On 6th and 7th March 2023, renowned personalities and experts from the fields of cosmetics, dermatology, toxicology, law and analytics from all over Germany, Austria and Switzerland met to exchange knowledge, ideas and opinions at this year’s Karlsruhe Cosmetics Day (KKT). The aim was to learn about new trends and innovations in the cosmetics market and to assess the risks associated with them. In this first part of four, Prof Dr Johannes Geier, Dr Tilman Reuther, and Prof Dr Rolf Daniels talk about active Ingredients and the challenges they bring.
SPEAKER
Prof Dr Johannes Geier
Head of the Information Network of Dermatological Clinics (IVDK)
Contact allergies to ingredients
The prevalence of contact allergies to the preservative methylisothiazolinone (MI), which had been triggered by its increased use in cosmetic products and reached its peak in 2013/2014, has since decreased due to its removal from leave-on cosmetics. Only painters and varnishers continue to experience increasing sensitisation rates, likely due to the still unregulated use of MI in wall paints.
Sensitisation rates for other classical preservatives remain at very low levels. In particular, benzyl alcohol, which is also used as a fragrance and as a solvent, leads to sensitisation so rarely that one must ask whether it is a significant contact allergen at all. Reaction rates to fragrance mixtures tested for screening purposes have been declining more or less continuously since 2012. This is mainly due to the fact that the use of the main allergens of these mixes – atranol and chloratranol in oakmoss and hydroxyisohexyl 3-cyclohexene carboxaldehyde – has been banned in cosmetic products throughout the EU.
Sensitisations to other fragrances are – with few exceptions – rare and show no tendency to increase. Among the essential oils and natural extracts, ylang ylang (I+II) oil, lemongrass oil, jasmine absolute, sandalwood oil and clove oil lead to more than 1% positive reactions. Mainly patients with leg eczema and highly exposed persons such as masseurs and cosmeticians were affected. However, due to the inherent variability of the composition, it is unclear to what extent the tested oils/extracts correspond to the exposure of consumers. The hydroperoxides of limonene and linalool are currently in the focus of allergological interests. Many positive test reactions with unclear clinical relevance are opposed by chemical analyses of
consumer products which indicate – if at all – an extremely low exposure. Remarkable reaction rates were also observed in the IVDK. However, the test preparations did not prove to be particularly discriminating in diagnostic terms; false-positive reactions are likely, especially to the higher (too high) concentrated hydroperoxides of linalool tested.
Nevertheless, sensitisation is obviously possible.
The comparison of patients with a positive reaction with those with a negative reaction indicates the acquisition of sensitisation by possibly long-term and extensive application of corresponding local therapeutics and/or skin care products on previously damaged skin. Further studies are required and planned. Sensitisation to ethylhexylglycerol was observed only rarely. In case of positive epicutaneous reactions to decyl and lauryl glucoside, it should be noted that these surface-active substances may cause increased irritative and false-positive test reactions.
SPEAKER
Dr Tilmann Reuther
Dermatologist and lecturer
in cosmetic science at the
University of Hamburg, Germany
Effects and side effects
Today the use of active ingredients in cosmetic products is a widespread strategy for influencing various skin conditions, which in principle can be relevant for both dermatological and cosmetic issues. In this context, the treatment of dry skin and skin ageing symptoms is of particular importance. From a dermatological point of view, it is always interesting which active ingredients have been investigated within the framework of study designs known from clinical trials. The use of active ingredients against dry skin is often investigated in clear skin in atopy. Recent studies confirm the importance of water-binding molecules such as glycerol and urea compared to pure film-forming bases. In addition, current studies conclude that the direct use of ceramides and free fatty acids to improve the stability of the skin barrier is also possible. Among the active agents in the narrower sense, niacinamide, for which an effect on the skin barrier was already shown a while ago, should also be mentioned. In more recent studies this serves as a reference, for example, to evaluate the effect of birch bark extracts on the skin barrier function in the search for sustainable and natural ingredients.1,2,3,4
For influencing skin ageing, ascorbic acid and retinol are particularly worth mentioning, as they are on the one hand considered established and on the other hand the subject of current innovations. In 2022, for example, a study was published on the use of a tetra-isopalmitoyl derivative of ascorbic acid, also known as lipophilised ascorbic acid. Effects against skin ageing could be found from concentrations as low as 1%. This is also interesting because the effective concentrations of hydrophilic ascorbic acid are usually higher. In a study on retinol published in 2022, it was concluded that, in the case of photoageing, a so-called retinol complex (retinol 1%, retinyl acetate 0.05% and retinyl palmitate 0.05%) shows better tolerability and has comparable effects to retinoic acid 0.02%, which is only available as a drug. Since the authors also found differences in the effect on collagen-fragmenting enzymes (MMP), they conclude that the effects of the retinol complex cannot be attributed exclusively to the previously assumed conversion to retinoic acid.5,6
In conclusion, the use of active ingredients in common emerging issues such as xerosis cutis or skin ageing has shown interesting effects in various controlled studies. Even if the type of application and the results from these studies cannot always be applied to purely cosmetic issues, they show the spectrum of possible desirable and un-
desirable effects and can therefore not only deepen the mutual understanding but also be helpful for questions of delimitation.
References:
1 Danby SG et al. Clin Exp Dermatol 2022; 47: 1154-1164
2 Danby SG et al. Br J Dermal 2022; 186; 875-886
3 Bojanowski et al. J Invest Dermatol 2021; 141; 1416-1427
4 Smiljanic et al. Int J Mol Sci 2022; 23: 12507
5 Yokata et al. J Cosmet Dermatol 2022;21: 3503-3514
6 Chien et al. JAMA 2022; 158: 879-886
SPEAKER
Prof Dr Rolf Daniels
Department of Pharmaceutical Technology at the Eberhard Karls University Tübingen, Germany
Influence of formulation components
In a first approximation, there are three ways to influence pharmacokinetics: increasing the concentration of drug dissolved in the vehicle (thermodynamic activity), the distribution coefficient between vehicle and skin and the diffusion coefficient in the skin barrier (stratum corneum). In the pharmaceutical field, these three possibilities are actively used to increase efficacy. For example, by adding propylene glycol, both the solubility in the vehicle and the distribution coefficient can be influenced to increase efficacy.
In this context, it was interesting to answer the question to what extent alternative preservatives from the group of alkanediols (2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol) influence the absorption of active substances from a classic O/W cream.
The release of the model drug triamcinolone acetonide (TAA) was surprisingly slightly decreased by the shorter-chain alkanediols and significantly decreased by the longer-chain alkanediols, although the alkanediols increased the water solubility of the drug. Skin penetration of TAA was increased by all alkanediols. The penetration-promoting effect increased with increasing chain length. Since only the longer-chain alkanediols caused a significant disruption of the stratum corneum lipid arrangement, the penetration-enhancing effect of the shorter-chain alkanediols appears to be caused by other factors.
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Further PartsThe lectures were held on the KKT organized by the Chemical and Veterinary Investigation Office Karlsruhe (CVUA Karlsruhe). More information: www.ua-bw.de Part Two: Controversy in cosmetic regulations |
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