Preservatives and fragrances in selected consumer-available cosmetics and detergents

Contact Dermatitis Original Article COD Contact Dermatitis Preservatives and fragrances in selected consumer-available cosmetics and detergents Kerem Yazar, Stina Johnsson, Marie-Louise Lind, Anders Boman and Carola Lidén Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden doi:10.1111/j.1600-0536.2010.01828.x Summary Background. Preservatives and fragrances are important and frequent skin sensitizers, found in a wide range of products intended for personal and occupational use. Objectives. To examine the use of preservatives and fragrances in certain cosmetics and detergents on the market. The product types studied were shampoos, hair conditioners, liquid soaps, wet tissues, washing-up liquids, and multi-purpose cleaners. Materials/methods. Ingredient labels of 204 cosmetic products and ingredient data sheets of 97 detergents, available on company websites, were examined. Results. The preservatives most frequently identified were phenoxyethanol, methylparaben, sodium benzoate, propylparaben, and methylchloroisothiazolinone/methylisothiazolinone. Parabens were found in 44% of cosmetics and 9% of detergents; formaldehyde-releasers in 25% of cosmetics and 8% of detergents; and isothiazolinones in 23% of cosmetics and 28% of detergents. The fragrances most frequently identified were linalool, limonene, hexyl cinnamal, butylphenyl methylpropional, and citronellol. Eighty-eight per cent of the products contained fragrances, and any of the 26 fragrances requiring labelling were found in half of the cosmetics and one-third of the detergents. Conclusions. Several preservatives and fragrances with well-known skin-sensitizing potential were common in the examined product types. Such products may be used several times a day by consumers and workers. Key words: allergic contact dermatitis; consumer product safety; cosmetics; detergents; fragrances; preservatives. Preservatives and fragrances are important and frequent skin sensitizers, found in a wide range of products intended for personal and occupational use (1, 2). Fragrances are the most frequent causes of contact allergy to cosmetics, including products for personal hygiene, followed by preservatives (3, 4). It has been suggested that fragrances account for 30 45% of allergic reactions to cosmetics (5). According to the Cosmetics Directive, fragrances must be identified by the term parfum on the ingredient Correspondence: Kerem Yazar, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden. Tel: +46 8524 80042; Fax: +46 8 336981. E-mail: kerem.yazar@ki.se Conflicts of interest: The authors have no conflicts of interest to declare. Funding by the Swedish Council for Working Life and Social Research. Accepted for publication 22 September 2010 label. In addition, 26 fragrances that have been identified as skin sensitizers should be listed by name on the label of a cosmetic product if used in concentrations exceeding 10 ppm (0.001%) in leave-on products and 100 ppm (0.01%) in rinse-off products (6). Similarly, the regulation on detergents requires labelling of these 26 fragrance substances if their concentration exceeds 100 ppm (7). Several of the 26 fragrances are well-recognized skin sensitizers, whereas some have been questioned regarding their importance as allergens (8, 9). The list of the 26 is currently under review by the European Commission s Scientific Committee on Consumer Safety. In contrast to fragrances, preservatives must always be declared by name on the ingredient labels of cosmetics and detergents. In the work environment, sources of preservative allergy and dermatitis include, for example, metalworking fluids, adhesives/glues, water-based paints and lacquers, 2010 John Wiley & Sons A/S Contact Dermatitis, 64, 265 272 265

