COSMETICS

K. Weber, J. Siebert*

Organic acids a modern alternative for preservation of cosmetics Keywords: Organic acids, mild cosmetic preservatives, low sensitisation potential,

comparative tests, colour stability

Introduction

Cosmetic products are an ideal nutri­ent media for microorganisms. In ad­dition to the water, there are more than adequate amounts of a wide va­riety of nutrients. Even with optimal manufacturing con­ditions and faultless microbiological quality of the raw materials used, there is a need for preservation be­cause of the conditions of use. After the pack has been opened the product must be protected during the period of use from the unavoidable contami­nation. Today, when choosing the preserva­tive, the decision is made with particu­lar care and attention in order to guar­antee optimal consumer protection. This results in new demands constant­ly being made of the preservatives and the active substances used in them.

Preservatives Fifty-six active substances for the preser­vation of cosmetic products are listed in Annex VI of the European Cosmetic Directive (761768 EEC). Of these, only about a dozen are actually encoun­tered on the cosmetic market. Para­bens, CMI/MI/8z0H, MDGN / PhOEtOH, bronopol, formaldehyde donors such as DMDM hydantoin, imidazolidinyl urea and diazolidinyl urea, organic acids and aromatic alcohols are among the most widely used substances in cosmetic preparations throughout the world. According to the most recent ecologi­cal and toxicolog ical knowledge, al­most all the listed substances display certain disadvantages that increasing­ly restrict the cosmetic chemist when selecting the preservation system.

8

Products without preservatives, or so­ca lled self-preserving systems, have captured a corner of the market. In the case of these products, of course, the risk to the consumer as a result of microbial contamination of body care products must always be weighed against the risks and benefits of the use of chemical preservatives.

Trends Corresponding to the classification in­to nucleophilic (e.g. isothiazolinones, forma ldehyde, methyldibromo gluta-

100 .9. ~. . ..

90

'\ ••• 80

~ 70 0

.E ." .. , .. 60 c:: :>

\ 0 50 E co en 40 III '6 -. 33 c:: 30 :> \

20

10

3 3,5 4 4,5

ronit rile) and membrane-active sub­stances (e.g. pa ra bens, aromatic alco­hols, organic acids) a clear trend to­wards so-ca lled mild, i.e. in genera l membrane-active, substances can be seen. Particularly in Germany, preser­vation systems based on organic acids are enjoying great popularity. Further criteria result from regionally influenced public debates about e.g. formaldehyde and halogen-organic compounds. In addition, the strategic plans of the individua l companies in the cosmetic industry are obviously re levant for the product developer.

~ I • Benzoic acid

Sorbic acid •

. 37

\." ." "----.. ~- • 5,5 - ... .. 5 5,5 6 6,5 7 L' pH value

Fig. 1 Degree of dissociation of selected carboxylic acids as a function of the pH value

SOFW-Journal, 129. Jahrgang 6-2003

Liquid active substance concentrate based on organic acids

Concept The objective of the development of Euxyl- K 700 was to make available a liquid active substance concentrate based on organic acids or their salts. This class of substances is also used in food preservation, and is considered to be particularly mild and tolerable. The only restrictions upon the use of organic acids results from the pH va l­ue of the end product. As only the undissociated acids are effective, the nature and amount of the acids used re­quire different pH values. Fig. 1 shows the degree of dissociation of selected carboxylic acids as a function of the pH value. An important parameter is the acid constant pK, of the organic acid. At a pH corresponding to the acid constant, 50 % of the acid is present in undisso­ciated form . The acid constants of the acids shown in Fig. 1:

Benzoic acid: Sorbic acid :

4.2 4.8

As a rule of thumb for the range 4 - 6 however, the following basically ap­plies: the lower the pH value, the greater the effectiveness. Adjustment of the pH of cosmetic prod­ucts into the acidic range approaches the natural pH value of skin, which is in the range 5.0 - 5.5.

