CHRISTINE OLESCHKEWITZ¹, ANDREA MALTAGLIATI²
1.    Chair of EFfCI Working Group Preservatives
2.    EFfCI Secretary General

The cosmetics market is strongly regulated from a public safety standpoint as laid down in Article 3 of the European Cosmetics Product Regulation No. 1223/2009 (CPR), where it is stated that ”…a cosmetic product made available on the market shall be safe for human health when used under normal or reasonably foreseeable conditions of use.”
This includes that cosmetic products must be protected from possible contamination and germs that could be hazardous to the health of the consumer. Ultimately, the cosmetic product must be safe, regardless of whether a preservative is used or not.
From authorities’ special attention is paid to following ingredients, independent from their natural or synthetic origin:

• CMR substances: substances which are classified as carcinogenic, mutagenic or toxic for reproduction
• Endocrine Disruptors: substances that may have an influence on the hormonal system and cause adverse health effects in an intact organism, or its progeny
• Allergenic compounds: substances that trigger a hypersensitivity disorder of the immune system with superficially similar symptoms to skin irritation.

Since the implementation of the first European Cosmetics Directive in the 1970s, the evaluation criteria for cosmetic ingredients have become significantly stricter. It is therefore not surprising that the European Commission (COM) is striving to close data gaps and is committed to investigating any suspected health hazard.

When it comes to preservatives, the following substances from Annex V of the CPR, the positive list of permitted preservatives, have been affected in recent years.

In Europe, ECHA regulates the classification of a substance as a CMR substance under the Classification, Labeling and Packaging (CLP) Regulation (EC) No. 1272/2008. Article 15 of the CPR foresees a ban of substances classified as CMR for use in cosmetics except if an exemption is adopted by the COM. To ensure a smooth process the COM revised its interpretation of Article 15. CMR substances following CLP classification are not automatically banned, but an implementation act, called the “Omnibus Act”, is needed to provide legal certainty. Since the introduction of this process, some preservatives have been banned, some have been further restricted, and one has been shown to be safe at the previous use concentration. 

A second key topic is the influence of endocrine disruptors on the hormonal system. The possible adverse effects in humans can include developmental malformations, reproductive disorders and an increased cancer risk.
The subject is not new in the cosmetics industry; in fact, the COM launched a data call back in 2019 to prepare requests for scientific opinions to the Scientific Committee on Consumer Safety (SCCS) (1). Interested parties were invited to submit all relevant scientific information to confirm a safe concentration limit. There are also six preservatives on the list of 28 cosmetic ingredients. Three parabens received a positive SCCS opinion and can continue to be used in the approved use-concentrations. The other three preservatives, triclosan, triclocarban and salicylic acid, are considered safe, but their use has been further restricted for certain applications and for certain age groups.

Preservatives are biologically active molecules that are designed to prevent or inhibit germ growth to ensure both product and health protection. While they have antimicrobial properties, they may also cause unwanted reactions, such as contact allergies. Even though most preservatives have a low prevalence, they are under observation, particularly as exposure increases. There are only a few Annex V substances that have led to increasing allergy rates in recent decades due to their high exposure, not least triggered by uses outside of cosmetic products. Prominent examples include Methyldibromo Glutaronitrile, which was banned in 2008, and isothiazolinones (Methylchloroisothiazolinone and/or Methylisothiazolinone), whose use in leave-on products was banned a few years ago.

However, the COM’s last initiative on possible allergenic substances was not about a ban, but rather a stricter labeling requirement to warn allergy sufferers about all substances from Annex V, which may under certain conditions release formaldehyde over time (2).

Free formaldehyde can be released by Annex V substances such as Benzylhemiformal; Diazolidinyl Urea; Dimethyl Oxazolidine; DMDM Hydantoin; 7-Ethylbicyclooxazolidine; Hexetidine; Imidazolidinyl Urea; Methenamine and Sodium Hydroxymethylglycinate.  It is not described whether the COM will also monitor 2-Bromo-2-nitropropane-1,3-diol and 5-Bromo-5-nitro-1,3-dioxane. For Bronopol and Bronidox, they hardly release formaldehyde when used and have a different mechanism of action.

As expected, this step by the COM does not lead to an ‘informed decision making’ for possible allergy sufferers, but rather to a rapid phase-out of this group of substances in order to avoid the warning on the cosmetic package. Unlike food, for example, warnings on cosmetic products are viewed by consumers as threatening rather than informative.
A lot of educational work is still needed here because, just like with food ingredients, any cosmetic ingredient can trigger allergies in sensitized people. This should not worry consumers as cosmetic manufacturers are completely transparent about all ingredients and it would be easy to identify suitable cosmetic products through an individual profile, for example through a scanner app, without denigrating substances that are useful for the majority of the population. The biggest challenge at this point is to uncover the sensationalism and scaremongering of various interest groups and to counteract it with transparency and education in order to regain consumer trust in safe cosmetics.

