Bart Desmedt

Characterization of suspected illegal skin whitening cosmetics.

An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products. 163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin.

HS–GC–MS method for the analysis of fragrance allergens in complex cosmetic matrices

Potential allergenic fragrances are part of the Cosmetic Regulation with labelling and concentration restrictions. This means that they have to be declared on the ingredients list, when their concentration exceeds the labelling limit of 10 ppm or 100 ppm for leave-on or rinse-off cosmetics, respectively. Labelling is important regarding consumer safety. In this way, sensitised people towards fragrances might select their products based on the ingredients list to prevent elicitation of an allergic reaction. It is therefore important to quantify potential allergenic ingredients in cosmetic products. An easy to perform liquid extraction was developed, combined with a new headspace GC-MS method. The latter was capable of analysing 24 volatile allergenic fragrances in complex cosmetic formulations, such as hydrophilic (O/W) and lipophilic (W/O) creams, lotions and gels. This method was successfully validated using the total error approach. The trueness deviations for all components were smaller than 8%, and the expectation tolerance limits did not exceed the acceptance limits of ± 20% at the labelling limit. The current methodology was used to analyse 18 cosmetic samples that were already identified as being illegal on the EU market for containing forbidden skin whitening substances. Our results showed that these cosmetic products also contained undeclared fragrances above the limit value for labelling, which imposes an additional health risk for the consumer.

Detection of whitening agents in illegal cosmetics using attenuated total reflectance-infrared spectroscopy

Cosmetic products containing illegal whitening agents are still found on the European market. They represent a considerable risk to public health, since they are often characterised by severe side effects when used chronically. The detection of such products at customs is not always simple, due to misleading packaging and the existence of products containing only legal components. Therefore there is a need for easy to use equipment and techniques to perform an initial screening of samples. The use of attenuated total reflectance-infrared (ATR-IR) spectroscopy, combined with chemometrics, was evaluated for that purpose. It was found that the combination of ATR-IR with the simple chemometric technique k-nearest neighbours gave good results. A model was obtained in which a minimum of illegal samples was categorised as legal. The correctly classified illegal samples could be attributed to the illegal components present.

Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe

Lightening skin tone is an ancient and well‐documented practice, and remains common practice among many cultures. Whitening agents such as corticosteroids, tretinoin and hydroquinone are medically applied to effectively lighten the skin tone of hyperpigmented lesions. However, when these agents are used cosmetically, they are associated with a variety of side‐effect. Alternative agents, such as arbutin and its derivatives kojic acid and nicotinamide have been subsequently developed for cosmetic purposes. Unfortunately, some cosmetics contain whitening agents that are banned for use in cosmetic products. This article provides an overview of the mode of action and potential side‐effects of cosmetic legal and illegal whitening agents, and the pattern of use of these types of products. Finally, an EU analysis of the health problems due to the presence of illegal products on the market is summarized.

Illegal cosmetics on the EU market: a threat for human health?