Active substances The fungicidal and fungistatic proper­ties of sorbic acid form the basis of the effectiveness of Euxyl· K 700. The spectrum of activity is supplement­ed and balanced by the use of benzyl alcohol (Gram-positive bacteria) and phenoxyethanol (Gram-negative bac­teria) . All ingredients used are also permitted in Japan. For reasons of solubility and stabi lity potassium sorbate is used in Euxyl" K 700.

Incorporation As a result of the use of potassium sor­bate, Euxyle K 700 causes a slightly al ­kaline reaction and leads, especially when added at the end of the produc­tion process, to changes in the pH val­ue. After it has been incorporated in-

SOFW-Journal, 129. Jahrgang 6-2003

to the cosmetic product, the pH va lue of the product therefore has to be ad­justed. In solutions and OIW emulsions this generally causes no difficulties. In view of the difficult and unreliable measurement of pH in W/O emulsions, this adjustment should be made in the water phase. It must be ensured that the oi l phase contains no components that may again ra ise the pH. The best effect is achieved when EuxylO K 700 is used in the pH range below 5.5.

Colour stability Solutions of potassium sorbate and sorbic acid are genera lly considered to be unstable and not able to be stored (1). Sorbic acid is also said to have a general tendency to discoloration, es­pecially in cosmetic products. This is one reason why the use of benzoic acid is preferred as it has less of a tenden­cy to yellow, in the case of which this property is less pronounced. However, Fig . 2 shows t hat benzoic acid only de­velops its effectiveness at a consider­ably lower pH value. For products that are adjusted to a mean pH of 5.0, con­siderably larger amounts of benzoic acid are therefore necessary. As a result of the use of a stabilising antioxidant, we have succeeded in re­ducing t he discolouration tendency of sorbic acid both in the concentrate of Euxyle K 700 and in t he preserved cos­metic product. In Fig. 2 the discoloura­tion of a shower-gel containing differ­ent concentrations of EuxylO K 700 compared with amounts of sorbic acid

COSMETICS

and benzoic acid that are sufficient for preservation after storage at a high temperature is shown. The increase in the colour index when EuxylO K 700 is used is less than when benzoic acid is used. The effect shown is even greater in the preservative itself. Application for a patent has been made for appropriate stabilised liquid concentrates for the preservation of cosmetics (DE 19922538). The advantage of this development lies in the wider possibilities of use of sor­bic acid as a preservative.

Effectiveness

Test methods The effectiveness of various preserva­tives in comparison with EuxylO K 700 was tested in the S&M KoKo test (Table 1). This is a repetit ive cha llenge test over a period of six weeks. A mixed suspension of Gram-positive and Gram­negative bacteria, yeasts and moulds is used for inoculation: At weekly intervals, a sample ofthe test product is streaked out onto nutrient media, incubated, and evaluated semi­quantitatively. The first streaking out is to detect possible init ia l contam ina­tion. After each streaking out, the test product is re-inoculated and thus a mi­croorganism load of 10' to 10' CFU/g is produced.

~ start . 4 weeks 40·C 0 8 weeks 40~ I >< G> .., " ~

'" 0 200 "0 <.> 180

" 160 III ... co :I:

Fig. 2 Colour-stability of stored shower-gel

9

COSMETICS

Test organisms in the KoKo Test

Gram-positive I ----~S-t-a-PhyIOCOCCUs aureus ATCC 6538

Bacteria t Staphylococcus epidermidis ATCC 12228

Gram-negative Enterobacteria Enterobacter gergoviae ATCC 33028 Bacteria Escherichia coli ATCC 11229

Klebsiella pneumoniae ATCC 4352

Pseudomonads Pseudomonas aeruginosa ATCC 15442 Pseudomonas fluorescens ATCC 17397 Pseudomonas putida ATCC 12633

Yeasts

Moulds

Candida albicans

~Spergill-U-S -n-ig-e-r---­I Penicillium funiculosum

ATCC 10231

ATCC 6275 ATCC 36839

Table 1 Test organisms in the KoKo Test

The evaluation scheme differentiates between:

= free of microbial growth + = slight growth ++ = moderate growth +++ ::: massive growth

In addition, the growth is classified ac­cord ing to microorganisms (B = bacte­ria; Y = yeasts; M = moulds). The test generally ends after six inoc­ulation cycles or is discontinued earli~ er after several cases of +++. If a sample survives all six inoculation

Basic o/w lotion (unpreserved)

Phase A Aqua Propylene Glycol

cycles, i.e. if no growth is observed af­ter this repeated inoculation, a period of at least 30 months, which is recom­mended as the life of a cosmetic prod­uct, can be regarded as safe with re­gard to microbiological stability.

