fatal attrctiveness-the shady side of cosmetics

ELSEVIER

Fatal Attractiveness:
of Cosmetics
ANTON

C. DE GROOT,

MD,

The Shady Side

PhD

osmetics (which include skin-care products and
decorative cosmetics)
and toiletries (which include soap, shampoo,
bath-foam,
and toothpaste) are used by nearly everyone. Not surprisingly
and inevitably, these products will cause side effects in
some consumers.
Contrary
to what the title of this
article suggests, serious adverse reactions from cosmetics are infrequent; however,
mild unwanted
effects are
experienced by over 10% of the population.1,2 Diagnosing and treating patients with such reactions are part of
the daily routine of dermatologists.
In this contribution
cosmetic-related
irritation, photosensitivity,

and immediate contact reactions will be discussed briefly; contact
allergy as a side effect of cosmetics is presented in more
detail, highlighting
recently emerged important
cosmetic allergens.‘-”

C

Irritation
There are two forms of irritation: subjective and objective. Subjective irritation may be defined as chemically
induced burning, stinging, itching, or other skin discomfort without
visible, objective signs of inflammation. It is estimated that between
1 and 10% of all
(women) cosmetic users note this discomfort,
primarily
on the face. Objective irritation is defined as nonimmunologically mediated inflammation
of the skin. Its signs
are usually mild erythema and scaling, but frank dermatitis may occur. Irritation
may be observed with
cosmetic products containing detergents such as soap,
shampoo, and bath/shower
foam. Atopics and elderly
people with good/excessive
hygiene are particularly
susceptible to developing this side effect, mainly during
the winter when humidity is low. Itching usually starts
on the legs, arms and hips. The humid climate in, and
anatomical occlusion of, the axillae favor irritant responses to deodorants
and antiperspirants.
Surfactants

and emulsifiers
present in moisturizing
or emollient
creams may also cause irritation,
especially when applied to facial skin. Daily application of eye makeup
cosmetics and removal with cleansing products often
irritate the sensitive skin of the eyelids.
-~

-~~-

From the Department
of DematoIogy,
Carolus-Liduina
Hospital,
‘sHertogerlbosch,
The Netherlands.
Address correspondence
to Anton C. De Groot, M.D., Carolus-Liduina
Hospital, P.0. Box 3 102, 5200 BD’s-Hertogenbosch,
The Netherlands.

0 1998 by Elseuier Science Inc.
655 Azfetzue of tlw Americas, New York,

NY 10010

Photosensitivity
With the exception of the epidemic caused by the halogenated salicylanilides
in the 196Os, photosensitivity

has accounted for only a small proportion
of cosmeticrelated side effects. In a study from the United States,
photoallergy
and phototoxicity
were responsible
for
only 9 reactions in 713 patients investigated
for cosmetic dermatitis.7 Musk ambrette, a fragrance fixative
formerly used in many aftershaves, until recently was a
major cause of photocontact
allergy, often leading to
persistent light reactions;8 an association with chronic
actinic dermatitis has also been suggested.9 In 1985, the
International
Fragrance
Association
(IFRA)
recommended that musk ambrette not be utilized in products
in contact with skin; since then, the numbers of relevant
photocontact
allergic reactions have decreased considerably. Nowadays,
paradoxically
as this may seem, ultraviolet (UV) filters have become important causes of
photocontact allergy. The increased public awareness of
the risks of premature skin aging and cancer caused by
exposure to sunlight has led to more extensive use of
UV filters, not only in sunscreen preparations
but also
in skin-care products (notably facial creams); this is the
major cause of the recent increase of photocontact

allergic reactions to UV filters. Patients with photosensitive
diseases, such as chronic polymorphic
light eruption
(CPLE) and chronic actinic dermatitis,
who use sunscreens habitually are particularly
sensitive to developing photocontact
allergy. Most cases are caused by the
benzophenones
(notably oxybenzone)
and the UVAfiltering dibenzoylmethanes
(notably isopropyl
dibenzoylmethane,
butyl
methoxydibenzoylmethane).lOJi
Other less frequent photosensitizers
are p-aminobenzoic acid @‘ABA), octyl dimethyl
PABA, and ethylhexyl-p-methoxycinnamate.
Possibly, the frequency of
photocontact
allergy to cosmetics is underestimated.
When such reactions occur to sunscreens, the resulting
photoallergic reaction may be interpreted by the patient
as the failure of the product
to adequately
protect
against the sun’s rays rather than as an adverse reaction
to the product; medical consultation is then not sought.
In addition, probably only a minority of dermatologists
in private practice perform photopatch
testing, resulting in missed cases of photocontact

allergy.
0738-081X/98/$19.00
I’ZI SO738-081X(97)00179-X


168

DE GROOT

Immediate Contact Reactions
(Contact Urticaria)
The contact urticaria syndrome may comprise cutaneous reactions (localized urticaria, generalized urticaria)
as well as extracutaneous reactions (bronchial asthma,
rhinoconjunctivitis,
otolaryngeal symptoms, gastrointestinal symptoms, anaphylactic shock). Immediate
contact reactions are either nonimmunological (caused
by nonimmunological release of histamine and other
vasoactive substances) or immunological (IgE-mediated). Cosmetics rarely are the cause of contact urticaria;
however, many cases of “subjective irritation” might
actually represent very mild nonimmunological contact
reactions, caused especially by ingredients in cosmetic
products known to induce such symptoms, such as
sorbic acid, benzoates, and cinnamic aldehyde. In addition, immediate contact reactions to fragrance materials in perfumes may induce or worsen respiratory
problems such as shortness of breath, asthma, and
sneezing. People with respiratory allergy commonly
experience aggravation of their complaints around cosmetic counters, candle shops, and from perfumes worn
by other people, for example, in church.‘j

Contact Allergy
Epidemiology

Allergic contact reactions to cosmetics often go unrecognized for several reasons.7 (1) Frequently patients
have used the causative cosmetics for many years; the
development of skin problems from such products conflicts with the consumer’s perception of allergy, which
is based on the assumption that a new cosmetic has to
be introduced. (2) Cosmetic allergy is sometimes manifested by mild reactions only, for example, itching,
faint erythema, and mild scaling of the eyelids. (3)
Cosmetic dermatitis may sometimes
be noticed, but
wrongly interpreted. Psoriasis of the face may be exacerbated by cosmetic dermatitis; dermatitis caused by
emollient creams interpreted as worsening of dry skin
or atopic dermatitis for which it was applied; and contact allergy to sunscreens as failure of the product to
adequately protect the skin against the sun’s rays.
Nevertheless, allergic contact dermatitis to cosmetic
products is frequently observed. Of dermatological .patients patch tested for suspected allergic contact dermatitis, some 10% are allergic to cosmetic products.12 Six to
11% of routinely tested individuals react to the fragrance mix, a mixture of 8 commonly used fragrance
materials to detect sensitization to perfumes. In the list
of frequent allergens, the fragrance mix usually is number 2 after nickel sulfate.6 An estimated 1% of the general population is allergic to fragrances, and 2-3% are
allergic to substances that may be present in cosmetics
and toiletries 12,13

Clinics izz Dermatology

Clinical

l

1998;16:167-179

Picture

Sometimes, contact allergic dermatitis from cosmetic
products can be easily recognized. Examples include
reactions to deodorant, eye shadow, perfume dabbed
behind the ears or on the wrist, and lipstick. In more
than half of all cases,the diagnosis of cosmetic allergy is
suspected neither by the patient nor by the doctor.7
The clinical picture of allergic cosmetic dermatitis
depends on the type of products used (and consequently, the sites of application) and the degree of the
patient’s sensitivity. Usually, cosmetics and their ingredients are weak allergens, and the dermatitis resulting
from cosmetic allergy is mild: erythema, mild edema,
desquamation, and papules. Weeping vesicular dermatitis rarely occurs, although some products, especially
the permanent hair dyes, may cause fierce reactions,
notably on the face and ears and less on the scalp.
Allergic reactions on the scalp tend to be seborrheic
dermatitis-like with temporary hair loss, (HB van der
Walle, personal communication, 1997; personal unpublished observations).
Contact allergy to fragrances may resemble nummular eczema, seborrheic dermatitis, sycosis barbae, or
lupus erythematosus. 6 Lesions in the skin folds may be
mistaken for atopic dermatitis. Dermatitis due to perfumes or toilet water tends to be “streaky”. Allergy to
toluenesulfonamide/formaldehyde
resin in nail polish
may affect the fingers, 14but most allergic reactions are
located on the eyelids, in and behind the ears, in the
neck, and sometimes around the anus or perivulval.
The typical patient suffering from allergic cosmetic
dermatitis is a woman aged 20-45 years with mild
dermatitis of the eyelids. The face itself is also frequently involved, and often the dermatitis is limited to
the face and/or eyelids. Other predilection sites for
cosmetic dermatitis are the neck, the arms and the
hands; however, all parts of the body may be involved.

