Contact Dermatitis Original Article COD Contact Dermatitis Contact in commercial hair dye products sold in Thailand Waranya Boonchai, Monthathip Bunyavaree, Waranaree Winayanuwattikun and Pranee Kasemsarn Contact Dermatitis Clinic, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, 10700 Bangkok, Thailand doi:10.1111/cod.12542 Summary Background. Hair dyes are known to contain contact allergens for which sensitization rates have increased over the last decade. Objective. To examine the type and frequency of contact labelled on sold in metropolitan Bangkok, Thailand. Methods. During the 2013 2014 study period, labelled ingredient information from home use and professional hair dye products was collected. Results. Two hundred and fifty-two hair dye products were evaluated. One hundred and forty-nine products from 48 brands were domestically produced in Thailand, and 103 products were from 23 multinational brands produced in countries other than Thailand. Two hundred and fourteen of 252 (84.9%) hair dye products were found to contain strong skin, with 118 (46.8%) being found in domestically produced products, and 96 (38.1%) being found in multinational brand products. Thirty-eight hair dye products (15.1%) were free of skin. The number of domestically produced products (31, 20.8%) that were free of skin was significantly higher (p = 0.002) than the number of multinational brand products (7, 6.8%). Conclusions. p-phenylenediamine was the most prevalent sensitizer found among domestically produced available on the market. Our findings indicate regional differences in hair dye allergen exposure. Key words: sensitizer. contact allergens; hair colouring; hair dye; p-phenylenediamine; Hair colouring is currently very popular among women and men of all ages. During the past decade, the use of hair dye products has been continuously increasing (1). The increase has been especially notable in men, with an increase from 2% to 7% (2, 3). The main reasons for the growing number of hair dye users are: (i) an increasing number of older people who wish to disguise grey hair, (ii) the explosive popularity of hair colour as a fashion accessory (particularly among the young) (4), and (iii) Correspondence: Pranee Kasemsarn, Department of Dermatology Faculty of Medicine Siriraj Hospital, Mahidol University, 10700 Bangkok, Thailand. Tel: +662 419 7000, ext. 4320; Fax: +662 411 5031. E-mail: doctorpranee@gmail.com Conflicts of interest: The authors hereby declare no personal or professional conflicts of interest regarding any aspect of this study. Accepted for publication 15 December 2015 increases in the affordability and availability of products for consumers. Hair dyes are categorized as permanent, semipermanent, and temporary, according to their resistance to washing. Hair dyes are known to contain substances that are categorized as moderate, strong and extreme. p-phenylenediamine, an extreme sensitizer, belongs to the family of aromatic amines, and is known to be a common ingredient in oxidative and permanent hair dye products (5, 6). The people harmed by hair colouring include both the customer and the hairdresser in a hair salon setting, and the people who colour their hair at home (7 9). The global prevalence of p-phenylenediamine allergy has been reported to be high (8). There are >200 known chemical substances used in hair dye products, with some being strong skin, owing to their chemical structure (10). 222 Contact Dermatitis, 74, 222 229
Frequent hair dye use and the associated exposure to skin-sensitizing substances can have adverse health effects (11 14). The Food and Drug Administration Thailand (Thai FDA) has continued to update legislation on the ingredients contained in hair dye products available in Thailand. Market surveys of the hair dye ingredients listed on product labels conducted in Europe and the United States resulted in a better understanding of hair dye ingredients (5, 6, 15), and helped dermatologists to improve the treatment and clinical outcomes of hair dye allergy patients. According to our review of the literature, no similar study has been reported from Thailand a country with a high and