Basic formulations To test the effectiveness in the devel­opment phase, the preservative was incorporated into basic formulations, which were then subjected to the S&M Ko Ko test. Table 2 and Table 3 show basic formu­lations.

%w/w

83.5 2.0

I Phase B Paraffinum Liquidum 9.5 Cetearyl Alcohol Ceteareth-25

Table 2 Basis o/w lotion (un preserved)

r Basic shampoo (unpres_e_rv_e_d_) _____ _

Sodium Laureth Sulfate (70%) Hydrolysed Collagen Sodium Chloride Citric Acid/Sodium Hydroxide (pH value adjusted to 6.0)

Aqua

Table 3 Basic shampoo (un preserved)

10

3.0 2.0

=l %w/w

14.3 3.0 4.0

ca. 0.05 ad lOO

Comparative tests

In basic formulations The results of direct comparative tests with classic substance systems such as a para ben mix (EuxylO K 300), isothia­zolinones with benzyl alcohol (CMII Ml/BzOH = EuxylO K lOO) or methyl­dibromo glutaronitrile in phenoxy­ethanol (MDGN/PhOEtOH = EuxylO K 400) in the mentioned basic formula­tions are given in Table 4 and 5. It was shown that this formulation can be preserved with the recommended maximum concentration of the para­ben mix, but not with that of methyl­dibromo glutaronitrile in phenoxy­ethanol. A mean use-concentration of 1.0 % Euxyl" K 700 ensures adequate protection at a pH value of 5.0 (Table 4). The basic formulation forthe shampoo is obviously easier to preserve with the common preservation systems. 0.10 % of either isothiazolinones with benzyl alcohol or methyldibromo glutaroni­trUe in phenoxyethanol is sufficient. The paraben mix is not suitable for this product. When the formulation is adjusted to a pH va lue of 5.0, 0.75 % EuxylO K 700 is sufficient for good pre­servation (Table 5).

In popular market samples In our development of a product, new preservation systems are regularly tested in cosmetic products that are available on the market. Compared with the classic preservatives, compa­rable or even better results were ob­tained with Euxyl CII K 700. As an example, a silicone emulsion is shown in detail here, in which EuxylO K 700 was tested against methyldibro­mo glutaronitrile in phenoxyethanol (Table 6). The influence of the pH on the perfor­mance of Euxyle K 700 is clearly seen in this example. Whereas no adequate effectiveness can be found at pH 5.7 and 5.5, the sample with only 0.5 % EuxylO K 700 and a pH 5.0 survives all six inoculation cycles. This is also the case with methyldibromo glutaroni­trile in phenoxyethanol at 0.125 % (Table 7). In further customer samples EuxylO K 700 was subjected to comparative tests against isothiazolinones with benzyl alcohol, the paraben mix and methyl­dibromo glutaronitrile in phenoxy­ethanol. The overview shows the nec­essary use-concentrations of the dif-

SOFW-Journal, 129. Jahrgang 6-2003

Test material I product Inoculation cycles -------

Cosmetics

Basic o/w lo tion

unpreserved

+ 0.75 % paraben mix

+ , .00 % paraben mix

+ 0.10 % CMVMt(8z0H

+ 0.15 % CMlIMl/BzOH

+ 0.15 % MDGN/PhOEtOH

+ 0.20 % MDGN/PhOEtOH

+ 0.75 % Euxy'- K 700 (adjusted to pH 5.0 with citric add)

l + 1.00 % Euxy'· K 700 (adjusted to pH 5.0 with citric add)

o 1

+++ BYM

+++M

+M

+++Y

2

+++ BYM

+B

+++BY

+++M

+M

+++Y

3 4 5 6

i.

