Preserving personal care products from microbial degradation is quite challenging. Most topical cosmetics and dermatological products in the form of creams, lotions, gels, shampoos, body-washes and face-washes contain significant amount of water. This provides a very hospitable environment for the microbial growth. In addition to water, other cosmetic ingredients can also be a good source of nutrients to microbes. Another pertinent point to be reckoned here is that the shelf-life of the personal care products and the period after opening the container by the consumer is quite long compared to pharmaceutical products or food products. Unlike pharmaceutical products, cosmetics products are neither sterilized nor packed in hermetic conditions. Thus, the requirement for preservation of the personal care products is, indeed, quite challenging. This is further compounded by the limited choice of antimicrobials since the available approved antimicrobials are very few and those which have good antimicrobial activity are quite toxic. Consumers want products meant for topical applications to be free from toxic antimicrobials that are used as preservatives. Very effective antimicrobials that are used currently, are implicated in serious toxicity issues to human as well as to environment. For example, parabens are implicated in disrupting endocrine system, ultimately linked to breast cancer [(Pharmacology & Toxicology (Vol. 86(3), pp 110-13, March 2000, Toxicology and Applied Pharmacology (Vol. 153(1), pp. 12-19 (November 1998), Journal of Veterinary Medical Science (Vol. 64(3), pp. 227-35 (March 2002, Journal of Applied Toxicology, 24 (3): 167-176, (2004)]. Formaldehyde is classified as Category 3 CMR (carcinogenic, mutagenic and reproductive toxic) and hence all formaldehyde releasers are under the cloud. This class includes the work-horse preservatives such as DMDM hydantoin, diazolidinyl urea, imidazolidinyl urea and Quaternary 15.
Another class of very effective antimicrobials is ‘isothiazolinones’. Methyl and Chloromethyl isothiazolinones have been used in personal care but they are reported to be neurotoxic and skin sensitizers (Journal of Neuroscience 22 (17): 7408-7416. The Lancet, Volume 333, Issue 8633, Pages 314-316 (1989). Chloromethyl isothiazolinone (generally abbreviated as CIT) is far more toxic and most of the leading personal care products manufacturers have stopped using it.
Halogenated antimicrobials have their own share of toxicity issues. For example, Triclosan, once a popular antimicrobial for hand sanitizers, is being phased out due to its toxicity. It has been implicated in eco-toxicity issues (algae, dolphins). It is reported to be an endocrine disruptor (thyroid function) and is reported to impair cardiac and skeletal muscles. There seems to be special concern for children who are at higher risk of allergies and the immune systems (Toxicological Sciences, 2009, 107 (1): 56-64, Reproductive Toxicology, April 2009, 27(2): 177-185). Companies such as Johnson and Johnson, P & G and Reckitt Benckiser have either removed it or announced the plan of complete phasing it out from their products in a given short time frame. Triclosan's ecotoxicity is such a big concern that state of Minnesota in the USA has completely banned its use. Iodopropynyl butyl carbamate, another halogenated antimicrobial, is a contact allergen (American Journal of contact dermatitis 13(2), 77-79 (2002). The presence of iodine in the molecular structure gets it implicated in Goiter and malfunctioning thyroid gland. It is not allowed in Japan and in European Union (EU) and generally, elsewhere, it is allowed only up to 0.02% in leave-on products. Similarly, EU permits usage of methyl dibromo glutaronitrile only up to 0.1% and that too in only rinse-off products. Another brominated molecule is Bronopol, very widely used once upon a time, is banned today in countries like Canada for its application in cosmetics. It is involved in allergic reactions as well as generation of N-nitroso amines that are known to be carcinogenic. The quaternary ammonium compounds (examples are cetyl pyridinium chloride, benzethonium chloride, benzalkonium chloride) exhibit good antimicrobial activity but their utility in personal care industry is limited due to specific incompatibilities with other cosmetic ingredients, particularly with the ingredients of strong anionic nature.
To avoid the above mentioned toxic antimicrobials, the industry did come up with alternatives that are largely based on organic acids such as sorbic acid, benzoic acid, dehydroacetic acid, and alcohols such as phenoxyethanol, benzyl alcohol and other glycols or glycol ethers that are not listed as preservatives by Cosmetics Directive Annex VI (propylene glycol, 2-ethyl hexyl glycerin, caprylyl glycol, 1,2-hexane diol).
The survey of such recent products shows that the most common ingredient in these preservative blends is phenoxyethanol as shown in Table I below.