Most often, the cosmetics have been applied to previously healthy skin (especially the face), nails or hair.
Allergic cosmetic dermatitis may also be caused by
products used on previously damaged skin, for example to treat or prevent dry skin of the arms and legs or
irritant or atopic hand dermatitis.6

The Products

Causing Cosmetic Allergy

Most allergic reactions are caused by cosmetics that
remain on the skin: “stay-on” or “leave-on” products:
skin care products (moisturizing and cleansing creams,
lotions, milks, tonics), hair cosmetics (notably hair
dyes), nail cosmetics (nail polish, nail hardener), deodorants and other perfumes, and facial and eye
make-up products.3,6,7,15 “Rinse-off”
or “wash-off”
products such as soap, shampoo, bath foam, and
shower foam rarely elicit or induce contact allergic
reactions. This may be explained by the dilution of the


Clinics in Dermatology

l

1998;16:167-179

product (and, consequently, of the [potential] allergen)
under normal circumstances of use, and the fact that the
product is removed from the skin by washing after a

short period of time. One exception to this general rule
is allergy to the surfactant cocamidopropyl betaine,
which has caused many reactions to shampoo in consumers and occupational dermatitis in hairdressers,
and to shower gels (see later).16J7J8
Of course, trends in cosmetic usage, e.g. the growing
cosmetic market for men and the development of new
products (“kiddy cosmetics”, hair gel), may influence
the situation.

The Allergens
Although there are many publications on contact allergy to cosmetics and toiletries,>5 only 2 studies have
systematically investigated the allergens in such products.7J5 In both studies, fragrances and preservatives
were the most common causative ingredients in allergic
cosmetic dermatitis. Other important allergens are the hair
color y-phenylenediamine (and related permanent dyes),
lanolin and its derivatives, the nail lacquer resin toluenesulfonamide/formaldehyde resin, UV-filters (more often
photocontact allergy), and various emulsifiers. More recently, the surfactant cocamidopropyl betaine and the
preservative methyldibromo glutaronitrile have emerged
as important cosmetic allergens.16-20

Fragrances
Fragrances are the most frequent cause of cosmetic
allergy, both from products primarily used for their
scent (perfumes, colognes, eaux de toilette, aftershave,
deodorants) and from other scented products.6 Approximately 3000 chemical substances (of which 300-400 are
of natural origin) are used in the fragrance industry. A
perfume is a creative composition of fragrance materials, of which it may contain from a few to over 300.
Perfumes contain approximately 12-20% of the perfume compound, toilet water 5-8%, colognes 2-5%, and
cosmetics 0.5%. Most fragrance-sensitive patients are
identified by positive patch tests to personal products,

the “fragrance-mix”,
or the North American Contact
Dermatitis Group (NACDG) perfume-screening series.
The “fragrance mix” contains 8 commonly used fragrance ingredients: cw-amylcinnamic aldehyde, cinnamic alcohol, cinnamic aldehyde, eugenol, geraniol,
hydroxycitronellal,
isoeugenol, and oak moss absolute.
It is estimated that 70-80% of fragrance-allergic patients will react positively to the mix. Twenty to 30%
will remain undetected, and the mix causes both falsepositive and false-negative reactions. Approximately
100 fragrance materials have been identified as contact
allergens.”

THE

SHADY

SIDE

OF COSMETICS

169

Preservatives are added to water-containing cosmetics
to inhibit the growth of nonpathogenic and pathogenic
microorganisms, which may cause degradation of the
product or endanger the health of the consumer.21-23
Formaldehyde and Formaldehyde Donors
Formaldehyde is a frequent sensitizer
and ubiquitous allergen. Routine testing in patients
with suspected allergic contact dermatitis yields prevalence rates of sensitization of 3% or more, but most
cases are from non-cosmetic sources. The cosmetic industry uses free formaldehyde almost exclusively in

rinse-off products, which rarely gives rise to cosmetic
allergy. The literature on formaldehyde allergy has
been reviewed.21,22
FORMALDEHYDE

Formaldehyde donors are preservatives that, in the presence of water, release formaldehyde. Therefore, cosmetics preserved with such
chemicals will contain free formaldehyde, the amount
depending on the preservative used, its concentration,
and the amount of water present in the product. Formaldehyde donors used in cosmetics and toiletries include quaternium-15, imidazolidinyl urea, diazolidinyl
urea, 2-bromo-2-nitropropane-1,3-diol, and DMDM hydantoin. Quaternium-15 releases the most, imidazolidinyl urea the least free formaldehyde.2” Contact allergy
to formaldehyde donors may be due either to the preservative itself or to formaldehyde sensitivity.21,22
Whereas the formaldehyde donors appear to be gaining
in popularity as preservatives in cosmetics, formaldehyde itself has largely been replaced by other chemicals, because it is suspected (when inhaled as a gas), of
being a possible human carcinogen.25
FORMALDEHYDE DONORS

2OO@) Quaternium-15 is the
most frequent preservative sensitizer in cosmetic products.’ Routine testing by the NACDG yielded a prevalence rate of 9.6% in patients suspected of allergic contact dermatitis.26 Half of these reactions may be caused
by formaldehyde sensitivity.27 At the commonly used
concentration of O.l%, quaternium-15 releases about
100 ppm free formaldehyde, which in some formaldehyde-sensitive patients is sufficient to cause allergic
cosmetic dermatitis. In Europe, sensitization to quaternium-15 is less frequent.28
QUATERNIUM-15

(DOWICIL

UREA (GERMALL 1159 Imidazolidinyl
urea releases little formaldehyde, and consequently
poses little threat to formaldehyde-sensitive subjects. In
the United States, the prevalence rate of contact allergy

to imidazolidinyl urea is 2.3%.26Cross reactions to and
from the related preservative diazolidinyl urea may be
observed.28
IMIDAZOLIDINYL


170

Clitlics in Dermnfology

DE GROOT

DIAZOLIDINYL UREA (GERMALL II@) Diazolidinyl urea is
chemically related to imidazolidinyl urea. It has been in
use only since 1982, and is the most active preservative
of the imidazolidinyl urea group. Routine testing by the
NACDG resulted in a prevalence rate of sensitization of
3.0% in patients suspected of allergic contact dermatitis.z6 Diazolidinyl urea appears to be a stronger sensitizer than imidazolidinyl urea. Patients allergic to this
preservative may or may not react to formaldehyde.2*
(BRONOPOL)
Bronopol has been responsible for so many casesof allergic
cosmetic dermatitis from Eucerin@ cream in the United
States, that the manufacturer decided to replace it.29,30
Currently, its prevalence rate of sensitization in the
United States is 2.2%.26 Another concern is that its
interaction with amines and amides can result in the
formation of nitrosamines and nitrosamides, which are
suspected to be carcinogens. In Europe, bronopol in an
infrequent sensitizer.31
2-BROMO-2-NITROPROPANE-1,3-DIOL

DMDM
HYDANTOIN
Dimethylol dimethyl hydantoin
(Glydantm) has so far not been implicated as causing
cosmetic allergy, although routine testing in the United
States yielded a prevalence of 1.6% positive reactions.26
It has been demonstrated that some patients allergic to
formaldehyde may react upon patch testing to DMDM
hydantoin. 32In addition, provocation tests with a cream
containing 0.25% w/w DMDM hydantoin in formaldehyde-sensitive subjects elicited a positive response in
some of them, indicating that patients who are allergic
to formaldehyde may be at risk of developing allergic
cosmetic dermatitis from products preserved with
DMDM hydantoin.s2
Other Preservatives
The paraben esters (benzyl, butyl, ethyl,
methyl, propyl) are the most widely used preservatives
in cosmetic products, and may be considered very safe
in terms of causing allergy, especially in the low concentrations as used in cosmetics. In Europe, routine
testing with the parabens yields low rates of sensitization (less than 1%),33and in the United States, 2.3%.26
Most cases of sensitization to parabens are caused from
the use of topical pharmaceutical preparations on eczematous skin or leg ulcers. A review of paraben sensitivity has been published.23
PARABENS

