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S1-AWMF Guideline Occupational Skin Products: Protective Creams, Skin Cleansers and Skin Care Products DOI: 10.17147/ASUI.2015-05.05-02 M. Fartasch1, T.L. Diepgen 2, H. Drexler3, P. Elsner4, S.M. John5, S. Schliemann4  current tab: Abstract Abstract Occupational Skin Products: Protective Creams, Skin Cleansers, Skin Care Products S1-AWMF Guideline Job-related hand dermatitis heads up the list of reported occupational diseases. So-called skin products – understood to mean protective creams, skin cleansers and skin care products – are used for the primary and secondary prevention of job-related hand dermatitis. In the interests of evidence-based medicine, the only preventive measures and/or occupational skin products that should be used are those whose potential uses and efficacy are underpinned by scientific research. To this end, the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (Working Group for Occupational and Environmental Dermatology, ABD) of the DDG (German Dermatological Society) and the Deutsche Gesellschaft für Arbeits- und Umweltmedizin (German Society for Occupational and Environmental Medicine, DGAUM) have summed up the latest scientific findings and recommendations in the updated guideline. The benefit of the combined application of protective creams and skin care products in the primary and secondary prevention of work-related contact dermatitis has been widely confirmed by recent clinical-epidemiological studies. The guideline clearly explains the necessity of demonstrating the efficacy of protective creams and cleansing products by means of in vivo methods in the sense of repetitive applications. Transferable standardised testing systems designed to examine the irritation potential and thus the compatibility of occupational skin cleansers and the reduction of irritation by protective skin creams have now been developed and validated by multicentre studies for skin protection creams and cleansers. The status of the current assessment of the safety of occupational skin products is also summarised.

Keywords: Guideline – occupational contact dermatitis – prevention – protective creams – skin cleansers – skin care products Introduction The guideline deals with protective creams, skin cleansers and skin care products (summed up as "occupational skin products") provided by the employer for the employees of a business as part of an integrative skin protection concept for the prevention of job-related skin diseases. These products may also be prescribed by doctors at the expense of the respective accident insurance company in connection with a dermatologist consultation or a report of a suspected occupational disease. Unlike pharmaceutical products, the testing of the efficacy of skin products by means of clinical studies is not a statutory requirement. Skin products are subject to the Cosmetics Regulation, which requires proof of the efficacy of the claimed properties but does not stipulate how this should be done. In the past it was not possible to back up the claims made for protective creams (e.g. "liquid glove") either within the context of studies or in actual practice. Scientific research can be said to have disproved the conventional notion that hydrophilic skin products (e.g. o/w emulsions) are particularly effective when handling lipophilic working substances, and lipophilic skin products (e.g. w/o emulsions) when handling aqueous working substances. However, it is an undisputed fact that the external application of lipid-replenishing products and a gentle skin cleanser help to ensure that the skin better tolerates the stresses to which it is exposed in the workplace and regenerates faster if exposure occurs. In particular, if frequently working in damp environments (wet work, see TRGS [Technical Rule for Hazardous Substances] 401) it must be assumed that subclinical skin damage will occur. The use of skin products will have a positive effect here. However, it is not simply of academic interest to know whether skin products protect the skin or promote the regeneration of the damaged horny layer, because the mechanism of action gives rise to a variety of implications for prevention:  Selection of skin product (depends on working substances and skin condition)  Time of application (before or after activity stressful to skin)  Target group (focus on people with healthy skin or on employees with minimal skin lesions)  Health education recommendations ("Protect your skin with skin products", "Protect your skin by behaving sensibly and look after it"). Of all the reasons (further compliance, cost-benefit analysis, potential risks of preventive measures), it must be ensured that the efficacy of the recommended preventive measures is scientifically proven. It is in the interests of evidence-based medicine to examine any preventive tools to ascertain whether they do what they say and whether their benefits are greater than the potential risks. It is against this background that the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie (Working Group for Occupational and Environmental Dermatology) (ABD) in the DDG (German Dermatological Society) and the Deutsche Gesellschaft für Arbeits- und Umweltmedizin (German Society for Occupational and Environmental Medicine) (DGAUM) consider it necessary to compile a guideline for skin protection, care and cleansing. This guideline is based on current scientific knowledge as presented in national and international reference literature. The guideline is a revised and amplified version of the "Berufliche Hautmittel" (Occupational Skin Products) guideline, which was published in 2009 by Arbeitsgemeinschaft Berufs- und Umweltdermatologie (ABD) [1]. Neither this guideline nor the preceding one deal with skin creams which protect against UV rays and organic and/or inorganic UV filter substances and are of importance in certain occupational groups. 1 Occupational skin products – definition, use and application 1.1 General information The occupational skin products summarised in this guideline are understood to mean protective creams, skin cleansers and skin care products for job-related use. In the narrower sense, the term "protective creams" is understood to refer to products for topical use whose main purpose is to protect the skin from irritation (Protection) [2, 3]. Suitable products should be applied in the workplace before and during work as part of the integrative skin protection concept (also described as a 3-pillar model). For a so-called "3-pillar model", or integrative skin protection, the protective creams are supplemented by skin cleansers designed to remove dirt and aggressive substances without significant irritation (gentle) and by skin care products, i.e. products able to help restore/regenerate the skin barrier (care) [4–6]. From the perspective of manufacturers of protective creams, however, the term "protective creams" is understood to mean not only products designed to minimise potential irritation by working substances, but also products designed, for example, to make it easier to cleanse the skin by applying a protective cream beforehand or to reduce swelling caused by excessive perspiration and thus have an indirect effect on the condition of the skin and the epidermal barrier. Occupational skin products are seen as cosmetics in the legal sense. Like all cosmetic agents, they are subject to the European Union (EU) Cosmetics Regulation (see also section 3.1). In addition to this, occupational skin products are a recognised component of personal protective equipment (PPE) under the EU Use of PPE Directive. Personal protection measures are understood to be the wearing of protective gloves, the application of protective creams prior to working, appropriate skin cleansing and the use of skin care products to assist the regeneration of the skin after finishing work. The order of precedence of prevention measures requires that personal protection measures are used when substitute materials have been tested and all technical and organisational measures have been exhausted. A thorough analysis of skin stress in the workplace is a prerequisite for choosing the right skin protection measures. Measures to prevent skin damage should be adapted to the individual situation [6, 7], with the involvement of the company medical officer and the safety expert [8]. The predominant area of application of occupational skin products is in the prevention of cumulative subtoxic contact dermatitis (synonym: irritant contact dermatitis). This mainly occurs in jobs with repetitive exposure to potential irritants and work in damp conditions. As there is a close connection between irritation and the development of sensitisation, which is explained not only by the easier penetration of allergens but also by the proinflammatory stimulus of the irritation [9–11], the prevention of irritant contact dermatitis is particularly important. If an allergy already exists, the use of skin products to prevent allergic contact dermatitis must be regarded as critical [12]. As well as technical and organisational measures when handling corrosive, toxic, mutagenic or carcinogenic substances, however, the use of chemical-resistant protective gloves is essential and cannot be replaced by protective creams [6]. So-called "hand protection" (gloves used for work) is addressed in this guideline only in relation to the potential occlusive effect. In particular, the use of skin products must be classed as critical when handling substances absorbed through the skin if it cannot be ruled out that the absorption of substances into the body is influenced by them (see section 3.4.). 