micelles at lower concentrations, and form mixed micelles with cationic surfactants. Under these circumstances, the activity of quaternary ammonium compounds in the formulation can be reduced.
Quaternary ammonium compounds (QACs) are among the most commonly used disinfectants.
There has been concern that their widespread use will lead to the development of resistant organisms, and it has been suggested that limits should be place on their use.
While increases in tolerance to QACs have been observed, there is no clear evidence to support the development of resistance to QACs.
Since efflux pumps are believe to account for at least some of the increased tolerance found in bacteria, there has been concern that this will enhance the resistance of bacteria to certain antibiotics. QACs are membrane-active agents interacting with the cytoplasmic membrane of bacteria and lipids of viruses. The wide variety of chemical structures possible has seen an evolution in their effectiveness and expansion of applications over the last century, including non-lipid-containing viruses (i.e., noroviruses). Selection of formulations and methods of application have been shown to affect the efficacy of QACs. While numerous laboratory studies on the efficacy of QACs are available, relatively few studies have been conducted to assess their efficacy in practice.
Better standardized tests for assessing and defining the differences between increases in tolerance versus resistance are needed.
The ecological dynamics of microbial communities where QACs are a main line of defense against exposure to pathogens need to be better understood in terms of sublethal doses and antibiotic resistance.
Biocides (disinfectants) play a critical role in controlling the spread of environmentally transmitted pathogens in health care and food-processing environments, as well as in the home.
This review looks at a class of antimicrobials called quaternary ammonium compounds (QACs), with emphasis on understanding how formulations impact efficacy against target organisms and on the significance of resistance and cross-resistance with antibiotics in actual in-use applications.
The quaternary nitrogen moiety occurs naturally in living systems, where it plays an important role in various biological processes.
The first synthesis and recognition of their antimicrobial activity occurred almost 100 years ago, but it was not until after World War II that QACs came into widespread use.
Today, they are used in numerous consumer products and in the food and health care industries for cleaning, sanitizing, and disinfecting surfaces.
Their low toxicity and ability to be formulated for specific applications and target organisms help account for their widespread use.
QACs are cationic detergents (surfactants or surface-active agents).
They reduce surface tension and form micelles, allowing dispersion in a liquid
The cation portion consists of the central nitrogen with four attached groups, which occur in a variety of structures.
The negatively charged anion portion (X−) is usually chlorine or bromine and is linked to the nitrogen to form the QAC salt.
QACs are further classified on the basis of the nature of the R groups, which can include the number of nitrogen atoms, branching of the carbon chain, and the presence of aromatic groups.
These variations can affect the antimicrobial activity of the QAC in terms of dose and action against different groups of microorganisms.
Examples of the structures of three common QACs are shown in Fig. 2.
The length of the R groups can also greatly affect their antimicrobial activity.
Methyl group lengths of C12 to C16 usually show the greatest antimicrobial activity.
Many antimicrobial products contain mixtures of QACs and other adjuncts to increase their efficacy or to target a specific group of organisms.
The wide variety of chemical structures possible with QACs has allowed an evolution of their effectiveness and an expansion of their applications over the last century (Table 1).
This has resulted in a continued increase in efficacy while reducing costs and lowering toxicity.
Mechanism of action.QACs are membrane-active agents interacting with the cytoplasmic membrane of bacteria and the plasma membrane of yeast.
Their hydrophobic activity also makes them effective against lipid-containing viruses. QACs also interact with intracellular targets and bind to DNA.
They are also effective against non-lipid-containing viruses and spores, depending on the product formulation (Table 2).
At low concentrations (0.5 to 5 mg/liter) they are algistatic, bacteriostatic, tuberculostatic, sporostatic, and fungistatic.
At concentrations of 10 to 50 mg/liter, they are microbicidal for these same groups, depending upon the specific organism and formulation
McDonnell proposed the following series of events involved in the action of QACs against microorganisms:
(i) QAC adsorption to and penetration of the cell wall;
(ii) reaction with the cytoplasmic membrane (lipid or protein), followed by membrane disorganization;
(iii) leakage of intracellular lower-weight material;
(iv) degradation of proteins and nucleic acids; and
(v) cell wall lysis caused by autolytic enzymes.
Various formulations of QACs have been shown to be active against a wide variety of microbial types, as shown in Table 2.
Assessment of QAC activity.In the United States, the Environmental Protection Agency (EPA) is responsible for the registration of all disinfectants.
Standardized tests to assess both the bacteriostatic and disinfectant capabilities of products are available.
This usually includes the testing of both a Gram-negative and a Gram-positive bacterium before the product can be registered.
For claims against a specific organism, tests must be conducted with the specific organism to ensure its efficacy.
Numerous studies on QAC efficacy in various applications and against specific organisms have been published.
Unfortunately, several neglected to determine if the product had been registered for that specific organism or application.
In some cases, purified QACs from a chemical supplier or unidentified source were used rather than formulations designed for a specific organism or application, leading to generalized statements that QACs overall are not effective against the target organism.
Compounding the problem is the inability of some organisms to grow in the laboratory, requiring the use of surrogates or molecular methods for assessment of product efficacy.
This has become most evident in the case of norovirus.
Norovirus is believed to be the most common cause of foodborne illness in the United States and has caused numerous outbreaks on cruise ships, in hospitals, and in educational institutions.
Environmental transmission via contaminated hands and fomites is believed to be a major route of transmission.
Norovirus is also transmitted by contaminated food and water and via aerosols formed from vomit or diarrhea.
Numerous studies on the efficacy of disinfectants against this virus have been conducted (Table 3); mouse norovirus and feline calicivirus are the most commonly used surrogates.
The U.S. EPA has used the feline calicivirus for registration of efficacy against human norovirus.
While mouse norovirus has been shown to be more resistant to some environmental factors and disinfectants than the feline calicivirus is, a meta-analysis of existing studies suggests that the differences are modest.
Table 3 lists studies showing formulations registered for norovirus efficacy. When registered QAC formulations were used, efficacy was demonstrated.