MI/MCI(KathonCG@,
Euxyl K loo@) is a preservative system containing, as
active ingredients, a mixture of methylchloroisothiazolinone and methylisothiazoli.
The most widely used
commercial product is Kathon CG (where CG denotes

cosmetic grade), which contains 1.5% active ingredients.
In recent years, this highly effective preservative has become a major cause of cosmetic allergy in most European
countries. The subject has been reviewed.34,35 In the
METH~(CHLORO)ISOTHIAOUNONE

l

1998;16:167-179

United States, prevalence rates of 1.7%-1.9% (NACDG)
and 3.6% (Mayo Clinic) have been observed.%,37The use
concentration of MCI/MI is mostly between 3-15 ppm,
which is usually far below the threshold for detection of
allergy with patch tests, indicating that most allergic patients will not react to the product upon patch testing.
Therefore, MCI/MI
always has to be tested separately
(100 ppm water) whenever cosmetic allergy is suspected.
It is present in the European Environmental and Contact
Dermatitis Research Group (EECDRG) standard series.
Currently, MCI/MI is mainly used in rinse-off products at
low concentrations, which infrequently leads to induction
or elicitation of contact allergy.38 As a consequence, prevalence rates in Europe are decreasing.

Hair Colors
Hair colors may be temporary, semipermanent, or permanent. Most cases of cosmetic allergy from hair dyes
are caused by the (permanent) oxidation dyes of the
PARA-type (p-phenylenediamine and related dyes). In
recent years, the incidence of dermatitis due to hair
dyes containing p-phenylenediamine (derivatives) appears to have decreased. This is attributed to the provision of cautionary notices on the product, awareness
of the risk, patch testing of the product by future users,

improvements in the technical quality of the cosmetic
product, and improvements in the technique of application of these dyes. Nevertheless, p-phenylenediamine
remains an important cause of cosmetic allergy,7 6.3%
of all patients routinely tested by the NACDG reacting
to it.26 These oxidation dyes are also an occupational
hazard for hairdressers and beauticians.39

Glyceyl Thioglycolate
Glyceryl thioglycolate, a waving agent used in acid
permanent waving products, may sensitize consumers,
but it is usually an occupational hazard for the hairdresser.7,26,39,40
Patients allergic to glyceryl thioglycolate
infrequently react to ammonium thioglycolate, used in
“hot” permanent wave procedures.

Propylene Glycol
Propylene glycol is widely used in dermatologic and
nondermatologic topical formulations, including cosmetics, as well as in numerous oral and parenteral
medication, hygiene products, and food products.41-43
It was reported to be a common cause of cosmetic
dermatitis;7 however, irritant reactions are observed
regularly, and a test concentration low enough to cause
no irritation but high enough to detect all cases of
sensitization is lacking.
The following classification for skin reactions to propylene glycol has been suggested:41 (1) irritant contact
dermatitis; (2) allergic contact dermatitis; (3) nonimmunologic contact urticaria, and (4) subjective or sensory


Clinics in Dermatology

l

1998;16:167-179

irritation. There has been no evidence of photoallergy
or phototoxicity.
Irritant reactions are common reactions,
and they
should be a diagnosis of exclusion from clinical history,
physical examination,
and a negative patch test.
Allergic contact dermatitis is probably uncommon, and
the clinical significance has been overestimated. In earlier studies, higher concentrations of propylene glycol
may have induced many irritant patch test reactions.
Currently, a concentration of l%-10% is advised to
avoid such irritation, but cases of contact allergy are
probably then missed (false-negative reactions).*3 A diagnosis of allergic contact dermatitis should never be
made on the basis of one positive patch test alone.
Retesting should always be done after several weeks.
Next, retests with serial dilutions down to 1% propylene glycol help in dividing irritant responses from
true allergic ones. A negative reaction strongly suggests
a previously irritant response; a positive reaction suggests contact allergy. Repeated open application tests
(ROAT) and/or provocative use tests (PUT) can be
conducted to verify the allergic basis of a positive
patch-test result. In subjects with a negative patch test,
the ROAT/PUT may also be useful as a simulation of
normal application procedures.
Nonimmunolo~~iccmtact urticaria can also occur after
topical application of propylene glycol. The mechanism
entails microinjury to skin. Although this does not represent a contact urticaria in the strictest sense, it is

usually categorized as such.
Subjectivebr
sensory irritation, with itching, burning,
or stinging sensations but no signs of inflammation, is a
commonly noticed reaction among users of cosmetic
products and does not usually result in visits to dermatologists. It is a phenomenon that also occurs in volunteers after application of propylene glycol in different
concentrations81

Toluenesulfonamidelformaldehyde
Allergens) in Nail Lacquer

Resin (and Other

Several recent articles have discussed the allergens in
nail varnish, the features of allergic contact dermatitis,
and its frequency. ~44-48 Nail polish is intended to protect the nails and make them beautiful. This cosmetic
product was introduced to the market in 1919; the first
reports of contact allergy date from 1925. Since then,
more than 6700 caseshave been reported in the medical
literature. Every second case manifests as an eyelid
dermatitis. Eighty percent of all reactions are observed
as a dermatitis of the face and neck. Occasionally other
parts of the body are involved, including the thighs, the
genitals, and the trunk; generalized dermatitis is rare.
Periungual dermatitis may be far more common (60%)
than previously thought. 14 Partner (“connubial”) dermatitis has been observed. The main allergen is the
resin toluenesulfonamide/formaldehyde
resin [Interna-

THE

SHADY

SIDE

OF COSMETICS

171

tional Nomenclature of Cosmetic Ingredients (INCI)
name: tosylamide/formaldehyde
resin]. The exact allergenic ingredients of this resin are still unknown.46 Other
allergens have rarely been reported: formaldehyde, nitrocellulose (dubious), guanine, polyester resin, phthalates, amyl and butyl acetate, dye, ethylene dichloride,
Betonite@, and o-toluenesulfonamide.45r4h
Contact allergy to toluenesulfonamide/formaldehyde resin in nail varnish is far from rare. Up to 6.6% of
women habitually or occasionally using nail cosmetics
and presenting with dermatitis are allergic to it,44 and
the prevalence in patients routinely tested in the United
States was 1.9%.26The resin (10% petrolatum) should
always be tested on subjects using nail cosmetics, because neither the history nor the clinical features are
sufficient criteria for excluding or suggesting the diagnosis.44 Testing the patients’ own nail varnishes may
also be helpful. 14 The sociomedical consequences of
nail-varnish allergy may be severe and include sick
leave, hospitalization, and work loss14Allergic patients
should stop using nail varnishes or purchase varnishes
free of toluenesulfonamidelformaldehyde
resin (eg
Shiseido, Rot, Clinique); however, apparently some
products claiming not to contain the resin in fact do
so.49Also, such nail lacquers may contain other sensitizers, such as methyl acrylate and epoxy resin.50Useful

review articles on adverse reactions to nail cosmetics
and sculptured nails have recently been published.51-53

Lanolin

(Derivatives)

Lanolin and lanolin derivatives are used extensively in
cosmetic products as emollients and emulsifiers. The
allergens are the wool alcohols. In the United States, the
NACDG found a prevalence rate of 1.5% positive reactions in eczema patients.26 Most cases are caused by
topical pharmaceutical preparations containing it, especially for treating varicose ulcers and stasis dermatitis.
The-presence of-lanolin or its derivatives in cosmetics
rarely sensitizes patients, but patients presensitized
may experience cosmetic allergy from using cosmetics
containing lanolin or its derivatives. Avoidance of contact with lanolin or its derivatives often leads to disappearance of sensitivity.%

Stlnscreens
As drugs, sunscreens are used to prevent sunburn and
to prevent photosensitive dermatoses, such as herpes
labialis and chronic polymorphic light eruption (CPLE).
In cosmetics, they are added not only to protect the skin
of the user but also to prevent the product from photodegradation. The main classes of sunscreens are
PABA and its esters (amyl dimethyl, glyceryl, octyl
dimethyl), the cinnamates, the salicylates, the anthranilates, the benzophenones, and the dibenzoylmethanes.s5 The latter category is gaining popularity, because it absorbs mainly in the UVA region (315-400


