Allergic contact dermatitis caused by 2‐hydroxyethyl methacrylate and ethyl cyanoacrylate contained in cosmetic glues among hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications: A systematic review

Current cosmetic regulations primarily focus on protecting consumers, not the professional user who is subjected to a partly different, and certainly more intense exposure to hazardous substances. Against this background, this systematic review aims to compile and appraise evidence regarding skin toxicity of 2‐hydroxyethyl methacrylate (HEMA; CAS no. 212‐782‐2) and ethyl cyanoacrylate (ECA; CAS no. 7085‐85‐0) contained in cosmetic glues used among hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications. This systematic review followed the Preferred Reporting Items for Systematic review and Meta‐Analysis (PRISMA) 2020 recommendations for reporting systematic reviews and meta‐analysis. In total, six publications from six countries were eligible for this systematic review. A meta‐analysis revealed that hairdressers and beauticians have a ninefold increased risk of developing contact allergy to HEMA compared with controls who are not hairdressers and beauticians. Results for ECA are lacking. The results of this systematic review clearly show that—regarding contact allergy to acrylates—it is not appropriate to apply risk assessment for consumers to hairdressers and beauticians who occupationally handle cosmetic glues. The regulations in existence do not adequately address occupational risks for hairdressers and beauticians connected with the use of acrylate‐containing cosmetic substances and need reconsideration.

existence do not adequately address occupational risks for hairdressers and beauticians connected with the use of acrylate-containing cosmetic substances and need reconsideration.

| INTRODUCTION
Hairdressers and beauticians constitute a high-risk cohort for developing work-related skin damage and consequently occupational skin diseases (OSDs). Hand dermatitis (hand eczema [HE]) is thereby the most common OSD. 1,2 The most relevant factors that contribute to the pathogenesis of HE in this occupational group are wet work and skin contact with irritants and allergens. [3][4][5] This skin strain in everyday working life leads to impairment of the epidermal barrier function concomitant with the induction of a proinflammatory milieu; consequently, the risk of developing occupational contact dermatitis is increased. Initial irritant HE can easily lead to the development of allergic HE due to the fact that allergens penetrate the impaired skin barrier more easily. 6 An adequate risk assessment regarding hazardous substances, namely allergens, is indispensable to initiate appropriate protective measures and to ultimately protect the (skin) health of hairdressers and beauticians.
Occupational exposure is constantly changing due to changing compositions of products at work, which presents a major challenge for conducting risk assessment in the cosmetics sector. While taking the cosmetic products' instructions of use into account, it is important to consider that hairdressers and beauticians are exposed regularly and for significant hours and long periods to hazardous substances. The European Cosmetics Regulation, adopted in 2009, 7 is primarily focused on protecting consumers, not professional users. The Scientific Committee on Consumer Safety (SCCS) normally does not assess the risk of occupational exposures and therefore almost exclusively deals with 'consumer' aspects, targeting the general public. 8 Thereby, occupational risks associated with the use of cosmetic products are not sufficiently recognized. As one consequence, the European Commission is unable to initiate appropriate occupational risk management to adequately protect hairdressers and beauticians. This has to be regarded as highly problematic because OSD does not only entail suffering due to illness on an individual level but also presents a macrosocial problem as it may further result in high medical treatment costs for the social insurance system as well as social consequences such as a necessary occupational change or at worst, a premature withdrawal from the labour market. [9][10][11] Within the framework of the project 'Promoting the autonomous implementation of the European framework agreement on occupational health and safety in the hairdressing sector', a series of systematic reviews have been performed. 12 One of the product categories on which a focus has been put is cosmetic glues, used in the beauty sector for applying hair extensions, conducting nail treatments that This systematic review aims to compile and appraise clinical evidence regarding skin toxicity of HEMA and ECA contained in cosmetic glues.

| Eligibility criteria
Eligibility criteria for studies to be included in the systematic review are reported following the PECOS (participants, exposure, comparator, outcome, study design) scheme adapted from the CRD' (Centre for Reviews and Dissemination) guidance for undertaking reviews in health care 15 (Table 1).

| Registration and protocol
This systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42021238118. 77 The protocol has been published elsewhere. 12 No amendments to the information provided at registration or in the protocol were made.