increasing prevalence of contact allergy resulting from hair dye substances (16). The aim of this study was to investigate hair dye substances according to product ingredient labelling, most notably the presence of contact in hair dye products available to consumers in Thailand, and compare those findings across three continents. Methods This was a cross-sectional study. Hair dye ingredients from product labels from stores of different types in the Bangkok metropolitan area were collected and recorded during the 2013 2014 study period. Two hundred and fifty-two products from 48 brands were collected (Table 1), with no duplications. Seventeen hair dye substances with moderate to extreme skin-sensitizing properties according to the European Commission s Scientific Committee on Consumer Products (10, 17) were entered into a Microsoft Access database (Microsoft Corporation, Redmond, WA, USA) and analysed. Selection of products Ingredients from the majority of available for sale on the Thai markets were collected and recorded. In order to obtain a representative cross-section of hair dyes available to, and used by, all types of customer in the Bangkok metropolitan area, hair dye ingredients were collected from products sold in markets, supermarkets, department stores, and upper-class and lower-class professional hair salons, for the purpose of reflecting the real-life hair dye exposure of Thai consumers and hairdressers. All hair dye products were categorized according to the manufacturer (domestic or multinational), resistance to washing (permanent, semi-permanent, or temporary), and colour/shade. Hair dye shades were classified as follows: (i) natural shades (black to medium dark brown); (ii) brown shades; (iii) blonde shades; and (iv) fashion shades (shades other than the aforementioned colours). A list of target was created on the basis of the skin-sensitizing properties of hair dye substances according to Thai FDA legislation. Statistical analysis The data were analysed by the use of descriptive analysis. Pearson s chi-square test or Fisher s exact test was performed with PASW STATISTICS version 18.0 (SPSS Inc., Chicago, IL, USA) for comparison of hair dye products according to country of manufacture (domestic versus foreign). A p-value of <0.05 was considered to be statistically significant. Results Of 252 investigated hair dye products from a total of 48 brands, 149 products from 25 domestic brands were produced in Thailand. Thirty-three products from 12 multinational brands were made in Asia, as follows: China, 4; Japan, 4; India, 3; and South Korea, 1. Seventy products from 11 other multinational brands were produced in other countries, as follows: France, 3; Germany, 3; United States, 3; United Kingdom, 1; and Australia, 1 (Table 1). Different types of hair dye were evaluated, including: permanent (210, 83.3%), semi-permanent (14, 5.6%), temporary (14, 5.6%), vegetable (1, 0.4%), and metallic (13, 5.2%). Temporary rinse hair colour, vegetable dyes and metallic dyes contained no skin. Among 210 permanent that we evaluated, 201 (79.8%) were oxidative (Fig. 1). A list of 17 skin, including hair dye product origin and shade, is shown in Table 2. Potent skin were identified in both permanent and semi-permanent hair colorants. The maximum concentrations of these skin allowed by the Thai FDA (18) regulation and their skin-sensitizing properties are also shown in Table 2. According to product labels, 214 of 252 (84.9%) hair dye products were found to contain ingredients categorized as moderate to extreme skin (Fig. 1). One hundred and eighteen of 214 (55.1%) products were made in Thailand, and 96 of 214 (44.9%) products were from multinational brands produced in countries other than Thailand. The most frequently identified skin were resorcinol (63.9%) and p-phenylenediamine (56%) (Table 2). Among primary intermediates, p-phenylenediamine was used twice as much as toluene-2,5-diamine in Thailand, especially in natural black shade. The ranking of commonly found skin between domestically produced and Contact Dermatitis, 74, 222 229 223
