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Page 1: Contact dermatitis caused by fatty alcohols: may polyethoxylation of the fatty alcohols influence their sensitizing potential?

Contact Dermatitis • Contact Points

CONTACT DERMATITIS CAUSED BY FATTY ALCOHOLS • CORAZZA ET AL.

Contact dermatitis caused by fatty alcohols: may polyethoxylationof the fatty alcohols influence their sensitizing potential?

Monica Corazza1, Stefania Zauli1, Anna Bianchi2, Simonetta Benetti3, Alessandro Borghi1

and Annarosa Virgili11Department of Clinical and Experimental Medicine, Section of Dermatology, University of Ferrara, 44100 Ferrara, Italy, 2Department of PharmaceuticalSciences, University of Ferrara, 44100 Ferrara, Italy, and 3Department of Chemistry, University of Ferrara, 44100 Ferrara, Italy

doi:10.1111/cod.12020

Key words: allergic contact dermatitis; emulsifiers; fatty alcohols.

Emulsifiers are common constituents of skin careproducts, cosmetics and topical medicaments thatenhance the miscibility and stability of the aqueous andfatty components.

Fatty alcohols are widely used in topical formula-tions as consistency factors and as emulsifiers whenpolyethoxylated.

An unusual case of sensitization to different fattyalcohols is reported. Unexpectedly, the different levelsof polyethoxylation of the fatty alcohols appeared toinfluence the allergic response.

Case Report

A 41-year-old non-atopic woman complained of arelapsing itching dermatitis of the armpits after the use ofa ‘hypoallergenic’ roll-on deodorant (Defence deo�).

Patch tests applied with Haye’s Test Chambers�

(Haye’s Service AJ, Alphen aan den Rijn, The Netherlands)with the Italian Baseline Societa Italiana di DermatologiaAllergologica Professionale e Ambientale series and theintegrative preservatives and perfumes series (allergenssupplied by FIRMA, Florence, Italy) were performed.Readings were performed according to InternationalContact Dermatitis Research Group criteria. At D2 andD3, a ++/++ reaction to lanolin 30% pet. and a +/+reaction to fragrance mix 6% pet. were observed.

A repeated open application test with the patient’sdeodorant in an elbowfold induced an eczematousreaction after 6 days.

Correspondence: Dr Monica Corazza, Department of Clinical andExperimental Medicine, Section of Dermatology, University of Ferrara, ViaSavonarola 9, 44100 Ferrara, Italy. Tel: +39 0532 205825; Fax: +39 0532206791. E-mail: [email protected]

Conflicts of interest: The authors have declared no conflicts.

Further patch tests with all of the ingredients, providedby the Department of Pharmaceutical Sciences, wereperformed after 6 months (Table 1). Readings at D2 andD3 showed a +/+ reaction to myristyl alcohol (CAS 112-72-1) and +/++ reactions to ceteareth-2 (CAS 68439-49-6) and ceteareth-3 (CAS 68439-49-6); unexpectedly,no reactions were observed to ceteareth-20 (CAS 68439-49-6), ceteareth-25 (CAS 68439-49-6), and ceteareth-30(CAS 68439-49-6).

Allergic contact dermatitis caused by fatty alcoholscontained in the deodorant was diagnosed.

As ceteareth molecules are composed of cetyl-stearylalcohol and a variable number of molecules of ethoxylene,for research purposes further patch tests with cetyl alcohol(CAS 36653-82-4), stearyl alcohol (CAS 112-92-5) andcetyl-stearyl alcohol (CAS 67762-27-0/8005-44-5) 30%pet. were also performed. Positive reactions to cetyl

Table 1. Patch test with all of the ingredients of the patient’sdeodorant

Vehicle D2/D3 CAS number

Myristyl alcohol 5% pet. +/+ 112-72-1Ceteareth-2 20% pet. +/++ 68439-49-6 (generic)Ceteareth-3 20% pet. +/++ 68439-49-6 (generic)Ceteareth-20 20% pet. −/− 68439-49-6 (generic)Ceteareth-25 20% pet. −/− 68439-49-6 (generic)Ceteareth-30 20% pet. −/− 68439-49-6 (generic)Propylene glycol 5% aqua −/− 57-55-6Pentylene glycol 5% aqua −/− 5343-92-0Butylene glycol 5% pet. −/− 107-88-0Aluminium chlorhydrate 10% aqua −/− 12042-91-0Citronellyl

methylcrotonate5% pet. −/− 20770-40-5

Lonicera japonica flowerextract

5% aqua −/− 223749-79-9

Allantoin 2% aqua −/− 97-59-6Tocopheryl acetate 10% pet. −/− 7695-91-2/58-95-7Panthenol 10% aqua −/− 81-13-0/16485-10-2

© 2013 John Wiley & Sons A/SContact Dermatitis, 68, 181–192 189

Page 2: Contact dermatitis caused by fatty alcohols: may polyethoxylation of the fatty alcohols influence their sensitizing potential?