1.2 Protective creams and skin care products Manufacturers recommend applying protective skin creams prior to any exposure to noxa that irritate the skin, after breaks or even after a specific period of time (e.g. a half-shift). The skin should be cleaned and dried before each fresh application to prevent any irritants left on the skin from penetrating it [4]. As a rule, the efficacy of an occupational skin protection cream is linked to its overall formulation rather than to individual ingredients. Scientific knowledge basically allows a variety of galenic systems for the formulation of occupational skin protection creams, (e.g. w/o, o/w, amphiphilic and multiple emulsions, suspension salves, hydrogels and oleogels) [2]. Special ingredients can be used to broaden the therapeutic spectrum of a protective cream or to enhance the efficacy of a formulation [3]. Examples of such additives to protective skin creams are perfluoropolyether [13, 14], aluminium chlorohydrate [15] and synthetic tanning agents [15, 16], the last two being mainly recommended if it is thought that the horny layer is weakened by sweat [17, 18]. This is why it makes sense to have such ingredients in protective creams but not in skin care products applied after finishing work. Conversely, many of the ingredients typically used in skin care products are not entirely suitable for use in skin protectants. This applies, for example, to urea: owing to its potential to promote penetration, it is not advisable to apply this before work but it does make sense to use it in agents applied to the skin after finishing work. Items designated as so-called skin care products should be used to "promote the regeneration" of the skin. Their use is considered essential after finishing work and after cleansing the skin. A particularly important aspect of job-related skin care products – as defined by the guideline – is the barrier-regenerative effect, although there are still no consistent and/or standardised test protocols to provide evidence of this (for more details on this see section 2.2.1). It used to be assumed that recourse should be made exclusively to lipophilic formulations such as w/o emulsions or oleogels for protection against water-soluble noxa and for use on skin exposed to wet work and, conversely, that only hydrophilic formulations such as o/w emulsions or suspensions were effective on skin in contact with non-water-soluble working substances. Over 20 years ago, however, efficacy tests based on in vivo methods showed that this simplified classification is not generally valid [19]. This is why it is not possible to assess the efficacy of a protective skin cream on the basis of a theoretical observation of the respective galenic system. Furthermore, it is not possible to identify the irritant potential simply based on the pH value of protective creams and skin care products (leave-on products). Whilst some studies indicate a possible disruption of the barrier function by leave-on products with relatively high pH values [20], a direct study showed that leave-on products with relatively high pH values are well tolerated even by previously irritated skin [21]. An individual study of the efficacy of skin products using the methods mentioned in section 2.2 is therefore essential. For increased acceptance from the perspective of dermatology and occupational medicine, however, consideration must also be given to factors such as absorption capacity and the compatibility of the preparation used with job-related activities (e.g. reduction in grip and corrosion protection of a metalworking tool). The debate continues as to whether there is good reason to define individual components for use before, during and after work, especially in the distinction between protective creams and skin care products, as in the so-called "3-pillar model". The fact that it is useful to have not only a didactic/conceptual separation is now supported by current studies, which have been able to show that the simultaneous or additional use of skin protectants or the sole use of care products can protect and regenerate stressed skin [3, 22]. On the other hand, the protection of skin prior to exposure was the most important aspect of all measures in studies to date and could not be replaced simply by care products [22–25] (for more details on this see section 2). All in all, the available data on the changing interaction between protective creams/skin care products with the skin and irritants in the workplace are still not sufficient to reliably assess what specific mechanism of action of protective creams/skin care products is connected with the protection, stabilisation and regeneration of the epidermal barrier. 1.3 Skin protection inside gloves The increasing importance of jobs using gloves [26–31] gives rise to the question of what role skin protection preparations could play in these areas. If protective creams are used together with gloves, it must be ensured on the one hand that the protective effect of the latter is not impaired by the cream used [3] and, on the other, that due consideration is given to the potentially negative effect of occlusion on the epidermal barrier. It is difficult to evaluate a positive effect or a reduced occlusive effect by preparations designed for this purpose, as it has always been hard to provide evidence of occlusive effects on the skin in experiments. Experimental in vivo studies recently proved that skin occluded for a certain duration reacts more sensitively to exposure to detergents after occlusion [32]. Comparative studies building on this produced no convincing proof that protective creams (previous studies with gels), which are recommended inside gloves, actually do what the manufacturers claim, i.e. barrier stabilisation or reduction of sweat production by adding aluminium chlorohydrate and other astringent and sweat-reducing substances (e.g. tannic acids) [33]. For a discussion on the use of aluminium chlorohydrate see safety assessment (section 3.1). 2 Skin products in the primary and secondary prevention of work- related skin diseases – proof of efficacy 2.1 Use and significance in the workplace – epidemiological findings The incidence of work-related hand dermatitis is 0.5–1 per 1000 working people per year in Europe [34, 35], with the number of undetected cases being many times higher (at least 30 to 50 times) [36]. The prognosis is still poor to some extent. The socio-economic costs [37–39] and the impact on the quality of life of those affected appear to be considerable, as recent studies have revealed [40–43]. Work-related skin conditions have been at the top of the list of reported occupational diseases for many years, with over 90% of cases being contact dermatitis which nearly always occurs on the hands. Prevention (primary, secondary and tertiary) is thus very important. 