Efficacy is also dependent not only on the target organism(s) but also on the method of application.
Bolton et al. compared a hydraulic spray apparatus and a robotic wiping device for sanitizing produce surfaces.
It was found that the QAC was more effective than chlorine bleach (11) in the spray apparatus but not in the robotic wiping device.
This emphasizes that application methods have to be considered in the assessment of any disinfectant.
While numerous laboratory studies on the efficacy of QACs are available, relatively few studies have been conducted to assess efficacy in practice.
The use of sanitizers is important to reduce the chance of cross contamination of foods during preparation.
The use of a QAC spray disinfectant in household kitchens was found to significantly reduce the total numbers of staphylococcal and Pseudomonas aeruginosa bacteria.
No Salmonella or Campylobacter bacteria were detected after the use of the QAC.
Another study in household kitchens and bathrooms found that a QAC wipe reduced total bacterial numbers by 99.9% overall.
A study involving 30 households in Mexico showed that the use of a QAC product statistically significantly reduced the occurrence of Escherichia coli on countertops over the 5 weeks of the study.
In a study conducted in an elementary school, the use of QAC-based disinfectant wipes once a day on the desk of each student reduced absenteeism by almost 50%.
During an outbreak of norovirus in a school, a QAC was found not to have stopped virus transmission, but a nonregistered product for norovirus had been used.
The method of application of any disinfectant including QACs is important to ensure the proper dosage.
For example, the effective dose of the QAC can be compromised by combination with cotton mops and cleaning towels.
QAC concentrations can be reduced by 50 to 83% by cotton and microfiber cloths.
Thus, it is important that proper concentrations, as indicated on product labels, be used and monitored.
Another option is using disposable disinfecting wipes or other ready-to-use products to deliver an effective concentration of the QAC.
The selection of a QAC or any biocide for a particular application requires an understanding of the factors listed in Table 4.
Resistance.The term resistance is used to indicate the insusceptibility of a microorganism to a particular treatment under a given set of conditions.
Gilbert and McBain lamented the tendency in the disinfection field to use the term “resistant,” even where changes in the dose of disinfectant needed to kill or inhibit the organism was insufficient, resulting in treatment failures.
Tolerance may be the preferred term to describe any MIC increases, rather than resistance, which implies that the disinfectant can no longer be used for a specific application.
It is to be expected that some tolerance among some types of bacteria might occur with the long-term use of QACs.
While it is often implied that their continued use will result in the development of resistance, this is not the case.
The nonspecific action of QACs makes the development of resistance unlikely, and several recent reviews support this conclusion.
The multitarget nature of QACs means that mutation within a single target is unlikely to result in a treatment failure.
The MIC increases that occur are much smaller than those seen with antibiotics.
It has been suggested that rotating different QAC formulations in health care or other settings would reduce this probability, but at this time, there is no evidence that this practice is needed.
In the home environment, bacteria isolated from sink drains were found to have reduced susceptibility to QACs but no resistance was observed.
Because of their low toxicity, QACs are extensively used in food processing and the food service industry.
Several recent studies have focused on the potential for the development of resistance among bacterial pathogens.
A recent example of this is in the use of QACs to control Listeria in the food industry, where several studies have reported the occurrence of Listeria resistance to QACs.
Increases in MICs were reported, but the MICs were still below those used in practice.
Differences in the occurrence of increased MICs have been reported to vary greatly from food processing plant to food processing plant, but it was suggested that these differences may be due to sublethal disinfectant concentrations or other-less than-optimal hygiene practices.
Kastbjerg and Gram pointed out that while MIC increases are seen in food processing, high acquired tolerance is rare, and that disinfectants are still effective for controlling foodborne pathogens such as Listeria monocytogenes.
In a laboratory study of the impact of disinfectants on the tolerance of Salmonella to several different biocides, it was found that there was no development of cross tolerance among the different disinfectants studied, including a QAC.
It was also found that the increases in tolerance were not phenotypically stable.
A review of resistance to biocides used in the health care industry concluded that there was no clear evidence to support the development of resistance to QACs or other biocides.
Under in-use conditions, most problems turn out to be related to pseudoresistance or user error, such as overdilution or incorrect handling of the product.
Cross-resistance to antibiotics.Efflux pumps act to exclude substances damaging to the microbial cell.
Efflux pumps can be induced by many substances besides biocides or antibiotics, including common household chemicals and natural products.
In some cases, efflux pumps account for the resistance of bacteria to certain antibiotics.
Thus, it has been suggested that activation of efflux pumps by biocides enhances antibiotic resistance in bacteria.
Studies examining the use of biocides and antibiotic resistance in household drains and in the health care environment and in industry have not observed any antibiotic-resistant bacteria in greater numbers in areas where biocides had been employed than in areas where they had not been used.
Several studies have shown no relationship between antibiotic resistance and the use of disinfectants (including QACs) in the home.
In one study, samples of fomites in the kitchen and bathroom were collected from homes that used disinfectants and those that did not.
No antibiotic cross-resistance was shown in the target bacteria recovered from the homes of disinfectant product users and nonusers.
For Gram-positive bacteria resistant to one or more antibiotics, the greatest number was found in the nonuser group.
It was also observed that while antibiotic multiresistance was common in households, there was no significant difference between homes that used disinfectants (including QACs) and those that did not.
The American Medical Association has called for the removal of agents in hygiene cleaning products that have exhibited induction of antibiotic resistance, and European regulations have suggested restricting the use of numerous active substances.
Current evidence does not appear to justify such action.
Lack of testing protocols and a definition of the minimal disinfectant concentration that affects antibiotic resistance for a defined strain are not established at present.
Clearly, quantitative-risk-based approaches are needed before any recommendations for limitations on the use of biocides important in reducing exposure to pathogens are considered.
In conclusion, it is important to recognize that many factors have to be considered carefully in selecting a QAC or any other disinfectant or sanitizer.
Every QAC formulation has its advantages and disadvantages for a particular situation.
