An increasing awareness of the role of contaminated environmental surfaces in transmission of healthcare-associated pathogens has highlighted the need for effective methods for cleaning and disinfecting inanimate surfaces.Reference Otter, Yezli and French 1 – Reference Kanamori, Rutala and Weber 6 Although excellent reviews of disinfectants used in health care are available,Reference Rutala and Weber 7 – Reference Rutala and Weber 9 in the last 20 years, comprehensive reviews of individual disinfectant agents have been provided for only sodium hypochlorite and quaternary ammonium compounds.Reference Rutala and Weber 10 , Reference Gerba 11 Because alcohols and alcohol-containing disinfectant products have been used for many years, the purpose of this article is to review the use of alcohols as disinfectants in healthcare settings.
DEFINITIONS
The nomenclature used to describe alcohols can be somewhat confusing. Variations in the names given to the 3 types of alcohol used most commonly in healthcare include (1) ethyl alcohol or ethanol; (2) isopropyl alcohol, isopropanol, 2-propanol, or propan-2-ol; and (3) n-propanol, 1-propanol, or propan-1-ol. In the United States, “rubbing alcohol” usually contains 70% isopropyl alcohol. N-propanol is used in health care more commonly in Europe than in the United States. Concentrations of alcohol solutions can be expressed as percentage by volume (% mL/mL or v/v), or percentage by weight (% g/g or w/w). For example, 70% ethyl alcohol (v/v) at 20°C represents 62.6% (w/w).Reference Ali, Dolan, Fendler and Larson 12 In healthcare guidelines, alcohol concentrations are most frequently expressed as percentage by volume.Reference Sehulster and Chinn 13 , Reference Rutala and Weber 14
HISTORY
Studies published in the late 1800s on the use of alcohols as disinfectants or antiseptics have been summarized by Price.Reference Price 15 One study in 1897 tested alcohol concentrations of 25% to 99% on silk thread and found 50% to be the most germicidal. Studies by HarringtonReference Harrington and Walker 16 exposed moist and dried silk threads contaminated with a variety of pathogens to 15% to 99% alcohol and found that 60%–70% was the most active against gram-positive pathogens (ie, Staphylococcus aureus). PriceReference Price 15 conducted in vitro tests using 3 pathogens exposed to 30%, 60%, and 70% alcohol (w/w) and found that 70% was the most effective after a 1-minute exposure, especially against S. aureus.
Subsequent in vitro suspension tests by PriceReference Price 17 revealed that 60%–90% ethyl alcohol concentrations were the most effective in 1 minute against three healthcare pathogens. In vivo studies by PriceReference Price 17 showed that 40% and 50% were significantly less effective in reducing colony counts on the hands and arms of medical personnel than concentrations of 70% or more. Based on in vitro studies that exposed several pathogens to ethyl alcohol (20%–100% v/v), MortonReference Morton 18 found that concentrations of ≥50% were effective with short contact times. It is likely that the current guidelines recommending the use of 60%–90% alcohol for antisepsis and disinfection are based on these early studies.
A review by Ali et alReference Ali, Dolan, Fendler and Larson 12 of the use of alcohols as an antiseptic and disinfectant cited several early studies as well as mentioning that 70% isopropyl alcohol has been used as a surface spray in some food-handling situations. The review states that “Alcohols at concentrations of 70% are a reasonable choice for intermediate-level disinfection for noncritical and certain types of semicritical instruments that can be submerged for 10 minutes. Because alcohols are poor cleaners and evaporate rapidly, they are not appropriate for use on environmental surfaces.” The review does mention a number of older studies wherein 50% or 70% ethyl alcohol was used to disinfect small medical instruments such as thermometers. Notably, none of the aforementioned publications reported studies of the efficacy of various concentrations of ethyl alcohol or isopropyl alcohol when applied to large environmental surfaces in healthcare facilities.
