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International Journal

for Applied Science


■ Personal Care ■ Detergents ■ Specialities

Reprint
W. Beilfuss, M. Leschke, K. Weber
from
11-2005 A New Concept to Boost the Preservative
Efficacy of Phenoxyethanol
CO S M ET I C S
P R E S E R VAT I V E S

W. Beilfuss, M. Leschke, K. Weber*

A New Concept to Boost the Preservative


Efficacy of Phenoxyethanol

Keywords: cosmetic preservative, phenoxyethanol, ethylhexylglycerin

mental to the health of the user or to the tion, without causing harm to humans. In
Abstract aesthetic appearance of the product. Thus, addition, they should be globally ap-
it is necessary to protect the product from proved, cost effective and free of any pub-
such microbial contamination. To this end, lic discussion. Therefore, new concepts in
new cosmetic preservative

A
the cosmetic market demands multipur- preservation are required.
for leave-on products based pose cosmetic preservatives which are
on a combination of the ac- globally approved, cost effective and do
tive ingredient phenoxyethanol not contain actives under any public dis-  A sophisticated combination
and the skin care additive and de- cussion. However, the number of actives of phenoxyethanol and
odorant active ethylhexylglycerin
which can be used as preservatives for ethylhexylglycerin
cosmetic applications is limited. Approxi-
is presented. Ethylhexylglycerin mately 15 of the 57 preservative chemis- To address the complex requirements of
boosts the antimicrobial activity of tries listed in Annex VI of the European the cosmetic market, the new cosmetic
phenoxyethanol. Properties, an- Cosmetic Directive (76/768 EEC) are ac- preservative Euxyl® PE 9010 was devel-
timicrobial activity and a possible tively used. Only these few have the physi- oped primarily for the use in leave-on
mechanism of action are dis- cal-chemical properties, as well as the ef- products. This patented liquid concen-
ficacy and the safety assessment, which trate is formulated from phenoxyethanol,
cussed.
fulfil the requirements of the cosmetic the active ingredient, dissolving ethyl-
industry. Furthermore, there are rarely hexylglycerin, a multifunctional additive.
actives on the market due to their strict Phenoxyethanol (Fig. 1) (1,2) is a well-
control by the different legislatures of
European, American and Asian countries.
At present, almost every active actually
used to preserve cosmetic products is the
 Introduction subject of public controversy. The car-
cinogenic potential of formaldehyde and
Most cosmetic products designed for topi- formaldehyde-donors, as well as the sen-
cal application contain one or more mi- sitisation potential of organic halogen
crobicidal substances in their formula- compounds is discussed. Parabens are as-
tion. The reasons for this are obvious. The sociated with a pseudo-estrogenic and INCI name: Phenoxyethanol
raw materials used in the manufacturing –androgenic potential, resulting in the Molecular formula: C8H10O2
of these products are rarely perfectly ster- media to linking them to breast cancer.
ile. Finished products containing perfume, Although in most cases scientific assess- CAS-name: 2-Phenoxyethanol
biologically active compounds or vita- ment of the suspected risks is not yet CAS-no.: 122-99-6
mins are too fragile to withstand sterili- completed, the cosmetic industry has EINECS no.: 204-589-7
sation following conditioning. The manu- asked for alternatives to these well-known EINECS name: 2-Phenoxyethanol
facturing process is rarely aseptic. The preservative actives. That is why the cos-
No. according to 76/768/EEC: 29
packaging is not hermetically sealed. metic market urgently needs new and in-
Above all, the use conditions following novative, multipurpose cosmetic preser-
Fig. 1 Chemical structure of
opening are such that a microbial con- vatives that are able to protect cosmetic
phenoxyethanol
tamination can arise, possibly being detri- formulations from microbial contamina-