172

Clinics in Dermatology

DE GROOT

nm). UV filters have been identified with increasing
frequency
as allergens and photoallergens,
but reactions to them remain uncommon.
Photoallergic
reactions can easily be overlooked, because the resulting
dermatitis may be interpreted by the patient/consumer
as failure of the product to protect against sunburn or as
worsening of the photodermatosis for which the sunscreen was used. PABA is a common cause of photoallergic reactions. Recently, most such reactions have
been caused by benzophenones and the dibenzoylmethanes, isopropyl dibenzoylmethane and butyl methoxydibenzoylmethane. 55The literature on adverse reactions to sunscreens has been reviewed.55-57 The most
frequent adverse reaction to sunscreen preparations is
irritation, which may occur in over 15% of users.58Both
allergic and photoallergic reactions are reported to the
main classesof UVA filters: benzophenones and dibenzoylmethanes. 10~9-63Oxybenzone (benzophenone 3) especially causes many casesof photoallergic contact dermatitis, and to a lesser extent allergic contact
dermatitis.10,59-61,63Patients who regularly use sunscreens because they suffer from the photosensitivity
dermatitis/actinic
reticuloid syndrome may have an
increased risk for developing allergic side effects of
sunscreens.6:’In all casesof suspected adverse reactions
to sunscreens, both patch and photopatch tests should
be performed.‘O

New Important

Cosmetic

Allergens

New important contact allergens do not appear every
day; however, in recent years two chemicals, the surfactant cocamidopropyl betaine and the preservative
methyldibromo glutaronitrile (in Euxyl@ K 400), have
emerged as important causes of allergic cosmetic dermatitis. Tocopheryl linoleate, a vitamin E derivative
present in a new line of cosmetics, was the cause of an
epidemic of contact dermatitis; the products were hastily withdrawn from the market.

Cocamidopropyl

Befaine

Cocamidopropyl betaine is an amphoteric surfactant
that enjoys increasing popularity
among cosmetic
chemists because of its low potential for irritation of the
skin.‘b-18 In the United States, the surfactant in 1980 was
present in only 47 of 19,000 products on file with Food
and Drug Administration (FDA), in 1992 this number
had risen to 521.3 Most of the products are shampoos
and bath products, such as bath and shower gels.
Cocamidopropyl betaine is prepared by reacting coconut fatty acids (obtained from coconut oil) with dimethylaminopropylamine, yielding cocamidopropyl dimethylamine, which is subsequently allowed to react
with sodium monochloroacetate to give the end product cocamidopropyl betaine. The lipophilic tail is
formed by coconut fatty acids, a mixture of fatty acids

l

2998;16:167-179

with chain lengths varying between C, and C,,. Cocamidopropyl betaine is therefore a mixture of several

compounds with the same basic structure, but with
differing lipophilic tails. Depending on the source, cocamidopropyl betaine can still contain varying amounts
of the reactants and intermediates involved in its synthesis. A major impurity is dimethylaminopropylamine.
CaseReports of Contact Allergy to
Cocamidopropyl Betaine
The first case of cosmetic allergy to cocamidopropyl
betaine was reported in 1983. In many cases published
since then, shampoo was the causative cosmetic product. Thus, cocamidopropyl betaine is the exception to
the rule that allergic reactions are usually caused by
“stay-on” (“leave-on”) cosmetic products. Other cosmetic products that have caused cosmetic allergy from
the presence therein of cocamidopropyl betaine include
skin-care products (moisturizing and cleansing products), deodorant, shower gel, bath foam, and liquid
soap; in addition, several cases of contact allergy to
cocamidopropopyl betaine in contact lens fluids have
been described.
Epidemiology of Contact Dermatitis to Cocamidopropyl
Betaine
By its presence in shampoos, cocamidopropyl betaine
appears to be an important occupational hazard to hairdressers. Prevalence rates of sensitization to cocamidopropyl betaine range from 3.7% to 5%. One investigator
obtained 12 positive patch test reactions among 210
(5.7%) patients suspected to suffer from cosmetic-related allergic contact dermatitis and/or dermatitis of
the head and neck area.64Seven of these were considered definitely relevant. All of these were allergic to
shampoos containing cocamidopropyl
betaine.@ A
group of investigators tested 1200 consecutive patients
with dermatitis of various types with cocamidopropyl
betaine and found allergic reactions in 46 (3.8%).65
Patch tests were relevant in all, the causative products
being mostly shampoos and bath foam.65 In another
Italian study, 17 of 1190 unselected eczema patients

(1.4%) proved to be allergic to cocamidopropyl betaine.66 The products causing allergic contact dermatitis
were shampoos, face cleansing lotions, gynecological
antiseptic syndets, liquid shower soaps, and anal hygienic detergents. 66In Arnhem, the Netherlands, 56 out
of a population of 781 dermatitis patients (7.2%) reacted
to cocamidopropyl betaine; however, in only 17 of these
56 (30%, ie 2.2% of the population tested), were the
reactions scored as relevant.17
The Allergen(s) in Cocanzidopropyl Betaine
Depending on its source, cocamidopropyl betaine contams varying amounts of the reactants and intermediates involved in its synthesis. To determine the actual
allergenic ingredient in cocamidopropyl betaine, a


Clinics in Dernzatolqpy

l

1998;16:167-179

THE

group of investigators
tested 30 patients allergic to cocamidopropyl
betaine with the chemicals used for its
synthesis. 65 All reacted to dimethylaminopropylamine
1% aqua, whereas only 16 patients (53%) reacted to
cocamidopropyl
betaine of purer grade.65 The authors
suggest that dimethylaminopropylamine
is the (only)
allergen in cocamidopropyl

betaine.65 These results
were later confirmed.66 Thus, it would appear that dimethylaminopropylamine
is the major allergen in cocamidopropyl
betaine and other alkylamidobetaines.66,67
As the amounts of dimethylaminopropylamine
found
in commercial preparations
containing cocamidopropyl
betaine is far lower than the eliciting concentration,
this
concept may be challenged.68

Patch Testing With Cocamidopropyl

Betaine

Cocamidopropyl
betaine usually causes allergic reactions in rinse-off products. As patch testing with these
products
is likely to result in both false-positive
and
false-negative
reactions, and such procedures therefore
are often unreliable, it is imperative
that cocamidopropyl betaine be tested separately.
It is therefore
suggested
to include cocamidopropyl
betaine in the
hairdresser’s

series and in the cosmetic series. Cocamidopropyl
betaine in the usual and commercially
available concentration
of 1% in water is a marginal
irritant, and not all “positive”
patch test reactions indicate (relevant) contact allergy to it. Relevance can be
established only when allergic patients are actually exposed to products containing cocamidopropyl
betaine,
and avoidance results in clearing or obvious improvement of dermatitis.

Mefhyldibromoglutaronitrile

(EuxyP

K 400)

Euxyl K 400 (Schiilke & Mayr, Norderstedt,
Germany)
is a preservative
system for cosmetics and toiletries,
containing
2 active ingredients:
methyldibromoglutaronitrile (MDG; synonym: 1,2-dibromo-2,4-dicyanobutane) and phenoxyethanol
in a 1:4 ratio.ls-20 Typical use
concentrations
are 0.05%-0.20%.
Euxyl@ K 400 was introduced in Europe in the mid 198Os, and it has been
used in the United States for approximately
6 years. In
the Netherlands

in 1995,25%-35%
of all cosmetic products and two-thirds
of all moistened toilet tissues used
for anal hygiene were preserved with Euxyl K 400. In
the United States in 1992, methyldibromoglutaronitrile
was present in only 7 out of 20,000 products on file with
the FDA.” In 1995, this number had risen to 56 of 22,287
products. Methyldibromoglutaronitrile
is also available
for a variety of noncosmetic
(industrial)
applications.69
Contact Alleugj to Euxyl K 400 and its Ingredient
Methyldibromoglutavollitrile
The sensitizer in Euxyl K 400 is nearly always methyldibromoglutaronitrile.
The first cases of contact allergy
to Euxyl K 400 were reported from Germany in 1989.
Later case reports include sensitization
to moistened

