A bunch of flowers for preserving cosmetics

Thanks to evolution, plants have developed various defence mechanisms to protect these sessile organisms against enemies like herbivores, parasites, or microorganisms. There is physical defence such as thorns or chemical ones like toxic substances against herbivores. There are also secondary metabolites that attract the enemies of herbivores that will take note of the herbivore attack because the plant emits fragrance components from wounded leaves. These chemical signals will “call” for help by attracting the natural enemies, i.e., predators of herbivore insects (the “green” smell of (Z)-3-hexenyl acetate is one good example).

Another important defence line of plants is against microorganisms. Bacteria, yeasts, and molds can seriously damage and kill plants once they infect them. Like other defence mechanisms, plants have developed weapons against the intruders from the microscopic world as well. Usually, these antimicrobial compounds will be found at potential entry points for microorganisms. For example, roots in the soil may be protected as well as the bark of trees or flowers. The plant’s liquids may contain such defence systems as well and we regularly find them in essential oils.

View of nature

It is a good idea for chemists to have a look at these highly specialised antimicrobials that have evolved over millions of years. A common practice is to test and identify extracts or essential oils from plants that bear such biological activity.

However, there are some drawbacks in the use of extracts because they may have a high variance in quality or contain unwanted by-products with allergenic potential. This strongly depends on the variety of the plant, time of harvest, soil, or climatic conditions – all of which are very hard to control for a reliably uniform composition of such complex mixtures.

On top of that, sometimes raw materials are marketed for a nice, botanical INCI name rather than for a proven efficacy. Examples like honeysuckle extract or grapefruit seed extract have been known in the industry for lacking scientific proof and have been connected to adulteration with chemical preservatives. Chemicals like MIT (Methylisothiazolinone) or parabens found in a “natural preservative” of course are not what formulators expect behind such raw materials.

A good scientific approach therefore is to investigate natural systems and identify the active principle rather than using the complex mixtures (with a lot more activities that are not needed or even contra-productive) that are present in plants. By choosing the active materials, the right balance can be found between using nature’s wisdom and having a pure and highly active antimicrobial that can be sourced in the following ways:

• directly extracted from plant material and purified
• derived from natural sources and produced by green chemistry such as fermentation
• produced synthetically from a petrochemical source but being nature identical

With these highly purified raw materials can be built reliable active ingredients, effective blends and antimicrobial protection for cosmetic products that often makes chemical preservatives obsolete.

Chemical family

Chemically speaking, phenethyl alcohol is an aromatic alcohol, which bears structural similarities to a number of well-known ingredients used by formulators all around the world.

Benzylalcohol (A) is a fragrance chemical with strong antimicrobial properties. The substance occurs naturally in many fruits and essential oils, for example jasmine and hyacinth. It has been used as a preservative for several decades but has recently been criticised for its allergenic potential.

Phenoxyethanol (C) is another close structural analogue, in which an extra oxygen atom is present at the aromatic phenyl structure, converting it into a member of the ether group. It is among the most heavily used preservatives worldwide, is acknowledged for its safe toxicological profile and thus enjoys widespread application.

Phenylpropanol (D) is also a fragrance compound and displays a slightly longer aliphatic chain between phenyl ring and hydroxy group. It is another substance that is widely found in nature and is very often part of floral bouquets like in hyacinth flowers.

The biphenols honokiol (E) and magnolol (F), while structurally less similar to phenethyl alcohol, are another example of a plant’s strategy to defend itself against microbes with natural aromatic compounds. Both compounds are found in the bark and fruits of trees of the magnolia family.

What the six compounds have in common is not only their individual, distinct floral odour – they also each display a strong antimicrobial activity, which can be utilised to protect cosmetic formulations against bacteria and fungi. This is, of course, well known for benzyl alcohol and phenoxyethanol, which are both listed as preservatives in Annex V of European Cosmetics Directive 1223/2009, but for the others it is less known. All four substances are used by plants as part of their natural defence against microbes. For science-based and nature-friendly developers this is a perfect opportunity to learn from those plants. To better understand the application details for phenethyl alcohol, the necessary usage concentrations, advantageous substance combinations and formulation requirements were investigated.