| Information sources
Systematic searches were conducted within the electronic databases PubMed/MEDLINE and Web of Science Core Collection (WoS).
Assessment of risk of bias (ROB) within included studies and assessment of quality of evidence have been described in the protocol for this systematic review. 12 As we expected large heterogeneity in methods and outcomes, we conducted a narrative synthesis of results instead of a meta-analysis, except where quantitative pooling was feasible.

| Search strategy
Searches were performed in February 2021. Furthermore, we hand searched the bibliographies of all studies identified through the electronic database search and meeting the inclusion criteria. We also performed forward snowballing by using the six most important references identified, and checked all references citing any of these publications. This citation analysis was performed based on the WoS database. We used English search terms only.
Generally, we searched for title, abstract, and keywords. 12 Only accepted publications after 1999 (ie, 2000 and following) were considered.

| Selection process
For one search query, the search results were exported from MEDLINE and WoS in a suitable format and imported into Zotero libraries, documenting the number of references contributed by each export/import set. In the Zotero library, bibliographical duplicates were identified and the entry including less information (eg, no abstract) were discarded. 12 In case of discordant results, the entry was reviewed by a third experienced reviewer and a final decision was made. Reasons for noninclusion were documented, and summarized at the end for use in the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) for systematic review protocols (PRISMA-P) flow chart. 16 The final set of references eligible for full-text screening by two reviewers (C.S. and P.W.) were imported into a Zotero cloud-based reference database after the initial set of references had been archived. Full-text articles were, again, scrutinized and extracted independently by two reviewers, with a third senior reviewer (S.M.J. or W. U.) consensualizing divergent results between the two initial reviewers. All decisions and reasons leading to the exclusion of studies were documented, providing information on the individual assessments by both initial reviewers and the final decision. At the end of F I G U R E 1 Usual application of eyelash glue/adhesive onto (A) so-called cluster eyelash extensions and (B) a so-called eyelash band. The eyelash glue is usually placed on the back of the hand and the eyelash extension is then dipped into the glue with the help of tweezers. Oftentimes, the remaining eyelash glue dries on the hand and the residue will only be removed at the end of the working day, thereby exposing the hairdresser or beautician to the substances contained in the cosmetic glue for a considerable amount of time. Exposure might also be given when gloves are worn due to the short break-through times (<10 minutes) 13

| Effect measures
The risk ratio regarding skin sensitization/contact allergy for hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications versus comparators/controls, that is, people not working as hairdressers or beauticians, is provided by dividing contact allergy prevalence rates observed in hairdressers and beauticians by those observed in different comparator groups.

| Synthesis methods
A substantial heterogeneity in both methodologies (even in the subcategories of 'experimental' and 'clinical' research) and outcomes was to be expected. Instead of a meta-analysis, we primarily conducted a narrative synthesis following guidance from the CRD. 15

