Initial Screening

The European Surveillance System on Contact Allergies (ESSCA) requested from its participating centers a list of allergens that are routinely used when attempting to identify contact allergy to cosmetics.¹ This list was adapted and initially used to select the allergens:

Preservatives — benzyl alcohol, chloroacetamide, disodium EDTA, di-t-butylhydroquinone, ethylhexylglycerin, formaldehyde, bronopol, DMDM hydantoin, diazolidinyl urea, imidazolidinyl urea, quaternium 15, iodopropynyl butylcarbamate, methyldibromoglutaronitrile, methylisothiazolinone, sodium metabisulfite, paraben mix, methylchloroisothiazolinone/methylisothiazolinone, phenoxyethanol, potassium sorbate, sodium benzoate, sorbic acid, and p-chloro m-cresol.

Antimicrobials — benzalkonium chloride, chloroxylenol, chlorhexidine diacetate, and chlorhexidine digluconate.

Antioxidants — BHA (butylated hydroxyanisole), BHT (butylated hydroxytoluene), caprylyl gallate, and propyl gallate.

Emollients — lanolin alcohols, amerchol L101, cetearyl alcohol, and panthenol (dexpanthenol).

Emulsifiers/Surfactants — polysorbate 80, sorbitan sesquioleate, cocamide DEA, cocamidopropyl betaine, dimethylaminopropylamine, monoethanolamine, oleamidopropyl dimethylamine, triethanolamine, caprylyl glucoside, cetearyl glucoside, coco-glucoside, decyl glucoside, and lauryl glucoside.

Solvents/Vehicles — propylene glycol.

Face, Eye & Lip — colophonium, abitol, retinyl palmitate, and shellac.

Nail — tosylamide/formaldehyde resin, adipic acid/neopentyl glycol/trimellitic anhydride copolymer, phthalic anhydride/trimellitic anhydride/glycols copolymer, 2-hydroxyethyl methacrylate, and hydroquinone.

Relationship between baseline series and cosmetics series

Allergens contained in a baseline series, which should contain the main substances causing contact dermatitis, typically produce a frequency of at least 0.5–1% of positive reactions in tested individuals. This series already includes several cosmetic-related allergens that do not require retesting. However, they must be reevaluated when modifications occur in this reference series, as a decreased prevalence of a specific substance may indicate the need to transfer it from the baseline series to a dedicated cosmetics series.¹ Following this rationale, when investigating cosmetic allergies, the cosmetics series should always be used in conjunction with the baseline series, since many cosmetic components are already incorporated in the standard series.

Selection criteria

Allergens already present in the baseline series of the Associação Brasileira de Alergia e Imunologia (ASBAI) were initially excluded from our selection, as these are routinely tested as part of the standard protocol. This preliminary exclusion encompassed

18 allergens: formaldehyde, bronopol, diazolidinyl urea, quaternium-15, methylchloroisothiazolinone/methylisothiazolinone, methylisothiazolinone, sodium metabisulfite, paraben mix, propyl gallate, lanolin alcohol, amerchol L-101, propolis, cocamidopropyl betaine, decyl glucoside, propylene glycol, colophony, tosylamide/formaldehyde resin, 2-hydroxyethyl methacrylate.

To minimize the risk of omitting relevant cosmetic allergens, European researchers established a threshold of 0.3% positive patch test reactions for including a substance in their cosmetics series.³ We adopted this value as a minimum reference for our proposal. However, we enhanced our selection criteria by also considering studies from other regions of the world, thereby broadening the scope of our analysis.

Fragrances, despite being considered important components of cosmetics, were not included in the analysis.³ The primary reason is to prevent the proposed series from becoming excessively extensive. In the Brazilian baseline series (ASBAI series), fragrance allergy is already assessed through fragrance mix I and II, Lyral®, and balsam of Peru tests. Additionally, specific fragrance series exist for these cases.⁷ Therefore, when the patient’s history suggests sensitivity to perfumes, testing with the baseline series and/or the detailed fragrance series is recommended. The fragrance series proposed by the European Society of Contact Dermatitis comprises 47 substances.⁸ In Brazil, the fragrance series from IPT ASAC® contains 29 elements, which align with national legislation requirements for product labeling.⁹

Substances used in hair products frequently cause facial contact allergy, with greater relevance in the context of occupational eczema among hairdressers. Such situations are evaluated through specific hair series.³ While preservatives used in shampoos are also present in makeup, allergens primarily limited to hair products should be included in the related series. A classic example is ammonium thioglycolate, which should preferably be reallocated to the hair series.¹⁰

Special considerations

Testing with the patient's own potentially implicated products may be necessary and should be encouraged.^3,5,11 The possibility of false-negative reactions due to low allergen concentration in commercial products should be considered.³ It is important to note that leave-on cosmetics are safe for use in patch tests under occlusion. Rinse-off products, however, need to be diluted to avoid irritant reactions.¹²

Evaluation of the frequency of positive reactions in series

Studies from centers and internationally recognized groups were selected to evaluate the incidence of contact sensitivity to previously selected allergens Table 1.