inspectors, for the presence of legal and illegal skin-whitening agents. Study results revealed that 40 % of the 163 analyzed samples contained the very potent corticosteroid clobetasol propionate and almost 12 % were positive for tretinoin or hydroquinone. For almost all samples, concentrations were in the physiologically active range meaning that these belong to the world of pharmaceutical products and are definitely not cosmetic products (Desmedt et al. 2014). Other Member States such as the Netherlands and France, also investigated suspected skin-whitening cosmetics and likewise they detected hydroquinone and corticosteroids (ANSM 2009; VWA 2009). Probably, we are speaking here of a problem that is, not only present in Belgium but also in the different Member States. Cosmetic products are mostly used without any medical supervision, and side effects may occur induced by these products. This could especially be the case with skin-whitening cosmetics since they usually are applied excessively, repeatedly and over a long period of time, even cases as long as 5 years have been reported (Ladizinski et al. 2011). Several case reports describe as well systemic as local side effects, including nephropathy and exogenous ochronosis, respectively (Olumide et al. 2008; Charlin et al. 2008; Karamagi et al. 2001). We observed an additional problem for these illegal skin bleachers, namely they also contain allergenic fragrances, which need to be labeled, but in reality are not. Indeed, a cornerstone of prevention of allergic sensitization or elicitation reactions in already sensitized consumers consist of labeling suspected fragrance ingredients. Indeed, 26 allergenic cosmetic substances have been listed in the eU and others will follow (SCCNFP/0017/98; SCCS/1459/11). These must be taken up in the ingredients list on the package of the cosmetic products whenever they exceed the limits of 0.001 (w/w) and 0.01 % (w/w) for leave-on and Cosmetic products on the eU market must be safe for human health when applied under reasonable foreseeable conditions of use (eU 2009). This is achieved by prohibiting harmful substances (Annex II) and allowing a number of forbidden substances only under restricted concentrations or applications (Annex III). Also the use of colorants, preservatives and UV filters, which are considered to be potentially harmful for human health, is regulated via the positive Annexes IV, V and VI, respectively (eU 2009). From the reports of control laboratories, it is, however, known that in the eU, also cosmetics are commercialized that do not comply with the actual cosmetic regulation and contain banned substances. These are illegal products and could potentially be harmful for the consumer. Among these, skin-whitening cosmetics are well represented. They are used to generally lighten skin tone or bleach pigmentation spots of different origin. They often contain pharmaceutical actives that are forbidden in cosmetics, including hydroquinone, tretinoin or even potent corticosteroids (Desmedt et al. 2013; ANSM 2009; VWA 2009). To understand the situation on the Belgian market, we analyzed suspected and confiscated cosmetics by Belgian

Contents Vol. 29, 2016

N. Ahmad, Madison, Wis. C. Antoniou, Athens J.M. Baron, Aachen E. Benfeldt, Roskilde E. Berardesca, Rome K. De Paepe, Brussels P. Elsner, Jena A. Farkas, Zurich N. Garcia Bartels, Berlin M.W. Greaves, London R.H. Guy, Bath S. Hedtrich, Berlin E.M. Jackson, Bonney Lake, Wash. H. Kandárová, Ashland, Mass. L. Kemeny, Szeged J. Kresken, Viersen J. Krutmann, Düsseldorf B. Lange-Asschenfeldt, Klagenfurt am Wörthersee R. Neubert, Halle T. Ruzicka, Munich M. Schäfer-Korting, Berlin M. Schmuth, Innsbruck S. Seidenari, Modena P.W. Wertz, Iowa City, Iowa J. Wohlrab, Halle L. Zastrow, Monaco Journal of Pharmacological and Biophysical Research

In vitro Dermal Absorption of Hydroquinone: Protocol Validation and Applicability on Illegal Skin-Whitening Cosmetics.

In Europe, hydroquinone is a forbidden cosmetic ingredient. It is, however, still abundantly used because of its effective skin-whitening properties. The question arises as to whether the quantities of hydroquinone used become systemically available and may cause damage to human health. Dermal absorption studies can provide this information. In the EU, dermal absorption has to be assessed in vitro since the Cosmetic Regulation 1223/2009/EC forbids the use of animals. To obtain human-relevant data, a Franz diffusion cell protocol was validated using human skin. The results obtained were comparable to those from a multicentre validation study. The protocol was applied to hydroquinone and the dermal absorption ranged between 31 and 44%, which is within the range of published in vivo human values. This shows that a well-validated in vitro dermal absorption study using human skin provides relevant human data. The validated protocol was used to determine the dermal absorption of illegal skin-whitening cosmetics containing hydroquinone. All samples gave high dermal absorption values, rendering them all unsafe for human health. These results add to our knowledge of illegal cosmetics on the EU market, namely that they exhibit a negative toxicological profile and are likely to induce health problems.