Research | C&T

Understanding Fragrance Allergy

Is Fragrance-free Always Necessary?
Howard I. Maibach, MD
University of California San Francisco, San Francisco, USA

Garrett Coman and Nicholas Blickenstaff

University of California San Francisco, San Francisco, USA;
and University of Utah, Salt Lake City, USA

Ashley Edwards
Touro University, Vallejo, CA, USA

KEY WORDS
fragrance allergy patch
test use test repeat
open application test
dermatitis

ABSTRACT
This article reviews studies
to diagnose allergic
contact dermatitis due
to fragrance, including
a patch test designed to
measure such. Limitations
of patch testing, the
relevance of fragrance
concentration in products,
use testing of common
consumer products,
and dermatologist
recommendations to
manage fragrance contact
allergy also are discussed.

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ragrances have become ubiquitous in skin and hair care products

to appeal to the consumers senses. However, fragrances have been
associated with allergic contact dermatitis in applications including:
unspecified leave-on products, sun tan lotion,1 deodorants,2 scented lotion,
unspecified rinse-off products, fine fragrances, shampoo, liquid soap, aftershave, lipstick, sunscreen, hair styling products, shaving foam, mascara, hair
dye, eye shadow and makeup cream. An example of typical allergic contact
dermatitis of the axilla due to a deodorant fragrance is shown in Figure 1.
While some dermatologists recommend avoiding all fragrances yielding
positive patch test results, as shown in Figure2, it has become increasingly
difficult to avoid all fragrances and in the end, may be unnecessary for the
patch test positive patient.
To identify dermatitis caused by fragrance, a patch test3 for common
aromatic allergens was designed in which two fragrance mixes using
putative common allergens served as screens. Fragrance Mix#1 (FM1) was
developed from the fragrances used in an antifungal cream that had caused
an allergic contact dermatitis epidemic.4 It comprised: Evernia prunastri
(oak moss), isoeugenol, cinnamyl alcohol, eugenol, cinnamal, geraniol,
-amylcinnamal and hydroxycitronellal. Fragrance Mix #2 (FM2), a later
attempt5 to identify fragrance allergens, consisted of hydroxyisohexyl
3-cyclohexene carboxaldehyde (HICC), farnesol, citral, hexyl cinnamal,
citronellol and coumarin. These materials are considered EU fragrance allergens; Table 1 on Page 36 lists them with their FM designations, along with
additional EU fragrance allergens. These mixes have been used in fragrance
allergy testing reported in the literature, which are reviewed here.

Preliminary Questionnaire
The diagnosis of a fragrance contact allergy always starts with a detailed
medical history. Schollhammer et al. developed a questionnaire to determine if consumers had a certain, probable or possible allergy to fragrances
based on their recollection of adverse reactions to perfumes or perfumed
products.6 In this questionnaire, the certain allergy included an itching
dermatitis reaction to at least one fine perfume or aftershave, and reactions
to other perfumed products. The probable allergy involved reacting to
one or more perfumed products (e.g., deodorant) but no specific perfume
Reproduction in English or any other language of all or part
of this article is strictly prohibited. 2014 Allured Business Media.

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Research | C&T
being identified as causing the clinical reaction. The
possible allergy meant reacting to various cosmetic
products with and without perfume, where materials
other than fragrance constituted the possible cause
of the reaction. Finally, those identified without a
fragrance allergy had never reacted to a perfumed
material.
This questionnaire allows the dermatologist to
determine which patients have the highest probability
of fragrance contact allergy before patch testing. With
the proper clinical history, patients then proceed
to the patch testing of FM1 and FM2, to define the
possible role of fragrance in the dermatitis.

Figure 1. Typical allergic contact

dermatitis of the axilla due to a deodorant
fragrance Note: The fold of the axilla
is partly spared; a classic observation
believed to be due to axillary sweating
diluting the allergen.

As IFRA has learned

more about fragrances,
recommended
concentrations for
fragrance use continue
to decrease.
Patch Testing
Patch testing is used by dermatologists to
determine if a chemical is causing an individuals
allergic inflammatory reaction on the skin. Usually, a
sampling of diluted potential allergens is arranged in
a grid pattern on an individuals back. Since this test
is for a type IV hypersensitivity reaction, or delayed
type of hypersensitivity, the skin must be checked
two and four days later to assess for reaction, which is
contained to the area of application.
Testing with FM1 is a common practice when
dermatitis is suspected to be from fragrance. Nardelli
et al.3 showed that 9.6% of patients investigated
for fragrance contact allergy reacted positively to
FM1, and 6% to FM2. Of those with suspected
fragrance induced dermatitis, sensitivity for FM1 has
been shown to be 27.2%, and 8.721.5% for FM2.7
Additional patch testing for FM2 helps to minimize
fragrance-induced clinical dermatitis false negatives, with an estimated additional 6% of patients
identified.3
Additionally, Larsen et al. report false negatives
to be 33%, suggesting neither FM1 or FM2 alone
are sufficient screening tools.8 Schnuch noted that
46% of patients react negatively when tested for the
individual constituents of FM1 but positively to the
mixture.9 This may be due to false positive reactions
to the mix, lowered allergen threshold, false negative