TABLE INameCompany NameINCI NameMcKinley CG4McKinley ResourcesPhenoxyethanol, Caprylyl GlycolIncorporatedeuxyl ® K 940Schülke Inc.Phenoxyethanol, Benzyl Alcohol,Ethylhexylglycerineuxyl ® PE 9010Schülke Inc.Phenoxyethanol, EthylhexylglycerinCaribNat KCaribbean NaturalPhenoxyethanol, Potassium SorbateProducts Inc.Sharon BiomixSharon LabsPhenoxyethanol, Citrus Aurantium AmaraClear Liquid(Bitter Orange) Fruit Extract, CitrusReticulata (Tangerine) Fruit Extract,Citrus Aurantium Sinensis Peel ExtractSharomix HPDSharon LabsPhenoxyethanol, 1,2-Hexanediol,Dehydroacetic AcidSaliguard ® BDPSalicylates andPhenoxyethanol, Benzoic Acid,ChemicalsDehydroacetic AcidVerstatil ® BPDr. StraetmansPhenoxyethanol, Benzoic AcidSolbrol ® PEHLanxess DistributionPhenoxyethanol, EthylhexylglycerinSymOcide ® PTSymrisePhenoxyethanol, TropoloneSharomix EG14Sharon LabsPhenoxyethanol, EthylhexylglycerinVerstatil ® MPCDr. StraetmansPhenoxyethanol, Methylpropanediol,Caprylyl GlycolPentaglycan PFDSM NutritionalPhenoxyethanol, Glycosaminoglycans,Products, LLCBenzoic Acid, Dehydroacetic Acid,Sodium HyaluronateNipaguard ® SCVClariant - PersonalPhenoxyethanol, Sorbitan Caprylate,CarePhenoxyethanol, Benzyl Alcohol, BenzoicAcidSaliguard ® PCGSalicylates andPhenoxyethanol, Caprylyl Glycol,ChemicalsPhenoxyethanol, Propylene GlycolSaliguard ® PGSalicylates andPhenoxyethanol, Caprylyl GlycolChemicalsSaliguard ® UCPSalicylates andPhenoxyethanol, Undecylenic acid,ChemicalsCaprylyl GlycolRokonsal ™ BSPAshland Inc.Phenoxyethanol, Propylene Glycol,Benzoic Acid, Sorbic AcidOptiphen ™ 200Ashland Inc.Phenoxyethanol, Caprylyl GlycolOptiphen ™ NDAshland Inc.Phenoxyethanol, Benzoic Acid,Dehydroacetic AcidOptiphen ™ PlusAshland Inc.Phenoxyethanol, Caprylyl Glycol, SorbicAcidOptiphen ™ 300Ashland Inc.Phenoxyethanol, Caprylyl GlycolSharomix 710Sharon LabsPhenoxyethanol, Benzoic Acid, SorbicAcid, Dehydroacetic Acid CaprylylGlycol, PhenoxyethanolSharomix 704Sharon LabsPhenoxyethanol, Benzoic Acid, SorbicAcid, Dehydroacetic AcidSharomix 702Sharon LabsPhenoxyethanol, Dehydroacetic Acid,Benzoic AcidOptiphen ™ BSPAshland Inc.Phenoxyethanol, Benzoic Acid, SorbicAcidNipaguard ™ POBClariant - PersonalPhenoxyethanol, Benzoic Acid,CarePiroctone OlamineNipaguard ™ PO 5Clariant - PersonalPhenoxyethanol, Piroctone OlamineCareUnigard OA-94Givaudan ActivePhenoxyethanol, Benzoic Acid,BeautyDehydroacetic AcidLincocide ™Lincoln FinePhenoxyethanol, Propylene Glycol,PHOE - BSIngredientsBenzoic Acid, Sorbic AcidSymOcide ® PSSymrisePhenoxyethanol, Decylene Glycol, 1,2-HexanediolVerstatil ® PCDr. StraetmansPhenoxyethanol, Caprylyl GlycolRokonsal ™ NDAshland Inc.Phenoxyethanol, Benzoic Acid,Dehydroacetic AcidSymOcide ® PHSymrisePhenoxyethanol, Caprylyl GlycolBlueguard C5Blue SunPhenoxyethanol, Caprylyl Glycol,InternationalPotassium Sorbate, Hexylene GlycolLexgard ® HPOINOLEXPhenoxyethanol, Caprylyl Glycol,Hexylene GlycolPhenostat ™INOLEXPhenoxyethanol, Caprylhydroxamic Acid,MethylpropanediolSharoSENSE ™Sharon LabsPhenoxyethanol, Thymol, Linalool250
These compositions listed in Table I avoid toxic antimicrobials like halogenated, phenolic molecules or isothiazolinones and rely heavily on phenoxyethanol wherein phenoxyethanol is combined with 2-ethyl hexyl glycerin, caprylyl glycol, benzoic acid and dehydroacetic acid, and fruit extracts.