SHADY

SIDE

OF COSMETICS

173

toilet tissues (especially in the Netherlands),
skin-care

products, cucumber eye gel, barrier cream gel, cleansing cream, ultrasonic gel, and makeup.19 In the Netherlands, the prevalence of contact allergy to methyldibromoglutaronitrile
rose from 0.5% in 1991 to 4.0% in
1994.20,70 It is now the most frequent cosmetic allergen.
In Bologna, Italy, the prevalence of allergy to Euxyl K
400 rose from 1.2% in 1988-1990 to 2.3-2.9% in 19911994.71~7zIn Germany, approximately
2.3% of suspected
contact dermatitis patients are currently allergic to Euxyl K 400 and the members of the North American
Contact Dermatitis
Group in 1992-1994 found a prevalence of 1.5%.26,73 Between 23% and 75% of positive
patch-test reactions are considered to be relevant. Usually, cosmetics, both of the stay-on and of the rinse-off
variety, and, in the Netherlands,
moistened toilet tissues, were the cause of the reaction.2”

The Profile of Patients Sensitized to Euxyl K 400
Allergic patients have either cosmetic dermatitis
or
perianal eczema. The former
category
are usually
women, the latter mainly men. Cosmetic dermatitis is
often localized on the face and/or periorbital and on the
neck. Skin-care products
used for prevention
and/or
treatment of dry skin may also be the cause of cosmetic
dermatitis,
which may thus be localized, especially on
the hands, but also on the arms, the neck; widespread;
or even generalized. Occupational hand dermatitis may
be observed in hairdressers

and masseurs.
The Appropriate Test Concentration
Most investigators
have used Euxyl K 400 “per se” as
test allergen. As the allergen in Euxyl K 400 is nearly
always
its ingredient
methyldibromoglutaronitrile,
MDG can thus be conveniently
utilized as a single
allergen indicator
for allergy to Euxyl K 400.74 The
optimal test concentration
(and vehicle, MDG has thus
far been tested only in petrolatum)
has yet to be established, but it may be 0.5% in petrolatum.
In our experience, it is necessary to add an emulsifier, such as soy
lecithin, to obtain homogeneous
dispersions.
With the
currently available commercial allergens, methyldibromoglutaronitrile
0.1% pet (Trolab) and Euxyl K 400
0.5% pet (Chemotechnique),
false-negative
reactions
may occur.74

Folliculav Reactions
in Cosmef its

fo Tocopheryl

Linoleafe

In spring 1992, an epidemic outbreak of skin eruption
caused by a new line of cosmetics occurred throughout
Switzerland.75,76 Within a 3-month period, this outbreak
affected at least 263 people who consulted dermatologists and at least 642 people who did not. The lesions
were mainly papular and follicular, widely distributed,
with pronounced
pruritus,
which was aggravated by
sweating or heat exposure, and were long lasting. Epidemiological and clinical data incriminated
a new line


174

DE GROOT

of cosmetics containing vitamin E linoleatem, a mixture
of fatty acid esters of DL-a-tocopherol composed not
only of tocopheryl linoleate but also of tocopheryl
oleate, palmitate, and myristate. The lesions appeared
after l-160 days (mean 14 days) following the initial
application of the tocopheryl linoleate-containing cosmetics. In many cases, the rash extended and the pruritus increased several days after the application had
been stopped. In l/5 of the cases, a secondary extension
to the face was seen, though the cosmetics had not been
applied to these sites.
Patch testing showed positive patch tests with the

undiluted final cosmetic products, ranging from 21% to
64%, depending on the individual product. None of the
control subjects showed a positive test reaction. In addition, 60% of patients had positive or doubtful reactions to undiluted vitamin E linoleate, while none of
controls had. Thirteen out of 45 (29%) tested patients
presented a positive or doubtful reaction to tocopheryl
linoleate 10% in petrolatum. Patch tests with other vitamin E derivatives induced only a few positive reactions. Twelve of 15 (80%) patients who performed repeated open-application tests reacted to the body lotion
containing tocopheryl linoleate; however, several also
reacted to the lotion without tocopheryl linoleate.
Skin biopsies performed on lesional skin showed
spongiosis of the follicular epidermis with a perifollicular and perivascular infiltrate containing a predominantly mononuclear clear cell infiltrate with some neutrophils. An in vitro time-dependent formation of
oxidative products under storage or oxidation-stimulating conditions was observed. The authors conclude that
oxidized vitamin E derivatives could act in vivo as
haptens and/or irritants, possibly with synergistic effects.75 An allergic mechanism was later favored by the
authors.76
This is a unique study of a very curious cosmetic
reaction. The mechanism remains unknown. Several
factors favor an allergic etiology, others suggest irritation rather than contact allergy. Probably more than one
mechanism was involved. However, there can be no
doubt that tocopheryl linoleate was the cause of this
outbreak of cosmetic contact dermatitis.

Diagnostic

Procedures

The diagnosis of cosmetic allergy should strongly be
suspected in any patient presenting with dermatitis of
the face, eyelids, lips, and neck.7L78 Cosmetic allergic
dermatitis may develop on previously healthy skin of
the face or on already damaged skin (irritant contact

dermatitis, atopic dermatitis, seborrheic dermatitis,, allergic contact dermatitis from other sources). Also, dermatitis of the arms and hands may be caused or worsened by skin-care products to treat or prevent dry skin
and irritant or atopic dermatitis. Patchy dermatitis in
the neck and around the eyes is suggestive of cosmetic

Clinics in Dermatology

l

1998;16:167-179

allergy from nail lacquers or hardeners. A thorough
history of cosmetic usage should always be obtained. It
must be stressed that most women think of “cosmetics”
in terms of decorative cosmetics such as eye shadow,
rouge, lipsticks, hair colors, and nail lacquers. Therefore, it is necessary to specifically inquire about products such as day and night cream, cleansers, makeup
removing pads, perfume, eye cream, and so forth. The
“classic” cosmetic dermatitis of periorbital dermatitis
may be caused by any product used on the hair, the
scalp, the face, the hands, and the nails.
When the diagnosis of cosmetic allergy is suspected,
patch tests should be performed to confirm the diagnosis and identify the sensitizer. Only in this manner can
the patient be counseled about future use of cosmetic
(and other) products and the prevention of recurrences
of dermatitis from cosmetic
or noncosmetic sources.
Patch tests should be performed with the NACDG or
EECDRG routine series, a “cosmetic series” containing
known cosmetic allergens, and, of course, all products
used by the patient. The NACDG routine series contains a number of allergens that may cause allergic
cosmetic dermatitis: rosin (colophony, an indicator for

perfume allergy, and a possible allergen in eyeshadow);
the preservatives diazolidinyl
urea, imidazolidinyl
urea, formaldehyde and quaternium-15; the fragrances
cinnamic aldehyde and cinnamic alcohol and balsam of
Peru (indicator for perfume sensitivity); the hair color
p-phenylenediamine; and lanolin alcoho1.26The EECDRG
routine series contains colophony, balsam of Peru, the
fragrance mix, formaldehyde, quaternium-15, methyl(chloro)isothiazolinone, wool alcohols, and p-phenylenediamine. A suggested “cosmetic series” is shown in
Table 1. Most of these allergens are available from
Chemotechnique (Malmo, Sweden) or from Hermal
Chemie (Reinbek/Hamburg, Germany). Although the
patient’s products should always be tested (for test
concentrations, see Table 2), patch testing with cosmetics has some important drawbacks. Patients often use
many cosmetic products, which makes the investigation
very laborious. More importantly, both false-negative
and false-positive reactions occur frequently. False-negative means that the patient is allergic to a certain
cosmetic, but the patch test reaction to the product itself
remains negative. This is due to the low concentration
of some allergens and the usually weak sensitivity of
the patient. The product does cause allergic cosmetic
dermatitis when applied repeatedly (eg daily), when
applied to damaged (dry or eczematous) skin, or when
applied to very sensitive skin, for example, the eyelids.
One application on the thick and intact skin of the back,
even under occlusion (as is the case with patch testing)
is insufficient to cause a positive patch test reaction.
Classic examples of false-negative reactions are with
methyl(chloro)isothiazolinone
and paraben sensitivity.34,“6 Therefore, such allergens have to be routinely

Clinics in Dermatology

l

1998;16:167-2

Table 1.