SELECTED CHEMICAL PROPERTIES OF ALCOHOLS
Ethyl alcohol, isopropyl alcohol, and n-propanol all have unlimited solubility in water.Reference Ali, Dolan, Fendler and Larson 12 Ethyl alcohol has a mild odor, whereas isopropyl alcohol has a stronger chemical odor. The rate at which alcohols evaporate is an issue because rapid evaporation of alcohol solutions applied to surfaces limits the time that they can exert their disinfectant effect (contact time).Reference Rutala and Weber 7 Higher concentrations of alcohol evaporate more quickly than lower concentrations.Reference O’Hare and Spedding 19 Evaporation rates are similar for ethyl alcohol and isopropyl alcohol. The evaporation rate (and related contact time) of alcohol-based disinfectants are also affected by product formulation. For example, contact times can be prolonged by the addition of surfactants.Reference Rutala and Weber 7
The ability of an alcohol to serve as a cleaner/disinfectant (in contrast to a disinfectant only) is poor compared with several other disinfectant agents used in health care.Reference Rutala and Weber 9 According to the EPA product performance test guidelines, for a disinfectant to be considered a 1-step cleaner/disinfectant, the product must yield effective log reductions when the bacterial inoculum is suspended in 5% blood serum. 20 All alcohols used in health care are flammable. The flammability of alcohol is expressed as a flash point, that is, the minimum temperature at which a flammable substance can be ignited by an open flame. Higher concentrations have lower flash points (undesirable) than lower alcohol concentrations. For example, the flash points of 70% ethyl and 70% isopropyl alcohol are 20.5°C and 21.0°C, respectively,Reference Rotter 21 while the flash point of 30% ethyl alcohol is 29°C.
Mode of Action
The major mode of action of alcohols against microorganisms is most likely due to denaturation of proteins.Reference Rutala and Weber 14 This mode of action is supported by the facts that denaturation of proteins requires water and that absolute alcohol is less bactericidal than solutions containing a mixture of alcohol and water.Reference Rutala and Weber 14 , Reference Price 17 Recent studies utilizing Escherichia coli suggest that ethyl alcohol causes inhibition and uncoupling of messenger ribonucleic acid (RNA) and protein synthesis via direct effects on ribosomes and RNA polymerase.Reference Haft, Keating and Schwaegler 22 Other potential modes of action include interference with cellular metabolism, disruptions of cytoplasmic integrity, and cell lysis.Reference Ali, Dolan, Fendler and Larson 12
Antimicrobial Activity
Ethyl alcohol, isopropyl alcohol, and n-propanol all have rapid bactericidal activity against vegetative bacteria, including mycobacteria.Reference Ali, Dolan, Fendler and Larson 12 , Reference Price 17 , Reference McDonnell and Russell 23 Early studies found that the microbicidal activity of ethyl alcohol decreased substantially at concentrations <50%.Reference Price 17 , Reference Morton 18 It is widely agreed that alcohols are not sporicidal. However, the activity of ethyl alcohol against spores can be enhanced by combination with alkali, mineral acids, hydrogen peroxide, and some surfactants.Reference Ali, Dolan, Fendler and Larson 12 , Reference Nerandzic, Sunkesula, TS, Setlow and Donskey 24 Alcohols are also fungicidal and virucidal, particularly for lipophilic viruses such as herpes virus, influenza virus, human immunodeficiency virus-1, hepatitis B and C viruses, and vaccinia.Reference Rutala and Weber 14 , Reference Doerrbecker, Friesland and Ciesek 25 They also have activity against some hydrophilic viruses such as adenovirus, rhinovirus, enterovirus and rotaviruses, but have poor activity against hepatitis A virus and poliovirus. Kurtz et alReference Kurtz, Lee and Parsons 26 studied the efficacy of 20%–90% ethyl alcohol against rotavirus, astrovirus, and Echo virus in suspension tests and found that concentrations of 30% or greater eliminated bovine rotavirus. None of the alcohols at a 50% concentration had any effect on astrovirus or echovirus. The 90% ethyl alcohol solution was more effective against the latter 2 viruses. Rabenau et alReference Rabenau, Steinmann, Rapp, Schwebke and Eggers 27 reported that concentrations of ≥55% (v/v) ethyl alcohol and ≥30% (v/v) n-propanol reduced adenovirus type 5 titers by at least 4 log10. Isopropyl alcohol had poor activity against adenovirus. Ethyl alcohol and n-propanol (both at 10%–50%) as well as isopropyl alcohol (20%–60%) had no useful activity against parvoviruses when tested using a carrier test method.Reference Rabenau, Steinmann, Rapp, Schwebke and Eggers 27
Magulski et alReference Magulski, Paulmann and Bischoff 28 reported that 50% ethyl alcohol (v/v) eliminated murine norovirus from stainless steel carrier discs, while isopropyl alcohol was less effective at even 60%. Another study that included carrier tests of 70% ethyl alcohol found that it had poor activity against feline calicivirus but was effective against murine norovirus, which is a more suitable surrogate for human norovirus.Reference Rabenau, Steinmann, Rapp, Schwebke and Eggers 27 , Reference Zonta, Mauroy, Farnir and Thiry 29 , Reference Belliot, Lavaux, Souihel, Agnello and Pothier 30 Belliot et alReference Belliot, Lavaux, Souihel, Agnello and Pothier 30 found that 60% ethyl alcohol and isopropyl alcohol reduced murine norovirus by 4.0 and 3.5 log10, respectively.
