International Journal for Applied Science - Schülke & Mayr

Reprint
from
11-2005
International Journal
for Applied Science
■ Personal Care ■ Detergents ■ Specialities
W. Beilfuss, M. Leschke, K. Weber
A New Concept to Boost the Preservative
Efficacy of Phenoxyethanol

COSMETICS
PRESERVATIVES
W. Beilfuss, M. Leschke, K. Weber*
A New Concept to Boost the Preservative
Efficacy of Phenoxyethanol
Keywords: cosmetic preservative, phenoxyethanol, ethylhexylglycerin
� Introduction
Abstract
Anew cosmetic preservative
for leave-on products based
on a combination of the active
ingredient phenoxyethanol
and the skin care additive and deodorant
active ethylhexylglycerin
is presented. Ethylhexylglycerin
boosts the antimicrobial activity of
phenoxyethanol. Properties, antimicrobial
activity and a possible
mechanism of action are discussed.
Most cosmetic products designed for topical
application contain one or more microbicidal
substances in their formulation.
The reasons for this are obvious. The
raw materials used in the manufacturing
of these products are rarely perfectly sterile.
Finished products containing perfume,
biologically active compounds or vitamins
are too fragile to withstand sterilisation
following conditioning. The manufacturing
process is rarely aseptic. The
packaging is not hermetically sealed.
Above all, the use conditions following
opening are such that a microbial contamination
can arise, possibly being detri-
mental to the health of the user or to the
aesthetic appearance of the product. Thus,
it is necessary to protect the product from
such microbial contamination. To this end,
the cosmetic market demands multipurpose
cosmetic preservatives which are
globally approved, cost effective and do
not contain actives under any public discussion.
However, the number of actives
which can be used as preservatives for
cosmetic applications is limited. Approximately
15 of the 57 preservative chemistries
listed in Annex VI of the European
Cosmetic Directive (76/768 EEC) are actively
used. Only these few have the physical-chemical
properties, as well as the efficacy
and the safety assessment, which
fulfil the requirements of the cosmetic
industry. Furthermore, there are rarely
actives on the market due to their strict
control by the different legislatures of
European, American and Asian countries.
At present, almost every active actually
used to preserve cosmetic products is the
subject of public controversy. The carcinogenic
potential of formaldehyde and
formaldehyde-donors, as well as the sensitisation
potential of organic halogen
compounds is discussed. Parabens are associated
with a pseudo-estrogenic and
–androgenic potential, resulting in the
media to linking them to breast cancer.
Although in most cases scientific assessment
of the suspected risks is not yet
completed, the cosmetic industry has
asked for alternatives to these well-known
preservative actives. That is why the cosmetic
market urgently needs new and innovative,
multipurpose cosmetic preservatives
that are able to protect cosmetic
formulations from microbial contamina-
tion, without causing harm to humans. In
addition, they should be globally approved,
cost effective and free of any public
discussion. Therefore, new concepts in
preservation are required.
� A sophisticated combination
of phenoxyethanol and
ethylhexylglycerin
To address the complex requirements of
the cosmetic market, the new cosmetic
preservative Euxyl® PE 9010 was developed
primarily for the use in leave-on
products. This patented liquid concentrate
is formulated from phenoxyethanol,
the active ingredient, dissolving ethylhexylglycerin,
a multifunctional additive.
Phenoxyethanol (Fig. 1) (1,2) is a well-
INCI name: Phenoxyethanol
Molecular formula: C8H10O2 CAS-name: 2-Phenoxyethanol
CAS-no.: 122-99-6
EINECS no.: 204-589-7
EINECS name: 2-Phenoxyethanol
No. according to 76/768/EEC: 29
Fig. 1 Chemical structure of
phenoxyethanol
2 SÖFW-Journal | 131 | 11-2005