In addition to above commercial products some recent patent applications also disclose preservative combinations wherein Phenoxyethanol is combined with molecules like undecylenoyl monoethanolamide, undecylenoyl glycine or capryloyl glycine (US20140309302 A1 and US20130101530 A1).
2-Phenoxyethanol is indeed a work-horse antimicrobial for personal care industry. In the recent past some doubts have been cast and the regulatory committee from EU did clear it after a thorough review. Despite the clearance from the Scientific Community of Consumer Safety of EU the concern remains because of inadequate data on toxicity. Maximum concentration that has been generally allowed is up to 1.0% (Cosmetics Directive Annex VI), however, for last few years France has been raising their concern for its use level for children's products, particularly nappy area products. In South Korea it is not allowed in products like wet wipes particularly meant for babies.
In September 2012, the Commission received a risk assessment submitted by the French Agency ANSM (Agence nationale de sécurité des médicaments et des produits de santé) which rose concerns about the use of Phenoxyethanol as preservatives in cosmetic products.
The ANSM report (Evaluation du risque lié à l'utilisation du phénoxyéthanol dans les produits cosmétiques) concludes that the maximum authorized concentration (currently of 1%) of Phenoxyethanol for use as a preservative should be lowered to 0.4% in cosmetic products for children who are less than three years old.
On October 6th 2016 Scientific Community of Consumer Safety (SCCS) finally declared it to be safe up to 1.0% level for cosmetics. However, the concern remains with the manufacturers of personal care products because of Phenoxyethanol's belonging to the dangerous glycol ether family (methyl cellosolve or ethyl cellosolve, phenoxy ethanol is phenyl cellosolve (scheme 1). The scheme 1 as depicted below explains the structural similarity between glycol ethers (methyl, ethyl cellosolves) and phenoxy ethanol.

Phenoxyethanol is also reported to depress the central nervous system (Schmuck G, Steffens W, Bomhard E (July 2000). “2-Phenoxyethanol: a neurotoxicant?” Archives of Toxicology. 74 (4-5): 281-7) and it may cause vomiting and diarrhea, which can lead to dehydration in infants. US FDA warned about Mommy's Bliss nipple cream where phenoxyethanol is used as preservative along with chlorphenesin.
In view of phenoxyethanol's structural similarity to glycol ether family (Scheme 1) and its reported neurotoxicity, manufacturers of personal care products and particularly, the baby care products, are wary of using it as preservative and are looking for safe alternatives.
For example, Colgate's baby care brand Tom's of Maine, avoids use of phenoxyethanol in moisturizing lotion for babies.
There has been an attempt in the commercial world to avoid all toxic antimicrobials including phenoxyethanol. Examples of such products are Sharon Mix 705, Sharon Mix 705plus, Sharon Mix 706 and Sharon Mix 706plus from Sharon Laboratories, Israel. These products are based on benzyl alcohol and organic acids like benzoic acid, sorbic acid and dehydroacetic acid.
Though these commercial compositions from Sharon Labs avoid use of phenoxyethanol, the choice of benzyl alcohol is not the most ideal one. Benzyl alcohol has comparable antimicrobial properties to phenoxyethanol. In fact, benzyl alcohol has slightly better antimicrobial activity than phenoxy ethanol (Minimum growth inhibition concentrations). The simple reason for benzyl alcohol's lesser usage than phenoxyethanol is benzyl alcohol's strong benzaldehyde like odor. This strong aromatic odor puts limitation on the usage since it is difficult to mask the characteristic odor of benzyl alcohol. Also, serious allergic contact dermatitis reactions have been reported with products containing benzyl alcohol (E. J. Curry and E. M. Warshaw, Dermatitis, 2005; 16 (4):203-208). Delayed contact dermatitis reactions as well as immediate, urticarial and systemic reactions have been reported to occur with its use in these various formulations (Sharon Jacob and Giuseppe Militello, Allergen Focus, Skin and Aging, 32-35, May 2005). Benzyl alcohol is a rare allergen but the fact is that it is an allergen.
So in view of the limitations, restrictions and concerns cited above for the majority of antimicrobials, it is important to develop a safe, broad spectrum, organoleptically acceptable antimicrobial composition, avoiding all the toxic and controversial substances for personal care and for home care industry.
USPTO Backgrounds
USPTO Backgrounds