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Photo Credit: Jean-Marie Lachapelle, MD

Figure 2. Positive patch test reaction

scored as ++ according to International
Contact Dermatitis Research Group
recommendations

Photo Credit: Jean-Marie Lachapelle, MD

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reactions to individual constituents, or the existence

of a compound allergy.6
To increase sensitivity, Hesiterberg et al. recommend using four screening markers: FM1, FM2,
M. pereirae (balsam of Peru) and HICC. Further, in
addition to the 14 fragrance allergens used in FM1
and FM2 for patch testing, they recommend testing
for 12 fragrance constituents, including: butylphenyl methylpropional, Evernia furfuracea, linalool,
benzyl salicylate, benzyl alcohol, anise alcohol,
benzyl cinnamate, amylcinnamyl alcohol, limonene,
alpha-isomethyl ionone, benzyl benzoate and methyl
2-octynoate.1 Recently, additional allergens have
been commercialized, including hydroperoxides of
linalool, hydroperoxides of limonene and perfume
mix (Mx-08).10

Fragrance Concentration
Consideration of fragrance concentration and its
impact on dermatitis adds another layer of complexity when managing fragrance-allergic consumers.
The International Fragrance Research Association
(IFRA) publishes safe guidelines on fragrance use.
Based on research, the IFRA Code of Practice
includes 186 standards that either restrict or prohibit
the use of selected fragrance materials for all types

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of applications. Producers of fragranced cosmetics

and household products are expected to comply with
IFRA standards.11
In addition to regulating specific fragrance
compounds, IFRA sets acceptable fragrance exposure
levels. Allowable concentrations are determined by
the quantitative risk assessment of factors such as
volume of use, dermal exposure, and structural alerts
for dermal sensitization. Broad categories organize
products by exposure level, including: Category 1
for lip products, toys and waxes for mechanical hair
removal; Category 2 for deodorants, antiperspirants

Market Intelligence
n Mintel

analyst Meredith Hollihan notes that

beauty products having a strong fragrance
component often have an edge in the marketplace,
and that quality fragrance is becoming a distinct
branding markerand that younger consumers
name scent as a top attribute when selecting bath
and body products.
Source: GCI (GCImagazine.com)

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Research | C&T
and fragranced bracelets; and Category 3 for aftershave, eye products, facial creams, tampons, baby
creams and body paint for children. Exposure levels
vary by product, but the concentration level for
eugenol, for example, is 0.20% for Categories 1 and 2
and 0.50% for Categories 3 (and 4).11
As IFRA has learned more about fragrances, recommended concentrations for fragrance use continue
to decrease. This suggests fragrance concentration is
relevant to dermatitis; however the tolerated level is
unlikely to be discerned by patch testing alone.

0.05% and 0.005% w/v of eugenol, a weak sensitizer.

The highest ROAT concentration (0.5%) was selected
based on the current allowable concentration for use
in hydroalcoholic products according to the IFRA.
These tests involve the once or twice daily application
of the product to a convenient anatomic site, such as
the elbow pit, for up to 28 days. At the levels mentioned, eugenol did not induce reactions in eugenol
patch test positive volunteers.12 Additional use test
studies with fragrances are welcomed by the dermatology and dermatotoxicology community.

Repeat Open Application Test

Dermatologist
Recommendations

IFRA regulations underscore the importance of

fragrance concentration, and an understanding of
time-dose relationship is important for consumers
to integrate into their daily use or abstinence from
scented products. Svedman et al. described threeweek, repeat open application tests (ROAT) in which
individuals were tested with concentrations of 0.5%,

Table 1. Fragrance Mix Allergens and

Additional EU Allergens
Material

Fragrance mix

Amyl cinnamal

FM1

Cinnamal

FM1

Cinnamyl alcohol

FM1

Citral

FM2

Citronellol

FM2

Coumarin

FM2

Eugenol

FM1

Evernia prunastri

FM1

Farnesol

FM2

Geraniol

FM1

Hexyl cinnamal

FM2

HICC

FM2

Hydroxycitronella

FM1

Isoeugenol

FM1
Additional EU Allergens

Alpha-isomethyl
ionone

Butylphenyl
methylpropional

Amylcinnamyl alcohol

Evernia furfuracea

Anise alcohol

Limonene

Benzyl alcohol

Linalool

Benzyl benzoate

Methyl 2-octynoate

Benzyl cinnamate

Sorbitan
sesquioleate

Benzyl salicylate

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If a patients clinical history suggests contact