known, broadly accepted cosmetic preservative
and is frequently combined with
other preservative actives. It is widely
used in cosmetics and toiletries in concentrations
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
time.
Phenoxyethanol is listed in Annex VI of
the European Cosmetic Directive (76/768
EEC). It is known to be a membrane active
agent. A Ph. Eur. monograph on phenoxyethanol
has been issued (3).
Ethylhexylglycerin (Fig. 2) belongs to the
class of 1-alkyl glyceryl ethers. It is a high
purity, colourless and almost odourless
liquid; excellent properties for use in cosmetic
formulations.
1-Alkyl glyceryl ethers with a large variety
of alkyl chains are well-known natural
products. They are present in mammals,
birds, plants, protozoa and bacteria
and are particularly wide spread in
marine animals.
Ethylhexylglycerin was introduced to the
cosmetic market as a commercial product
(Sensiva® SC 50) in the year 1992 as
a skin care additive and deodorant active.
As a new substance it is listed on the
ELINCS file.
Ethylhexylglycerin is a unique, multifunctional
additive for cosmetic preparations
(4,5). It is accepted world-wide as a
deodorant active, being a very good alternative
to triclosan (6,7). Ethylhexyl-
glycerin is gentle to the skin, safe and,
when used as a multifunctional additive,
it provides effective wetting by lowering
the surface tension in aqueous systems.
Euxyl® PE 9010 is a liquid preservative
for cosmetics and toiletries based on
phenoxyethanol. Unlike organohalogen-,
isothiazolinone- or formaldehyde-based
preservatives, it can be classified as a
mild biocidal active (»soft preservative«).
Euxyl® PE 9010 consists solely of
phenoxyethanol (90%) and ethylhexylglycerin
(10%). The INCI name of Euxyl®
PE 9010 is phenoxyethanol (and) ethylhexylglycerin.
Both components in Euxyl® PE 9010 are
globally approved (Table 1).
COSMETICS
PRESERVATIVES
INCI name: Ethylhexylglycerin
Molecular formula: C11H24O3 CAS-name: 3-[(2-Ethylhexyl)oxy]-1,2-propandiol
CAS-no.: 70445-33-9
ELINCS name: Sensiva® SC 50
ELINCS no.: 408-080-2
Fig. 2 Chemical structure of ethylhexylglycerin
� Properties
Phenoxyethanol Ethylhexylglycerin
In Euxyl® PE 9010 the efficacy of the
well-known preservative active phenoxyethanol
has been enhanced. It is a clear,
colourless liquid suitable for leave-on
products, including the preparation of
clear gels.
Euxyl® PE 9010 is soluble in water up
to 1.0%. In polar solvents, such as
1,2-propylene glycol, propanol or acetone,
it is readily soluble. In polyalcohols,
such as glycerol and sorbitol, it is moderately
soluble. Pure aliphatic solvents
or aliphatic solvents with hydrophilic
groups, such as 2-octyldecanol and isopropyl
myristate, exhibit only a limited
solubility.
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
SÖFW-Journal | 131 | 11-2005 3