The North American Contact Dermatitis Group (NACDG) conducts extensive surveys of patch tests performed in 13 centers using a series of 80 substances, many of which could be included in cosmetics series (survey with 4,121 patients).¹³

The Mayo Clinic, a world-renowned reference center, periodically publishes data on patch tests performed (survey with 2,667 patients).¹⁴

ESSCA, a working group of the European Society of Contact Dermatitis (ESCD), evaluated cosmetics series used in its 26 centers.³

The British Society for Cutaneous Allergy (BSCA) published data on patch tests with facial series from its 12 centers in the United Kingdom (survey with 4,224 patients).⁶

Determination of Relevance for Allergens

At an individual level, a patch test result can be clinically relevant depending on past or current exposure to the substance found positive in the exam. Past relevance occurs when a patch test is positive, but the exposure may have been long ago and no longer exists.¹⁵ A classic example is thimerosal, a substance with high positivity prevalence due to exposure that typically no longer occurs.¹⁶ A search in the Environmental Working Group's Skin-Deep Cosmetic Database revealed no commercial products containing this allergen. Therefore, including such substances in a new series is not justified.

Thus, the relevance of substances chosen for inclusion in the series in question would be their presence in commercially sold cosmetics. To this end, we searched large databases to ratify the choice by frequency data or replace substances if not properly found.

Databases

We evaluated the substances previously selected in frequency studies using the Consumer Product Information Database® (CPID) (https://www.whatsinproducts.com), a widely used database that shows products through component searches. This publicly accessible source contains approximately 8,000 products.¹⁷ As the database includes several classes of non-cosmetic products, we used it for initial screening Table 2.

Three substances were excluded due to the absence of retail products containing them: caprylyl gallate, oleamidopropyl dimethylamine, and abitol.

Caprylyl gallate, an antioxidant, was also not found in other databases. Allergy to gallates is frequently reported in the literature.⁶ Therefore, we decided to use, instead, another allergen from the same group: dodecyl gallate (lauryl gallate), pointed by some authors as one of the main allergens for cosmetic consumers.⁵ Although its presence in products is low, we believe it represents the entire family of gallates, explaining its inclusion.

The allergen oleamidopropyl dimethylamine was excluded for the same reason. In other databases, the number of products containing this substance was minimal (SkinSAFE: 1; EWG: 1). It is a surfactant from the same betaine group as cocamidopropyl betaine, already in the baseline series, and cocamide diethanolamine, in this cosmetics series proposal. Instead, another quaternary ammonium surfactant was selected — benzalkonium chloride, which is used in various topical and household products, besides cosmetics.¹⁸

Abitol (hydroabletyl alcohol) also yielded negative results in the CPID platform, as in other databases (SkinSAFE: 0; EWG: 1). Therefore, its replacement with another substance was justified. Following the specific series from Chemotechnique®, peppermint oil was selected.⁸ This essential oil has been implicated in at least 45 published cases of contact dermatitis, with menthol appearing to be the primary allergen.¹⁹

Thereafter, it was decided to exclude one more substance. Methenamine, an antiseptic, was also excluded. Although found in the CPID platform, many of these products were not cosmetics. In other databases, the occurrence of products was low (SkinSAFE: 3; EWG: 1). Moreover, a PubMed search revealed no specific publications emphasizing the current testing of this substance. Consequently, it was replaced with coco glucoside. The current perspective suggests that all possible alkyl glucosides should be tested when suspecting cosmetic allergy.²⁰

Subsequently, the allergens were evaluated using SkinSAFE, a platform developed by Mayo Clinic to identify suitable products for sensitive individuals. It contains approximately 43,000 products and allows ingredient searches, categorizing beauty products into various cosmetic subgroups.¹⁷ (Table 3)

Next, we examined the allergens in the Environmental Working Group's Skin-Deep Cosmetic Database® (Washington, District of Columbia), a free online database. This platform allows ingredient searches among over 107,000 personal care products (https://www.ewg.org/skindeep).²¹ We grouped the substances by categories such as lip products, hair products, men's products, etc. (Table 4)

The American Contact Dermatitis Society (ACDS) has developed a tool called the Contact Allergy Management Program (CAMP) to assist specialists in recommending topical products free of contact allergens.¹⁷ This database contains approximately 5,000 retail products,¹⁷ categorized into eye care, hair care, household products, makeup, medications, nail products, skin care, and oral care.²² The selected substances were evaluated in the context of the makeup and skin care categories, with emphasis on explicating the type of cosmetic in which they are frequently found. (Table 5)

The Table 6 presents the complete selection with concentration, vehicle, and respective CAS number of the 20 components of this new proposed cosmetic series.