detergents,andpesticides,aswellascosmetics.frequently used rinse-off products, such as liquid soaps, can contribute significantly to exposure to preservatives in the work environment, and this has been well demonstrated with regard to methyldibromo glutaronitrile (MDBGN) (10 12). Many of the preservatives causing contact allergy and dermatitis are present both in consumer products and in occupationally used products (13), and this contributes to difficulties in allergy prevention and avoidance of unwanted skin exposure. Sources of exposure to fragrance allergens in the occupational setting include predominantly cosmetics and detergents; moreover, spices and flavours used by chefs and bakers may contain fragrance allergens (14). Information on the use of various allergens in cosmetics and other products in Europe is scarce. Gaining more knowledge on the exposure to allergens in products on the market can be of great importance for prevention and diagnostic purposes, as new allergens emerge and exposures to known allergens change. The present aim was to examine the presence of preservatives and fragrances in products that come into frequent contact with the skin of large parts of the population. Preservatives used in large volumes or with known skin-sensitizing properties, and 26 fragrances that currently must be listed on the labels of cosmetics and detergents, were investigated. The product types studied were shampoos, hair conditioners, liquid soaps, wet tissues, washing-up liquids, and multi-purpose cleaners. Materials and Methods Selection of preservatives and fragrances for assessment A list of preservatives of concern for the present study was created. The intention was to include largevolume preservatives used in chemicals and cosmetics. Preservativeswithknownskin-sensitizingpropertieswere also included. The selection of substances was based on the following sources of information. Data were obtained from the Swedish Chemicals Agency s Products Register on the 30 most frequently used preservatives in registered chemical products. Preservatives known as clinically relevant skin sensitizers were identified in published reviews on preservative contact allergy (4, 15). All preservatives in the cosmetic series for patch testing of Chemotechnique Diagnostics AB (Vellinge, Sweden) were included. Antioxidants were not included, although they are sometimes considered as preservatives. In total, 57 preservatives were included in the present study. The 26 fragrances that, according to the Cosmetics Directive, must be listed on the label by their name were included (14). Selection of products and examination of labels Four types of frequently used cosmetic products for personal hygiene that come into contact with the skin, including shampoos, hair conditioners, liquid soaps, and wet tissues, were selected. Owing to the large number of shampoos and hair conditioners on the market, only such products specified to be used for normal hair, coloured hair, anti-dandruff purposes, men or children were included. A total of 20 shops in Stockholm were visited between May and June 2008. These were mainly large shops with nationwide coverage, including department stores, supermarkets, beauty shops, pharmacies, hairdresser salons, and grocery stores. No data are available to the public on sales rates of specific products. Thus, a crude selection of products estimated to be sold in large volume was made, on the basis of information from shop assistants and the authors own perceptions, gained while visiting the shops. A total of 206 cosmetic products were purchased. One shampoo and one hair conditioner did not have any ingredient declaration and were therefore excluded, leaving 204 products for further examination: shampoos (n = 92), hair conditioners (n = 61), liquid soaps (n = 34), and wet tissues (n = 17). The prevalence of the included preservatives and fragrances in the products was studied on the basis of information provided by their ingredient labels. In April 2010, the same shops were visited once again in order to add information on detergents to that on the previous sample of cosmetic products. Two types of product were selected, including washing-up liquids (n = 44) and multi-purpose cleaners (n = 53), specified either for use on nearly all washable surfaces or for general use in the bathroom or kitchen. According to the detergent regulations, consumer-available detergent products must have a website address on the label where information on chemical composition can be found. Website addresses were recorded from the labels of all multi-purpose cleaners and washing-up liquids that were found in the stores. The prevalence of the included preservatives and fragrances in the products was studied on the basis of ingredient data sheets available on the companies websites. The selected preservatives and fragrances that were identified were recorded in Microsoft Excel, and their prevalences were calculated. No chemical analyses were performed in the present study. Results The results of the study are displayed in Tables 1 and 2 and in Figs. 1 and 2. Altogether, 30 of 57 preservatives selected for the study and 20 of the 26 fragrances 266 2010 John Wiley & Sons A/S Contact Dermatitis, 64, 265 272