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known, broadly accepted cosmetic preser-


vative and is frequently combined with
other preservative actives. It is widely
used in cosmetics and toiletries in con-
centrations up to 1.0% for preservation,
as per the European Cosmetic Directive.
It is an oily liquid with a characteristic
aromatic odour and a solubility in water
of 2.67 g/100 ml, after sufficient stirring INCI name: Ethylhexylglycerin
time. Molecular formula: C11H24O3
Phenoxyethanol is listed in Annex VI of CAS-name: 3-[(2-Ethylhexyl)oxy]-1,2-propandiol
the European Cosmetic Directive (76/768
CAS-no.: 70445-33-9
EEC). It is known to be a membrane ac-
tive agent. A Ph. Eur. monograph on phe- ELINCS name: Sensiva® SC 50
noxyethanol has been issued (3). ELINCS no.: 408-080-2
Ethylhexylglycerin (Fig. 2) belongs to the
class of 1-alkyl glyceryl ethers. It is a high Fig. 2 Chemical structure of ethylhexylglycerin
purity, colourless and almost odourless
liquid; excellent properties for use in cos-
metic formulations.
1-Alkyl glyceryl ethers with a large vari- glycerin is gentle to the skin, safe and,  Properties
ety of alkyl chains are well-known nat- when used as a multifunctional additive,
ural products. They are present in mam- it provides effective wetting by lowering In Euxyl® PE 9010 the efficacy of the
mals, birds, plants, protozoa and bacte- the surface tension in aqueous systems. well-known preservative active phenoxy-
ria and are particularly wide spread in Euxyl® PE 9010 is a liquid preservative ethanol has been enhanced. It is a clear,
marine animals. for cosmetics and toiletries based on colourless liquid suitable for leave-on
Ethylhexylglycerin was introduced to the phenoxyethanol. Unlike organohalogen-, products, including the preparation of
cosmetic market as a commercial prod- isothiazolinone- or formaldehyde-based clear gels.
uct (Sensiva® SC 50) in the year 1992 as preservatives, it can be classified as a Euxyl® PE 9010 is soluble in water up
a skin care additive and deodorant ac- mild biocidal active (»soft preserva- to 1.0%. In polar solvents, such as
tive. As a new substance it is listed on the tive«). Euxyl® PE 9010 consists solely of 1,2-propylene glycol, propanol or ace-
ELINCS file. phenoxyethanol (90%) and ethylhexyl- tone, it is readily soluble. In polyalcohols,
Ethylhexylglycerin is a unique, multifunc- glycerin (10%). The INCI name of Euxyl® such as glycerol and sorbitol, it is mod-
tional additive for cosmetic preparations PE 9010 is phenoxyethanol (and) ethyl- erately soluble. Pure aliphatic solvents
(4,5). It is accepted world-wide as a hexylglycerin. or aliphatic solvents with hydrophilic
deodorant active, being a very good al- Both components in Euxyl® PE 9010 are groups, such as 2-octyldecanol and iso-
ternative to triclosan (6,7). Ethylhexyl- globally approved (Table 1). propyl myristate, exhibit only a limited
solubility.

Phenoxyethanol Ethylhexylglycerin
Europe / USA: INCI name: INCI name:
Phenoxyethanol (active ingredient) Ethylhexylglycerin (auxiliary)
Australia: listed on AICS listed on AICS/NICNAS (NA/966)
Canada: listed on DSL listed on DSL
Japan: phenoxyethanol is approved as a cosmetic ENCS as glycerin monoalkyl (or alkenyl, C8-C24)
preservative up to 1.0% for all types of ether (No.: 2-414)
cosmetics and toiletries without restrictions CLS 1999:
- registered name: 2-Ethylhexyl Glycerylether
- ingredient code: 532289
- fully approved in all categories except eyeliner
preparations, oral preparations, bath preparations
(not allowed) and lip preparations (max. 1.0%)