80% of cases of occupational hand dermatitis occur in just 7 occupational groups/areas. These are hairdressing, the metalworking industry, the health professions, employees in the food industry, the construction trade, painters and cleaners [34]. The one-year prevalence in population-based studies among employees in various occupations is well over 10% [44]. In a prospective epidemiological study of apprentices in the metal industry the one-year prevalence was 9% and the 3-year prevalence was actually 15% [45], with at least one case of hand dermatitis occurring in 30% after a follow-up observation period of 13 years (median) [46]. In 40% of those who had already developed hand dermatitis during training, the condition persisted after training [46]. A Danish study showed that job-related hand dermatitis led to 23% of people losing their job within a year, with 20% unfit to work for a long period of time [47]. The poor prognosis for job-related hand dermatitis is backed up by a Swedish 15-year follow-up study [48]: it healed up in only 28% of cases, 70% reported symptoms of the disease in the last year, and 52% had dermatological reactions for half of the 15-year follow-up study. Although experimental methods to prove the effectiveness of protective creams have been steadily improved and complemented by many more methods in recent years (see section 2.2.1), in vitro and in vivo methods to prove the effectiveness of protective creams often fail to consider the actual situation in the workplace or only do so to a very limited extent [8, 49, 50]. From the perspective of evidence-based medicine, large randomised clinical trials are considered to be the best quality whilst, depending on the problem in question, epidemiological studies have the same value or may even be more suitable [51]. The proof of the efficacy of skin products within the context of epidemiological studies is difficult for methodological reasons. Very few intervention studies have been done to prove the effectiveness of skin products in businesses to date and they are difficult to interpret owing to the low number of cases [50]. A controlled study to monitor a prevention programme in the case of wet work was carried out in a number of homes for the elderly in Copenhagen [52, 53]. Individual jobs in different homes were randomly assigned to an intervention group and a control group. A training programme on the use of skin protection (correct use of gloves, correct hand cleaning, correct application of hand disinfectants and skin care products) was carried out in the intervention group and the relevant products were provided. The intervention group (n = 207) and the control group (n = 168) were examined at the start of the study and five months later. At the end of the study, significantly fewer skin problems were detected in the intervention group than in the control group. Compared to the control group, the intervention group also had a superior understanding of skin protection measures and the avoidance of activities stressful to the skin. In another intervention study in a metalworking plant with very high levels of exposure to skin irritants, it was possible to significantly reduce the incidence of work-related dermatological reactions, especially hand dermatitis, after introducing a skin protection programme [8]. It was possible to rule out any changes to production processes as a reason for the decline in work-related hand dermatitis. A pilot study conducted in the mineral oil industry likewise showed that the introduction of an integrative skin protection concept can reduce the incidence of hand dermatitis [54]. Depending on the study group, clinical studies that prove the efficacy of protective creams and skin care preparations examine either the primary preventive aspect (i.e. only employees with healthy skin are involved [15, 52, 53, 55, 56]) or the therapeutic aspect (i.e. the employees already have skin lesions such as erythema and flaking, or manifest skin conditions such as eczema and the secondary/tertiary aspects of skin protection are thus appraised [57–63]). In addition to this, there is a series of clinical studies that investigates acceptance and the correct application of skin protection products [64–66]. Other studies report on the value of skin products within the context of secondary prevention, especially when running so-called seminars on secondary individual prevention [67, 68]. It has also become clear in the process that the success of a skin protection programme depends not only on the provided protective creams, skin cleansers and skin care products being attuned to one another and selected in line with the individual workplace exposure, but also on the employees being suitably informed about the skin protection measures provided. A recent controlled intervention study looked into the effectiveness of the generally publicised skin protection concept [25]. 1020 male test subjects who were fit for work volunteered to take part in the intervention study. They were randomly assigned to one of a total of four measures. Every test subject was observed for exactly 12 months. Both hands were examined three times during the one-year observation period with the help of a quantitative skin score and a standardised interview was held. The changes in the skin score after one year compared to the original findings were defined as the primary outcome. Visits to the doctor and incapacity to work due to hand dermatitis were recorded as a surrogate for the severity of the disease during the observation period. After 12 months, it was possible to analyse 800 test subjects (78.4% of all those recruited). Compliance with the randomised measure depended on the measure in question and ranged from 73.7% to 88.7%. Whereas a significant worsening of the skin findings was recorded for the control group, the greatest and most significant improvement was observed in the group that used protective creams and skin care products. The sole use of skin protection cream had the second-best score. An incapacity to work owing to hand dermatitis within the 12-month observation period only occurred in three test subjects (0.4%), who actually abstained from using protective creams and skin care preparations. Table 1 summarises the scientific evidence for the skin protection and skin care elements, and for the overall concept based on clinical studies (exception: [69]). Protective preparations serve above all to treat cumulative toxic contact dermatitis, although some prevent secondary skin problems by wearing protecting clothing and facilitating hand cleansing. To guard against specific hazards, protective preparations should be applied before and during work with care, i.e. between the fingers and on the nailbed as well. The protective action of special protectants is directed against individual skin hazards rather than all of them. There is no universal protection cream: the properties of products must be attuned to the physicochemical profile of the respective noxa When using skin cleansers, it must be noted that products with comparable cleansing actions can still differ greatly in terms of their skin compatibility [81]. This is why it is especially important to choose a suitable cleanser. The selection and composition of cleansers essentially depends on the nature of the contaminants (ordinary, coarse, special), whereby a graduated scheme should be observed depending on the degree of soiling. Cleaning procedures with technical cleaning agents, brushes or pumice stones and the use of hand cleaning agents with highly abrasive additives such as sand or pumice powder exert a lot of stress on the skin and are to be avoided at all costs. A gentler skin cleansing routine may take more time. Skin care after work is an essential component of prevention whenever the skin is dried out by water, surfactants, grease solvents or other job-related factors. Suitable skin care preparations are designed to feed the skin with lipid components, moisture and hygroscopic substances outside working hours when it is not under stress. It may thus be possible to normalise increased transepidermal water loss as a result of work-related stress, which indicates a disturbed barrier function. If the epidermal barrier has already been damaged, however, skin care can be expected to have little effect. It is vital to restore the barrier function as fully as possible with the help of dermatological measures, otherwise an immediate relapse and a worsening skin condition are to be expected. 