COSMETICS
PRESERVATIVES
The maximum allowed concentration
according to EU Cosmetic Directive is
1.1%, due to the limit of 1.0% for phenoxyethanol.
At the recommended useconcentration
of 0.5 to 1.0% Euxyl® PE
9010 is soluble in most cosmetic formulations.
The low surface tension of
Euxyl® PE 9010 solutions assures good
dispersion in various systems, even at
low temperature.
As phenoxyethanol and ethylhexylglycerin
are alcohols, the product is
stable to hydrolysis, to higher temperatures
(e.g. 100 °C) and to low as well as
high (pH 2 - 12) pH values. Furthermore,
it remains liquid with a moderate viscosity
at temperatures as low as -20 °C.
In general, Euxyl® PE 9010 displays good
compatibility with other cosmetic ingredients.
No discolourations have been detected.
The product shows no interactions
with sulphite ions or with pigments
like TiO 2 . It can tolerate high salt content.
Cationic and amphoteric substances do
not adversely affect the preservative activity.
However, it is yet not recommended
for formulations containing comparatively
high amounts of ethoxylated surfactants
because these surfactants are
able to neutralise the boosting activity
of ethylhexylglycerin.
Due to its high solvency, Euxyl® PE 9010
can serve as a solvent for lipophilic additives
like perfumes, vitamins and essential
oils. Formulas containing natural
raw materials are particularly susceptible
to microbial growth. Fast-acting
Euxyl® PE 9010 can eliminate microorganisms
quickly, making it more effective
than slower acting preservatives.
Designed as a substitute for parabencontaining
preservative systems, it also
offers an alternative to formaldehydereleasers
and isothiazolinones. Its use is
recommended in leave-on preparations,
such as lotions, creams, sun care products,
transparent gels and others, as well
as cosmetic wet wipes.
� Microbiological efficacy
Euxyl® PE 9010 is equally effective against
bacteria, yeasts and fungi. It is effective
within a broad pH range, up to pH 12. It
shows higher activity, e.g. in preservative
efficacy tests (S&M KoKo test) (8,9) or in
germ count reduction tests, compared
Species ATCC- Euxyl® PE 9010 Phenoxy-
Nr.: [%] ethanol [%]
Gram-negative:
Enterobacter gergoviae 33028 0.5 0.5
Escherichia coli 11229 0.5 0.5
Klebsiella pneumoniae 4352 0.25 0.5
Pseudomonas aeruginosa 15442 0.5 0.5
Pseudomonas fluorescens 17397 0.25 0.5
Pseudomonas putida
Gram-positive:
12633 0.5 0.5
Staphylococcus aureus 6538 0.5 1.0
Staphylococcus epidermidis
Mould fungi:
12228 0.5 1.0
Aspergillus niger 6275 0.25 0.5
Penicillium funiculosum
Yeast:
36839 0.25 0.25
Candida albicans 10231 0.25 0.5
Table 2 MIC values (dilution test) of Euxyl® PE 9010 compared to phenoxyethanol
against different microorganisms
with phenoxyethanol and ethylhexylglycerin
individually. The efficacy can be
illustrated by the determination of
the Minimum Inhibitory Concentration
(MIC) values and by performing germ
count reduction tests.
MIC values
To compare the MIC values of Euxyl® PE
9010 with phenoxyethanol, the minimum
inhibitory concentration against
different microorganisms in a serial dilution
test was determined (Table 2).
While ethylhexylglycerin alone has no
appreciable effect on microorganisms,
the enhanced phenoxyethanol in Euxyl®
PE 9010 is proven to have better efficacy
against many microorganisms than
phenoxyethanol alone.
Germ count reduction test
To show the effect of ethylhexylglycerin
on the performance of phenoxyethanol
as a preservative, germ count reduction
tests on Pseudomonas aeruginosa (ATCC
no. 15442) and Aspergillus niger (ATCC
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
each inoculated with 0.5 ml microorganism
suspension and stirred. The initial
microorganism count of the test solutions
is approximately 10 8 cfu/ml.
These solutions are streaked out onto
tryptone soya agar (Pseudomonas aeruginosa)
or sabouraud-dextrose 4.0% agar
(Aspergillus niger) after 3, 6, 24, 48, 72
and 168 hours depending on the test organism.
The cultures are incubated for
48 hours at 37 °C or 72 hours at 25 -
27 °C.
The evaluation is made on the basis of
semi-quantitative assessment of the microbial
growth of the streaks.
As Fig. 3 clearly demonstrate, ethylhexylglycerin,
without having any efficacy
against Pseudomonas aeruginosa or Aspergillus
niger alone (green line), boosts
the efficacy of phenoxyethanol as the
preservative active in Euxyl® PE 9010 (blue
line) compared to phenoxyethanol alone
(red line). The improved efficacy of the
combination can be seen after a short
period of time.
4 SÖFW-Journal | 131 | 11-2005