| Study selection and study characteristics
A flow diagram of the study selection is presented in Figure 2. The initial search yielded 579 study records. Following the removal of bibliographic duplicates, 163 records were left to be screened on the fulltest level. Another eight references were found by manually searching references (ie, backward and forward snowballing). A number of studies appeared to meet the inclusion criteria at first, 21-37 but they had to be omitted because they focused on a population that was inappropriate for this review. Case reports [38][39][40][41] and case series [42][43][44][45][46][47] were not included in the actual review, but compiled and extracted as supplemental information in case they were relevant in terms of including hairdressers and beauticians. We arrived at a final number of six papers after excluding publications that were extraneous to this review.
Characteristics of the included studies were recorded using a PRF (Table S1). All included studies (n = 6) were multicentric, retrospective patch test studies. [48][49][50][51][52][53] Regarding the patch testing context, special series were tested in four studies, [49][50][51]53 consecutive patients were tested in one study, 52 and an epidemiological sample was tested in one study. 48 The tested population comprised all patch tested patients (n = 5) [48][49][50][51]53 or patients patch tested for occupational contact dermatitis only (n = 1). 52 All of the six included studies reported on patch testing results for HEMA in hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications. [48][49][50][51][52][53] Four of these studies also provided a comparator/control, that is, patch test results with other occupations or without occupational context. [49][50][51]53 Because of their oftentimes comparable exposure to cosmetic glues while performing diverse work tasks (nail treatments/nail art, make-up services including the application of artificial eyelashes, etc.), occupational groups related to hairdressers within the cosmetic sector (manicurists, beauticians, aestheticians, nail designers, etc.) were considered relevant for this systematic review.
The included studies were conducted in the European Union (n = 4), namely, in Germany (n = 1), 49 Portugal (n = 1), 51 Spain (n = 1), 53 and Sweden (n = 1), 50 Australia (n = 1), 52 and the United States (n = 1). 48 All studies report on a high share of female participants (>50% for all studies). [48][49][50][51][52][53] All of the six studies included gave information on HEMA, but none offered information on ECA regarding the inclusion criteria/ for the six studies included in this systematic review are presented in Table S2. All of the studies (n = 6) received high scores regarding appropriate design, sampling, and sample description; justification of methodology; and justification/presentation of results. As a result, we found the ROB to be low in all of the reports. There were no reports of active sensitization (ie, the patient being newly sensitized due to the patch test procedure) in the studies reviewed.  HPMA, and HEA were reported to be the source of allergic contact dermatitis in people working in the beauty industry. 39,40,[42][43][44][45][46] This highlights the prevailing problem of cross-reactions, that is, sensitization induced by one acrylic compound extending to one or more other acrylics. 37,56 As a result, many people sensitized to acrylics are multiply sensitized and, as a consequence, need to strictly avoid exposure to many other acrylics, 56 with the notable exception of cyano-versus other acrylates/methacrylates which seem to not cross-react, 57 although past studies provided conflicting clinical results. 58,59 In view of a lack of hairdresser-specific results on ECA, we examined a random sample of eyelash glues for temporary and permanent application of eyelash extensions, nail glues, and hair extension glues regarding their ingredients. Eyelash glues for temporary application of eyelash extensions mostly comprised ethylhexyl acrylate co-polymer and ammonium acrylates co-polymer (Table 3); in eyelash glues for permanent application of eyelash extensions, mostly ECA was found ( Table 3). All of the nail glues within our random sample contained ECA ( also been shown to contain acrylates (  64 Moreover, the reported risk of severe burns by nail glues should be mentioned which can happen when cyanoacrylatecontaining glues get on textiles/clothes in contact with skin. [65][66][67] By dint of the results of the present systematic review it seems appropriate that prevention strategies are developed for raising awareness in hairdressers and beauticians about the risk that handling cosmetic glues-especially without adequate protection-might entail.

| Results of syntheses
Such topical information (in any medial format) could be prepared under health pedagogical considerations and might be then presented within the framework of health education programs. This might also apply to other occupational fields for which relevant acrylate exposure has been evidenced in previous studies, such as dental personnel. [68][69][70][71][72][73] The German Social Accident Insurance (DGUV) has recognized the problem for dental personnel and initially launched information brochures about acrylate allergy and its prevention. These existing informational materials might serve as a point of entry for developing potential awareness campaigns and future training measures tailored to the needs of workers in occupational groups exposed to acrylates. 74 The present systematic review clearly shows that it is not appropriate to assess the risk of hairdressers and beauticians who handle cosmetic glues within their occupational surroundings regarding contact allergy to acrylates the same way as the risk of other people not working as hairdressers and beauticians such as consumers or clients.
It was confirmed that the occupational risks associated with the use of cosmetic products are not sufficiently recognized by the regulations in force. The current SCCS opinion on the use of HEMA for nail cosmetics (SCCS/1592/17) seems not to be satisfactory for protecting hairdressers and beauticians who perform nail treatments and eyelash extension as well as hair extension applications. 75 The results of this paper point in favour of the notion that presumably an increase of the prevalence of sensitization against acrylates-such as HEMA-and consequently of contact dermatitis from cosmetic products containing acrylates might be expected in the future. 75 The proven higher risk of hairdressers and beauticians regarding development of contact allergy against acrylates should lead to reconsidering current risk assessment. Only this way it will be possible to efficiently contribute to prevention of OSD in terms of HE in hairdressers and beauticians-according to the minimum standards set out in the position paper of the COST Action StanDerm (TD 1206) 76 -to obviate personal suffering due to illness as well as high costs for the social insurance system and consequently the general population.

DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.

SUPPORTING INFORMATION
Additional supporting information may be found in the online version of the article at the publisher's website.
How to cite this article: Symanzik C, Weinert P, Babi c Ž, et al.