2.2 In vitro and in vivo methods to prove the efficacy of occupational skin products 2.2.1 Proof of efficacy of protective creams and skin care products The gold standard for the proof of efficacy of occupational protective creams and skin care products are cohort and intervention studies that consider the actual workplace situation. In contrast, it is hard to conduct randomised, double-blind and controlled studies including a placebo in specific workplace conditions owing to organisational and methodological difficulties and the resources needed [3, 50]. The present intervention studies did not aim to test the effectiveness of individual protective creams or skin care preparations. On the contrary, a complete skin protection programme was studied, which included employee training courses, the optimisation of work processes and other organisational measures [8, 24, 50, 60, 82]. The findings of these studies are difficult to interpret owing to the small number of cases or relatively short observation periods and cannot therefore be compared. Further intervention studies investigated the use of a combination of pre-exposure skin protection and post-exposure skin care compared to the use of individual components of the integrative skin protection concept ("3-pillar concept"). A four-way randomised prospective intervention study of 1020 metalworkers incorporated a large number of businesses using a variety of protective creams and skin care products. The overall evaluation revealed that the combination of skin protection and skin care was significantly superior in terms of improving skin condition, followed by the sole use of skin protection [25] (for more details on this see section 2.1). Another four-way intervention study with 1006 employees in the building trade likewise showed that the combination of skin protection and skin care produced the best results [22]. In the area of secondary prevention, an intervention was carried out as part of a Danish prospective intervention study with nurses [26, 31] who already exhibited hand dermatitis (n = 255 – an intervention was carried out with 123, 132 served as control). The effectiveness of the skin protection programme was documented with a reduction in the eczema score. A fragrance-free "lipid-rich moisturiser" was applied externally before, during and after work. As is generally known, most international studies do not differ in principle or for didactic purposes between skin protection and skin care. As an alternative to intervention studies, the efficacy of individual preparations can be tested in model experiments under idealised conditions. The test methods and study design must be adapted to the intended use or to the efficacy claim of the product to be tested. Whilst the same methods can in principle be used to test the efficacy of occupational skin care preparations as for other skin care products that claim to stabilise and/or regenerate the skin barrier, the efficacy of occupational skin care preparations must be tested by methods that have been specially developed for this product class (Overview by [2, 3]). A distinction must be made here between in vitro, ex vivo and in vivo methods, which can be used individually or in combination [83–85]. The outcomes of the various techniques differ in terms of their significance and must be duly taken into account. In vitro and ex vivo methods to prove the efficacy of skin products The object slide test [86], filter paper membrane tests [84], chamber penetration tests with synthetic membrane or excised human or animal skin [87–89], membrane diffusion tests [90], a multilayer membrane model [91], absorption studies on excised human skin [92], three-dimensional human skin models [93–100] and the model of isolated perfused bovine udder skin [101–103] have been described as in vitro and ex vivo methods to prove the efficacy of skin products. Studies based on the binding of dye molecules to the skin after applying protective cream are done in vivo [104] or on excised skin [16, 105–107]. These methods can provide information on penetration but not about the changes to be expected in terms of diminished irritation. On the whole, it is currently thought that any test outcomes obtained with in vitro methods serve only as guidance. The outcomes of these methods can only indicate partial aspects of a possible protective action, because physiological effects in vivo are substantially more complex. Furthermore, the methods have not been correlated with the in vivo methods to date and thus provide very limited information for assessing the efficacy of protective cream. The same is also true of ex vivo models (horny layer-forming keratinocyte cultures, three- dimensional human skin models, perfused bovine udder skin), which also test biochemical, immunological and/or morphological parameters. These can only give indirect information about expected efficacy. Dermal components of an inflammatory reaction, such as dermal inflammatory reaction with enlargement of blood vessels and inflammatory cell migration cannot be simulated here. Furthermore, these methods only deal with mostly short-term/one- time exposure to noxa. This is why the results obtained are not suitable for drawing any conclusions about a possible protective effect in the case of cumulative irritancy exposure. Regardless of initial evidence of a correlation with in vivo data [100–102], these methods have not been validated to date either, and their significance for a protective effect against cumulative irritation is not as yet proven in vivo. Consequently, as an alternative to intervention studies, the efficacy of individual preparations should be tested in model experiments under idealised conditions. The test methods and study design must be adapted to the intended use or to the efficacy claim of the product to be tested. In summary, it is preferable for proof of efficacy to be tested by in vivo methods (e.g. repetitive irritation model) if it is not possible to conduct cohort and intervention studies. In vivo methods to prove the efficacy of skin products Owing to the uncertain/limited suitability of in vitro and ex vivo methods to provide information, testing to prove the efficacy of protective creams should be complemented by studies using in vivo methods that reflect the latest scientific findings. This particularly applies to those creams that claim to protect against skin-irritating working substances. Special irritation models have been developed to test the effectiveness of these protective creams. Due to the diversity of occupational noxa and the fact that many of them cannot be incorporated into such model trials for ethical and often methodological reasons, use was made in the past of standard irritants (sodium lauryl sulphate, caustic soda, lactic acid and toluene) that were considered to be approximately representative of groups of noxa with differing properties. Current research indicates that the different noxa - owing to their physicochemical characteristics - result not only in different penetration routes or compounds (deposit build-up) within the epidermal barrier of the skin but also in different responses by the skin to the infiltrating agent [108–115]. When selecting a method, priority must be given to repetitive irritation models, which are better from a practical point of view, rather than models with one-off application. With repetitive models, the products and irritants to be tested are applied several times over a defined period either as occlusive patch [19, 115–119] or open within the context of standardised underarm washing [120, 121]. Repetitive irritation tests have become the accepted standard in many places in recent years, but with different protocols. It was possible to show that, with suitable test concentrations and application times, a one-week repetitive application of diluted irritants is sufficient to permit testing of the efficacy of skin protectants [119, 122]. This was backed up in a blind multicentre study by the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie (ABD). This study looked at the protective action of several standard formulations against sodium lauryl sulphate and toluene during a five-day repetitive application in the underarm region. In terms of irritation reduction, it revealed differences between the tested formulations which could be confirmed and reproduced in equal measure in a comparison of all six of the participating centres [118]. As well as a visual assessment, non-invasive biophysical (skin physiological) measuring systems are used to record the irritant effects in virtually all studies. Some of these are experimental methods such as Fourier transform infrared (ATR-FTIR) spectroscopy [123] and laser scanning microscopy [124], as well as the now widely used bioengineering techniques which have become increasingly important in evaluating barrier changes and quantifying inflammatory reactions by the skin [125, 126]. These methods are based on published international guidelines [127–132] and are suitable for the standardised testing of the efficacy of protective creams insofar as they provide relevant, reproducible and valid outcomes [131, 133–135]. Most of the protective creams examined in repetitive irritation tests to date were only effective against certain irritants or a spectrum of irritants with similar physicochemical properties. This underlines the concept of diversified skin protection