Contact Dermatitis • Contact Points

CONTACT DERMATITIS CAUSED BY FATTY ALCOHOLS • CORAZZA ET AL.

alcohol (+/++), stearyl alcohol (+/+) and cetyl-stearylalcohol (+/+) were also observed.

Discussion

The prevalence of contact allergy to emulsifier agentshas not been established, and only sporadic cases havebeen described; emulsifiers are therefore considered to beuncommon sensitizers (1).

Lauryl, myristyl, oleyl, cetyl and stearyl alcohols arethe fatty alcohols most frequently used as thickeners incosmetic products. A previous study in a large numberof patients with contact dermatitis showed positive reac-tions to these fatty alcohols in 23.2% of patients (2). Mostof them reacted to oleyl alcohol, whereas myristyl alcoholand stearyl alcohol gave only sporadic reactions. Somepatients showed more than one reaction.

Contact sensitization to myristyl alcohol contained incosmetic products is occasionally described in case reportsand small series, as in our patient (2–5).

The INCI denomination ceteareth-n [R(OCH2CH2)nOH] means that a variable number (n) of molecules ofethoxylene (OCH2CH2) is linked with a mixture of cetyland stearyl alcohol (R). The suffix ‘eth’ is the abbrevia-tion for the ethoxylene group. The mixture of cetyl andstearyl alcohol represents the lipophilic component, andthe molecules of ethoxylene represent the hydrophiliccomponent.

Our patient showed positive reactions to ceteareth-2and ceteareth-3 present in the cosmetic. Unexpectedly,no reactions were observed to ceteareth-20, ceteareth-25,and ceteareth-30, all of which contain a higher numberof molecules of ethoxylene. Further tests, performed for

research, confirmed sensitization to cetyl, stearyl andcetyl-stearyl alcohol.

Various hypotheses could explain the different reactiv-ities to the different ceteareths.

The higher molecular weights (MWs) of ceteareth-20, ceteareth-25 and ceteareth-30 (>1000) than ofceteareth-2 and ceteareth-3 (<500) could influence theallergenicity of the molecules. The higher number ofmolecules of ethoxylene may influence the interaction ofthe ceteareth with the carrier proteins and the T lym-phocytes. This could explain the lower allergenicity ofceteareth-20, ceteareth-25, and ceteareth-30.

Moreover, with an increase in the number of ethoxy-lene groups, as in ceteareth-20, ceteareth-25, andceteareth-30, the molecules become more hydrophilic;as a consequence, their lower lipophilicity may lead toreduced penetration in comparison with ceteareth-2 andceteareth-3.

Finally, with a reduction in the number of the ethoxy-lene chains, the critical micelle concentration of the emul-sifiers increases, increasing the number of free monomers.As a consequence, irritant power also increases. There-fore, ceteareth-2 and cetereth-3 are more irritant thanceteareth-20, ceteareth-25, and ceteareth-30; by induc-ing irritation, they may decrease the elicitation threshold,and promote their own transepidermal penetration.

The case reported highlights the allergenic potentialof emulsifiers, and indicates the possibility of multiplereactions to different fatty alcohols, a fact occasionallyreported in the literature (2, 6). Moreover, it also showsthat the level of polyethoxylation of the fatty alcohols caninfluence their allergenic response.

References1 Tosti A, Guerra L, Morelli R, Bardazzi F.

Prevalence and sources of sensitization toemulsifiers: a clinical study. ContactDermatitis 1990: 23: 68–72.

2 Tosti A, Vincenzi C, Guerra L, Andrisano E.Contact dermatitis from fatty alcohols.Contact Dermatitis 1996: 35: 287–289.

3 De Groot A C, Bruynzeel D P, van Joost T,Weyland J W. Cosmetic allergy frommyristyl alcohol. Contact Dermatitis 1988:19: 76–77.

4 Pecegueiro M, Brandao M, Pinto J, ConcaloS. Contact dermatitis to Hirudoid cream.Contact Dermatitis 1987: 17: 290–293.

5 Geier J, Lessmann H, Fuchs T,Andersen K E. Patch testing with myristylalcohol. Contact Dermatitis 2006: 55:366–367.

6 Guidetti M S, Vincenzi C, Guerra L, Tosti A.Contact dermatitis due to oleyl alcohol.Contact Dermatitis 1994: 31: 260–261.

© 2013 John Wiley & Sons A/S190 Contact Dermatitis, 68, 181–192