++B Y H+BY .I.

+++ .1. BYM

Hay .+BM H +BM +++ BYM

i.

+M +M +M ++M

.I.

Table 4 Results of direct comparative tests

Inoculat ion cycles r Test material I product ____________ _

Kosmetika 0

Basic shampoo unpreserved

+ 075 % paraben mix

+ , .00 % para ben mix

+ 0.05 % CMl/MVBzOH

+ 0.15 % CMIIMl/BzOH

+ 005 % MOGN/PhOEtOH

+ 0. 10 % MOGN/PhOEtOH

+ 0.50 % Euxy'· K 700 (adjusted to pH 5.0 with citric acid)

+ 0.7S % Euxy'- K 700 (adjusted to pH 5.0 with citric add)

+++B

+++B

+++B

++B

2 3

+++8 i.

+++8 i .

+++B i.

++B ++B

4 5 6

+++8 +++BY

+++B +++B i.

+B +B +++8

Table 5 Results of d irect comparative tests

ferent products in percent. NP (not preserva ble ) ind icates the combina­tions t hat could not be preserved even w ith the highest recommended use­concentration . A - sign indicates that tests were not carried out.

SOFW-Journal, 129. Jahrgang 6-2003

It can be seen (Table 8) with EuxylO K 700 a preservation system is available that is equal, if not superior, and must be regarded as an alternative to the classic combinations of active sub­stances.

COSMETICS

Dermal tolerability

The three active substances used in EuxylO K 700 (potassium sorbate, ben­zyl alcohol and phenoxyethanol) are substances t hat are listed in Annex VI of the Cosmetic Directive for use with­out restriction up to concentrations of max. 0.6 % (sorbic acid) and 1.0 % (benzyl alcohol, phenoxyethanol), and up to these use-concentrations are considered safe . These concentration limits correspond to a use-concentra­tion of max. 3.2 % Euxyl" K 700. Sorbic acid and its salts have proved in many different test series to be toxi ­cologically safe (2,3). No mucous mem­brane irritation occurred up to con­centrations of 10 %. The sensitisation potential can be described as slight. In more than 16000 patients with sus­pected allergic contact eczema who were tested between 1996 and 1998 for definite allergic reactions, with 0.1 % a virtually negligible sensitisa­tion rate was seen (5). In subjects with suspected contact allergy to preserva­tives the rate was 0.7 % (7). Like sorbic acid, benzyl alcohol is also a natural compound, and is used in various applications and areas. Benzyl alcohol is a natural component of many plants. It occurs in some edible fruits (up to 5 mglkg) and in green and black tea (1 - 30 and 1 - 15 mg l kg). 8en­zyl alcohol is added as a flavouring sub­stance to some foods and beverages in concentrations of up to 400 mg I kg (chewing gum 1254 mgl kg). The ADI (Acceptable Daily Intake) value has been set by the WHO as 5 mg / kg body­weight. Benzyl alcohol is used in a large variety of cosmetic formulations as a fragrance component, preserva­tive, solvent and to reduce viscosity. The US Food and Drug Administration reported in 1998 that benzyl alcohol is used in 322 cosmetic formulations in 43 cosmetic categories. In view of the w idespread and frequent use of ben­zyl alcohol and the associated expo­sure to it, the occurrence and rate of allergic reactions can be said to be low. Reports of skin reactions are due among other things to Peru balsam. On application of 0.65 - 10 % benzyl alcohol in repeated patch tests on healthy volunteers (RIPT, Kligman Maximization Study) no signs of con­tact allergy whatsoever were ob­served . Men and women who were tested for benzyl alcohol for diagnos­tic reasons, and in whom an allergic re-

11

COSMETICS

action to preservatives was suspected, showed a positive result in 0.4 % ofthe cases (7). Phenoxyethanol can be regarded as virtually non-toxic on oral and dermal administration. Unlike the short-chain

Silicone emulsion (unpreserved)

Phase A

ethylene glycol methyl/ethyl ethers, with which testicular atrophy, terato­genic and foetotoxic properties and myelosuppression were observed, w ith dermal application of phenoxyethanol neither teratogenic, ernbryotoxic nor

