Coniaci Dermatilis. 1994. 31. :88-290
`Primed in Denmark . Alt rtghls reserved
`
`Copyright © Munksgaard
`1994
`CONTACT DERMATITIS
`ISSN 0105-IS73
`
`Allergic contact dermatitis from the synthetic
`fragrances Lyral and acetyl cedrene in separate
`underarm deodorant preparations
`
`J. HANDLEY AND D. BURROWS
`Department of Dermatology, Royal Victoria Hospital, Belfast, N. Ireland, UK
`
`The case is reported of a 28-year-oId man who developed allergic contact dermatitis from 2 synthetic
`fragrance ingredients, Lyral (3- and 4-{4-hydroxy-4-methylpentyl)-3-cyclohexene-l-aldehyde) and
`acetyl cedrene, in separate underarm deodorant preparations. The implications of the patient's
`negative patch test reactions to the European standard series (Trolab) and cosmetics and fragrance
`series (both Chemotechnique Diagnostics) are discussed. The importance is stressed of patch
`testing with the patient's own preparations when cosmetic dermatitis is suspected, and of identifying
`and reporting offending fragrance ingredients, with a view possibly to updating the European
`standard series and commercially available cosmetics and fragrance series.
`Key words: allergic contact dermatitis; fragrances; Lyral; acety! cedrene; underarm deodorants;
`cosmetics and toiletries; patch testing technique. © Munksgaard, 1994.
`Accepted for publication 7 December 1993
`
`Fragrances are stated to be the most frequent cause
`of cosmetic allergy (1,2). They are a blend of natural
`plant and flower oils, or synthetic compounds such
`as alcohols, aldehydes or ketones. Patch test screen-
`ing with the European standard series' fragrance
`mix (eugenol, isoeugenol, oak moss absolute, ger-
`aniol, cinnamic aldehyde, amyl cinnamaldehyde,
`hydroxycitronellal and cinnamic alcohol, emulsified
`in sorbitan sesquioleate) (3) is estimated to detect
`only 70-80% of cases of fragrance allergy (4).
`As new fragrances are continuously being de-
`veloped, it is important constantly to update knowl-
`edge of the most common allergens by identifying
`the fragrance ingredient(s) responsible in any pa-
`tient who develops perfume dermatitis. This can be
`a lengthy and unrewarding task, as cosmetic formu-
`lations are often a closely guarded secret. In this re-
`gard, we report a patient who developed allergic
`contact dermatitis from 2 synthetic fragrance com-
`pounds, Lyral and acetyl cedrene, in separate under-
`arm deodorants. Only 3 previous cases of Lyral sen-
`sitivity have been reported {2, 5, 6) and allergy to
`acetyl cedrene is hitherto unrecognized.
`
`Case Report
`A 28-year-old man developed dermatitis of both
`axillae after 3 months' use of 2 separate deodorant
`
`preparations (A and B). Patch testing showed posi-
`tive reactions at 3 days to both preparations (as is),
`and negative responses to the European standard
`series (Trolab), including fragrance mix, balsam of
`Peru and colophony, and cosmetics and fragrance
`series (both Chemotechnique Diagnostics). He was
`advised against further use of these preparations
`and his rash settled quickly with topical cortico-
`steroids with no subsequent recurrence.
`The manufacturer kindly provided the individual
`constituents of the 2 deodorants, and patch testing
`showed positive responses to the perfume used in
`each of them. The suppliers of these perfumes were
`asked to provide the ingredients of their prepara-
`tions with a view to identification of the fragrance
`allergens.
`One perfume company initially provided 4 frac-
`tions of their perfume compound (I) and patch
`testing showed a positive response to fraction 2. 5
`further ingredients of fraction 2 (fraction 2, frac-
`tion 2 ingredients 3, 4, 6 (each separate), fraction
`2 ingredients 1/2/5 (one sample)) were supplied
`and patch testing showed positive responses to
`fraction 2 and fraction 2 ingredient 6, which the
`company identified as Lyral and provided us with
`the product safety data sheet of.