and shows the problematic nature of a general claim of protection. The significance of the results of model irritation tests is also limited by the fact that there may often be complex exposure to both hydrophilic and lipophilic substances in the workplace, which can damage the skin individually and/or in combination [3, 136, 137]. In such cases, protective creams that have been specifically developed for workplaces with complex or changing contaminant loads may be useful [3, 138]. Given the fact that methods were not previously standardised, the development of a standardised procedure for testing hydrophilic irritants in a multicentre study was completed in 2013 as part of a joint project by university research centres. This study was able to confirm the transferability of the methods and the reproducibility of outcomes in the centres (http://www.dguv.de/Projektdatenbank/0275/3111319v1.pdf – last access 20.12.2014). The irritation model allows a number of protective creams to be tested simultaneously for 3 categories of aqueous irritants that appear to be particularly significant in the development of irritant contact dermatitis in a working environment. A 4-day human in vivo repetitive irritation model is done on back skin, whereby an "effect index" is calculated on the basis of measurements of transepidermal water loss [127]. This allows a comparison between products and the known efficacy of skin protection reference samples, thus establishing a quality standard. The dose applied in the model was 3 mg/cm2 – closer to the amount of protective creams applied in working conditions according to more recent findings – and was thus lower [139] than in the majority of previously published experimental studies on the effectiveness of protective products [19, 117, 118, 124]. The establishment of consistent in vivo testing standards should thus create the conditions for product comparability and improved market transparency for users of protective skin products. According to some manufacturers, protective creams should also make it easier to cleanse the skin. This sort of effect can help to alleviate the intensity and frequency of aggressive skin cleansing procedures, although no scientific studies have confirmed this to date. The hope is that even this claim can be backed up by suitable experimental models in future. Invasive in vivo methods on humans, such as microdialysis [140, 141], are not yet suitable for comparative tests on the efficacy of protective creams. However, these methods can be used to study changes in the penetration of substances by protective creams and changes in inflammation parameters between intact and artificially pre-damaged skin barrier, which contribute to an understanding of the mechanism of interaction between noxa and protective products (see also section 3.4). In vivo methods to prove the efficacy of skin care products As well as smoothing the surface of the skin and producing a subjective feeling of nourishment, skin care products can also increase the lipid and water content of the skin. According to the guideline "Dermokosmetika zur Reinigung und Pflege trockener Haut" (Dermocosmetics for the cleansing and care of dry skin) by the Gesellschaft für Dermopharmazie (Society of Dermopharmacy) [142], such effects should be objectivised with biophysical test methods such as the measurement of skin roughness, moisture content, transepidermal water loss and fat content. Study outcomes with suitable testing approaches are available for the prevention and regeneration of irritant contact dermatitis [143]. Alongside investigations into efficacy within the context of bioengineering studies on test subjects with healthy skin [144–147], numerous studies with a more practical approach have also been published. These concentrated more on testing the efficacy of skin care preparations on various acute and cumulative irritant stimuli under conditions of daily exposure [55, 148–154]. As well as a barrier-regenerative effect, it was also possible to identify a protective effect in one skin care product [155]. Whether or not regular care in the sense of prevention really protects against further irritation has long been a subject for debate [73]. It was recently shown that, after long-term use (7 weeks) followed by irritation with sodium lauryl sulphate, the irritant effect was alleviated for some people, depending on the formulation of the skin care product [156]. 2.2.2 Proof of efficacy of skin cleansers Appropriate skin cleansing at work is crucial to the prevention of occupational skin diseases. A skin cleanser is deemed appropriate if it removes irritants and allergens from the surface of the skin both effectively and gently. On the other hand, the suboptimal removal of deposit build-up or an excessive cleansing procedure can actually be conducive to skin disorders, particularly irritant contact dermatitis. When choosing a skin cleanser, it must be ensured that it is proven to be effective and is compatible with the skin. This being the case, the user needs to understand how a skin cleanser has been tested before choosing a suitable one. The product information should clearly state the methods used for proof of efficacy and compatibility (see also section 4, Documentation). The many contaminants present in working environments were previously categorised as follows: water-soluble contaminants (hydrophilic particles, water-based dyes, cooling water, cleaning agents, paste, all protein contaminants such as bodily fluids and human secretions), oil and grease contaminants including hydrophobic particles, pigment contaminants, calcite- bound contaminants, calcium deposits and microbial contaminants. Although some of these contamination categories differ greatly, models to assess efficacy took a standardised approach in the past. There was therefore very limited opportunity to make a rational product choice based on data from controlled studies. To compare the cleaning power of skin cleansers containing surfactants in the past, researchers would mainly conduct studies with dirt formulation models based on dye pigments which used clinical assessment parameters as well as biophysical measuring systems [157, 158]. Various controlled hand-washing tests were also described, which used realistic contamination models to test the effect of skin cleansers containing abrasives and solvents [84, 159, 160]. Previous approaches to the standardisation of cleaning models concentrated on the washing process, whereby studies were undertaken with various materials such as foam rollers [157, 161] and a brush model [136] as well as manual washing tests, most of which were done on the volar underarm. No commercial preparations were tested in most of these studies, however, but individual surfactants, mainly sodium lauryl sulphate. The studies usually took place over a period of 3, 5 or 7 days and were thus heterogeneous on the whole. The models described so far did not have uniform test criteria. This meant that there was no suitable basis for recommendations or for the choice of occupational skin cleansers for users. For the first time, a multicentre study/joint research project has developed transferable methods to test the efficacy and safety of occupational skin cleansers (http://www.dguv.de/medien/ifa/de/pro/pro1/ff-fp0276/AbschlussberichtFINAL02.pdf – last access on 21.10.2014). The aim of the project was to standardise and scale the properties of skin cleansers, with the best possible adaptation to real conditions of exposure at work. Job- related contamination situations first had to be classified before developing representative models of soiling [162], followed by appropriate model hand cleansers and a washing device designed especially for the project [163, 164]. A single centre then developed a reproducible method to determine the cleaning effect of these standard cleansers when using similarly standardised contamination models, after which a multicentre evaluation was done [165, 166]. The findings of efficacy and safety testing could be correlated for the first time as a result. The test methods are suitable for the future standardised testing of occupational skin cleansers in comparison with the developed model hand cleansers and should lead to better product transparency. 