dermatitis from a fragrance, the fragranced product should be discontinued for 8-12 weeks. If this
improves the dermatitis, patch testing for common
aromatic allergens included in FM1 and FM2
should be attempted to identify clinically relevant
fragrances. Dermatologist offices equipped with more
complete fragrance batteries permit the identification of additional fragrance allergens. In Europe, if
the concentration of 26 known fragrance allergens
exceeds 100 ppm in a rinse-off product, or 10 ppm in
a leave-on skin products, they must be listed on the
label so the consumer has more freedom and awareness when choosing products.13
If an individual tests positive to FM1 or FM2,
some dermatologists advise that individual to avoid
all FM1 and FM2 fragrance compounds. This is not
straightforward for that person, as these ingredients
are not always listed on products. Other dermatologists advise patients to eliminate exposure to all
fragrances. This is not a simple task, considering the
pervasive use of fragrance in products. It may be
possible to find a fragrance-free body lotion, but few
brands produce entire fragrance-free product lines.
If an individual is motivated to use a specific
product after the period of abstinence, a ROAT can
be performed to ascertain if there is an acceptable
exposure concentration. As noted, this consists of
once to twice-daily applications of the product for up
to 28 days, typically to the elbow pit. Identification of
the offending fragrance and a ROAT to understand
appropriate concentration may allow the patient
to resume use of the fragranced product in a safe
manner.
Much remains to be learned about the clinical
relevance of a positive fragrance mix patch test.
Banning life-long fragrance use is practiced but often
cumbersome for a consumer. With the exception of
overt dermatitis from fine fragrances and toilet water,
and axillary dermatitis from deodorants and antiperspirants, clinical relevance is often not obvious.
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References
1. MV Heisterberg, T Menn and JD Johansen, Contact allergy to the 26 specific fragrance ingredients
to be declared on cosmetic products in accordance with the EU cosmetics directive, Contact Dermatitis 65(5) 266275 (2011)
2. MV Heisterberg et al, Deodorants are the leading cause of allergic contact dermatitis to fragrance
ingredients, Contact Dermatitis 64(5) 258264 (2011)
3. A Nardelli, A Carbonez, J Drieghe and A Goossens, Results of patch testing with fragrance mix 1,
fragrance mix 2, and their ingredients, and Myroxylon pereirae and colophonium, over a 21-year
period, Contact Dermatitis 68(5) 307313 (2013)
4. WG Larsen, Allergic contact dermatitis to the perfume in Mycolog cream, J Am Acad Dermatol 1(2)
131-133 (1979)
5. PJ Frosch, JD Johansen, IR White and JC Congress, Fragrances: Beneficial and Adverse Effects,
Springer, New York, USA (1998)
6. L Schollhammer, KE Andersen and CG Mortz, The diagnostic value of patch tests with two fragrance
mix I preparations for detection of clinically relevant perfume allergy, Contact Dermatitis 66(6) 350352
(2012)
7. PJ Frosch et al, Patch testing with a new fragrance mix detects additional patients sensitive to
perfumes and missed by the current fragrance mix, Contact Dermatitis 52(4) 207215 (2005)
8. W Larsen et al, A study of new fragrance mixtures, Am J Contact Dermatol 9(4) 202206 (1998)
9. A Schnuch, J Geier, W Uter and PJ Frosch, Another look at allergies to fragrances: Frequencies of
sensitisation to the fragrance mix and its constituents, Exog Dermatol 1(5) 231237 (2002)
10. Patch Test Products and Reference Manual 2014, Chemotechnique Diagnostics, www.chemotechnique.se/ckfinder/userfiles/files/Patch%20Test%20Products%20and%20Reference%20Manual%20
2014%20-%20For%20digital%20distribution(1).pdf (accessed Mar 14, 2014)
11. IFRA RIFM QRA Information Booklet Version 6.0, International Fragrance Association, www.ifraorg.
org (2011) (accessed Oct 15, 2013)
12. C Svedman et al, Does the new standard for eugenol designed to protect against contact sensitization protect those sensitized from elicitation of the reaction? Dermat Contact Atopic Occup Drug
23(1) 3238 (2012)
13. DA Buckley, Fragrance ingredient labelling in products on sale in the UK, Br J Dermatol 157(2)
295300 (2007)

Guest Contributors
Garrett Coman is a senior medical student at the University of Utah,
currently completing a research fellowship at Maibachs lab. He has a
background in economics and biomedical engineering, with a focus on
medical innovation and research in dermatology.

Nick Blickenstaff is a senior medical student at the University of Utah, with

a background in psychology and biomedical engineering. He is currently
completing a research fellowship at Maibachs lab, performing research
focused on dermatopharmacology and dermatotoxicology.

Ashley Edwards is a senior medical student at Touro University California.

She plans to pursue pediatric dermatology. After graduating from Columbia
University in chemical engineering and visual arts, she worked in medical
ethics and public health research at Columbia University Medical Center.

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