Selecting formulations registered for a particular pathogen is crucial.
It is also important to recognize that observed effects in laboratory studies of small increases in tolerance to some QAC formulations and association with antibiotic resistance have to be balanced against the benefits to public health from their use.
QAC chemistry is a continually evolving area, with new product formulations appearing in the market to meet challenges posed by emerging pathogens.
Appropriate use of QACs in food processing and food service, schools, health care facilities, and the home can significantly impact health by reducing the number of infections.
Better standardized tests for assessing and defining the differences between increases in tolerance versus resistance are needed.
The ecological dynamics of microbial communities where QACs are a main line of defense against exposure to pathogens need to be better understood in terms of sublethal doses and antibiotic resistance.
At this time, there appears to be no reason for the restricted use of QACs based on increases in tolerance or induction of efflux pumps.
Quaternary ammonium compounds (QACs) are active ingredients in over 200 disinfectants currently recommended by the U.S. EPA for use to inactivate the SARS-CoV-2 (COVID-19) virus.
The amounts of these compounds used in household, workplace, and industry settings has very likely increased, and usage will continue to be elevated given the scope of the pandemic.
QACs have been previously detected in wastewater, surface waters, and sediments, and effects on antibiotic resistance have been explored.
Thus, it is important to assess potential environmental and engineering impacts of elevated QAC usage, which may include disruption of wastewater treatment unit operations, proliferation of antibiotic resistance, formation of nitrosamine disinfection byproducts, and impacts on biota in surface waters.
The threat caused by COVID-19 is clear, and a reasonable response is elevated use of QACs to mitigate spread of infection. Exploration of potential effects, environmental fate, and technologies to minimize environmental releases of QACs, however, is warranted.
During the SARS-CoV-2 (COVID-19) pandemic, many disinfection practices, including hand washing and surface cleaning, have changed to limit disease transmission.
These practices will continue to evolve as people return to work and resume other activities, leading to more routine and thorough disinfection to minimize virus transmission.
These new cleaning routines and habits may continue past the time when SARS-CoV-2 is an urgent threat.
Quaternary ammonium compounds (QACs) are known to be effective at inactivating enveloped viruses, such as SARS-CoV-2, and the U.S. Environmental Protection Agency’s (EPA) List N: Disinfectants for Use Against SARS-CoV-2 has 430 products, of which 216 contain QACs as the active ingredient,3 with specifics shown in Figure.
Of the 18 virucidal products for surface disinfection listed by the Association for Applied Hygiene in Germany, three contain QACs.
It has been recently noted, however, that additional evaluation of the effectiveness of QACs against coronaviruses is needed.5
Active ingredients in products on the EPA List N as of June 21, 2020.
The benzalkyl dimethylammonium compounds (BACs) are benzalkyl dimethyl or ethylbenzalkyl dimethyl ammonium compounds or a combination of the two.
The dialkyldimethylammonium compounds (DADMACs) are predominantly dioctyl, octyl decyl, or didecyl dimethylammonium chloride or a combination of these.
Eight of the products containing only DADMAC, 14 containing only BACs, and four with both also contain ethanol or isopropanol.
A peroxy acid is present for 25% of the products contaning hydrogen perioxde. Other disinfectants include citric acid, dodecylbenzenesulfonic acid + lactic acid, ethanol, glycolic acid, 1,2-hexandiol, hydrochloric acid, isopropanol, lactic acid, octanoic acid (1), peroxyacetic acid (8), phenolic compounds (11), potassium peroxymonosulfate (3), silver ion (2), sodium dichloroisocyanurate (4), sodium dichloro-S-triazinetrione (2), and thymol (4).
Before the pandemic, QACs, including benzalkyl dimethylammonium compounds (BACs or benzalkonium compounds), alkyltrimethylammonium compounds (ATMACs), and dialkyldimethylammonium compounds (DADMACs) were already widely used in the U.S.;
i.e., all of these were designated high production volume chemicals by the EPA and the Organization for Economic Cooperation and Development with over 1 million pounds per year manufactured or imported.
In Europe, however, uses of QACs have recently been limited in food products and consumer hand and body washes.
Past reviews have focused on the detection, fate, impacts, and regulation of QACs,6−9 but usage has likely increased in various settings during the pandemic, including hospitals, long-term care facilities, households, and workplaces considered essential (like grocery stores and food processing plants).
Increased handwashing with antibacterial soaps will also lead to more use.
After the ban on triclosan, BACs are used as replacements in many over-the-counter antibacterial hand soaps, particularly because BACs were not disallowed ingredients by the U.S. Food and Drug Administration.
As economies begin to open, and disinfection protocols for office, retail, manufacturing, and other industrial workspaces are required, usage of products containing QACs will likely continue to increase.
There may also be usage in heavily trafficked areas such as outdoor common spaces and public transit systems. This usage is understandable given the ubiquity of QACs in disinfectant wipes and surface spray cleaners and the current recommendations to use these compounds to limit virus transmission.
The increased consumption of QACs, however, will lead to increased loads to wastewater treatment systems and to the environment.
Thus, it is important to identify
(i) resulting concentrations from elevated loads and their environmental fate,
(ii) potential impacts to wastewater treatment infrastructure and aquatic systems, and
(iii) the processes that lead to degradation/removal.
This is not to say that use should be restricted at this time; rather we are noting that, in addition to more data regarding effectiveness, ancillary environmental impacts need exploration along with means to ameliorate identified risks.
Coupled with effectiveness data, evaluation of environmental risks is important information for developing a hierarchy for disinfectant product usage recommendations that maximize efficacy and minimize environmental and other risks.
The majority of QACs used ultimately enter wastewater treatment plants (WWTPs) indicating this is one location where effects could manifest.
QACs are present in the effluent water and sorbed to sludge, which provides two pathways to the environment if biosolids are used as a soil amendment.
If use increases in outdoor spaces or in transit systems, stormwater runoff could also carry QACs.