Table 1. Brands and national/regional origin of examined hair dye products available for sale on the Thai market Asia Thailand Other Asian countries Other regions Company No. of products Company No. of products Company No. of products Aily 1 Arfrin s 1 Garnier 4 Anya 1 Beautylabo 2 Just for Men 4 Audace 9 Bigen 9 La Bourse 3 Berina 5 Bingo 3 L Oreal 14 Biowoman 8 Farger 3 Matrix 1 Carebeau 3 Liese 5 Morgan 1 Caring 22 Moonstar 1 Restoria 4 Catherine 8 Omar Sharif 1 Revlon 4 Cruset 15 Paon 3 Schwarzkopf 28 Dcash 24 Pacare Bessie 3 Syoss 6 Dipso 5 Rani Satti Mehandi 1 Ultronic 1 Fwiyer 1 Yuudai 1 Herbal Prim Perfect 3 Isme 2 Just Modern 6 Lolane 21 Mano Dark Hair 5 Melins 1 Miracle 2 Nightingale 1 Prexim 1 Purete 2 7kings 1 Spring Man 1 Jiabao 1 Total 149 Total 33 Total 70 252 210 Permanent 42 Nonpermanent 201 Oxidative hair dye 9 Nonoxidative hair dye 14 Semipermanent 14 Temporary 1 Vegetable hair dye 13 Metallic 199 contained 2 contained no 9 contained 6 contained 8 contained no Fig. 1. Classification of all investigated. multinational hair dye products was different. Among domestically produced hair dye products, p-phenylenediamine (58.4%) was the most frequent skin sensitizer, followed by resorcinol (53.7%), and m-aminophenol (42.3%) (Table 2). Among multinational hair dye products, resorcinol (78.6%) was the most common, followed by m-aminophenol (72.8%), and p-phenylenediamine (52.4%). 1-Naphthol, 4-amino-m-cresol and phenyl methyl pyrazolone were more frequently found in domestically produced hair dye products, with 2,4-diaminophenoxyethanol, 2-amino-3-hydroxypyridine, m-aminophenol and 224 Contact Dermatitis, 74, 222 229
Table 2. Comparison of in 252 hair dye products available for sale on the Thai market according to country/region of manufacture and hair dye shade INCI name CAS no. Maximum authorized concentration (%) (18 20) Sensitizing potency category, based on results from LLNA or guinea-pig Substancecontaining products Thailand Multinational Origin Hair dye shade Natural (black) shade Sparkling dark shade Brown shade Blonde shade assays (21) N % N % N % N % N % N % N % 1-Hydroxyethyl-4,5- diaminopyrazole sulfate 155601-30-2 NR Strong 8 3.2 2 1.3 6 5.8 1 0.8* 7 9.2* 0 0* 0 0* 1-Naphthol 90-15-3 2.00 Strong 22 8.7 19 12.8* 3 2.9* 13 10.6 4 5.3 1 7.7 4 10 2,4-Diaminophenoxyethanol 66422-95-5 2.00 Moderate 55 21.8 18 12.1* 37 35.9* 30 24.4 17 22.4 2 15.4 6 15 HCl 2-Amino-3-16867-03-1 1.00 Not classifiable 14 5.6 4 2.7* 10 9.7* 1 0.8* 8 10.5* 1 7.7* 4 10* hydroxypyridine 2-Methyl-5-hydroxy 55302-96-0 1.50 Not classifiable 19 7.5 13 8.7 6 5.8 2 1.6* 12 15.8* 0 0* 5 12.5* ethylaminophenol 2-Methylresorcinol 608-25-3 1.80 Moderate 52 20.6 36 24.2 16 15.5 14 11.4* 22 28.9* 5 38.5* 11 27.5* 2-Nitro-p-phenylenediamine 5307-14-2 NA Toxic 1 0.4 1 0.7 0 0 0 0 1 1.3 0 0 0 0 4-Amino-2-hydroxy 2835-95-2 1.50 Strong 56 22.2 28 18.8 28 27.2 8 6.5* 35 46.1* 6 46.2* 7 17.5* toluene 4-Amino-m-cresol 2835-99-6 1.50 Strong 17 6.7 14 9.4* 3 2.9* 2 1.6* 9 11.8* 1 7.7* 5 12.5* 4-Chlororesorcinol 95-88-5 2.50 Moderate 22 8.7 17 11.4 5 4.9 7 5.7 7 9.2 1 7.7 7 17.5 m-aminophenol 591-27-5 1.20 Strong 138 54.8 63 42.3* 75 72.8* 76 61.8 34 44.7 9 69.2 19 47.5 N,N-bis(2-hydroxyethyl) -p-phenylenediamine sulfate 54381-16-7 2.50 Strong 31 12.3 23 15.4 8 7.8 15 12.2 6 7.9 1 7.7 9 22.5 p-aminophenol 123-30-8 NR Results indicate sensitizing ial 94 37.3 55 36.9 39 37.9 36 29.3* 35 46.1* 9 69.2* 14 35* Phenyl methyl pyrazolone 89-25-8 0.25 Strong 24 9.5 23 15.4* 1 1.0* 7 5.7* 7 9.2* 2 15.4* 8 20* p-phenylenediamine 106-50-3 6.00 Extreme 141 56 87 58.4 54 52.4 84 68.3* 39 51.3* 6 46.2* 12 30* Resorcinol 108-46-3 5.00 Strong 161 63.9 80 53.7* 81 78.6* 80 65 42 55.3 8 61.5 31 77.5 Toluene-2,5-diamine 95-70-5 4.00 Extreme 72 28.6 36 24.2 36 35.0 20 16.3* 30 39.5* 6 46.2* 16 40* INCI, Inventory of Cosmetic Ingredients; LLNA, local lymph node assay; NA, not allowed; NR, no restriction. *p < 0.05, compared between the same subgroups. Contact Dermatitis, 74, 222 229 225