`The other perfume company initially provided 4
`fractions of their compound (II) (esters, aldehydes
`
`Petitioner Dr. Squatch
` Ex. 1032
`
`

`

`CONTACT DERMATITIS FROM LYRAL AND ACETYL CEDRENE
`
`289
`
`plus ketones, alcohols, naturals) and patch testing
`showed a positive response to the aldehyde and
`ketone fractions. 4 further ingredients of the alde-
`hyde and ketone fraction were provided (ketone
`A, aldehyde Z, aldehyde Y, ketone B) and positive
`patch test responses were obtained to aldehyde Z
`and ketone B, which the company then identified
`as Lyral (aldehyde Z), and acetyl cedrene (ketone
`B). Relevant product safety and data sheets were
`provided.
`Thus, the allergen in perfume compound I (de-
`odorant A) was Lyral (3- and 4-(4-hydroxy-4-
`methylpentyl)-3-cyclohexene-l-aldehyde), and the
`allergens in perfume compound II (deodorant B)
`were Lyral and acetyl cedrene. These findings are
`summarized in Table 1. The patient showed posi-
`tive 3-day patch test reactions to (1) Lyral (0.075%,
`0.125%, 0.25% in petrolatum (pet.) and Lyral 6.5%
`in diisopropylene glycol (DIPG) (2) acetyl cedrene
`(10.8% DIPG). Patch tests to acetyl cedrene in
`dilutions of 0.108%, 0.54%, 1.08% were all nega-
`tive. Negative results were obtained in all 20 con-
`trols (attending the patch test clinic for other unre-
`lated reasons) on patch testing to Lyral (0.25% pet.,
`6.5% DIPG) and acetyl cedrene (10.8% DIPG).
`9 months after initial presentation, the patient
`was diagnosed as having allergic contact dermatitis
`from the synthetic fragrance ingredients Lyral and
`acetyl cedrene.
`
`Discussion
`This patient developed allergic contact dermatitis
`from 2 synthetic fragrance ingredients, Lyral (an
`aldehyde) and acetyl cedrene (a ketone), in separate
`underarm deodorant preparations. This case is of
`interest as it aptly demonstrates the difficulties and
`time involved in identifying fragrance allergens in
`patients with cosmetic dermatitis. In addition, only
`3 cases of Lyral sensitivity have previously been
`reported (2, 5, 6) and, to our knowledge, contact
`allergy to acetyl cedrene has not hitherto been rec-
`ognized.
`Contact allergy to Lyral was proven by: (a) posi-
`tive patch
`testing
`to concentrations between
`0.075-6.5%; Research Institute for Fragrance Ma-
`terials (RIFM) test data show Lyral to be non-
`irritating in concentrations of 10% pet. on human
`patch testing; (b) negative responses to Lyral in
`control patients. The case for acetyl cedrene allergy
`in this patient is less certain. Alternative expla-
`nations for the positive patch test response to ace-
`tyl cedrene (10.8% DIPG) could be: (a) false-posi-
`tive irritant reaction; (b) cross-reactivity between
`Lyral and acetyl cedrene. We believe that the posi-
`tive patch test response to acetyl cedrene (10.8%)
`is a true allergic rather than false-positive irritant
`response on the basis that: (a) RIFM test data
`shows acetyl cedrene 30% pet. to be non-irritating
`
`Positive response (grade)
`fraction 2 ( +)
`(contains 0.075% Lyral)
`fraction 2 ( +)
`fraction 2, ingr. 6 (+)
`(contains 0.125%. 0.25% Lyral)
`
`Table 1. Patch testing identification of allergens in perfume compound I (deodorant A) and perfume compound II (deodorant B)
`Perfume Compound I
`Patch testing to
`(i) fractions I, 2, 3, 4
`(all 5% pet.)
`(ii) fraction 2
`fraction 2, ingredients 3, 4, 6
`fraction 2, ingredients 1, 2, 5
`(all 1%, 2% pet.)