79

THE

SHADY

SIDE

OF COSMETICS

175

Suggested Allergens for a “Cosmetic Screening Series”

Allergen

Test Concentration
and Vehicle

Function

Amerchol
L lOl*
Benzophenone-3
(oxybenzone)
Benzophenone-10
(mexenone)
BHA (butylated
hydroxyanisole)
BHT (butylated
hydroxytoluene)
2-Bromo-2-nitropropane-1,3-diol
Cetearyl
alcoholt
Cocamidopropyl
betaine
Diazolidinyl
meaS
Fragrance
mix§
Glyceryl
thioglycolate
Imidazolidinyl
urea$
Isopropyl
dibenzoylmethane
Methyl(chloro)isothiazolinone§
Methyldibromo
glutaronitrile
Octyl dimethyl

PABA
PABA
Parabenss
Propolis
Propylene
glycol
Toluenesulfonamide/formaldehyde

resinq[

Emulsifier
Sunscreen
Sunscreen
Antioxidant
Antioxidant
Preservative
Emulsifier
Surfactant
Preservative
Fragrance
Permanent
waving
Preservative
Sunscreen
Preservative
Preservative
Sunscreen
Sunscreen
Preservatives
Natural

ingredient
Humectant
Nail lacquer resin

agent

50% pet
2% pet
2% pet
2% pet
2% pet
0.5% pet
30% pet
1% water
2% water or pet
8X1% pet
1% pet
2”%i pet
2% pet
100 ppm in water
0.5% pet
2% pet
2% pet
5X3% pet.
10% pet
10% water
10% pet

pet= petrolatum.
* INCl name: innolin alcohol and paraffinurn

liquidurn.
f 1NCl nnme: cetyl alcohol, stearyl alcohol.
#Present
in the NACDG
series.
5 Present in the EECDRG
series.
y TNCJ name: tosylamide/formaldehyde
resin.

tested in the appropriate concentration in a cosmetic
screening series. False-positive reactions may occur
with any cosmetic product, but especially with products containing detergents/surfactants such as shampoo, soap, bath, and shower foam. As a consequence,
these products are usually diluted to 1% in water before
testing. Even then, mild irritant reactions are observed
frequently; and, of course, the (necessary) dilution of
Table 2.
Products

Recommended Test Concentrations

for Cosmetic

Cosmetic Product

Test Concentration

Bleach
Depilatory
Foaming

bath product
Foaming
cleanser
Hair dyes
Mascara
Nail cuticle remover
Nail glue
Nail polish
Nail polish remover
Permanent
wave solution
Shampoo
Shaving
lather or cream
Skin lightener
Soap or detergent
Straightener
Toothpaste

Ammonium
persulfate
1% pet
Thioglycolate
1% pet
1% Water
1% Water
2% Water
Pure (allow to dry)
Individual
ingredients

Individual
ingredients
Pure (allow to dry)
Individual
ingredients
Glyceryl
thioglycolate
1% pet
1% Water
1% Water
Hydroquinone
1% pet
1% Water
Individual
ingredients
2% Water

Adapted from De Groat, Weijlmd
and N&r.”
Most cosmetics not mentioned
in this table cm be tested

undiluted.

and Vehicle

these products may result in false-negative results in
patients who are actually allergic to them. Testing these
products, therefore, is highly unreliable. In many cases,
testing with the NACDG/EECDRG

routine series, the
suspected products, and a cosmetic screening series will
establish the diagnosis of cosmetic allergy and identify
one or more contact allergens. On the incriminated
product or the label can be found whether or not the
product actually contains the allergen(s). If not, the
possibility of a false-positive reaction to the product
should be suspected. The test should be repeated and/
or control tests on nonexposed individuals should be
performed. If allergy is confirmed, an ingredient of the
product that was not tested in the NACDG/EECDRG
series and the cosmetic screening series may have been
responsible. In such cases, the manufacturer should be
asked for samples of the ingredients, and these can be
tested on the patient after proper dilution.79
In certain cases, allergy to cosmetics is strongly suspected, but patch testing remains negative. In such
patients, ROAT and/or usage tests can be performed.
In the ROAT, the product is applied twice daily for a
maximum of 14 days to the antecubital fossa. A negative reaction after 2 weeks makes sensitivity highly
unlikely. This procedure should be performed with all
suspected products. In the usage test, all cosmetic products are stopped until the dermatitis has disappeared.
Then, cosmetics are reintroduced as normally used, one
at a time, with an interval of 3 days for each product,


176

DE GROOT

until a reaction develops. Diagnostic problems with

propylene glycol were discussed in a previous section.
Photopatch testing should be performed whenever
photoallergic cosmetic dermatitis is suspected. When
all tests have remained negative, the possibility of
seborrheic dermatitis (scalp, eyelids, face, axillae,
trunk), atopic dermatitis (all locations), irritant contact
dermatitis (also from cosmetic products), and allergic
contact dermatitis from other sources should first
be considered.

Therapy and &even tion
The therapy of allergic cosmetic dermatitis consists of
discontinuation of the (suspected) allergenic product(s)
and, if necessary, topical (and rarely systemic) steroids.
To prevent recurrences, the patient should receive the
Cosmetic, Toiletry and Fragrance Association (CTFA)
names (United States) or INCI names (European Union)
of the allergen(s) identified, and be instructed to avoid
cosmetic and non-cosmetic products containing them
and possible cross-reacting (chemically-related) substances. Cosmetic ingredient labelling enables the patient to choose products not containing these. In the
case of contact allergy to fragrances, balsam of Peru and
possibly colophony, unfragranced products should be
used. In some patients a fragrance may sometimes be
applied to clothing or hair without eliciting an allergic
response. “Connubial contact” (ie from the partner)
with fragrances should be avoided.6 Many allergens in
cosmetics are relatively easy to avoid, because they are
used only or mainly in cosmetics. Others have many
applications (eg methyl(chloro)isothiazolinone),
and

some are impossible to avoid (eg formaldehyde).

Finally!
Ingredient
Labelling
in the European
Union.
New Opportunities
but Also
New Problems
Cosmetic ingredient labelling (introduced in the United
States already 20 years ago!) has been a constant demand of European dermatologists and allergists for
years. 12,80,8*
The benefits are obvious: dermatologists
have a better chance to identify allergens in products
used by their patients; and, if a patient is allergic to one
or more cosmetic ingredients, he or she can avoid products containing this ingredient.
On January lst, 1997, the 6th Amendment to the
European Union Cosmetics Directive (76/768) came
into force. This directive requires, among others, that all
cosmetic products marketed in the European Union
display their ingredients on the outer package or, in
certain cases, on an accompanying leaflet, label, tape, or
tag.82 The primary purpose of ingredient labelling is to
allow dermatologists to identify specific ingredients
that cause allergic responses in their patients and enable
such patients to avoid cosmetic products containing the

Clinics in Dermatology

l

1998;16:167-179

substances to which they are allergic by checking their
labels.l* The nomenclature used throughout the European Union for labelling is the INCI (International Nomenclature Cosmetic Ingredient), based on the (American) CTFA
(Cosmetic, Toiletry
and Fragrance
Association) nomenclature. Most CTFA terms have
been retained unchanged. All colorants are listed as
color index (CI) numbers, except hair dyes, which have
INCI names. Plant ingredients are declared as genus/
species using the Linnaean system. The source of information on ingredients is the European Inventory published in all official European Union languages.
Provided are the INCI names (in alphabetical order),
CAS-number, EINECS-ELINCS numbers, chemical/IUPAC names, and functions. EINECS = European inventory of existing commercial chemical substances and
ELINCS = European list of notified chemical substances.
We have found that the inventory has several disadvantages. The major problem is the “translation” of
plant products and colors from the CTFA nomenclature
to the INCI. Lists of synonyms are not provided. Only
those who have access to botanical literature and specific literature on colors can find relevant names. Apart
from the fact that we will have to get used to some very
exotic names, who would be able to find “Myroxylon
Pereirae” for balsam of Peru, “Eugenia caryophyllus”
for clove oil or “CI 77000” for aluminum?
The order of listing is sometimes rather illogical: for
p-aminophenol, look under “pa. . .” instead of “Am. . .“.
Benzophenone-11 comes before benzophenone-2 (because 11 begins with 1, thus lower than 2).
It is stated that fragrances have not been included in
the INCI, because they need not to be declared; however, we found many fragrance names (eg geraniol,
hydroxycitronellal,

cinnamal, cinnamyl alcohol). Their
function is described as “additives”. Additives are defined as “Substances which, often in fairly small
amounts, are added to cosmetic products to create or
improve desired properties or minimize or suppress
undesired properties”. In this context one may think of
“masking perfumes”, the classic example of which is
ethylene brassylate (indeed mentioned in the inventory). We do not know whether producers of cosmetics
will actually declare such fragrances on the label. In
addition, dermatologists will have to check the inventory as to whether or not a specific fragrance is included
before advising patients allergic to these individual
fragrance compounds.
In spite of the fact that fragrances do not need to be
declared, part II of the inventory lists some 2500 fragrances (including plant extracts) and aroma chemicals.
In itself this could be very useful; however, the chemicals are not listed in alphabetical order, but in order of
ascending EINECS/ELINCS numbers, and thus impossible to trace for almost all dermatologists.