In vitro quantitative carrier tests with several variants of Ebola virus revealed that 70% ethyl alcohol inactivated most Ebola variants after a 1-minute contact time; only the Makona variant required a 2.5-minute contact time.Reference Cook, Cutts and Nikiforuk 31 Quantitative carrier tests have also revealed that 70% ethyl alcohol was effective against 2 coronvirus surrogates (mouse hepatitis virus and transmissible gastroenteritis virus) with a contact time of 1 minute,Reference Hulkower, Casanova, Rutala, Weber and Sobsey 32 and 70% isopropyl alcohol was effective against SARS-CoV in 30 seconds.Reference Rabenau, Cinatl and Morgenstern 33 In general, ethyl alcohol has greater activity against hydrophilic (nonenveloped) viruses than isopropyl alcohol.Reference Ali, Dolan, Fendler and Larson 12 , Reference Rabenau, Steinmann, Rapp, Schwebke and Eggers 27
ADVANTAGES AND DISADVANTAGES OF ALCOHOLS AS LOW-LEVEL DISINFECTANTS
Disinfectant properties and uses of ethyl alcohol or isopropyl alcohol (60%–90%) (v/v), when used as aqueous solutions without other ingredients, have been addressed in multiple guidelines and recent review articles.Reference Rutala and Weber 7 , Reference Rutala and Weber 9 , Reference Sehulster and Chinn 13 , Reference Rutala and Weber 14 , Reference Rutala 34 Advantages include the fact that they are easy to use, are nonstaining, and have acceptable odor, rapid onset of action, and a broad spectrum of antimicrobial activity. Limitations include their slow action against nonenveloped viruses, lack of sporicidal activity, reduced activity in the presence of organic matter, limited detergent properties, flammability, EPA toxicity ratings of category I, II, or III with a single exception, and adverse effects on some types of medical equipment.
ALCOHOL-CONTAINING DISINFECTANT FORMULATIONS
Alcohol-containing disinfectant formulations include products that contain only aqueous solutions of isopropyl or ethyl alcohol (usually 60%–90%), which do not require EPA registration, and formulations registered by the EPA.
The EPA lists 14 primary registrations (disinfectant formulations) that contain either ethyl alcohol (N=8) or isopropyl alcohol (N=6) as the only active agent in addition to small amounts of other substances that act as denaturants (eg, methanol) or other ingredients that may affect their performance (Table 1). Five of the 8 formulations containing ethyl alcohol, and all 6 of those containing isopropyl alcohol are registered for use in healthcare settings. One formulation contains only 29.4% ethyl alcohol, while the others contain 59.2% to 90% ethyl alcohol or 62.7% to 70% isopropyl alcohol (Table 1).
Table 1 Environmental Protection Agency (EPA)-registered primary registration disinfectant formulations containing either ethyl alcohol or isopropyl alcohol or both.

NOTE. ETOH, ethyl alcohol; IPA, isopropyl alcohol.