resorcinol being frequently observed ingredients in multinational hair dye products. Potent sensitizing substances were more common in permanent than in semi-permanent. Various shades of hair dye contained significantly different amounts of skin (Table 2). 2-Nitro-pphenylenediamine was found in only one locally made product, with no 2-nitro-p-phenylenediamine being identified in multinational hair dye products. None of the investigated hair colour products contained glyceryl monothioglycolate, p-chloro-m-cresol, or chloroxylenol. Regarding the 201 oxidative that we identified, skin from across three continents are ranked and compared in Fig. 2. Resorcinol was the most frequent strong sensitizer used in oxidative, followed by m-aminophenol and p-phenylenediamine. The number of found in individual products ranged from 0 to 9. Thirty-eight (15.1%) hair dye products were free of skin, as follows: 2 permanent, 8 semi-permanent, 14 temporary, 1 vegetable hair dye, and 13 metallic. The number of domestically produced products (31, 20.8%) that were free of skin was significantly higher (p = 0.002) than the number of multinational products (7, 6.8%). The mean number of skin found in individual hair dye products was 3.7. A majority of products contained at least four skin (149/252, 59.2%) (Fig. 3). Discussion This is the first market survey of hair dye ingredients from Asia. Similar market surveys of hair dye ingredients have been conducted in Sweden, Spain, and the United States (5, 6, 15). From a total of 48 brands, 252 hair dye products were found to be available for sale in markets and salons in metropolitan Bangkok, which represents twice as much hair dye variety for consumers than reported in previous studies (5, 6, 15). More than half of the hair dye products that we evaluated were domestically produced in Thailand. The most common types of hair colorant available were permanent (83.3%), most of which were oxidative that contain skin. Oxidative currently make up 79.8% of the market share in Thailand, which is similar to rates reported in the EU and the United States (1). The authorized maximum concentrations of individual sensitizer hair dye substances as authorized by the Thai FDA were largely comparable to the concentrations authorized in other parts of the world. However, higher concentrations of such as toluene-2,5-diamine and N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate are authorized in Thailand than in the EU and United States (18). A total of 17 skin were identified from hair dye product labels. From our previous report in 2011, the rate of sensitization to 2-nitro-p-phenylenediamine was extremely high (53.8%) (16). As a result, the use of 2-nitro-p-phenylenediamine as a hair dye additive has been prohibited in Thailand since 2013 (19). 2-Nitro-p-phenylenediamine was found in only one domestically produced product, which was produced and sold illegally. p-phenylenediamine was the most frequently found extreme skin sensitizer among domestically produced, and the third ranked skin sensitizer among oxidative. p-phenylenediamine was most commonly found in black shade, and was found least often in blonde shade. Natural black shade were four times more likely to contain p-phenylenediamine than toluene-2,5-diamine. Curiously, p-phenylenediamine was ranked 11th among the oxidative available in Sweden (5). This finding suggests that the natural hair colour of the local population influences the types and amounts of hair dye ingredients in a given market. Our previous report described an increase in the rate of contact allergy to p-phenylenediamine from 6.5% to 9.8%, as observed at the Siriraj Contact Dermatitis Clinic over the last decade (16, 22), which may be attributable to: (i) increased use by males, (ii) an increase in the older population, and (iii) it being more fashionable to dye hair. Another study that investigated the prevalence of p-phenylenediamine allergy in the normal Thai adult population found a high rate (mean, 2.7%; males, 2.4%; females, 3.2%) of p-phenylenediamine contact allergy, and a 1.3% incidence of sensitization resulting from the monthly application of standard commercial hair dye preparations over a 6-month period (23). Consequently, p-phenylenediamine as a contact allergen is a public health issue in our country. In Thailand, p-phenylenediamine was used much more frequently than toluene-2,5-diamine as