Table 1 Approval of phenoxyethanol and ethylhexylglycerin

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The maximum allowed concentration able to neutralise the boosting activity with phenoxyethanol and ethylhexyl-
according to EU Cosmetic Directive is of ethylhexylglycerin. glycerin individually. The efficacy can be
1.1%, due to the limit of 1.0% for phe- Due to its high solvency, Euxyl® PE 9010 illustrated by the determination of
noxyethanol. At the recommended use- can serve as a solvent for lipophilic ad- the Minimum Inhibitory Concentration
concentration of 0.5 to 1.0% Euxyl® PE ditives like perfumes, vitamins and es- (MIC) values and by performing germ
9010 is soluble in most cosmetic for- sential oils. Formulas containing natural count reduction tests.
mulations. The low surface tension of raw materials are particularly suscepti-
Euxyl® PE 9010 solutions assures good ble to microbial growth. Fast-acting
dispersion in various systems, even at Euxyl® PE 9010 can eliminate microor- MIC values
low temperature. ganisms quickly, making it more effec- To compare the MIC values of Euxyl® PE
As phenoxyethanol and ethylhexyl- tive than slower acting preservatives. 9010 with phenoxyethanol, the mini-
glycerin are alcohols, the product is Designed as a substitute for paraben- mum inhibitory concentration against
stable to hydrolysis, to higher tempera- containing preservative systems, it also different microorganisms in a serial di-
tures (e.g. 100 °C) and to low as well as offers an alternative to formaldehyde- lution test was determined (Table 2).
high (pH 2 - 12) pH values. Furthermore, releasers and isothiazolinones. Its use is While ethylhexylglycerin alone has no
it remains liquid with a moderate viscos- recommended in leave-on preparations, appreciable effect on microorganisms,
ity at temperatures as low as -20 °C. such as lotions, creams, sun care prod- the enhanced phenoxyethanol in Euxyl®
In general, Euxyl® PE 9010 displays good ucts, transparent gels and others, as well PE 9010 is proven to have better effica-
compatibility with other cosmetic ingre- as cosmetic wet wipes. cy against many microorganisms than
dients. No discolourations have been de- phenoxyethanol alone.
tected. The product shows no interac-
tions with sulphite ions or with pigments  Microbiological efficacy
like TiO2. It can tolerate high salt content. Germ count reduction test
Cationic and amphoteric substances do Euxyl® PE 9010 is equally effective against To show the effect of ethylhexylglycerin
not adversely affect the preservative ac- bacteria, yeasts and fungi. It is effective on the performance of phenoxyethanol
tivity. However, it is yet not recommend- within a broad pH range, up to pH 12. It as a preservative, germ count reduction
ed for formulations containing compar- shows higher activity, e.g. in preservative tests on Pseudomonas aeruginosa (ATCC
atively high amounts of ethoxylated sur- efficacy tests (S&M KoKo test) (8,9) or in no. 15442) and Aspergillus niger (ATCC
factants because these surfactants are germ count reduction tests, compared no. 6275) were performed with dilutions
of Euxyl® PE 9010 in sterile tap water
and compared to the single components.
Fifty-ml portions of the end solutions are
Species ATCC- Euxyl® PE 9010 Phenoxy- each inoculated with 0.5 ml microor-
Nr.: [%] ethanol [%] ganism suspension and stirred. The ini-
tial microorganism count of the test so-
Gram-negative: lutions is approximately 108 cfu/ml.
Enterobacter gergoviae 33028 0.5 0.5 These solutions are streaked out onto
Escherichia coli 11229 0.5 0.5 tryptone soya agar (Pseudomonas aeru-
ginosa) or sabouraud-dextrose 4.0% agar
Klebsiella pneumoniae 4352 0.25 0.5
(Aspergillus niger) after 3, 6, 24, 48, 72
Pseudomonas aeruginosa 15442 0.5 0.5 and 168 hours depending on the test or-
Pseudomonas fluorescens 17397 0.25 0.5 ganism. The cultures are incubated for
Pseudomonas putida 12633 0.5 0.5 48 hours at 37 °C or 72 hours at 25 -
27 °C.
Gram-positive: The evaluation is made on the basis of
Staphylococcus aureus 6538 0.5 1.0 semi-quantitative assessment of the mi-
Staphylococcus epidermidis 12228 0.5 1.0 crobial growth of the streaks.
As Fig. 3 clearly demonstrate, ethylhexyl-
Mould fungi: glycerin, without having any efficacy
Aspergillus niger 6275 0.25 0.5 against Pseudomonas aeruginosa or As-
Penicillium funiculosum 36839 0.25 0.25 pergillus niger alone (green line), boosts
the efficacy of phenoxyethanol as the
Yeast:
preservative active in Euxyl® PE 9010 (blue
Candida albicans 10231 0.25 0.5 line) compared to phenoxyethanol alone
Table 2 MIC values (dilution test) of Euxyl® PE 9010 compared to phenoxyethanol (red line). The improved efficacy of the
against different microorganisms combination can be seen after a short
period of time.

