The preservation of consumer products can be achieved biologically, using enzymes or microorganisms to control contamination, or physically, by methods of irradiation or UV.
However, the most widely accepted and reliable method of preservation is by using chemicals that are either synthesised, in most cases from petroleum derivatives (conventional synthetic preservatives), sourced from vegetable extracts (“green” preservatives), or by using natural substances or extracts with antimicrobial properties but which are not classified as permitted preservatives by the European authorities. The use of natural substances or extracts with antimicrobial properties has received much media and consumer attention in the last decade as their name and origin implies that these chemicals are safer, less toxic and better for the environment. However, are they really a better alternative to conventional synthetic preservatives? Are conventional synthetic preservatives genuinely bad and should they be replaced? So, while the use of natural non-listed substances is a fashionable marketing wave to ride, what is the underlying reality? Are the assumptions that there is a need to replace conventional synthetic preservatives based on logic and science? If so, what steps are the regulatory authorities taking and why is the cosmetic industry not responding more quickly to address this public health problem? When members of the public are interrogated about the sensitivity of their skin, allergic reactions they may have encountered and the products or substances that they believe to be responsible for these problems, preservatives are much more commonly perceived to be the causal agent than pollens, seafood or dust mites. In contrast, statistics published by dermatologists show that the reality is quite different to public perception and that the true proportion of the population suffering allergic skin reactions is actually much lower. Thus, a large portion of respondents think they have problems when they do not and they focus on preservatives as being responsible when they are actually the cause of only a minority of cases. This is complicated by the fact that the identification of sensitive skin is a grey area. Dermatologists regularly identify more and more cases of topical reactions such as rashes, eczema and itching which are not necessarily in the context of an allergic reaction. The skin patch test can indicate if a person has a skin allergy called contact dermatitis (Fig. 1). Regulations governing the food industry list the ingredients or allergens that must appear on the labels of foodstuffs (Table 1). It is interesting to note that no preservative is present in this list. The Cosmetic Directive 76/768/EEC – 7th Amendment includes a list of 26 allergens of which only one is a preservative: benzyl alcohol (Table 2). Of the 26 allergens listed in the Cosmetics Directive, eight exist in nature. However, they can also be synthesised in order to be used on a large industrial scale e.g. benzyl alcohol (solvent and preservative) or for the perfume industry. The standard Fragrance Mix allergy test (Table 3) used in allergy diagnosis testing uses eight of these allergens. Between 1% and 2% of the general population is allergic to this mixture. If we only consider those suffering from eczema, (Fig. 2) this range is increased to 10%. The proportion of the population allergic to preservatives is significantly lower than those allergic to other common compounds of cosmetics like fragrances (perfumes). The debate on preservatives is an image problem or a marketing issue and not a public health problem. There is more and more advertising for cosmetics claiming “NO”: no parabens, no preservatives etc. The public does not like preservatives, but does not exactly know why - and therefore their absence is a selling carrier. The tendency would be to remove them, but do we all know what preservatives are? What is their purpose and especially what would be the consequences of their absence? Chapter II, Article 3 of the cosmetic regulation dealing with the safety of cosmetics states: Cosmetic products available on the market must be harmless to human health when applied under normal or reasonably foreseeable conditions of use. The official definition of a preservative for cosmetics is as follows: “Preservatives” means substances which are exclusively or primarily intended to prevent the growth of microorganisms in the cosmetic product. Microbial contamination causes instability and degradation of cosmetic formulations, such as:
• Change in texture.
• Change in viscosity.
• Formation of lumpy or gritty emulsion.
• Separation of emulsion.
• Change of odour or colour.
• Change in pH.
• Change in redox potential.
• Production of gas.
High levels of microbial contamination of cosmetics can induce harmful effects on the skin and endanger human health. Microbiological degradation of the ingredients can generate allergic, toxic or mutagenic products. Microorganisms can also induce direct effects including:
• Production of toxins or other metabolites with pharmacological activity (e.g. allergic dermatitis) which may persist even when the microorganism is no longer present.
• Growth of pathogenic microorganisms such as Staphylococcus aureus or Pseudomonas aeruginosa.
Therefore, it is clear that some microorganisms are harmful to human health. Cosmetics must be safe for human health and preservatives are intended to prevent the growth of microorganisms in the cosmetic product. Preservatives therefore have a function which is more prominent than any perceived health effect. Hence they are indispensable and justified for use in cosmetic products.
If preservatives are necessary, are they safe?