In total, 56 EPA primary registrations for formulations contain ethyl alcohol, or isopropyl alcohol, or both plus other active ingredients such as quaternary ammonium compounds, and less commonly phenolic compounds (Table 1). A list of alcohol-containing surface disinfectants can be obtained by entering the chemical name of the active agent (eg, ethanol) into a search form on an EPA website. 35
Clinical Uses
Alcohol-containing formulations are used for disinfecting a wide variety of items and surfaces in healthcare settings.
Small noncritical items
Alcohol prep pads or towelettes containing isopropyl alcohol (often 70%) or ethyl alcohol are often marketed for use as skin antiseptics or wound care, and as such, they fall under control of the Food and Drug Administration (FDA), and do not require EPA registration. However, alcohol prep pads marketed for skin antisepsis are not uncommonly used for disinfection of small noncritical items such as stethoscopes, thermometers, hospital pagers, scissors, rubber stoppers of multidose medication vials or blood culture bottles, injection ports of bags of intravenous solutions or medications, or vaccine vials.Reference Rutala and Weber 14 Some healthcare personnel have used alcohol to disinfect mobile phones. Alcohol prep pads are inexpensive and easy to use. Some are labeled as sterile, while others are not. On several occasions in the past 10 years, the FDA has issued recalls of alcohol prep pads that were contaminated with various pathogens.Reference Dolan, Dowell and Littlehorn 36 , 37
Vascular access devices
It has been recommended that catheter hubs, needleless connectors, and injection ports be disinfected by vigorous application (with mechanical friction) of either an alcoholic chlorhexidine solution, 70% alcohol, or povidone iodine to reduce the risk of central line-associated bloodstream infections (CLABSIs).Reference Marschall, Mermel and Fakih 38 Alcohol prep pads are widely used for these purposes. Port protectors containing 63%–70% isopropyl alcohol have been employed to reduce CLABSI.Reference Sweet, Cumpston, Briggs, Craig and Hamadani 39 – Reference Martino, Thompson and Mitchell 41
Pharmacies and other controlled areas
Sterile 70% isopropyl alcohol and ethyl alcohol formulations are used in compounding pharmacy facilities (including those located in acute-care hospitals) to disinfect work surfaces as well as smaller items.Reference Kastango, Douglass and Patel 42 Furthermore, 3 isopropyl alcohol and 3 ethyl alcohol formulations are EPA-registered specifically for use only in pharmacies and other controlled areas.
Endoscopes
Guidelines for reprocessing flexible gastrointestinal endoscopes recommend flushing endoscopes with 70%–90% ethyl alcohol or isopropyl alcohol after high-level disinfection.Reference Petersen, Cohen and Hambrick 43 Disinfection of other types of medical equipment such as tonometer tips, reuseable transducer heads, or surgical instruments using only isopropyl alcohol or ethyl alcohol is not recommended.Reference Rutala and Weber 14
Environmental surfaces
The 2003 Centers for Disease Control and Prevention (CDC) environmental guidelines and 2008 disinfection and sterilization guidelines have recommended against the use of alcohol alone for disinfection of large surface areas because of their rapid evaporation rates (drying times) and associated short contact times.Reference Sehulster and Chinn 13 , Reference Rutala and Weber 14 Only 3 formulations containing isopropyl alcohol as the only active agent plus other ingredients are registered for disinfection of environmental surfaces, one of which is listed as a 1-step product. Another 2 formulations containing ethyl alcohol as the only active agent plus other ingredients are both registered as 1-step disinfectants for use on environmental surfaces. Of these 2 formulations, 1 is a newly developed product registered for use in hospitals and other healthcare settings that is unique because it contains only 29.4% ethyl alcohol, has a 30-second contact time against a variety of pathogens, has an EPA toxicity rating of category IV, and an EPA Designed for Environment (DfE) label. Despite having only 29.4% ethyl alcohol, the new formulation was significantly more effective than 70% ethyl alcohol in quantitative carrier tests. It achieved log reductions of the bacteriophage MS2 on steel disks similar to reductions achieved with 10% bleach, and it rapidly reduced vegetative bacterial pathogens on hard and soft surfaces in a healthcare setting without causing staining of soft surfaces.Reference Alhmidi, Koganti and Cadnum 44 , Reference Koganti, Alhmidi and Tomas 45