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 Mode of action

Ethylhexylglycerin has a chemical struc-


ture comparable to surfactants. A calcu-
lated HLB-value of 7.4 means that it be-
longs to the group of wetting agents or
water-in-oil emulsifiers. It is able to re-
duce the surface tension of water sig-
nificantly (Fig. 4a).
In combination with phenoxyethanol in
Euxyl® PE 9010 an additional reduction
of the surface tension can be observed.
For a 1.0% solution of Euxyl® PE 9010 in
water the surface tension is 32.1 mN/m
(water: 72.6 mN/m). This is even lower
than the surface tension of 0.1% ethyl-
hexylglycerin, as the contact angles of
the corresponding water drops on mate-
rials like polyethylene clearly demon-
strate (Fig. 4b). Fig. 3 Germ count reduction in tap water achieved by Euxyl® PE 9010 compared
Although Euxyl® PE 9010 significantly re- to the single components against Pseudomonas aeruginosa and Aspergillus niger
duces the interfacial tension in a foaming
test according to DIN 53 902, a 1.0% so-
lution in demineralised water proved to
be non-foaming.  Practical experience is used for inoculation. At weekly inter-
It is postulated that the addition of ethyl- vals, a sample of the test product is
hexylglycerin affects the interfacial ten- The effectiveness of this system in cos- streaked out onto nutrient media, incu-
sion at the cell membrane of microor- metic formulations has been tested in bated and evaluated semi-quantitative-
ganisms. This improves the contact of the S&M KoKo test. This is a multiple-in- ly. The longer the time before the occur-
phenoxyethanol with the cell membrane oculation, preservative efficacy test de- rence of the first microbial growth, the
resulting in a better interaction of phe- signed and validated by Schülke & Mayr. more effective the preservative. Experi-
noxyethanol at the cell membrane and A mixed suspension of Gram-positive and ence has shown that a well-preserved
an improved antimicrobial efficacy. Gram-negative bacteria, yeast and mould product should remain growth-free for

4a 4b

Fig. 4a Surface tension [mN/m] of 1.0% Euxyl® PE 9010 in water compared to 0.9% phenoxyethanol, 0.1% ethylhexylglycerin
and water as well as 4b the corresponding water drops on a polyethylene surface

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six inoculation cycles to ensure the shelf-


life required in practice (30 months in
the original packaging).
Oil-in-water and water-in-oil systems
preserved with use-concentrations of
between 0.5 and 1.0% Euxyl® PE 9010
proved to be well preserved even after
three months storage at +40 °C.
Fig. 5 shows the result of the S&M KoKo
test on a Moisturizing Soothing Balm
preserved with 1.0% Euxyl® PE 9010, as
well as with the single components.
Only the sample preserved with 1.0%
Euxyl® PE 9010 was proved to be well
preserved after 6 inoculation cycles,
while 0.9% phenoxyethanol as well as
0.1% ethylhexylglycerin were ineffec- Fig. 5 Result of preservative efficacy test on the Moisturizing Soothing Balm
tive. during 6 inoculation cycles
Whereas ethylhexylglycerin alone has no
and phenoxyethanol alone shows no
sufficient efficacy against microorgan-
isms the enhanced phenoxyethanol in
Euxyl® PE 9010 is proven to preserve this
Moisturizing Soothing Balm very well.
In rinse-off products containing high
amounts ethoxylated surfactants the
product is yet not recommended because
these surfactants are able to neutralise
the boosting activity of ethylhexyl-
glycerin. As the interest is high in using
Euxyl® PE 9010 also in rinse-off products
efforts were made to decrease the loss of
efficacy by adding complexing agents. In
aqueous surfactant solutions (10% a. i.)
germ count reduction tests of the com-
bination of complexing agents with
Euxyl® PE 9010 gave better results than
alone. Fig. 6 shows how 0.05% EDTA
and 1.0% Euxyl® PE 9010 can reduce Fig. 6 Germ count reduction test in ethoxylated surfactant solutions against
Pseudomonas aeruginosa in the presence of complexing agents