The use of preservatives in food or cosmetics is highly regulated. In Europe, preservatives are listed in Annex V of the new cosmetic regulation (no. 1223/2009 of the European Parliament and of the Council of 30 November 2009 on cosmetic products) on a positive list that, for each application, includes maximum utilisation threshold and restrictions for use. The preservatives positive list is created and updated by a committee of independent experts delegated by the European Commission (Scientific Committee on Consumer Safety – SCCS) who scrutinise toxicological records for all new entries or modifications of this list. The average delay from the point of new substance submission and its acceptance varies between 5 and 10 years and is dependent on the nature of information available and the time necessary to constitute the data that the scientific committee may request in addition to the submitted dossier. When a cosmetics ingredient dossier is submitted for evaluation by the SCCS, the manufacturer should provide the Commission with the information set out below (minimum package for a new preservative): Acute toxicity (if available); carcinogenicity; irritation and corrosivity; reproductive toxicity; skin sensitisation; toxicokinetics; mutagenicity/genotoxicity; dermal/percutaneous absorption; photoinduced toxicity; repeated dose toxicity; human data. The risk assessment procedure is divided into four parts:
• Hazard identification: based on the results of in vitro tests, in vivo tests, clinical studies, accidents, human epidemiological studies and, when available, quantitative structure activity relationship (QSAR) studies. The intrinsic physical, chemical and toxicological properties of the molecule under consideration are studied to identify whether the substance has the potential to damage human health.
• Dose-response assessment: where the relationship between the toxic response and the exposure is studied. In the case of a threshold effect, the dose at which no adverse effects are observed (NOAEL) is determined. If the NOAEL cannot be determined, the lowest dose at which an adverse effect is observed (LOAEL) is used. In the case of non-threshold carcinogens, a dose descriptor is determined [Dybing et al. 1997].
• Exposure assessment: where the amount and frequency of human exposure to the compound is determined (including potential vulnerable risk groups, e.g. children, pregnant women, etc.).
• Risk characterisation: where the probability that the molecule causes damage to human health and the level of risk is examined. In the case of a threshold effect, the Margin of Safety (MoS) is calculated according to the formula: MoS = NOAEL SED where SED represents the Systemic Exposure Dosage.
For non-threshold effects (e.g. nonthreshold carcinogenic effect), the lifetime risk is usually determined through the use of a dose-descriptor, defined as the calculated amount of a test substance administered daily (e.g. mg/kg body weight/day) that increases the net frequency of tumours at a specific site by a certain percentage [Dybing et al. 1997]. It is interesting to note that this information is only required for those molecules present in Annexes II to VI and does not apply to all other ingredients used in cosmetics. Preservatives are therefore some of the most highly scrutinised substances used in cosmetics!
What are the properties required for a modern cosmetic preservative?
• Broad spectrum antimicrobial activity.
• Microbiocidal rather than microbiostatic.
• Active at low concentrations.
• Effective over the anticipated shelf life.
• Should not encourage the development of resistant microbiological species.
• Chemically defined.
• Regulatory approval.
• Easy to use and analyse.
• Cost effective.
• Safe to use.
• Stable and compatible with other ingredients.
• Not deactivated by other ingredients in the formulation.
• Odourless, colourless and taste free.
• Effective over a wide pH range.
• Water soluble.
• Non-bio-accumulating and nonpersistent in the environment.
Obviously, none of the 58 molecules currently allowed on Annex V of the European cosmetics regulations fully satisfy all of the above criteria. It is for this reason that the phrase “preservation system” is used instead of “preservatives” and that the preservation system must be selected according to its compatibility with the formulation to be protected. Indeed, each formulation will require a dedicated and adapted preservation system. If the product is sensitive to fungi, the addition of a fungicide may be necessary. If the formula is alkaline, the preservative should be active and stable at alkaline pH. The skill therefore lies in the use of different molecules to correct the weaknesses of others with the aim of achieving real synergies. The work of the formulators becomes increasingly difficult as they face new marketing challenges, as pressure from consumers mounts and as regulatory requirements become stricter. This severely restricts the choices. To meet new marketing demands, many formulators try to substitute the molecules listed which are available, with others that are not listed as preservatives. We thus see the appearance of more and more novel molecules which are described as antimicrobial agents in cosmetics ingredients lists. None of these is officially listed as a preservative and therefore is not required to satisfy the same regulatory requirements as conventional preservatives. This does not necessarily represent a health risk, but doubt remains. At least Annex V lists only the molecules that have been assessed and judged to be safe!
Is this strategic option, chosen deliberately by formulators, legal?
In the preamble to Annex V of the new cosmetics regulation, the text has been amended as follows: The list of preservatives which cosmetic products may contain has become the list of preservatives allowed in cosmetic products. The conclusion is simple: only molecules listed in this Annex may be used for the preservation of cosmetics. It is therefore the responsibility of the cosmetics manufacturer to prove that these novel substances are present due to other key and quantifiable properties that will prevail over the associated antimicrobial properties. A little balance is needed in response to initial assumptions:
Are preservatives harmful?
Although some molecules in their pure form may have a “negative” reputation, regulations require that at user levels, there is no risk to human health. Specifically, if a molecule is a sensitiser, it will only be authorised by law below the minimum dose that could cause sensitisation. To integrate risk of multiple usage, a margin of safety is calculated. Thus the maximum use level allowed by law is further reduced. However, people already sensitised to a molecule may react even at very low levels of exposure (Fig. 3).