Clinics in Dermatolq~y

l

1998;16:167-2 79

Evidently, patients allergic to certain ingredients
of
cosmetics should be supplied with the INCI names of
their allergens. They will fruitlessly seek for names such
as Kathon CG, oxybenzone, balsam of Peru, Amerchol
L 101, dibromodicyanobutane,
or orange oil. Therefore,

dermatologists
should be familiar with INCI names.
From the above it is clear that the relevant names are
sometimes
very hard or impossible
to find. To overcome this problem, a list of substances
that can be
present in cosmetics and have been described as allergens was made, and their names (CTFA, Merck Index,
names provided
by the producers
of commercially
available allergens [Chemotechnique,
Trolab], “common names”, commonly used trade names) were compared with INCI. 3,h All allergens for which the INCI
names were different were tabulated alphabetically.83
In spite of these shortcomings,
ingredient labelling will
be extremely useful to dermatologists,
allergic patients,
and interested consumers.

References
1. De Groot AC, Nater JP, van der Lende R, et al. Adverse
effects of cosmetics: A retrospective
study in the general
population.
Int J Cosm Sci 1987;9:255-9.
2. Berne B, Lundin A, Enander Malmros I. Side effects of
cosmetics and toiletries in relation to use. A retrospective
study in a Swedish population.
Eur J Dermatol

1994;4:
189-93.
3. De Groot AC, Weijland JW, Nater JP. Unwanted
effects of
cosmetics and drugs used in dermatology.
3rd ed. Amsterdam: Elsevier, 1994:422-724.
4. De Groot AC, White IR. Cosmetics and skin care products.
In: Rycroft RJG, Menne T, Frosch PJ, editors. Textbook of
contact dermatitis. 2nd ed. Berlin: Springer-Verlag,
1995:
461-76.
5. De Groot AC. Cosmetics. In: JD Guin, editor. Practical
contact dermatitis. New York: McGraw-Hill,
1995:333-54.
6. De Groot AC, Frosch PJ. Adverse reactions to fragrances.
A clinical review. Contact Dermatitis 1997;36:57-86.
7. Adams RM, Maibach HI. A five-year study of cosmetic
reactions. J Am Acad Dermatol 1985;13:1062-9.
8. Lan LR, Lee JYY, Kao HF, et al. Persistent light reaction
with erythroderma
caused by musk ambrette. Cutis 1994;
54~167-70.
9. Du Menage H, Ross JS, Norris PG, et al. Contact and
photocontact
sensitization
in chronic actinic dermatitis;
Sesquiterpene
lactone mix is an important
allergen. Br J
Dermatol 1995;132:543-7.

10. Szczurko C, Dompmartin
A, Michel M, et al. Photocontact
allergy to oxybenzone: Ten years of experience. Photodermatol Photoimmunol
Photomed 1994;10:144-7.
11. Jeanmougin
M, Manciet JR, Pons-Guiraud
A, et al. Contact and photocontact
allergies to sunscreens. A six-year
experience. Nouv Dermatol 1994;13:372-8.
12. De Groot AC. Labelling cosmetics with their ingredients.
Br Med J 1990;300:1636-8.
13. Nielsen NH, Menne T. Allergic contact sensitization
in an

THE SHADY

SIDE

OF COSMETICS

177

unselectedDanish population. Acta Derm Venereol 1992;
72:456-60.
14. Liden C, Berg M, F;irm G, et al. Nail varnish allergy with

far-reaching consequences.Br J Dermatol 1993;128:57-62.
15. De Groot AC, Bruynzeel DP, BosJD, et al. The allergensin

cosmetics.Arch Dermatol 1988;124:525-9.

16. De Groot AC. Cocamidopropyl

betaine:

A “new”

impor-

tant cosmeticallergen. Dermatosen 1997;45:60-3.
17. De Groot AC, van der Walle HB, Weijland JW. Contact
allergy to cocamidopropyl
betaine. Contact Dermatitis
1995;33:419-22.
18. De Groot AC. Contact allergens-What’s
new? Cosmetic

dermatitis. Clin Dermatol 1997;15:485-91.
19. De Groot AC, van Ginkel CJW, Weijland JW. Methyldibromoglutaronitrile
(Euxyl K 400): An important “new“
allergen in cosmetics. J Am Acad Dermatol 1996;35:743-7.
20. De Groot AC, de Cock PAJJM, Coenraads PJ, et al. Methyldibromoglutaronitrile
is an important
contact allergen
in the Netherlands.
Contact Dermatitis 1996;34:118-20.
21. Fransway AF. The problem of preservation in the 1990s.I.
Statement of the problem, solution(s) of the industry and
the current use of formaldehyde and formaldehyde releasing biocides. Am J Contact Dermat 1991;2:6-23.
22. Fransway AF, Schmitz NA. The problem of preservation
in the 1990s. II. Formaldehyde

and formaldehyde-releasing biocides: Incidences of cross-reactivity
and the significance of the positive response to formaldehyde.
Am J
Contact Dermat 1991;2:78-88.
23. Fransway AF. The problem of preservation in the 1990s.
III. Agents with preservative
function independent
of
formaldehyde
release. Am J Contact Dermat 1991;2:
145-74.
24. Rosen M, McFarland
AG. Free formaldehyde
in anionic
shampoos. J Sot Cosm Chem 1984;35:157-69.
25. Council on Scientific Affairs. Formaldehyde.
JAMA 1989;
261:1183-7.
26. Marks JG, Belsito DV, DeLeo VA, et al. North American

Contact Dermatitis Group standard tray patch test results
(1992to 1994).Am J Contact Dermat 1995;6:160-5.
27. Parker LU, Taylor JS. A 5-year study of contact allergy to
quaternium-15.
Am J Contact Dermat 1991;2:231-4.
28. Jacobs M-C, White IR, Rycroft RJG, et al. Patch testing

with preservatives at St John’sfrom 1982to 1993.Contact
Dermatitis 1995;33:247-54.
29. Storrs F, Bell DE. Allergic contact dermatitis to 2-bromo2-nitropropane-1,3-diol

in a hydrophilic
ointment. J Am
Acad Dermatol 1983;8:157-64.
30. Peters MS, Connolly SM, Schroeter AL. Bronopol allergic

contact dermatitis. Contact Dermatitis 1983;9:397-401.
31. Frosch PJ, White IR, Rycroft RJG, et al. Contact allergy to
bronopol. Contact Dermatitis 1990;22:24-6.
32. De Groot AC, van Joost T, Bos JD, et al. Patch test reactivity to DMDM
hydantoin.
Relationship
to formaldehyde. Contact Dermatitis 1988;18:197-201.
33. Menne T, Hjorth N. Routine testing with paraben esters.
Contact Dermatitis 1988;19:189-91.
34. De Groot AC, Weijland JW. Kathon CG: A review. J Am
Acad Dermatol 1988;18:350-8.
35. De Groot AC. Methylisothiazolinone/methylchloroisothiazolinone
(Kathon CG) allergy: An updated review.
Am J Contact Dermat 1990;1:151-6.


178

Clivrics in Dermakdogy

DE GROOT

36. Marks JG, Moss JN, Parno JR, et al. Methylchloroisothiazolinone/methylisothiazolinone
(Kathon CG) biocideUnited States multicenter
study of human skin sensitization. Am J Contact Dermat 1990;1:157-61.