The list of permitted preservatives in cosmetic products includes 60 entries and taking all derivatives into account, approximately 130 substances can be used for the purpose of preservation. At first glance it looks like an extensive portfolio but taking the reassessments of the last few years into account and the actual use in the industry, a completely different picture emerges. 
To give just a few examples: 8 entries are already deleted, 5 entries are banned for leave-on applications, another 6 entries are forbidden for oral care, 3 entries cannot be used in aerosols dispensers, and 5 entries are not allowed for children products. There are now 21 entries that require a warning if they are used in certain applications or if concentrations exceed a certain limit. This has resulted in these substances being avoided by manufacturers. In the end, from the initial 130 substances, only 30 – 40 remain that are standardly used. And depending on the cosmetic formulation, they are also subject to other aspects that influence their use, such as:

• Technical aspects: efficacy, incompatibilities, usability, pH, odor, color, etc.
• Economical aspects: availability, costs
• Ecological aspects: sourcing, sustainability
• Market demands and trends: natural and sustainable ingredients, no animal testing, free from animal derived material, free from discussed ingredients, etc.
• Public opinion: loss of reputation of approved substances due to derogatory reporting and marketing claims

With the shrinking toolbox, the call for new preservatives is obvious. But to glimpse into the future, a look into the past is required first.
Preservatives were first listed in the mid-1970s with the first European Cosmetics Directive.
39 substances and their families that were already on the market were included in the positive list.
In the decades that followed, only a few other substances have met the criteria. In the last 20 years in particular, no truly new chemicals have been added to the list and it is not expected that many more will be added under today’s conditions.
EFfCI members reported on why it is so difficult to add new substances to Annex V in Europe.

First, the raw material manufacturer must find a substance whose primary function is preservation, and then a long journey begins:

• Full safety dossiers that cost several million Euros are required prior to product launch and regardless of sales volume.
• The review timescales to gain approvals are long, usually it takes years. For some of the last entries it took almost 10 years to get the approval.
• Conservative approaches to data review mean that a positive outcome is uncertain.
• The animal testing ban means the required data for sub-chronic and chronic endpoints cannot be generated as the relevant validated in-vitro tests are not available yet.
• Once listed in Annex V an ingredient can be supplied by any company, therefore, there is no protection on the investment of the original applicant.

New incentives are needed in the future to promote the industry’s innovative strength.

It is common practice of the authorities to reassess cosmetic ingredients. Discussions about active ingredients require clarification from a scientific and regulatory perspective. This takes time, usually several months or even years. However, discussions about active ingredients quickly attract the attention of the media, NGOs and consumers within a very short period of time. Often within just a few days.
Today, just the suspicion of a health risk quickly leads to preventive measures and avoidance strategies along the supply chain. By the time that a substance has been reassessed by the authorities, its reputation has suffered unrecoverable damaged, and the market already looked for alternatives. Cosmetics manufacturers bow to consumers’ fears and remove safe substances from their formulas; many manufacturers are also tempted to advertise with this and thus promote the denigration.
In Europe, a first step to prevent denigration of approved ingredients is the Technical Document on Cosmetic Claims, which came into force in 2019 (3). Meanwhile many stakeholders from the cosmetics industry use “free-from” claims only for informed decision-making and no longer against permitted substances. 
In Europe, this is particularly evident in the decline of the claim “paraben-free”, while it is still increasing in other regions.
This is a good example showing how the industry can make a difference if wanted to.

Increased scrutiny and reassessments of traditional preservatives by legislative bodies has become part of the normal regulatory process. While several preservatives have been banned or restricted for certain uses, others have been approved safe as already used. Unfortunately, safety approvals do not necessarily improve the reputation of preservatives once rejected by consumers.

The cosmetic industry is fully aware of the correlation between those different factors and is concerned about the declining number of allowed listed preservatives. Interested parties from across the spectrum of the cosmetic industry are investigating in preservative protection projects and are promoting a holistic approach to maintain a wide palette of antimicrobial substances and technologies to protect cosmetic products from microbial growth. The shared mission is to enable the continued delivery of safe and acceptable ingredients to the cosmetic formulation market by ensuring that the regulatory environment not only meets current needs, but also enables innovation for future generations.