3 Occupational skin products – safety assessment and undesirable effects 3.1 Safety assessment in cosmetology Occupational skin products as defined by this guideline are regulated by law as cosmetics in Germany. According to Regulation (EC) no. 1223/2009 of the European Parliament and the Council dated 30 November 2009, cosmetics are defined as "any substance or mixture intended to be placed in contact with the external parts of the human body (epidermis, hair system, nails, lips and external genital organs) or with the teeth and the mucous membranes of the oral cavity with a view exclusively or mainly to cleaning them, perfuming them, changing their appearance, protecting them, keeping them in good condition or correcting body odours" [167]. European legislation on cosmetics was implemented by the Federal Republic of Germany in the Food and Feed Code (Lebensmittel-, Bedarfsgegenstände- und Futtermittelgesetzbuch) dated 01.09.2005, last amended by Art. 1 V dated 28.05.2014. Unlike pharmaceutical products, cosmetics are not tested in a licensing procedure but can be put on the market as long as there is compliance with statutory frameworks. The latter are essentially defined by Article 3 of Regulation (EC) no. 1223/2009, which stipulates that "Cosmetic products should be safe under normal or reasonably foreseeable conditions of use" [167]. In order to guarantee the safety of cosmetic products and facilitate their monitoring, before placing a cosmetic product on the market the responsible person ensures that it has undergone a safety assessment based on the relevant information and that a safety report has been compiled for it. Article 11 states that the responsible person must keep a product information file containing the following data: to make the following information (so-called product dossier) from the manufacturer available to the responsible authorities for inspection purposes:  A description of the cosmetic product which enables the product information file to be clearly attributed to the cosmetic product  The cosmetic product safety report  A description of the method of manufacturing and a statement on compliance with good manufacturing practice  Where justified by the nature or the effect of the cosmetic product, proof of the effect claimed for the cosmetic product  Data on any animal testing performed by the manufacturer, his agents or suppliers, relating to the development or safety assessment of the cosmetic product or its ingredients, including any animal testing performed to meet the legislative or regulatory requirements of third countries The safety assessment of the finished product for human health has now been prescribed in detail; the report must contain:  Quantitative and qualitative composition of the product  Physical/chemical characteristics and stability of the cosmetic product  Microbiological quality  Impurities, traces, informationabout packaging material  Normal and reasonably foreseeable use  Exposure to the cosmetic product  Exposure to substances  Toxicological profile of the substances  Undesirable effects and serious undesirable effects  Information on the cosmetic product  Assessment conclusions  Labelling warnings and instructions for use  Reasoning  Assessor’s credentials These rules have far-reaching implications for the safety assessment of occupational skin products. These products are used not only by people with healthy, low-sensitivity skin but also by people with very sensitive skin which is often pre-damaged or even has manifestations of disease. Even if the manufacturer specifically warns against use on pre-damaged or diseased skin, such use is still reasonably foreseeable; evidence must therefore be provided that the skin product is safe under these conditions. The question from a regulatory point of view is whether skin products used on pre-damaged or diseased skin with the intention of preventing an actual illness should be licensed medical products. The Scientific Committee on Consumer Safety (SCCS), which acts on behalf of the EU Commission, has provided guidelines for assessing the safety of cosmetic ingredients; these are updated regularly [168] (http://ec.europa.eu/health/scientific_committees/consumer_safety/docs/sccs_s_004.pdf). The general view of the SCCS is that the safety assessment of a cosmetic finished product can be done on the basis of knowledge of the toxicity of its constituent parts. In special situations, however, the SCCS is of the view that testing of the finished product is scientifically and ethically necessary in order to confirm the "compatibility" of the cosmetic and that the product meets expectations. According to the SCCS, predictive sensitisation tests of cosmetic ingredients should be not carried out on people for ethical reasons [169]. In exceptional circumstances, however, additional knowledge about the end product is essential for the safety assessment. Examples cited by the SCCS are cosmetics for specific consumer groups (babies, people with sensitive skin, for instance) and the presence of constituent parts that may promote skin penetration and/or irritation. There is no doubt that these criteria apply to occupational skin products, in which case a special safety assessment must be demanded for the end product. An assessment based on the ingredients alone will not suffice. This assessment must examine skin penetration and skin irritation with typical workplace exposure and the use of the products by people with sensitive or pre-damaged skin. The predecessor of the SCCS, the Scientific Committee on Consumer and Non-Food Products (SCCNFP), gave detailed recommendations for proof of safety with regard to irritation by cosmetics [169]. A safety assessment for protective creams containing aluminium chlorohydrate (5%) was carried out in a recent report (report no. 007/2014 of the BfR of 26 February 2014 [170]). The Federal Institute for Risk Assessment (Bundesinstitut für Risikobewertung - BfR) has called for the intake of aluminium, the vast majority of which comes from food, to be restricted from cosmetics as well, even though there is no scientific evidence of a causal link between increased aluminium intake and the occurrence of breast cancer or Alzheimer's disease [170]. This related in particular to the percutaneous absorption of aluminium from antiperspirants, but also referred to protective creams. The calculations of skin penetration and percutaneous absorption of aluminium were done on the basis of a singular in vitro Franz diffusion cell study with antiperspirants (penetration rate = 5.9%) [171]. In contrast, however, the penetration rate measured in an in vivo study with biomonitoring of voluntary test subjects was lower by a factor of 12 (penetration rate 0.014%) [172], so there is still a need for clarification here. To date, there are no studies on the percutaneous penetration of aluminium salts from protective creams. A voluntary warning ("Not for use on injured skin") is under discussion. 3.2 Sensitisation by the ingredients of occupational skin products Reference literature is dominated by observations of individual cases of sensitisation by skin products. Only one, more recent, major overview is based on data from the Information Network of Departments of Dermatology (Informationsverbund Dermatologischer Kliniken - IVDK) [173]. The problem is that skin products are used frequently (to begin with) on affected skin [174]; the theoretical risks of the inducement of sensitisation by skin products are increased as a result. In practice, the difficulty often lies in separating exposure to skin products from other incidents of exposure in daily life. Another reason why there still is a lack of reliable epidemiological data on the subject is that there is no systematic analysis of product tests on exposed people. These would also be very expensive; as a rule, if sensitisation is suspected, breakdown tests on the ingredients are required as well as native product tests. The legally prescribed INCI declarations can be helpful here, although they are not always specific enough for tests (e.g. fragrances outside the list of 26 substances subject to declaration since March 2005). The discussed analysis by the IVDK [173] has tried to resolve this dilemma by comparing the incidence of sensitisation in a collective of 670 patients with work-related hand dermatitis, who are in at-risk jobs and whose anamnesis suggests triggering by skin products, with comparison groups with different kinds of anamnestic profiles (total collective: 88,504; the following jobs, which involve regular contact with various external factors independently of skin products in the proper sense, had been excluded beforehand: hairdresser, beautician, elderly care nurse, pool attendant). Significantly increased risks for fragrances were found in the target collective (fragrance mix, oak moss absolute, isoeugenol, Peru balsam), certain preservatives (methyldibromo