Therefore, loadings to WWTPs, discharges to surface waters receiving effluent, and direct inputs into the environment are likely to increase in the immediate and foreseeable future.
Potential concerns regarding increased usage include disruption of treatment plant operation and impacts on the spread of antibiotic resistance.
Toxicity to aquatic organisms is of concern, as is the formation of N-nitrosamines via reaction with chloramines.
The following sections provide an overview of QAC history and environmental fate and explore potential impacts of increased QAC loadings to both wastewater treatment systems and aquatic environments, identify situations where increased monitoring of QAC levels may be needed, and propose potential ways to reduce these impacts.
History and Usage
QACs were first introduced as derivatives of hexamethylene tetramine, and the bactericidal properties of these salts were explored in several publications from 1915 to 1916.
It was not until 1935 that the broader use of QACs began with the development of benzalkyl dimethylammonium chloride (ADBAC or benzalkonium chloride or BAC), in which the alkyl group can be a chain containing eight to 18 carbon atoms.
The new surface disinfectant was marketed as Zephirol (sold in the U.S. as Zephiran, Roccal, or BTC).
By the 1940s, QACs were increasingly used as surface-active agents and detergent disinfectants.
Proposed and actual applications ranged from disinfection of utensils and glassware to prevent disease transmission in public eateries and military mess halls; to curbing infection in military settings and hospitals, in particular to combat drug resistant strains of bacteria; to the dairy industry to wash udders and to disinfect milking machines, processing and pasteurization equipment, and dairy tanks and cans used to transport milk.
In addition to BACs, the other major classes of QACs are the ATMACs and DADMACs.
Other historically commonly used QACs include Cetavlon or CTAB (cetyltrimethylammonium bromide) and DTDMAC (ditallow dimethylammonium chloride), which was a common fabric softener ingredient until voluntary phase-out and replacement by a less hydrophobic, more readily biodegradable surfactant.
Demand for QACs has increased over the decades, and they continue to be widely used chemicals, chemical mixtures, and additives in a variety of industrial, agricultural, clinical, and consumer products and applications.7,9,24 In 1945, the U.S. produced 3 million pounds of surface-active agents; by 1993, that number reached 7787 million pounds.23 U.S. production of QACs was estimated to be approximately 100 million pounds in 1979 with DADMACs accounting for the largest production volume due to use in fabric softeners and oil-based drilling muds. The estimated consumption of the other major class of QACs, BACs, was 20–25 million pounds. Approximately 80% of the market for BACs was in biocides, sanitizers, and disinfectants, with the remainder being in hair conditioners in shampoos and cream rinses, emulsifying agents, and constituents in deodorizers.25 On the basis of U.S. EPA Chemical Data Reporting in 2015, national aggregate production volumes ranged from 10 to 50 million pounds each for several BAC, ATMAC, and DADMAC mixtures.26
QACs are some of the most extensively used classes of biocides, disinfectants, sanitizers, antimicrobials, and cleaners.
Because of their broad-spectrum antimicrobial properties against bacteria, fungi, and viruses, QACs are applied in household, food-processing, agriculture, and clinical settings to control the spread of environmentally transmitted pathogens.
Many commercial cleaning products marketed as antibacterial and personal care products including antibacterial soaps and alcohol-free hand sanitizers contain QACs as active ingredients.
The carbon chain influences the antimicrobial activity of QACs.
Generally, alkyl chain lengths from C12 to C16 exhibit greater antimicrobial activity, and twin-chained compounds such as DADMACs demonstrate better bioactivity toward some Gram-positive bacteria compared to BACs.
Due to their amphiphilic nature, QACs act as detergents or surface-active agents against microorganisms.
QACs target bacterial cell membranes through electrostatic interactions between the positively charged headgroup and negatively charged cytoplasmic membrane, adsorption, and then permeation of side chains into the intramembrane region.
The lipid layer of enveloped viruses makes them sensitive to the hydrophobic activity of QACs.
Environmental Inputs and Fate
QACs have been detected worldwide not just in domestic wastewater and sludge but also in treated effluent, surface water, and sediment.
It is anticipated that the majority of QAC applications leads to their eventual release (∼75%) into sewers and WWTPs.
Though QACs are removed from the liquid stream during conventional wastewater treatment via a combination of sorption to biosolids and biodegradation, these compounds are still detected in aquatic environments, especially at higher concentrations in locations downstream of the discharge of municipal WWTP effluents and hospital and industrial (e.g., laundry and food processing) effluents.
The reason elevated environmental concentrations are found despite ∼90% removal from the liquid stream in wastewater treatment is because QACs are high production volume chemicals; consequently, as the global appetite for QACs grows, these compounds will increasingly enter the environment through point source pollution, land application of biosolids, or treated municipal and industrial effluent discharges.
Concentrations of QACs detected worldwide in surface water and wastewater effluent range from less than 1 μg/L to approximately 60 μg/L, and QACs have been found to be up to 10 times these levels in influent wastewater.
A study in Germany detected average total C12-BAC concentrations of 4.7 and 7.7 μg/L in wastewater samples collected directly from two neighborhood street sanitary sewers.
On the basis of product surveys in households, the researchers tentatively linked BAC detection to use in surface disinfectants, soaps, and/or washing and cleaning agents.
BACs are the most frequently found QAC group worldwide in municipal or industrial wastewater effluents at levels up to the mg/L range in indirect discharge wastewater and effluent from hospitals.
Ruan et al. detected total concentrations of homologues of ATMAC, BAC, and DADMAC ranging from 1.12 to 505 mg/kg dry weight in municipal biosolids throughout China.
Of the different homologues, C8- to C18-DADMACs, C12- to C18-ATMACs, and C12- to C18-BACs are identified as the most frequently detected in the environment.
We note that while there are many reports of BAC detection there is minimal information on the ethylbenzalkyl dimethylammonium compounds that are components of many of the BAC-containing products in FigureFigure11, and the environmental levels of these compounds merit study. Benzethonium chloride is another QAC active ingredient in a few of the hard-surface disinfectant products on the EPA list, which has a paucity of environmental data and might warrant further study.