Should they therefore be eliminated?
The role of preservatives is to protect against microbial contamination and there should be no discussion about removing them all on a large scale. Nevertheless, some formulations may not require the addition of preservatives. These products are often anhydrous or contain a significant amount of alcohol which prevents microbial growth. Different products without preservatives exist, but no single method can resolve all preservation issues on a large scale. The option to market powders rather than liquids, which do not support microbiological growth, and which the consumer can re-hydrate at home is not viable because it is impossible to control the level of microbiological contamination in the water that each user will use. Therefore, to avoid microbial growth, the product should be used immediately after rehydration and the excess immediately disposed of. This generates large volume waste. To make the product under sterile conditions in single-dose packaging also poses problems such as increased production and packaging costs. Finally, monitoring the cold chain for cosmetics, as is required for perishable food items, is also a problem (products should therefore be stored at 4°C). Without preservatives, it would be necessary to produce sterile goods, to transport and distribute cosmetics and toiletries while respecting the cold chain and for consumers to keep them refrigerated. Once opened, these products should be treated like any other perishable food and discarded after the expiration date. This is a totally unrealistic situation because it generates higher prices, increased amounts of packaging, very limited distribution circuits, important risk of costly wastage, risk that children will confuse cosmetic products stored in the refrigerator with food and an inconvenient and unpleasant experience applying cold products to the skin!
Are natural preservatives better than conventional (synthetic) preservatives?
Synthetic and natural preservatives can never be clearly separated by definition since all consumer substances must be chemically characterised regardless of production method. To illustrate this point, one can use the example of water obtained either by distillation, through the combustion of hydrogen in an oxygen atmosphere, or collection from a river. The water molecule is structurally the same regardless of its manufacturing process and this same argument can be applied for any molecule. Of course, other factors must be considered, such as product quality, purity and its carbon footprint. Indeed, a molecule produced by extraction from a vegetable may contain other by-products that may vary in nature and amount over time, depending on the origin of culture (a cultivated field at the edge of a highway or at the edge of a forest, or a culture in tropical countries or Nordic countries will not have the same impurities). On the other hand, a synthesis reaction, that can also have impurities, is more easily controlled. The impurities are more easily quantifiable and purification steps can be added whereas natural versions are limited by the nature of the processes of extraction and purification tolerated by the repositories of bio-cosmetics. In terms of quality and reproducibility, synthetic products are therefore better. Also the carbon footprint of a chemical reaction is much lower than that of an extraction from a vegetable that has been cultivated in another part of the world. Table 5 shows clearly that natural substances, e.g. botulin, can be many more times more toxic than synthetic preservatives, e.g. formaldehyde and parabens. In addition, the Directive 76/768/EEC Annex II listing substances that must not form part of the composition of a cosmetic product (Table 4), includes in addition to several chemicals, many plants that are considered as dangerous to human health and are therefore prohibited!
Conclusion
That a chemical is synthesised or extracted makes no difference to the dangers or risks linked to its usage in personal care. Indeed any ingredient should be exhaustively evaluated using a wide number of toxicological tests. It remains the responsibility of the cosmetic manufacturer to ensure that their formulations comply with the European cosmetic regulation. Natural preservatives cannot replace conventional substances on a large scale for regulatory and cost reasons, but mostly due to common sense and technical constraint. The choice given to formulators is already extremely limited, the formulation cost very high and the balance sheet does not favour this. This article considers only the existing solutions and cannot incorporate the innovations of tomorrow. It might indeed be possible to change this situation by finding and adding new natural molecules in Annex V: substances that will better meet the requirements of formulators, authorities, bio-cosmetics standards and consumers. In the longer term, it may be possible to consider the use of “friendly” microorganisms in order that they could live harmoniously in the environment and out-compete the growth of pathogenic microorganisms, as is already the case in the food industry, e.g. in sausages and yoghurt. However, this will require a change in the law as currently it is not only forbidden to place cosmetic products containing pathogenic microorganisms on the market, but also to exceed a certain threshold of total microorganisms (including non-pathogenic) in the finished product. As life always finds a way to survive, it would be necessary to regulate their growth to a level sufficient to ensure product safety while also ensuring consumer safety. This still leaves many years of research for the players in this market.
References
1 National Institute for Occupational Safety and Health (NIOSH), US & Centers for Disease Control and Prevention (CDC). 2 http://www.mitchellzhomes.com/AZAPAA/ azapaa_allergy.htm 3 European Directive 2000/13/EC & modifications. 4 Cosmetic Directive 76/768/EEC – 7th amendment 5 http://leflacon.free.fr/ 6 Regulation (EC) no 1223/2009 of the European parliament and of the council of 30 November 2009 on cosmetic products. 7 SCCP’s notes of guidance for the testing of cosmetic ingredients and their safety evaluation; 6th revision. 8 Natural Preservatives, Myth or Magic? Kevin Roden; Regional Technical Manager Asia Pacific; Thor Specialties.