Pseudomonas aeruginosa also in fre- As Fig. 7 shows, gels preserved with the
quently used ethoxylated surfactant so- product (gel 2) stay clear and transpar-
lutions. ent compared to a standard paraben
These results may encourage formulators mixture in phenoxyethanol (gel 3).
to check if the combination of Euxyl® PE
9010 with complexing agents can suc-
cessfully preserve surfactant based rinse-  Conclusion
off products. At this early stage of expe-
rience it is strongly recommended to check Euxyl® PE 9010 is an answer to the per-
Fig. 7 Carbomer gels, gel 1: unpreserved; gel the individual finished product as the ef- sonal care industry’s increasing demands
2: preserved with 1.0% Euxyl® PE 9010; gel 3: ficacy might depend on the particular for new preservation concepts. It is an
preserved with 1.0% of a standard paraben formulation. broad-spectrum preservative based on
mixture in phenoxyethanol Furthermore Euxyl® PE 9010 is ideal for phenoxyethanol in combination with the
the preservation of clear, transparent gels. multifunctional ethylhexylglycerin. The

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addition of ethylhexylglycerin affects the


interfacial tension at the cell membrane
of microorganisms, improving the preser-
vation activity of phenoxyethanol im-
pressively. It is is a patented liquid con-
centrate with extensive toxicological da-
ta on its ingredients. Its physical and
chemical properties, as well as its micro-
biological efficacy, make Euxyl® PE 9010
ideal for the formulation of skin care
products. It is focused for leave-on prod-
ucts and ideal for the preservation of
clear, transparent gels. This new preser-
vative system is a reasonable alternative
to classical preservation blends.

Literature

(1) The Merck Index, Thirteenth Ed., Monograph Nr.


7341

(2) H. P. Fiedler, Lexikon der Hilfsstoffe für Phar-


mazie, Kosmetik und angrenzenden Gebiete,
Editio Verlag Aulendorf, 5. Aufl., 2002, 1305 –
1306

(3) Hagers Handbuch der pharmazeutischen Praxis,


Springer-Verlag Berlin, 5. Auflage, Folgeband 5,
1999, 425 – 426

(4) H. Eggensperger, Multiaktive Wirkstoffe für


Kosmetika, Verlag für chemische Industrie H.
Ziolkowsky GmbH Augsburg, 1995, 141 – 159

(5) W. Beilfuß, W. Siegert, Cossma, 2003, 6, 54 – 55

(6) W. Beilfuß, SÖFW Journal, 1998, 6, 360 – 366


(German edition)

(7) H. M. Fishman, Happi, 2005, Vol. 42, No. 2, part


1 of 2, 35

(8) K. Weber, J. Siebert, SÖFW-Journal, 2003, 6, 44 –


50 (English); 48 – 55 (German edition)

(9) W. Siegert, Cosmetic Science Technology, 2005,


189 – 195.

* Authors’ address:
Dr. Wolfgang Beilfuss
Dr. Marion Leschke
Dr. Klaus Weber
Schülke & Mayr GmbH
22840 Norderstedt
Germany
Email: sai@schuelke-mayr.com

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