There are three main attenuation mechanisms for QACs in the aquatic environment: photolysis, biodegradation, and sorption to suspended particles followed by sedimentation. Generally, QACs have been considered stable or relatively slow to degrade by hydrolysis, photolysis, or microbial activity. While the ethylbenzalkyl dimethylammonium compounds have not received specific attention, it is expected that their fate would be similar to other QACs. The photochemical processing of QACs in the environment has been explored in a limited capacity. Although some QACs contain chromophoric functional groups that would make them susceptible to direct photodegradation, many lack these groups or weakly absorb light in the solar spectrum. QACs like BACs and DADMACs have previously exhibited relatively long photolysis half-lives in aqueous and soil environments.45,46 Recent work exploring indirect photolysis of QACs including two BAC homologues, a DADMAC, an ATMAC, and benzethonium chloride in surface waters estimated half-lives from 12 to 94 days.47
Most studies of biodegradation of QACs have been performed using activated sludge or enrichment cultures, but there is some evidence for degradation over a period of 5–10 days of ATMACs and BACs by marine bacteria.48−54 From previous studies relying on enrichment and isolation of QAC-resistant bacteria, species that degrade and even mineralize QACs to carbon dioxide have been identified.24,28,55−57 These include strains of Pseudomonas, Xanthomonas, Aeromonas, Stenetrophomonas, and Achromobacter.48,57−60 Biotransformation pathways have also been elucidated for several QACs by bacterial isolates. A few studies have reported the microbial degradation of BAC by several pure cultures (Pseudomonas nitroreducens, Aeromonas hydrophila, and Bacillus niabensis) to benzyldimethylamine by dealkylating amine oxidase and related enzymes.28 Other identified enzymes include tetradecyl trimethylammonium bromide monooxygenase, a Rieske-type oxygenase oxyBAC, as well as three genes encoding oxygenases that metabolize naturally occurring QACs.48 Work is needed, however, to assess if such degradation occurs in aquatic systems by complex microbial communities.
Due to their strong affinity to organic and inorganic particles, a large fraction of QACs is removed from surface waters by sedimentation.
Consequently, QACs have been identified in surface sediment samples from rivers in Austria, WWTP effluent-impacted estuaries in New York City, and sewage-impacted lakes in Minnesota with total QAC concentrations between 1 ng/g (μg/kg) and 74 μg/g (mg/kg).30,39,41,61,62 Concentrations of BACs and DADMACs are typically much higher than concentrations of ATMACs with C12-BAC (3.6 μg/g), C14-BAC (7.2 μg/g), C18-DADMAC (26 μg/g), and C22-ATMAC (6.8 μg/g) reaching the highest recorded levels of individual QACs.
Surface sediment samples from effluent-impacted estuaries in New York City were found to contain especially high QAC concentrations, with median total QAC concentration about 25 times higher than the median sum of polycyclic aromatic hydrocarbons at the same location.30 QACs have also been quantified in dated sediment cores from lakes in Minnesota and from urban estuaries near New York City, Hong Kong, and Tokyo.39,62−64 A common pattern to all these sediment cores, which represent a temporal archive of contaminant input into aquatic environments, is positive detection of QACs since the 1950s and peak concentrations (0.7–400 μg/g total QAC) corresponding to depositions between the 1960s and the 1980s. Sediment concentrations decrease afterward, likely due to implementations of improved domestic and industrial wastewater treatment, for most QACs and locations, except for certain short-chain DADMACs and long-chain ATMACs. Increased current and future usage in response to the COVID-19 pandemic, however, could lead to increasing levels in sediments. Despite being detected worldwide at high levels in sediments, conclusive data about the bioavailability of QACs once sorbed are scarce. So far only Li et al. were able to show that total masses of BACs and ATMACs were reduced by 39%–55% in two dated sediment cores from the same location taken 12 years apart, indicating in situ degradation of ATMACs and BACs (particularly those with short chains), while DADMACs were concluded to be recalcitrant.
Another route of QACs to the environment is inputs to soils via amendments of biosolids.
Mulder et al. predict environmental concentrations of QACs in biosolids-amended soil ranging from high μg/kg to mg/kg, but this may arise from animal manure instead of municipal biosolids.
While biodegradation in soil is possible, it has not been specifically studied and will be a function of bioavailability, and QACs are known to sorb to clays.
Because biosolids retain QACs, potential effects of land application of biosolids with QAC levels higher than those previously used need attention.
QACs kill bacteria by gross membrane disruption, and the impacts of QACs on selecting for antibiotic resistance in pure cultures has been well documented and reviewed in detail elsewhere.
This selection is not of concern for chlorine-based disinfectants or hydrogen peroxide, which decompose more rapidly.
Perhaps of greatest concern is the proliferation of pathogenic multidrug resistant bacteria (“superbugs”), following exposure to QACs.
Indeed, methicillin-resistant Staphylococcus aureus (MRSA) strains exposed to BAC as well as benzethonium chloride had increased resistance to oxacillin and β-lactam antibiotics.
Salmonella enterica and Escherichia coli O157 exposed to BAC also developed cross-resistance to antibiotics.
Of great interest following the heightened use of QACs during the COVID-19 pandemic will be what effects QACs have on antibiotic resistance in mixed microbial communities,
i.e., the microbial communities present in natural and engineered environments.
Exposure to BAC at subinhibitory levels in an aerobic sediment microbial community altered microbial community composition and increased resistance to BAC as well as penicillin G, tetracycline, and ciprofloxacin.
The increased resistance was attributed to the selection for bacteria that harbored efflux pumps and other resistance mechanisms.
Follow-up research on the aerobic sediment communities revealed that BAC selected for BAC resistance and antibiotic resistance in multiple sediment strains, including Archromobacter sp., Citrobacter freundii sp., Klebsiella michiganesis sp., and Pseudomonas aeruginosa sp.
Resistance was due to multiple mechanisms, including mutations and overexpression of multidrug efflux pumps.