37. Fransway AF. Sensitivity to Kathon CG: Findings in 365
consecutive patients. Contact Dermatitis 1988;19:342-7.
38. Frosch PJ, Hannuksela
M, Andersen
KE, et al. Chloromethylisothiazolinone/methylisothiazolinone
(CMI/MI)
use test with a shampoo on patch-test-positive
subjects.
Contact Dermatitis 1995;32:210-7.
39. Conde-Salazar
L, Baz M, Guimaraens
D, et al. Contact
dermatitis in hairdressers:
Patch test results in 379 hairdressers. Am J Contact Dermat 1995;6:19-23.
40. Guerra I,, Bardazzi F, Tosti A. Contact dermatitis in hairdressers’ clients. Contact Dermatitis 1992;26:108-11.
41. Funk JO, Maibach HI. Propylene glycol dermatitis:
reevaluation of an old problem. Contact Dermatitis 1994;31:
236-41.
42. Aberer W, Fuchs Th, Peters K-P, et al. Propylenglykol:
Kutane Nebenwirkungen
und Testmethodik.
Dermatosen
1993;41:25-7.
43. Wahlberg JE. Propylene glycol: Search for a proper and
nonirritant
patch test preparation.
Am J Contact Dermat
1994;5:156-9.
44. Tosti A, Guerra L, Vincenzi C, et al. Contact sensitization
caused by toluene sulfonamide-formaldehyde

resin in
women who use nail cosmetics. Am J Contact Dermat
1993;4:150-3.
45. Hausen BM. Nagellack-Allergie.
H+G Z Hautkr 1994;69:
252-62.
46. Hausen BM, Milbrodt
M, Koenig WA. The allergens of
nail polish (I). Allergenic
constituents
of common
nail
polish and toluenesulfonamide-formaldehyde
resin (TSF-R). Contact Dermatitis 1995;33:157-64.
47. Giorgini
S, Brusi C, Francalanci
S, et al. Prevention
of
allergic contact dermatitis from nail varnishes and hardeners. Contact Dermatitis 1994;31:325-6.
48. Kardorff B, Fuchs M, Kunze J. Kontaktallergien
auf Nagellack. Akt Dermatol 1995;21:349-52.
49. Hausen BM. A simple method of determining
TS-F-R in
nail polish. Contact Dermatitis 1995;32:188-9.
50. Kanerva L, Lauerma A, Jolanki R, et al. Methyl acrylate: A
new sensitizer in nail lacquer. Contact Dermatitis 1995;33:
203-4.
51. Rosenzweig
R, Scher RK. Nail cosmetics: Adverse reactions. Am J Contact Dermat 1993;4:71-7.
52. Bamett JM, Scher RK. Nail cosmetics. Int J Dermatol1992;

31:675-81.
53. Kanerva L, Lauerma A, Estlander T, et al. Occupational
allergic contact dermatitis caused by photobonded
sculptured nails and a review of (meth)acrylates
in nail cosmetics. Am J Contact Dermat 1996;7:109-15.
54. Carmichael
AJ, Foulds IS, Bradbury DS. Loss of lanolin
patch-test reactivity. Br J Dermatol 1991;125:573-6.
55. Freeman S, Frederiksen P. Sunscreen allergy. Am J Contact Dermat 1990;1:240-3.
56. Dromgoole
SH, Maibach HI. Sunscreen intolerance: Contact and photocontact
sensitization
and contact urticaria.
J Am Acad Dermatol 1990;22:1068-78.
57. Funk JO, Dromgoole
SH, Maibach HI. Sunscreen intolerance, Contact sensitization,
photocontact
sensitization,

58.

59.

60.

61.

62.

63.

64.

65.

66.

67.

68.

69.

70.

71.
72.

73.
74.

75.

76.

l

1998;26:267-179

and irritancy of sunscreen agents. Dermatol Clin 1995;13:

473-81.
Foley P, Nixon R, Marks R, et al. The frequency of reactions to sunscreens: Results of a longitudinal
populationbased study on the regular use of sunscreens in Australia.
Br J Dermatol 1993;128:512-8.
Pons-Guiraud
A, Jeanmougin
M. Allergie et photo-allergie de contact aux cremes de photoprotection.
Ann Dermatol Venereol 1993;120:727-31.
Trevisi I’, Vincenzi C, Chierewgato
C, et al. Sunscreen
sensitization:
A three-year study. Dermatology
1994;189:
55-7.
Goncalo M, Ruas E, Figueiredo
A, et al. Contact and
photocontact sensitivity to sunscreens. Contact Dermatitis
1995;33:278-80.
Parry EJ, Bilsland D, Morley WN. Photocontact allergy to
4-tert-butyl-4’-methoxy-dibenzoylmethane
(Parsol 1789).
Contact Dermatitis 1995;32:251-2.
B&land
D, Ferguson J. Contact allergy to sunscreens
chemicals in photosensitivity
dermatitis/actinic
reticuloid
syndrome
(PD/AR)
and polymorphic

light eruption.
Contact Dermatitis 1993;29:70-3.
Fowler JF. Cocamidopropyl
betaine: The significance of
positive patch test results in twelve patients. Cutis 1993;
52:281-4.
Angelini G, Foti C, Rigano L, et al. 3-Dimethylaminopropylamine: A key substance in contact allergy to cocamidopropylbetaine?
Contact Dermatitis 1995;32:96-9.
Pigatto PD, Bigardi AS, Cusano F. Contact dermatitis
to
cocamidopropylbetaine
is caused by residual amines: Relevance, clinical characteristics,
and review of the literature. Am J Contact
Dermat 1995;6:13-6.
Angelini
G, Rigano L, Foti C, et al. Contact allergy to
impurities in surfactants: Amount, chemical structure and
carrier effect in reactions
to 3-dimethylaminopropylamine. Contact Dermatitis 1996;34:248-52.
Basketter DA, Lea L, Ross JS. Does DMAPA play a role in
CAPB allergy? In Book of abstracts, Jadassohn Centenary
Congress, London, 9-12 October 1996;44.
Aalto-Korte
K, Jolanki R, Estlander T, et al. Occupational
allergic contact dermatitis caused by Euxyl K 400. Contact
Dermatitis 1996;35:193-4.
De Groot AC, Bruynzeel
DP, Coenraads
PJ, et al. Frequency of allergic reactions to methyldibromoglutaronitrile (1,2-dibromo-2,4-dicyanobutane)
in The Netherlands.

Contact Dermatitis 1991;25:270-1.
Tosti A, Guerra L, Bardazzi F, et al. Euxyl K 400: A new
sensitizer in cosmetics. Contact Dermatitis 1991;25:89-93.
Tosti A, Vincenzi C, Trevisi I’, Guerra L. Euxyl K 400:
Incidence of sensitization,
patch test concentration
and
vehicle, Contact Dermatitis 1995;33:193-5.
Schnuch A, Geier J, Die haufigsten Kontaktallergene
im
zweiten Halbjahr 1993. Dermatosen 1994;42:210-1.
De Groot AC, van Ginkel CJW, Weijland
JW. How to
detect sensitization
to Euxyl K 400. Contact Dermatitis
1996;34:373.
Perrenoud
D, Homberger
HP, Auderset PC, et al. An
epidemic outbreak of papular and follicular contact dermatitis to tocopheryl linoleate in cosmetics. Dermatology
1994;189:225-33.
Perrenoud D, and the Swiss Contact Dermatitis Research


Clinics irz Dermatolqgy

l

1998;16:167-179

Group. Papular and follicular
contact dermatitis:
Irritation and/or allergy? Curr Probl Dermatol 1995;23:9-17.
77. Dooms-Goossens
A. The red face: Contact and photocontact dermatitis.
Clinics
in Dermatology
1993;ll:
289 -95.
78. Dooms-Goossens
A. Cosmetics as causes of allergic contact dermatitis. Cutis 1993;52:316-20.
79. De Groot AC. Patch testing: Test concentrations
and vehicles for 3700 allergens,
2nd edition.
Amsterdam:
Elsevier, 1994.

THE

SHADY

SIDE

OF COSMETICS

179

80. De Groot AC, White IR. Cosmetic ingredient
labelling in
the European Community.

Contact Dermatitis
1991;25:
273-5.
81. Elsner P. What is the state of cosmetic labelling in Europe?
Am J Contact Dermat 1993;4:198-200.
82. Dillarstone
A. Letter to the Editor. Contact Dermatitis
1996;35:64-5.
83. De Groot AC, Weijland
JW. Conversion
of common
names of cosmetic allergens to the INCI-nomenclature.
Contact Dermatitis 1997;37:145-50.