% w/w I

Cyclomethicone Dow Cornlng 345 Fluid 11,00 Cyclomethicone (and) Dimethicone Copelycl Dow Corning 3225 C Formu1.Aid 9,50 Trimethylolpropane I Triethylhexanoate Pelemol TMPO (Phoenix Chemical) 4,0

Polysorbate 20 Tween 20 (Uniqema Americas) 0, SO

Phase B

Demineralised water

Sodium chloride

Table 6 Silicone emulsion

Test material I product Inocu lation cycles -------

Cosmetics 0

Silicone emulsion

unpreserved

+ 0.050 % MDGNJPhOEtOH

+ 0.100 % MDGNJPhOEtOH

+ 0, 125 % MDGNJPhOEtOH

+ 0.500 % Euxyl K 700

(pH 5.5)

+ 1,000 % Euxyl- K 700

(pH 5.7)

+ 0.500 % Euxyl- K 700 (pH 5.0)

'---

Table 7 Silicone emulsion

1 2 3 4

+++BY +++ .I. 8YM

+++BM +++BM 1.

++8 +++8 +++B 1.

++8 ++8 ++8 ++8

5

+M

++8

74,50 0,50

100,00

-1 6

+++B

Test product CMl/ Ml/BzOH Paraben mix MOGN/PhOEtOH Euxyl K 700 + ----~--

Rich moisturisi ng lotion, pH 6.3

Vitamin E mask

Aftersun lotion

Body butter

Ultrasound gel

Shower lotion

Table 8 Use·concentrations

12

NP

NP NP 1.5 (pH 5.0)

Combination: 0.5 + 0.2

1.5 (pH 5.5)

1.5 (pH 5.5)

1.5 (pH 5.5)

1.0 (pH 5.0)

1.5 (pH 5.5)

NP

NP

NP 0.2

foetotoxic effects were observed (4). After dermal application phenoxy· ethanol is absorbed transcutaneously, and virtually all is excreted via the kid­neys as phenoxyacetic acid (PAA). On routine testing of phenoxyethanol in patients with contact eczema, almost no contact-allergic reactions were found . The prevalence rate deter­mined in volunteers by the German In­formation Association of Dermatolog­ical Clinics (IVDK) has for years been 0.1 % (7) . Despite the known high lev­el of exposure to this substance, this rate must be evaluated as low.

Summary

For cosmetics that have a slightly acidic pH value (pH < 5.5), Euxyl" K 700 is a modern alternative to other preserva­tives and surpasses some of these in ef­fectiveness. It follows the market trend for mild and tolerable preservatives. Compared with other preservatives, the active substances used in this prod· uct are characterised in particular by their low sensitisation potential.

Literature

(1) Fiedler. H. P: Lexikon der Hilfsstoffe fur Phar­maziet Kosmetik und angrenzende Gebiete, Editlo Verlag Aulendorf S. Aufl . (Bd. 2) 1560· 1563 (2002)

(2) Walker R. Toxicology of sorbic acid and 50r­bates. Food Additives and Cont aminants 7 (5): 671·6 (1990)

(3) BIBRA Working Group. Sorbic add and its common salts. Toxicity Profile . BIBRA Toxicol. International : 11 (1995)

(4) ECETOC Working Group: The toxicology of glycol ethers and its relevance to man. ECHOC Technical Teport 64: 348 p. (1995)

(5) IVDK, unpublished

(6) Nowes. D.: Absorption and Metabolism of 2-Phenoxyethanol in rat and man. 15th IFSCC Int . Congress 26.-29.09.1988

(7) Schnuch A .; Geier J., Uter w., Frosch P.1. Patch testing with preservatives, anti microbials and industrial biocides. Results from a multicentre study. Br. J. Dermatot. 138: 467-76 (1998)

"'Author's address: Dr. Klaus Weber, Dr. Jorg Siebert Schulke & Mayr GmbH Special Additives International 22840 Norderstedt Germany e·mail: sai@schuelke-mayr.com

50FW-Journal, 129. Jahrgang 6-2003