Another key finding was that antibiotic resistance can arise due to coresistance,
i.e., acquisition of two colocated genes, one that confers resistance to BAC and one that confers resistance to an antibiotic.
Of note, though, is that increased resistance was not universal. Of the seven antibiotics tested, resistance increased to three antibiotics.
A similar finding was observed in a study on a mixed microbial community taken from a freshwater lake used for drinking water.
BAC selected for resistance to the fluoroquinolone antibiotic ciprofloxacin at only 0.1 μg/L and also selected for resistance to sulfamethoxazole.
The resistance of the community to other antibiotics, though, declined after exposure to BAC.
Collectively, these studies indicate that BAC is not a universal selective agent for antibiotic resistance, but rather it will alter the antibiotic resistance profiles of microbial communities.
If this effect will be better or worse from a public health standpoint depends on the clinical need for the particular antibiotics that are less effective after BAC exposure.
Multiple studies revealed that BAC increased resistance to ciprofloxacin, which is currently a top 5 prescribed antibiotic, and was the most abundant antibiotic found in biosolids in the U.S., an indication of its high usage.
As concentrations of BAC increase, it is possible that BAC will promote more clinically relevant antibiotic resistance.
As noted in the above sections, a majority of BAC passes through anaerobic digesters.
Yet, to the best of our knowledge, no research has been conducted to elucidate the impacts of BAC on selection of antibiotic resistance in anaerobic digesters.
Previous work on the broad-spectrum antimicrobials triclosan and triclocarban revealed their selection for antibiotic resistance genes as well as functional cross-resistance to antibiotics in anaerobic digestion.
The QACs DTDMAC and CTAB were also found to correlate with higher frequencies of intI1 and antibiotic resistance genes.
Class 1 integrons often contain qac genes which confer resistance to QACs via efflux.
This is an especially interesting phenomenon because integrons allow bacteria to acquire other antibiotic resistance genes via horizontal gene transfer.
Thus, increased QAC concentrations could select for bacteria that harbor qac genes and integrons/antibiotic resistance genes, ultimately leading to more multidrug resistant bacteria.
Another unintended consequence of more frequent QAC usage, especially in food preparation and clinical settings, is increasing tolerance or resistance to a particular QAC and development of cross-tolerance to other QAC formulations among pathogenic bacteria.
The impact of QACs on antibiotic resistance, including impacts on horizontal gene transfer rates and multidrug resistance, in environments that will be exposed to higher QAC concentrations should be further researched, including anaerobic digestion and soils amended with municipal biosolids.
Disinfection Byproducts: N-Nitrosamines
The last treatment step in wastewater treatment is often disinfection. Even when disinfection is performed with chlorine, there are still chloramines formed from reaction with ammonia present, even in nitrified effluents.
Chloramines are known to react with organic amines to form nitrosamines.95N-Nitrosodimethylamine (NDMA), a known carcinogen, receives the most attention.
Gray and black waters containing various cleaning and bathing products have been shown to produce N-nitrosamines upon exposure to chloramine.
While likely responsible for only a fraction of the production, QACs do form NDMA with low molar yields (∼0.03%–0.3%).
The yield is not reduced upon purification, indicating that trace tertiary amines are likely not the precursors, as seen for polymers treated to remove tertiary amines.
NDMA, however, is only a small fraction of the total production of N-nitrosamines.
Recent work has demonstrated that while NDMA yield for a BAC and an ATMAC are minimal, total N-nitrosamine molar yields range from 0.7% (pH 6) to 5% (pH 8) upon treatment with chloramine.
While release of N-nitrosamines into the environment is undesirable, they are subject to decay processes.
The production of elevated levels of N-nitrosamines from increased levels of QACs upon chlor(am)ination of wastewater is likely to be of greatest concern for direct or indirect potable reuse scenarios, where there is potential for human exposure to the N-nitrosamines.
In these situations, increased monitoring of QAC levels and N-nitrosamine formation is likely needed.
Toxicity to Aquatic and Soil Organisms
A more in-depth overview of the toxicity of QACs on aquatic organisms can be found in recently published reviews.
QACs are algistatic and bacteriostatic at concentrations ranging from 0.5 to 5 mg L–1 and microbiocidal at concentrations from 10 to 50 mg/L.
Acute toxic effects on marine bacteria of the Vibrionaceae family, however, have already been observed at high μg/L concentrations (EC50 = 57–630 μg/L).
The largest number of toxicity studies with QACs over the past 20 years were performed with various algae species.
Typical acute toxicity thresholds (EC50–96h) were between 0.1 and 1.8 mg/.
Large variations were observed between different algae species, as well as for different endpoints and QAC structures.
Overall, the toxicity of QACs toward algae increased with exposure time and with chain lengths of ATMACs and BACs but not with chain lengths of DADMACs.
Aquatic organisms also frequently studied are protozoa, daphnids, and fish. Protozoa (Tetrahymena thermophila and Spirostomum ambiguum) appear less sensitive than algae with EC50-24h of 1.5–10 mg/L and LC50-24h of 0.2–0.9 mg/L, while Daphnia magna are especially sensitive to QACs with average EC50-24h of 0.18 mg/L and EC50-48h of 0.03 mg/L.
Chronic toxicity thresholds for aquatic species were only reported for the green algae Dunaliella bardawil (IC50-10d = 0.78 mg/L), Daphnia magna (EC50-21d = 1.0 μg/L), and Ceriodaphnia dubia (EC50-7d = 0.04 mg/L).
Lethal toxicity of ATMACs toward rainbow trout increased with chain length, and LC50-24h of 0.6–41 mg/L were reported.
Interestingly, chronic effects on cell lines from rainbow trout appear to be in the same range with EC50 or IC50 values of 0.3–2.7 mg/L.
Chen et al. as well as van Wijk et al. studied the effects of adding sediments, clays, or dissolved organic matter to their toxicity tests and found that the freely dissolved fraction of QACs is predominantly responsible for causing toxic effects, likely because sorbed QACs are not as bioavailable.