Table 1. Selected preservatives identified on the ingredient declarations of cosmetic products [shampoos (n = 92), hair conditioners (n = 61), liquid soaps (n = 34), and wet tissues n = 17)] in May 2008, and of detergents [multi-purpose cleaners (n = 53) and washing-up liquids (n = 44)] in April 2010, on the market in Sweden. Hazard classification as skin sensitizer (H317, former R43) is according to the EC regulation on the classification, labelling and packaging of substances and mixtures (CLP) (16). Limit of content of preservatives in cosmetic products is according to the Cosmetics Directive (6) Products containing certain preservatives (%) Preservative (INCI name or used abbreviation) CAS no. All products (n = 301) Cosmetic (n = 204) Detergent (n = 97) Limitofcontentin cosmetics (%) Classified skin sensitizer In European patch test baseline series Phenoxyethanol 122-99-6 33 39 19 1 Methylparaben 99-76-3 29 41 4 0.4 a PM Sodium benzoate 532-32-1 27 34 11 2.5 b, 0.5 c,d Propylparaben 94-13-3 19 25 4 0.4 a PM MCI/MI 55965-84-9 18 22 9 0.0015 x x Ethylparaben 120-47-8 15 22 1 0.4 a PM DMDM hydantoin 6440-58-0 13 17 4 0.6 e Cetrimonium chloride 112-02-7 13 19 0 0.1 Butylparaben 94-26-8 9 14 0 0.4 a PM Isobutylparaben 4247-02-3 9 13 0 0.4 a Benzoic acid 65-85-0 8 11 2 2.5 b 0.5 c,d Potassium sorbate 24634-61-5 7 9 4 0.6 Benzyl alcohol 100-51-6 7 9 1 1 f 2-Bromo-2-nitropropane-1,3-diol 52-51-7 7 6 7 0.1 e Sodium methylparaben 5026-62-0 7 7 5 0.4 a Methylisothiazolinone 2682-20-4 6 0.5 16 0.01 Imidazolidinyl urea 39236-46-9 4 5 0 0.6 e Chlorhexidine dihydrochloride 3697-42-5 3 5 0 0.3 g Benzisothiazolinone 2634-33-5 3 0 9 x Formic acid 64-18-6 2 2 0 0.5 Sodium propylparaben 35285-69-9 2 0 5 0.4 a Methyldibromo glutaronitrile 35691-65-7 1 1 0 Before 23 June x 2008:0.1% in rinseoff products only From 23 June 2008: not allowed Octylisothiazolinone 26530-20-1 1 0 3 x Quaternium-15 4080-31-3 0.7 1 0 0.2 e x Sodium salicylate 54-21-7 0.7 1 0 0.5 Chlorhexidine digluconate 18472-51-0 0.3 0.5 0 0.3 g Chlorphenesin 104-29-0 0.3 0.5 0 0.3 Iodopropynyl butylcarbamate 55406-53-6 0.3 0.5 0 0.02 b, 0.01 d Triclosan 3380-34-5 0.3 0.5 0 0.3 Glutaral 111-30-8 0.3 0 1 0.1 x Any formaldehyde-releaser 19 25 8 Any isothiazolinone 24 23 28 Any paraben 33 44 9 MCI/MI, methylchloroisothiazolinone/methylisothiazolinone; INCI, International Nomenclature of Cosmetic Ingredients; PM, paraben mix. a Paraben; the accumulated content of mixtures of esters is restricted to 0.8%. b Rinse-off products. c The accumulated content of benzoic acid and its sodium salt is restricted to these concentrations. d Leave-on products. e Formaldehyde-releasing preservative. f One per cent if added as preservative. No limit to content if added for other purposes (fragrance, solvent). g The accumulated content of chlorhexidine is restricted to 0.3%. 2010 John Wiley & Sons A/S Contact Dermatitis, 64, 265 272 267

Table 2. Fragrances that must be listed on the label of cosmetics and consumer-available detergents by their name and that were identified on the ingredient declarations of shampoos (n = 92), hair conditioners (n = 61), liquid soaps (n = 34) and wet tissues (n = 17) in May 2008, and of multi-purpose cleaners (n = 53) and washing-up liquids (n = 44) in April 2010, on the market in Sweden. Hazard classification as skin sensitizer (H317, former R43) is according to the EC regulation on the classification, labelling and packaging of substances and mixtures (CLP) (16). Limit of content of preservatives in cosmetic products is according to the Cosmetics Directive (6) Products containing certain fragrances (%) Fragrance (INCI name) CAS no. All products (n = 301) Cosmetic (n = 204) Detergent (n = 97) Limit of content in cosmetics (%) Classified skin sensitizer In European patch test baseline series Linalool 78-70-6 29 38 10 Limonene 138-86-3 27 28 25 x Hexyl cinnamal 101-86-0 26 32 13 FM II Butylphenyl methylpropional 80-54-6 23 29 9 Citronellol 106-22-9 17 20 9 FM II Benzyl salicylate 118-58-1 11 16 2 Geraniol 106-24-1 9 11 3 FM α-isomethyl ionone 127-51-5 8 11 1 Benzyl alcohol 100-51-6 7 9 1 Coumarin 91-64-5 5 6 1 FM II Hydroxyisohexyl 3-cyclohexene 31906-04-4 5 7 0 FM II and separate carboxaldehyde Amyl cinnamal 122-40-7 4 6 1 FM Benzyl benzoate 120-51-4 3 4 1 Citral 5392-40-5 3 2 5 x FM II Hydroxycitronellal 107-75-5 2 2 