� Mode of action
Ethylhexylglycerin has a chemical structure
comparable to surfactants. A calculated
HLB-value of 7.4 means that it belongs
to the group of wetting agents or
water-in-oil emulsifiers. It is able to reduce
the surface tension of water significantly
(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% ethylhexylglycerin,
as the contact angles of
the corresponding water drops on materials
like polyethylene clearly demonstrate
(Fig. 4b).
Although Euxyl® PE 9010 significantly reduces
the interfacial tension in a foaming
test according to DIN 53 902, a 1.0% solution
in demineralised water proved to
be non-foaming.
It is postulated that the addition of ethylhexylglycerin
affects the interfacial tension
at the cell membrane of microorganisms.
This improves the contact of
phenoxyethanol with the cell membrane
resulting in a better interaction of phenoxyethanol
at the cell membrane and
an improved antimicrobial efficacy.
� Practical experience
4a 4b
The effectiveness of this system in cosmetic
formulations has been tested in
the S&M KoKo test. This is a multiple-inoculation,
preservative efficacy test designed
and validated by Schülke & Mayr.
A mixed suspension of Gram-positive and
Gram-negative bacteria, yeast and mould
COSMETICS
PRESERVATIVES
Fig. 3 Germ count reduction in tap water achieved by Euxyl® PE 9010 compared
to the single components against Pseudomonas aeruginosa and Aspergillus niger
is used for inoculation. At weekly intervals,
a sample of the test product is
streaked out onto nutrient media, incubated
and evaluated semi-quantitatively.
The longer the time before the occurrence
of the first microbial growth, the
more effective the preservative. Experience
has shown that a well-preserved
product should remain growth-free for
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
SÖFW-Journal | 131 | 11-2005 5

COSMETICS
PRESERVATIVES
six inoculation cycles to ensure the shelflife
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 ineffective.
Whereas ethylhexylglycerin alone has no
and phenoxyethanol alone shows no
sufficient efficacy against microorganisms
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 ethylhexylglycerin.
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 combination
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. 7 Carbomer gels, gel 1: unpreserved; gel
2: preserved with 1.0% Euxyl® PE 9010; gel 3:
preserved with 1.0% of a standard paraben
mixture in phenoxyethanol
Fig. 5 Result of preservative efficacy test on the Moisturizing Soothing Balm
during 6 inoculation cycles
Fig. 6 Germ count reduction test in ethoxylated surfactant solutions against
Pseudomonas aeruginosa in the presence of complexing agents
Pseudomonas aeruginosa also in frequently
used ethoxylated surfactant solutions.
These results may encourage formulators
to check if the combination of Euxyl® PE
9010 with complexing agents can successfully
preserve surfactant based rinseoff
products. At this early stage of experience
it is strongly recommended to check
the individual finished product as the efficacy
might depend on the particular
formulation.
Furthermore Euxyl® PE 9010 is ideal for
the preservation of clear, transparent gels.
As Fig. 7 shows, gels preserved with the
product (gel 2) stay clear and transparent
compared to a standard paraben
mixture in phenoxyethanol (gel 3).
� Conclusion
Euxyl® PE 9010 is an answer to the personal
care industry’s increasing demands
for new preservation concepts. It is an
broad-spectrum preservative based on
phenoxyethanol in combination with the
multifunctional ethylhexylglycerin. The
6 SÖFW-Journal | 131 | 11-2005

addition of ethylhexylglycerin affects the
interfacial tension at the cell membrane
of microorganisms, improving the preservation
activity of phenoxyethanol impressively.
It is is a patented liquid concentrate
with extensive toxicological data
on its ingredients. Its physical and
chemical properties, as well as its microbiological
efficacy, make Euxyl® PE 9010
ideal for the formulation of skin care
products. It is focused for leave-on products
and ideal for the preservation of
clear, transparent gels. This new preservative
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 Pharmazie,
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
�
COSMETICS
PRESERVATIVES
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