For similar reasons, toxicity thresholds are substantially higher for benthic organisms and terrestrial and aquatic plants.
It is assumed that QACs sorbed to sediments or soils are not bioavailable, and thus, only the freely dissolved fraction in pore water causes toxic effects in benthic organisms and plants.
Performing a systematic risk assessment for QACs is difficult due to the lack of chronic toxicity data and limited number of exposure measurements in surface waters.
The available toxicity and exposure data, however, indicate that high ratios of predicted environmental concentrations (PEC) to predicted no-effect concentrations (PNEC) could be reached for aquatic systems, whereas PEC/PNEC ratios are unlikely to be elevated for sediments and soils.
A similar conclusion has been reached previously by Kreuzinger et al.
A crude estimate of PNEC was made here based on acute toxicity data from studies with Daphnia magna, which appears to be the most sensitive aquatic organism toward adverse effects by QACs.
Using the geometric mean of all EC50 values available and an assessment factor of 1000, a conservative PNEC estimate would amount to approximately 100 ng/L.
Considering average reported surface water concentrations on the order of 70 ng/L for single QAC compounds and 280 ng/L for total QAC concentrations, PEC/PNEC ratio estimates range from 0.7 to 2.8 with a large degree of uncertainty.
It is currently difficult to assess whether aquatic organisms are at risk by the levels of QACs seen today or expected in the future.
Better chronic toxicity data, studies on mixture toxicity, and more comprehensive exposure measurements, especially for effluent dominated systems or those near chemical manufacturing and medical facilities, are needed.
Implications and Interventions
The amount of disinfectants being used has risen, with one manufacturer reporting production in May 2020 equivalent to the entire year of 2019,118 and U.S. sales of disinfectant wipes were 146% higher than the same period last spring.
While it is unclear if this level will be sustained, some companies that produce hygiene and cleaning products anticipate lasting changes in consumer behavior and increased demand after the COVID-19 pandemic begins to wane.
The global surface disinfectant market has a forecasted 9.1% compound annual growth rate from 2020 to 2027.
Thus, it should be anticipated that the amounts of QACs used and released to the environment will increase.
Because QACs are biologically active compounds, there are several potential environmental impacts that need to be considered due to elevated usage during the COVID-19 pandemic, and these need to be balanced with product efficiency for usage recommendations.
Moreover, these unanticipated impacts could persist or heighten if human behaviors (hand washing, surface disinfection) and product purchasing patterns are altered in the long term.
With all biologically active compounds, there are both potential acute toxicity and chronic low-dose exposure issues.
If there are short-term, high concentration doses sent to a WWTP, for example, from cleaning of a hospital or building, functional processes such as activated sludge basins or anaerobic digesters could be negatively impacted by the slug of QACs entering the treatment system.
Because QACs are surfactants, an influx of the compounds could contribute to or exacerbate existing issues with foaming in WWTPs, which might temporarily disrupt or reduce treatment efficiency.
More likely, increasing QAC concentrations steadily over time would lead to changes in microbial communities that may harbor more antibiotic resistance both in treatment systems and in the environment, especially downstream of WWTPs.
Implications of elevated QAC levels in surface waters, sediments, and soils due to biosolids applications indicate a need for further testing of chronic toxicity for aquatic, benthic, and soil organisms to better evaluate potential impacts that may need to be addressed in the current unusual situation.
Overall, increased monitoring of QAC levels in WWTP effluents and biosolids is indicated, and assessment of levels in surface waters (especially in cases of (in)direct potable reuse) and soils receiving these effluents and biosolids, respectively, should be considered as well.
A better understanding of the ecologically relevant risks associated with low-level QAC exposure is required.
The processes that are known to facilitate degradation of QACs also indicate potential opportunities to improve treatment, limit environmental releases, and minimize environmental impacts.
Extended aeration (longer SRT)71 or aeration with pure oxygen39 or membrane systems could lead to better removal and degradation of the QACs.
Treatment wetlands, which facilitate extended biodegradation, photolysis, and removal via particle settling would likely lead to QAC removal.
Pyrolysis of biosolids to generate biochar would very likely lead to QAC removal from biosolids.
Various advanced oxidation processes, including O3/H2O2, UV/chlorine, and O3/HOCl, have been shown to degrade QACs and eliminate the toxicity to bacteria or algae.
The threat posed by the COVID-19 pandemic is real and apparent, and priority needs to be given to protecting the health and safety of people in their homes and when in public.
As part of the response to the pandemic, QAC usage will increase.
Environmental engineers and scientists must be aware of and monitor the fate of QACs so that other aspects of society including wastewater treatment are not compromised.
Ironically, fighting the virus could lead to increased infections from antibiotic resistant bacteria if elevated QAC exposure jolts the spread of antibiotic resistance.
Fortunately, we cannot claim to be surprised by increases in QACs in our engineered and environmental systems, but we must now pay due diligence to monitor their presence, note concentrations of concern, and develop and implement technologies to remediate their presence when needed.
The quaternary ammonium compounds (or quats) are a family of low-level disinfectants with most quats being derived from benzalkonium.
Quats are reacted to provide a varity of chain lengths and molecular strutures so that the mix of quats used in the disinfectant provide a wider range of efficacy than a single chain.
Quats are generally used to disinfect countertops, toilets and other high touch environmental surfaces and floors.
They are low cost, and used in many applications.
Quaternary ammonium compounds are cationic disinfectants.
This means the quats chain carries a positive (plus) charge on one end of the molecule; many soils and soaps/detergents carry an anionic or negative (minus) charge.
Quats can also bind with, or be absorbed by, materials and fibers including cotton (e.g., cleaning rags and mops).
Quats generally take 3-10 minutes to disinfect, and should be used with cleaning tools that are tested to be compatible.
Quaternary ammonium compounds (QACs or Quats) share the common quaternary ammonium cation.
The nature of the substituents R1, R2, R3 and R4 are varied in order to influence the properties of the ion.