1 1 FM Eugenol 97-53-0 1 2 0 FM Methyl 2-octynoate 111-12-6 0.7 1 0 0.01 Evernia prunastri extract 90028-68-5 0.3 0.5 0 FM Farnesol 4602-84-0 0.3 0.5 0 FM II Isoeugenol 97-54-1 0.3 0.5 0 0.02 FM Any fragrance requiring labelling 45 50 32 Only the term parfum 44 37 59 Perfume-free 12 13 9 Any FM ingredient 11 15 4 Any FM II ingredient 30 36 16 FM, fragrance mix ingredient; FM II, fragrance mix II ingredient; INCI, International Nomenclature of Cosmetic Ingredients. requiring labelling were identified in the ingredient declarations of the examined products. Cosmetic products A total of 26 of the 57 selected preservatives were identified on the labels of the examined cosmetic products. Ninety-four per cent of the products were declared to contain at least one of the included preservatives. The most frequently identified preservatives were methylparaben (in 41% of the products), phenoxyethanol (39%), sodium benzoate (34%), propylparaben (25%), and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) (22%). Six different parabens were identified, and 44% of the cosmetic products contained one or more paraben. Correspondingly, four formaldehyde-releasers and two isothiazolinones were identified, and 25% and 23% of the products contained at least one formaldehyde-releaser or isothiazolinone, respectively. Of four formaldehyde-releasers identified, DMDM hydantoin was the most common (in 17% of the products), followed by 2-bromo-2-nitropropane-1,3-diol (6%), imidazolidinyl urea (5%), and quaternium-15 (1%). Five hair conditioners and five shampoos contained two different formaldehyde releasers. MDBGN was present in two shampoos and in one liquid soap. Twenty of the 26 fragrances were identified on the labels of the cosmetic products. Fifty per cent of the products were declared to contain at least 1 of the 26 fragrances. On 87%, the term parfum was listed, indicating the presence of fragrances. Thirteen per cent of the products did not contain any fragrance according to their ingredient labels. The most frequently identified fragrances were linalool (38%), hexyl cinnamal (32%), butylphenyl 268 2010 John Wiley & Sons A/S Contact Dermatitis, 64, 265 272

methylpropional (29%), limonene (28%) and citronellol (20%). Ingredients of the main indicators of fragrance allergy in the European baseline series for patch testing, fragrance mix and fragrance mix II, were found in 15% and 36% of the products, respectively. Fig. 1. The five most frequently identified preservatives in 204 cosmetic products in May 2008; and 97 detergents in April 2010, respectively. The percentages of products containing at least one paraben, isothiazolinone or formaldehyde-releaser are shown. The product types studied were shampoos ( )(n= 92), hair conditioners ( )(n= 61), liquid soaps ( )(n= 34), wet tissues ( )(n = 17), washing-up liquids ( )(n = 44) and multi-purpose cleaners ( )(n= 53) on the Swedish market. MCI/MI, methylchloroisothiazolinone/methylisothiazolinone; MI, methylisothiazolinone; BIT, benzisothiazolinone. Detergents A total of 17 of the 57 selected preservatives were identified in the ingredient data sheets of the examined washing-up liquids and multi-purpose cleaners. Seventy-one per cent of the products were declared to contain at least one of the included preservatives. The most frequently identified preservatives were phenoxyethanol (in 19% of the products), methylisothiazolinone(16%), sodium benzoate (11%), benzisothiazolinone (9%), and MCI/MI (9%). Four different isothiazolinones were identified, and 28% of the detergents contained one or more isothiazolinones. Correspondingly, five parabens and two formaldehydereleasers were identified, and 9% and 8% of the products contained at least one paraben or formaldehyde-releaser, respectively. MI was the most common of four identified isothiazolinones and was, with the exception of one liquid soap, always used in combination with some other preservative, predominantly phenoxyethanol (nine products) and benzisothiazolinone (seven products). Two formaldehyde-releasers were identified, of which 2- bromo-2-nitropropane-1,3-diol was the most common (7%), followed by DMDM hydantoin (4%). Fourteen of the 26 fragrances that require labelling were identified on the labels of the washing-up liquids and multi-purpose cleaners. Thirty-two per cent of the products were declared to contain at least one of the included fragrances. On 91% of the detergents, the term parfum was listed, and 9% of the