`Perfume Compound II
`Patch testing to
`(i) (a) esters 29% DIPG
`(b) alcohols 24% DIPG
`(c) naturals 15% DIPG
`(d) alcohols/Ketones 32% DIPG
`(all 5% pet.)
`(ii) Components of alcohols/ketones:
`(a) 5.3% ketone A + 94.7% DIPG
`(b) 1.1% aldehyde Y + 98.9% DIPG
`(c) 6.5% aldehyde Z + 93.5% DIPG
`(d) 10.8% ketone B + 89.2% DIPG
`(ail as is)
`(iii) Dilutions of 10.8% ketone B-K89.2% DIPG:
`(a) 1% pet. (0,108% acetyl cedrene)
`n
`(b) 5% pet. (0.54% acetyl cedrene)
`(c) 10% pet. (1.08% acetyl cedrene)
`NB. pet.: petrolatum
`DIPG: diisopropylene glycol.
`-t-: faint erythema: -t- +: marked erythema.
`
`Positive response (grade)
`
`(d) alcohols/ketones ( + +)
`
`(c) aldehyde Z(-i-+)
`(6.5% Lyral)
`(d) ketone B ( + +)
`(10.8% acetyl cedrene)
`
`

`

`290
`
`HANDLEY & BURROWS
`
`(a) Lyral: a mixture of isomers
`
`and
`
`OH
`
`OH
`
`(b) Acetyl cedrene (Vertofix Coeur) - a complex reaction
`mixture of which a principal constituent is methyl
`cedryl ketone
`
`O
`
`Fig. 1. Chemical structures of (a) Lyral (b) acetyl cedrene.
`
`on human patch testing; (b) patch testing with
`acetyl cedrene (10.8% DIPG) showed no positive
`responses in control patients. The negative patch
`test responses obtained with acetyl cedrene di-
`lutions between 0.108-1.08% were most likely be-
`cause these allergen concentrations were too low
`to provoke a cutaneous immune response. In our
`opinion, cross-reactivity between Lyral and acetyl
`cedrene is unlikely due to their completely different
`chemical structures (Fig. 1).
`It is noteworthy that patch test screening with
`the European standard series (specifically fragran-
`ce mix, and the indicators of fragrance sensitivity
`
`balsam of Peru and colophony) and the Chemo-
`technique cosmetics and fragrance series (neither
`of which contain Lyral or acetyl cedrene) was nega-
`tive in this patient. This stresses the importance
`of (1) patch testing to the individual preparations
`concerned in suspected cases of cosmetic derma-
`titis, and (2) identifying and reporting offending
`fragrance ingredients in individual cases of per-
`fume dermatitis, with a view to possibly updating
`the the European standard series and commercially
`available cosmetics and fragrance series.
`
`Acknowledgements
`The authors thank the companies concerned for
`their co-operation in these investigations.
`
`References
`1. Adams R M, Maibach H I. A 5-year study of cosmetic
`reactions. J Am Acad Dermatol 1985: 13: 1062-1069.
`2. De Groot A C, Bruynzeel D P, Weyiand J W et al. The
`allergens
`in cosmetics. Arch Dermatol 1988: 124-
`1525-1529.
`3. De Groot A C, White I R. Cosmetics and skin care prod-
`ucls. In: Rycroft R J G, Menne T, Frosch P J. Benezra C
`(eds): Textbook of contact dermatitis. Berlin, New York:
`Springer Verlag, 1992: 459-475.
`4. Larsen W G. Maibach H I. Fragrance contact allergy.
`Semin Dermatol 1982: /: 85-90.
`5. De Groot A C. Contact allergy to cosmetics: causative
`ingredients. Contact Dermatitis 1987: 17: 26-34.
`6. Benke G M, Larsen W G. Safety evaluation of perfumed
`shampoos: Dose/response relationships for product use
`testing by presensitised subjects. Journal of Toxicology -
`Cutaneous and Ocular Toxicology 1984: 3: 65-67.
`
`Address:
`/ Handley
`Department of Dermatology
`Royal Victoria Hospital
`Belfast BTI2 6BA
`N. Ireland
`UK
`
`