Water- and surfactant-based systems

While the water solubility of this molecule is not particularly high with approx. 1.8g per 100g of water, this is well within the boundaries of the recommended use concentration of 0.5 – 1.5%. The good solubility leads to crystal clear aqueous formulations with phenethyl alcohol, such as serums, gels, bodywashes or micellar waters, which all are in the scope of possible applications. In addition, unlike other preservatives, the formulation pH is not limited by phenethyl alcohol, as its antimicrobial action is not affected by pH changes. This is a major advantage for this multifunctional’s flexibility in usage.

To outline the possibilities of microbiological stabilisation, there have been several challenge tests conducted according to the guideline laid out in the European Pharmacopoeia. Results are displayed as bar diagrams of logarithmic microbe reduction at the five test intervals, individually for each test organism (figure 2).

During our testing it became apparent that usage concentrations of about 1.0% are sufficient in water- and surfactant-based formulations at varying pH levels. In many cases, no further addition of preservatives/antimicrobials is necessary to achieve full protection against micro-biological spoilage.

Still, considering the hurdle technology principle of cosmetic preservation, it can be advisable to reduce the application concentration of the major preservative, while adding another antimicrobial substance. This can further challenge microorganisms and improve microbiological stability, while at the same time saving formulation costs. In addition, in some formulations, especially those with a surfactant-base, the efficacy of phenethyl alcohol alone may be insufficient to achieve a top grade in the challenge test. In such cases it can be combined with substances such as caprylyl glycol, ethylhexylglycerin or hydroxyacetophenone (figure 3).

Preservation of O/W-systems

The microbiological protection of O/W emulsions often poses a greater challenge to preservatives, since the presence of oil droplets can hinder contact between microorganisms and antimicrobial substances, resulting in a reduced efficacy. Therefore, it is especially interesting to see how phenethyl alcohol would perform under such conditions.

It is indeed possible to achieve complete protection with phenethyl alcohol alone, though to be on the safe side it is often advisable to use combinations with other antimicrobials. A selection of challenge test results is shown in figure 4.

Application of 1.0% phenethyl alcohol alone at pH 7.0 in an O/W emulsion resulted in a passing B grade (Ph. Eur.), due to incomplete reduction of E.coli after two and seven days (figure 4, top left). While this result may be satisfactory in many cases, an A result is often desired. This can be achieved again through the addition of caprylyl glycol or ethylhexylglycerin.

In summary, phenethyl alcohol is an effective alternative preservative, capable of fully protecting formulations from microbial contamination. Depending on the formulation, concentrations of around 1.0% are needed. This can be further reduced if combined with other anti-microbials such as caprylyl glycol or ethylhexylglycerin. The formulation pH is variable and can range from anywhere between 3.5 and 12, which should cover all common formulation concepts. 

Life cycle considerations 

For users of phenethyl alcohol, two sourcing options are available: The standard grade is petrochemically derived and has a very cost-efficient market price, comparable to some standard preservatives. It is often manufactured through the oxida-
tion of styrene, followed by purifi-cation distillation.

Chemically identical but obtained from renewable sources is the green variant of this molecule. Starting from a starch source, phenyl alanine is produced, which is then fermented with baker’s yeast (Saccharomyces cerevisiae) to yield the target molecule, phenethyl alcohol which needs diligent purification. Due to the complexity of the process, the price per kg is increased compared to the quality from conventional chemical synthesis, which makes it unsuitable for price-sensitive applications. 

The multifunctional ingredient phe-nethyl alcohol is used in perfumes, leave-on and rinse-off cosmetic products. This means that concerning the substances end-of-life, two pathways must be considered, namely dermal adsorption and wastewater disposal. Both routes pose no danger to humans or the environment: 

• After dermal application, the majority of phenethyl alcohol is evaporated, so only a fraction is absorbed into the body. Here, it was found to be rapidly ex-creted via the kidneys. The main metabolite is nontoxic phenyl-acetic acid¹. 
• A biodegradation test in water following OECD method 301B found the substance to be readily biodegradable.