products did not contain any fragrance according to their ingredient data sheets. The most frequently identified fragrances were limonene (25%), hexyl cinnamal (13%), linalool (10%), citronellol (9%), and butylphenyl methylpropional (9%). Ingredients of fragrance mix and fragrance mix II were found in 4% and 16% of the detergents, respectively. Fig. 2. The five most frequently identified fragrances in 204 cosmetic products in May 2008, and 97 detergents in April 2010, respectively. The percentages of products containing fragrance (parfum), any of the 26 fragrances requiring labelling and fragrance mix or fragrance mix II ingredients are shown. The product types studied were shampoos ( )(n= 92), hair conditioners ( )(n= 61), liquid soaps ( )(n= 34), wet tissues ( )(n = 17), washing-up liquids ( )(n = 44) and multi-purpose cleaners ( )(n= 53) on the Swedish market. FM, fragrance mix ingredient; FM II, fragrance mix II ingredient. Discussion In this study, we have examined the presence of selected preservatives and fragrances in consumer-available products that are used by a large part of the population and that frequently come into contact with the skin. Undeclared substances or concentrations could not be identified in this study, as ingredient labels were examined and no chemical analyses were performed. However, 2010 John Wiley & Sons A/S Contact Dermatitis, 64, 265 272 269

studies based on ingredient labelling can provide valuable information on exposure to allergens (17). MCI/MI was widely prevalent, especially in the cosmetic products, indicating that a considerable proportion of the population is frequently exposed to this extremely potent skin sensitizer. MCI/MI was found even in wet tissues, which should be regarded as leave-on products. Areas wiped by moist toilet paper will be occluded, and allergic contact dermatitis resulting from such exposure is probably not uncommon (18, 19). In contrast to the maximum authorized concentration of 15 ppm in cosmetics specified by the Cosmetics Directive, MCI/MI is limited to 7.5 ppm in leave-on products in the USA, and is allowed only in rinse-off products (15 ppm) in Japan (15). MDBGN, which has been prohibited in rinse-off products since 23 June 2008, was found in three cosmetic products about 1 month before its prohibition in such products. This indicates that large producers and retailers had started phasing out this problematic cosmetic allergen (20, 21). In Denmark, the prevalence of MDBGN allergy has been reported to have decreased, and this was interpreted to be a result of the regulatory interventions in the Cosmetics Directive (22). Of interest, but less encouraging, is that large batches of shampoo and liquid soap containing MDBGN were discovered in 2009 by municipality environmental health inspectors in common grocery stores with nationwide coverage in different parts of Sweden (personal communication from Gunnar Guzikowski, Swedish Medical Products Agency, 2010). As a result, the responsible importers and retailers were obliged to withdraw the products from the market. This shows that cosmetic products on the EU market still may contain MDBGN, although it is prohibited, and that monitoring of the market by the competent authorities is essential for compliance with regulatory interventions. Formaldehyde-releasers are important sources of formaldehyde exposure and allergic contact dermatitis. Contact allergy to the formaldehyde-releaser itself, without allergy to free formaldehyde, is less frequent (23, 24). Formaldehyde-releasers were found in one-quarter of all cosmetic products. Our results were very similar to those from the USA Food and Drug Administration (FDA) Voluntary Cosmetic Registration Database, concerning the presence of formaldehyde-releasers in rinse-off cosmetics. Formaldehyde-releasers were found in approximately 27% of the rinse-off cosmetics, both in the present study and in the FDA data (23). Rinse-off products containing formaldehyde-releasers have been reported to be responsible for allergic contact dermatitis, from both occupational and non-occupational exposure (25). For the vast majority of preservatives in the present study, maximum use concentrations are specified in the Cosmetics Directive. There are no such limits for benzisothiazolinone and octylisothiazolinone in cosmetics. According to the European Commission database with information on cosmetic ingredients, CosIng (26), these substances are regarded as antimicrobials