a primary intermediate. In Sweden, however, toluene-2,5-diamine was found in 80% of oxidative (5). Uter et al. reported an increasing rate of allergy to toluene-2,5-diamine (9, 24). Our unreported data showed a rate of allergy to toluene-2,5-diamine of 16%, which we considered to be rather high. Moreover, consumers were more frequently sensitized to coupling agents, such as resorcinol, m-aminophenol, and p-aminophenol (9), which are commonly among the top five found in oxidative hair dyes. Previous studies reported results similar to our findings in terms of most frequent substances found in (5, 6, 15). Resorcinol, p-phenylenediamine and aromatic amines (e.g. m-aminophenol) were 226 Contact Dermatitis, 74, 222 229
100 90 89 80 77.6 82 81 76 75 78 80 70 60 68 64.2 63.7 60 % 50 50 49 42.3 40 32 35.3 30 25 20 16 21 10 0 Resorcinol m-aminophenol p-phenylenediamine p-aminophenol Toluene-2,5-diamine Our study Europe (Sweden) Europe (Spain) USA Fig. 2. Comparison of the top five in 201 oxidative across three continents. Fig. 3. Number of identified hair dye substances (classified as skin ) in 252 hair dye products available for sale on the Thai market. *Significant difference between numbers of Thai and multinational products. frequently detected in hair dye products in Thailand and the United States (15). We collected and analysed hair dye ingredient data for various types of hair dye product. Only permanent and semi-permanent contained contact. Generally, semi-permanent dyes contain a smaller number of contact than permanent. Recently, semi-permanent Contact Dermatitis, 74, 222 229 227
that contain a combination of natural dyes have become available for Thai consumers, and are claimed to be free of p-phenylenediamine. Given that black or dark brown is the natural hair colour of most Thai people, these are the hair dye shades in highest demand in Thailand. Although many consumers are aware that temporary are safer, most continue to use permanent or semi-permanent (25). Thirty-eight hair dye products available for sale in metropolitan Bangkok contained no skin, and 13 of these were metallic. Examples of the dyeing agents contained in those 25 hair dye products, except for the 13 metallic, were CI 77489, 77491, 77492, 77499, henna, CI 75470, CI 15850, CI 73360, CI 19140, and CI 61570. Interestingly, the number of products that were free of those skin was significantly higher among domestically produced hair dye products. Regarding oxidative hair dyes, 71.1% of products contained at least four skin, which was comparable to the findings of a previous study (5). Multinational hair dye brands adjust product formulations and chemical substances according to customer demands and legal regulations in each market. This variation results in significant differences in allergen exposure among countries and continents. Conclusion Potent contact in terms of dye substances are commonly found in oxidative and semi-permanent hair dye products available on the Thai market. Most of the products that we evaluated were found to contain multiple. p-phenylenediamine was the most prevalent sensitizer found among domestically produced sold in metropolitan Bangkok. Although there has been some speculation that p-phenylenediamine will be replaced by other substances, there is currently no evidence that this change is forthcoming in Thailand. Our findings indicated regional differences in hair dye allergen exposure, corresponding to previous studies conducted in the EU (6, 26). Dermatologists and physicians in Thailand should be aware that hair dye allergy is a common cause of dermatitis of the head and neck. Dermatologists should remain up-to-date regarding sensitizing hair dye ingredients that are available within the region of their practice, and adjust their patch test series for hair dye allergy patients accordingly. Acknowledgements The authors gratefully acknowledge Ms Pacharee Iamtharachai for technical assistance in the contact dermatitis clinic. References 1 Mcfadden J P, White I R, Frosch P J et al. Allergy to hair dye.bmj 2007: 334: 220. 