glutaronitrile, chlormethylisothiazolinone/methylisothiazolinone) and propolis. No notably increased risk was observed with ointment bases, such as lanolin alcohols and Amerchol L 101. In the case of occupational skin products, the authors recommended choosing ingredients with due regard for allergological aspects. A recent market analysis of 64 protective creams, 99 cleansers and 30 skin care preparations from 9 leading manufacturers with an approximately 60% market share in Germany [175] found in the case of preservatives (mainly parabens and phenoxyethanol) as well as bases (especially cetearyl alcohol) that particular use was actually made of substances that do not often cause sensitisation in spite of frequent use. What was surprising, however, was the relatively widespread use of the preservative bronopol; the use of this substance in skin products is questioned by the authors in the light of increasing rates of sensitisation. The recently observed significant rise in sensitisation to chlormethylisothiazolinone/methylisothiazolinone (CMI/MI) [176] means that the use of these substances in skin products is not advisable. This also applies to the sole use of MI, which is generally classed as less allergenic, because it is probably the main cause of the sharp rise in test reactions to the CMI/MI combination when used in the currently permitted maximum use concentration. As an independent committee of the European Commission, the SCCS (Scientific Committee on Consumer Safety) recommends in its current report for 2014 that MI should no longer be used in leave-on products such as protective creams and skin care. 71% of the products were scented for reasons of user acceptance. Current data suggests that the manufacturers, when making choices, must pay serious attention to the avoidance of fragrances with high sensitisation potential/rates in the population (hydroxyisohexyl 3- cyclohexene carboxaldehyde [e.g. Lyral®], tree moss, oak moss absolute, hydroxycitronellal, isoeugenol, cinnamaldehyde , farnesol) [177]. Unfortunately, the result of this is that 26 fragrances are now subject to declaration in the EU - not necessarily an improvement in consumer protection. The manufacturers could switch to fragrances that are not subject to declaration, whose allergological risks are still largely unknown and that have not yet been recorded in test batteries [177, 178]. This could also constitute a problem for the formulation of occupational skin products in future. It would be preferable for manufacturers who still want to make scented products to select from the 26 fragrances subject to declaration those with the lowest sensitisation rates (overview by [178]) and to name any fragrances used on a voluntary basis. Fragrances should not be used in protective creams if at all possible, particularly with pre-damaged skin. 3.3 Possible irritant effects of occupational skin products 3.3.1 Protective creams and skin care products Clinical trials with humans have shown that protective creams used to lessen irritation can actually end up making it worse in some unfortunate or individual cases [117]. This could be due to the irritant effect of the protective cream itself – depending on its composition – or such phenomena could arise through increased penetration or stronger binding of noxa within the skin. It was shown in the animal model, for example, that the use of a protective cream can intensify the irritation caused by cooling lubricant [179]. With regard to toluene, it was also noted in a study that one of the test preparations intensified the irritation [122]. A randomised double-blind study with repetitive irritation testing on test subjects likewise noticed a worsening of irritation with 2 of 6 protective creams against the lipophilic irritant n-octane and with one protective cream against cumene [180], so the use of protective creams appears to be a problem when handling solvents. In vitro diffusion cell studies were able to demonstrate stronger penetration by protective creams in connection with solvents. The diffusion cell is accepted by scientific and supervisory authorities as an in vitro method for quantifying skin penetration. Diffusion cell studies have indicated that the penetration of hydrophilic and lipophilic solvents through human skin pre-treated with protective creams was not reduced [92, 181], but promoted [181–185]. In theory, the above-mentioned observed worsening of irritation could also have been the result of deeper penetration. The significance of the pH value of protective creams and skin products has already been addressed (see section 1). There are also indications that the use of moisturisers can make the epidermal barrier more sensitive to irritants [72, 73, 186–189]. These findings must also be taken into consideration as there is currently no differentiation between occupational skin products and moisturisers. In this field there is also a lack of studies to examine the penetration modulation of working substances and job-related irritants when they interact with moisturisers applied beforehand. Such studies already exist for model irritants such as sodium lauryl sulphate [72, 73, 186, 187]. 3.3.2 Skin cleansers The removal of dirt particles nearly always lead to an alteration in epidermal functions and in some circumstances to signs of irritation [190]. The irritant effect depends on how intensively (mechanically) and how long the cleanser needs to work on the skin in order to cleanse it as required. The cleaning action is inversely proportional to compatibility – if the cleaning action is inadequate, then irritant effects may be intensified by the user washing his skin until he thinks it is clean enough. Studies of the irritant potential of skin cleansers are inconsistent. Individual standardised test models are used [161, 191] or criteria drawn up to classify the irritant effect of skin cleansers. Some of these surveys were only done for occupational skin cleansers [81, 192] and most of them for agents that are used at home or for hygienic hand cleaning in the health sector [193, 194]. A predictive in vitro method (corneosurfometry; [195]), which was developed for a comparative assessment of the irritant potential of cleansing products [196], is not yet fully established. Standardised wash tests [157, 158, 161, 191], a patch test [191] and a use test [191] are used for in vivo studies. The aforementioned multicentre study attempted to accommodate the linking of both parameters [166] (see section 2.2.2.). According to the latest findings, from a chemical perspective the irritancy potential depends primarily on the type of detergent used (anionic, cationic, amphoteric, nonionic) and the combination of the latter [197–199]. Safety assessments have been undertaken for some individual substances used in skin cleansers [200–203]. It is not known what role the pH value plays in the compatibility of skin cleansers. Previous studies show that an alkaline pH value should lead to more serious skin damage with more swelling in the horny layer than a neutral or acid pH value [20, 197, 204–207]. The irritability of the cleaning process with a skin cleanser is thus a function arising from the compatibility of the ingredients, especially the chosen detergents and abrasives, (perhaps) the pH value, the duration and mechanical intensity of the cleaning process as such and other possible unknown (e.g. constitutional) factors. 