Of the 56 EPA-registered formulations containing ethyl and/or isopropyl alcohol plus other active agents such as quaternary ammonium or phenolic compounds (Table 1), 49 are intended for use in hospitals and other healthcare settings. Formulations in this group are widely used in healthcare for disinfection of environmental surfaces during daily and postdischarge (terminal) disinfection of patient rooms and for disinfection of surfaces in nursing stations, operating rooms, and rooms used for invasive diagnostic procedures. Formulations are available as convenient ready-to-use wipes and as sprays. Product labels for a majority of formulations state that surfaces should be precleaned prior to application of the disinfectant, while a few products are listed as one-step disinfectants. Hospital disinfectants used for disinfection of environmental surfaces are also appropriate for disinfection of noncritical items in clinics, dental settings, and other medical-related facilities.Reference Rutala and Weber 14 , Reference Kohn, Collins and Cleveland 46
Contact times for products containing alcohol plus other active agents vary considerably based on their content. Formulations containing ethyl alcohol frequently have 10-minute contact times (range, 1–10 minutes), while those containing isopropyl alcohol often have contact times of 1–3 minutes (range, 1–10 minutes). Formulations containing both ethyl and isopropyl alcohol plus other active agents have contact times ranging from 1 to 3 minutes.
SAFETY
All EPA-registered disinfectants containing either ethyl alcohol or isopropyl alcohol (or both), with one exception, have EPA toxicity ratings of categories I, II, or III. Both isopropyl alcohol and ethyl alcohol can cause skin and eye irritation. When used in the form of solutions (instead of prep pads or towelettes), some isopropyl alcohol products recommend the use of protective gloves and eye and face protection. Isopropyl alcohol is toxic if ingested, which is usually accidental and is more common in children.Reference Slaughter, Mason, Beasley, Vale and Schep 47 However, Slaughter et alReference Slaughter, Mason, Beasley, Vale and Schep 47 concluded that dermal absorption of isopropyl alcohol is relatively slow and that measurable serum concentrations and systemic toxicity generally require large or prolonged exposures or exposures to nonintact skin.
Exposure of healthcare personnel to ethyl alcohol may occur using alcohol-containing disinfectants or by the use of alcohol-based hand rubs (antiseptic products that more commonly contain ethyl alcohol than isopropyl alcohol).Reference Quinot, Dumas and Henneberger 48 , Reference Maier, Ovesen and Allen 49 Recent assessments of the exposure of healthcare personnel to alcohol-based hand rubs concluded that such products are safe when used as intended.Reference Maier, Ovesen and Allen 49 , Reference Pires, Bellissimo-Rodrigues and Pittet 50 Despite the frequent exposure of healthcare personnel to alcohol-based disinfectants,Reference Quinot, Dumas and Henneberger 48 these products appear to pose little risk to healthcare personnel if used as directed. For example, a review of data from 69,075 full-time work years by healthcare personnel revealed that reported injuries or illnesses due to germicides, including alcohol, were very uncommon.Reference Weber, Consoli and Rutala 51 Because of their flammability, alcohols must be stored in cool, well-ventilated areas away from ignition sources.Reference Rutala and Weber 14
In conclusion, alcohols have been used as low-level disinfectants in healthcare settings for many years. Alcohol formulations that do not contain other ingredients are used for disinfection of small noncritical items, vascular access devices, and surfaces in pharmacies and for final steps in the disinfection of endoscopes. A formulation with several unique characteristics has recently been added to the armamentarium of disinfectants containing either ethyl alcohol or isopropyl alcohol (or both) combined with other ingredients that enhance their performance. These alcohol-based formulations are widely used for disinfection of environmental surfaces in healthcare settings.
Acknowledgments
The author would like to acknowledge Scientific and Regulatory Consultants, Inc, for providing lists of EPA-registered disinfectants containing ethyl alcohol and/or isopropyl alcohol as active agents.
Fin Financial support: No financial support was provided relevant to this article.
Potential conflicts of interest: J.M.B. is a consultant for 3M Company, Diversey Care, Gojo Industries, PDI Healthhcare, and Sodexo. He has received research funding and travel support from Diversey Care and Gojo Industries.