2 Daswani K. More men coloring their hair. The Los Angeles Times, 29 January 2012. Available at: http://articles.latimes.com/ 2012/jan/29/image/la-ig-mens-haircolor-20120129 (last accessed 15 October 2015). 3 Søsted H, Hesse U, Menné T et al. Contact dermatitis to in a Danish adult population: an interview-based study. Br J Dermatol 2005: 153: 132 135. 4 Hair dye: fast-growing business. The Economist Newspaper Limited 2015, 24 May 2001. Available at: http://www. economist.com/node/631692 (last accessed 15 October 2015). 5 Yazar K, Boman A, Lidén C. Potent skin in oxidative hair dye products on the Swedish market. Contact Dermatitis 2009: 61: 269 275. 6 Yazar K, Boman A, Lidén C. p-phenylenediamine and other hair dye in Spain. Contact Dermatitis 2012: 66: 27 32. 7 Schwensen J F, Johansen J D, Veien N K et al. Occupational contact dermatitis in hairdressers: an analysis of patch test data from the Danish Contact Dermatitis Group, 2002 2011. Contact Dermatitis 2014: 70: 233 237. 8 Thyssen J P, White J M, European Society of Contact Dermatitis. Epidemiological data on consumer allergy to p-phenylenediamine. Contact Dermatitis 2008: 59: 327 343. 9 Uter W, Gefeller O, John S M et al. Contact allergy to ingredients of hair cosmetics a comparison of female hairdressers and clients based on IVDK 2007 2012 data. Contact Dermatitis 2014: 71: 13 20. 10 Søsted H, Basketter D A, Estrada E et al. Ranking of hair dye substances according to predicted sensitization potency: quantitative structure activity relationships. Contact Dermatitis 2004: 51: 241 254. 11 Ishida W, Makino T, Shimizu T. Severe hair loss of the scalp due to a hair dye containing para phenylenediamine. ISRN Dermatol 2011: 2011: 947284. 12 Bolt H M, Golka K. The debate on carcinogenicity of permanent : new insights.crit Rev Toxicol 2007: 37: 521 536. 13 Søsted H, Agner T, Andersen K E, Menné T. 55 cases of allergic reactions to hair dye: a descriptive, consumer complaint-based study. Contact Dermatitis 2002: 47: 299 303. 14 Uehara S, Inomata N, Suzuki A et al. Severe contact urticarial syndrome due to oxidative hair dye containing para-aminophenol and sodium-methyl-oleoyl-taurate. JDermatol 2014: 41: 560 561. 15 Hamann D, Yazar K, Hamann C R et al. p-phenylenediamine and other allergens in hair dye products in the United States: a consumer exposure study. Contact Dermatitis 2014: 70: 213 218. 16 Boonchai W, Desomchoke R, Iamtharachai P. Trend of contact allergy to cosmetic ingredients in Thais over a period of 10 years. Contact Dermatitis 2011: 65: 311 316. 17 Basketter D A, Andersen K E, Lidén C et al. Evaluation of the skin sensitizing potency of chemicals by using the existing methods and considerations of relevance for elicitation. Contact Dermatitis 2005: 52: 39 43. 228 Contact Dermatitis, 74, 222 229
18 Academic Resource Center, Thailand FDA. Declaration of Thai Ministry of Public Health: Bangkok, Food and Drug Administration Thailand, 2014. 19 Minister of Public Health. The Government Gazette: Bangkok, Thai Government, 2013: pp. 11 23. 20 Minister of Public Health. The Government Gazette: Bangkok, Thai Government, 2008: pp. 12 29. 21 European Commission, Scientific Committee on Consumer Safety. Memorandum on hair dye chemical sensitisation. In: 18th Plenary SCCS Meeting, European Commission, Brussels, Belgium, 2013, pp. 1 18. 22 Boonchai W, Iamtharachai P, Sunthonpalin P. Prevalence of allergic contact dermatitis in Thailand. Dermatitis 2008: 19: 142 145. 23 White J M, Gilmour N J, Jeffries D et al. A general population from Thailand: incidence of common allergens with emphasis on para-phenylenediamine. Clin Exp Allergy 2007: 37: 1848 1853. 24 Uter W, Lessmann H, Geier J, Schnuch A. Contact allergy to ingredients of hair cosmetics in female hairdressers and clients an 8-year analysis of IVDK data. Contact Dermatitis 2003: 49: 236 240. 25 Patel D, Narayana S, Krishnaswamy B. Trends in use of hair dye: a cross-sectional study. Int J Trichol 2013: 5: 140 143. 26 Thyssen J P, Andersen K E, Bruze M et al. p-phenylenediamine sensitization is more prevalent in central and southern European patch test centres than in Scandinavian: results from a multicentre study. Contact Dermatitis 2009: 60: 314 319. Contact Dermatitis, 74, 222 229 229