3.4 Influence of the penetration of foreign substances through protective creams The intact stratum corneum forms the actual barrier against the dermal penetration of chemical substances. Only when the stratum corneum has been penetrated can a substance be reabsorbed [89]. Other than this, small molecules can get into the skin through the hair follicles [208]. The principle of transfollicular penetration is currently being studied in detail, particularly in connection with the application of nanoparticles. Numerous methods are employed to test the efficacy of protective creams (see section 2.2). Human field trials on exposed employees or test subjects in the laboratory are generally more informative than animal experiments. In vitro experiments with human skin seem more suitable than those with animal skin [89, 209–212]. Due to the complexity of the epidermal barrier, trials with keratinocyte cultures or other membranes yield hardly any information about the penetration of foreign substances through human skin. An intervention study in workplaces with biomonitoring studies (evidence of foreign substances or their metabolites) showed that employees exhibited higher levels of exposure if they had used hydrophilic protective creams prior to exposure to polycyclic aromatic hydrocarbons (PAH) than on days when they used no skin protection [213]. Similarly, in the case of workers in the rubber industry who were exposed to carcinogenic aromatic amines a definite link was found between internal stress and the frequency with which protective creams were used before and during work [184]. By contrast, the application of skin products after work reduced internal stress. Disruptive factors of this kind can generally be monitored more easily in experimental studies with voluntary test subjects than in field studies. No alteration in the penetration of butoxyethanol through healthy skin was found in studies using microdialysis [140, 184, 214]. This finding agrees with chamber tests by other authors [181]. After the quantitative reduction of the stratum corneum by means of "tape stripping", however, the penetration of butoxyethanol was slowed down significantly [140, 214]. There are two contradictory publications on the influence of the resorption of high-molecular allergens from latex gloves: in an exposure trial with test subjects with confirmed latex allergy, welts developed more frequently after the application of a skin cream than with no protective cream [215]. In a second experiment with a different protective cream (and presumably with different latex gloves), on the other hand, there were fewer allergic reactions [216]. The contradictory nature of the findings is not discussed in the second work, however, and it is still unclear whether some of the test subjects in the second study were the same people as those in the first. The diffusion cell is accepted by scientific and supervisory authorities as an in vitro method for quantifying skin penetration. Diffusion cell studies have indicated that the penetration of hydrophilic and lipophilic solvents through human skin pre-treated with protective creams is not reduced [92, 181], but generally promoted [181–185]. Accelerated penetration of carbon disulphide by skin products used in corresponding workplaces was also proven in vitro by means of microdialysis studies with excised human skin [217]. The often postulated efficacy principle, according to which w/o emulsions protect against the dermal absorption of aqueous hazardous substances and o/w emulsions against the absorption of lipid-soluble hazardous substances, could not be proven in diffusion cell experiments on human skin [182–184]. These study outcomes confirm the recommendations of legitimate providers of protective creams who say that the latter should be used only to protect the skin and not to protect against the percutaneous absorption of working substances toxic to the system. It is crucial to discuss older studies on laboratory animals [218]. These showed reduced penetration of hazardous substances after the prior application of protective cream containing some silicon. Protective creams containing silicon are not suitable for occupational use, however, because silicon compounds can disrupt business operations due to their known separator effect. Studies with substances that are barely able to penetrate the stratum corneum [104] or whose skin penetration has not been quantified [105] are likewise of little importance for the purpose of assessing barrier penetration by protective creams. Studies in which stratum corneum and epidermis obtained by heating up was used as test material [219] are very restricted in terms of transferability as the skin barrier is altered non-physiologically by this method. Inconsistent findings can be found in diffusion cell studies with chemical warfare agents. Modified skin creams, to which film formers and/or counteragents have been added in high concentrations, are used for military purposes [219, 220]. However, it is observed that even these preparations significantly promote penetration under normal work-related conditions of exposure [219]. The composition of these skin creams cannot be compared with those sold for occupational health and safety. The causes and mechanisms of penetration promotion/inhibition by protective creams are not yet clear. The promotion of the penetration of hazardous substances by protective creams is the responsibility of additives such as emulsifiers [182–184, 221], which are also used in transdermal therapeutic systems (TTS) in order to channel enough active ingredients through the skin [222]. A diffusion cell study with ingredients of sunscreen [223] backs up this assumption. It is questionable whether an inhibition of penetration can be explained by an additional physicochemical barrier. On the other hand, accelerated regeneration of the stratum corneum could explain inhibited penetration. In summary, it cannot be assumed that there is a general reduction in the percutaneous absorption of foreign substances as a result of applying protective creams prior to exposure. The danger that protective creams may accelerate penetration by foreign substances must be borne in mind when using and selecting them. If protective measures against working substances toxic to the skin/system are indicated, they should not be implemented by using protective creams but by making organisational and technical modifications to work processes, such as wearing suitable protective clothing. The German Society for Occupational Medicine (Deutsche Gesellschaft für Arbeitsmedizin) provides a revised version of a guideline on skin resorption, whose evidence is congruent (AWMF Guideline: Toxische Gefährdung durch Hautresorption (Toxic hazard of skin resorption) http://www.awmf.org/leitlinien/detail/ll/002-037.html). 4 Documentation Information required to assess the quality of an occupational skin product should be documented by the producer and/or distributor of the product and made available in professional circles. As a minimum, this documentation should contain information on the following points, most of which are based on the existing statutory requirements of the Cosmetics Regulation:  Description of the galenic systems  Information on shelf life and microbiological stability (minimum shelf life and shelf life after opening)  Name of proof of efficacy methodology in the form of a brief description with references and product classification (in the case of protective creams e.g. protective action against specific working substances/groups of working substances harmful to skin and/or ease of skin cleansing)  Summary of findings of compatibility tests with specific reference to methodology and testing institution [75]. User information such as  Specification of the main area of use and additional ones, if any  Specification of areas of non-use in the event of foreseeable misuse  Information on applicability to face  Information on applicability in occlusive conditions such as wearing protective gloves  Information on applicability on diseased skin  Information on ingredients as per INCI (International Nomenclature of Cosmetic Ingredients) on packaging to protect allergy sufferers  Advice on nature and frequency of application during/after a shift 5 Outlook The following problems should be addressed as a priority in the coming years by means of relevant studies:  Skin care: lack of differentiation between protective creams and skin care products and classification of individual components that justify previously made claims of suitability for use after work.  Review whether the skin changes publicised as occlusion effects could be improved by measures to protect skin. Standardised and evaluated procedures must be developed for this purpose.  Develop standardised in vivo methods to test manufacturer claims of easier skin cleansing as a result of using protective creams. ______Creation date: 23.10.2014 Next review planned: October 2017 Coordinator, corresponding author: Prof. Dr. med. Manigé Fartasch Department of Clinical & Experimental Occupational Dermatology Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Institute of the Ruhr-Universität Bochum Bürkle-de-la-Camp- Platz 1 44789 Bochum Tel: +49 (234) 302-4545 Fax: +49 (234) 302-4542 [email protected]

Consensus-building process The recommendations in the guideline were agreed by the authors in an informal process. This draft was published on the website of the ABD http://abd.dermis.net for comments and suggestions by other experts. The final version of the guideline was agreed by the authors on 15 October 2014. The work was coordinated by Prof. Dr. med. Manigé Fartasch, Bochum. The long and short versions of the guideline can also be found at www.awmf.org.

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