In pure form the QACs will also contain an anion such as chloride, bromide or methosulfate.
When in solution, like in a sewage system, the substances will be dissociated and the anion the QACs were once associated with will be irrelevant.
In this work QAC cations of the types alkyltrimethyl ammonium (ATAC, Figure 1c), alkyl dimethyl benzyl (benzalkonium, BAC ) and dialkyl dimethyl ammonium (DDAC ) were investigated.
The QACs and the nature of the substituents R1, R2, R3 and R4 in each analyte are listed.
Alternative abbreviations for ATAC used in the literature are ATMA, ATMAC and TMAC.
Names referring to the origin of the alkyl chains are often used.
“Tallow” in ditallowdimethyl ammonium chloride (DTDMAC) refers to alkyl chain lengths mainly C18 and C16, “coco” to C12 and C14.
ATAC-C16 can also be called cetrimonium ion, ATAC-C18 DSDMAC (for distearyldimethyl ammonium chloride).
The name behentrimonium,from behenic (docosanoic) acid, refers to products containing ATAC-C20 and ATAC-C22.
Table 1: Abbreviations and nature of substituents R1–R4 in ammonium cations (Figure 1a) included in this work
Name R1 R2 R3 R4
ATAC-C12 n-C12 Methyl Methyl Methyl
ATAC-C14 n-C14 Methyl Methyl Methyl
ATAC-C16 n-C16 Methyl Methyl Methyl
ATAC-C18 n-C18 Methyl Methyl Methyl
ATAC-C20 n-C20 Methyl Methyl Methyl
ATAC-C22 n-C22 Methyl Methyl Methyl
BAC-C12 n-C12 Benzyl Methyl Methyl
BAC-C14 n-C14 Benzyl Methyl Methyl
BAC-C16 n-C16 Benzyl Methyl Methyl
BAC-C18 n-C18 Benzyl Methyl Methyl
DDAC-C10 n-C10 n-C10 Methyl Methyl
DDAC-C12 n-C12 n-C12 Methyl Methyl
DDAC-C14 n-C14 n-C14 Methyl Methyl
DDAC-C14:16 n-C14 n-C16 Methyl Methyl
DDAC-C16 n-C16 n-C16 Methyl Methyl
DDAC-C16:18 n-C16 n-C18 Methyl Methyl
DDAC-C18 n-C18 n-C18 Methyl Methyl
BAC can also be abbreviated ADMBA or ADBAC.
Commercial benzalkonium chloride is a mixture of alkylbenzyldimethylammonium chlorides of various even-numbered alkyl chain lengths.
EPA (2006) lists twelve different CAS numbers for BACs where specifications of alkyl chain lengths are given.
They tend to group into three categories:
Dominated by C12:
Dominated by C14:
Almost only C14:
DDAC can also be abbreviated DADMA or DMAC.
For DDACs with two identical chains the length is indicated only once (DDAC-C10), if the chain lengths are different they are both indicated (DDAC-C14:16).
DDMAC refers to DDAC-C10.
The abbreviation DDAC (DD for DiDecyl) can sometimes refer to DDAC-C10 only (DD for Dialkyl Dimethyl).
The compound properties vary with alkyl chain length.
Water solubility decreases, and adsorptivity to surfaces increases, with increasing chain length.
Some general properties of DDACs are listed in Table 2.
Table 2: Solubility and properties DDACs of different chain length
Chain length Solubility Properties
2 C8 chains Very soluble in water Mild germicide
2 C10 chains Soluble in water Strong germicide
2 C12 chains Poor solubility in water Weak germicide
2 C14 chains Low solubility in water Antistatic
2 C16-18 chains Practically insoluble in water Softener and antistatic
QACs are widely used as ingredients in industrial applications and find widespread use in household products, including fabric softeners, detergents, disinfectants, preservatives, and a range of personal care products.
The major cationic surfactant used in fabric softeners worldwide DTDMAC (ATAC-C16, C18) is, due to its poor biodegradation kinetics, beeing replaced in Europe by the esterquat DEEDMAC (diethyl esterdimethyl ammonium chloride).
Behentrimonium chloride or methosulphate, containing ATAC-C20 and ATAC-C22 are used increasingly in personal care products, especially in hair care products.
The data on Log Kow and BCF is limited (Table 3) and lacking for ATAC-C20 and ATAC-C22.
However the available data suggests that bioaccumulation for ATACs might increase with increasing chain length.
QACs are cationic surfactants that strongly sorb onto suspended particulates and sludge, and therefore biodegradation in sediment and sludge is an important process for determination of their fate in the environment
Under aerobic conditions, the biodegradability of QACs generally decreases with the number of non-methyl alkyl groups
i.e. DDAC is less biodegradable than ATAC.
Moreover, substitution of a methyl group with a benzyl group can decrease biodegradability further i.e.
BAC is likely less biodegradable than ATAC.
In contrast, under anaerobic conditions, no or very poor primary biodegradation of QACs has been reported and no evidence of ultimate biodegradation.
Thus, except for ultrahydrophobic DTDMAC (DDAC-C16, DDAC-C18),aerobic biodegradation is an important process within WWTPs for QACs,such as DDAC-C10, ATAC-C12 – C16, and BAC-C12 – C18.
However, the very strong sorption properties and resistance to desorption of even the most soluble QACs gives an explanation to that these compounds are found in sediments downstream WWTPs in appreciable quantities and imply that QACs can be relatively persistent in receiving waters.
Moreover, QACs in sludge amended to soil are, also due to the adsorptive properties, not expected to contaminate surface and ground waters.
QACs have disinfectant properties and, thus, high concentrations may inhibit the microbial processes in WWTPs.
Available toxicity data suggest that the substitution of a methyl group with a benzyl group increases the toxicity but that there is no difference in toxicity between homologues of different chain length.
This could be attributed to a lower bioavailability of the longest chain homologues due to their decreasing solubility.
For instance in WWTPs the toxicity to methanogenesis has been reported to decrease with increasing alkyl-chain length.