and not as preservatives, meaning that their function is to control the growth of microorganisms on the skin. According to the new regulation on classification, labelling and packaging of chemical substances and mixtures (CLP regulation) (16), only four of 30 preservatives are classified as skin sensitizers (H317); benzisothiazolinone, MCI/MI, glutaral, and octylisothiazolinone. MDBGN has not yet attained this classification, which is remarkable, considering its well-established importance as a skin sensitizer. MDBGN is thus banned for use in cosmetics, whereas it can be included in other products without restriction or warning labelling. In approximately half of the cosmetics and one-third of the detergents examined, one or more of the 26 fragrances requiring labelling were identified, indicating that they are still frequently used in the examined product types. The fragrances most frequently found in the present study are the same as in a recent study from the UK (27). In total, 90% of the products contained fragrances according to their ingredient labels. Fragrance mix II ingredients were nearly twice as common in the cosmetics and four times as common in the detergents than fragrance mix ingredients. Wet tissues differed markedly from the other product types, with only seven of 17 products being declared to contain any fragrance, and only one product listing any of the 26 fragrances requiring labelling. Recent studies have pointed to oxidation products of limonene and linalool as important skin sensitizers (28, 29). Both substances were widespread in the products, linalool being the most frequently identified fragrance in the cosmetics, and limonene in the detergents. In contrast to the situation with preservatives, maximum use concentrations are specified in the Cosmetics Directive for only three of 20 identified fragrances (hydroxycitronellal, isoeugenol, and methyl- 2-octynoate). Only citral and limonene are classified as skin sensitizers (H317) according to the regulation on the classification, labelling and packaging of substances and mixtures (CLP). European legislation for prevention of adverse health effects of chemicals covers a wide range of product types and exposure situations with different directives and ordinances, based on different principles, and not always well coordinated. Examples concerning contact allergy are the Cosmetics Directive, including full ingredient 270 2010 John Wiley & Sons A/S Contact Dermatitis, 64, 265 272

labelling, and restrictions on content based on risk assessment; and the regulation on detergents, requiring labelling of preservatives and selected fragrances. The new regulation on classification, labelling and packaging of chemical substances and mixtures (CLP regulation) is based on hazard identification. It came into force 20 January 2009, and will stepwise replace the directives on dangerous substances and preparations. One noticeable change is the introduction of so-called hazard statements instead of risk phrases, with skin sensitizers being classified as H317 as a substitute for the preceding R43. Furthermore, the limitations on nickel in certain articles and chromate in cement have been successful legislative measures (30). The directive on general product safety has appeared to be useful for the protection of consumer health, as shown by the recent EU ban of the allergenic anti-mould agent dimethyl fumarate in articles, based on a Commission decision in 2009. It is concluded that several preservatives and fragrances with well-known skin-sensitizing potential are common in shampoos, hair conditioners, liquid soaps, wet tissues, washing-up liquids, and multi-purpose cleaners. Such products may be used several times a day by consumers and workers, leading to repeated exposure to some of the most important causes of contact allergy, often in combination with other allergens and skin irritants. In addition, we have elucidated some shortcomings in the present legislation for the prevention of adverse health effects from chemicals. No maximum use concentration limits are specified in the Cosmetics Directive for some well-known and much used skin-sensitizing preservatives and fragrances. Several of the preservatives and fragrances are not yet classified as skin sensitizers in the CLP regulation. We suggest that this should be done in order to better protect consumers and workers from harmful skin exposure. 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