Importance of patch testing in the safety assessment of cosmetics

According to European legislation, a cosmetic is a substance or a mixture of substances intended for application to the external surfaces of the human body (epidermis, hair, nails, lips and external genitalia), to the teeth and/or to the oral mucosa, for the sole or principal purpose of cleansing, perfuming, modifying the appearance and/or correcting body odours.This definition includes hygiene products (gels, soaps) and skin moisturisers (creams, lotions), hair cosmetics (shampoos, hair dyes), toothpastes, make-up, nail cosmetics (nail varnishes, artificial nails), fragrances (deodorants, perfumes), depilatory products and sunscreens.These cosmetics can be classified into stay-on or leave-on products, which are intended to remain in contact with the skin surface for a long time, and rinse-off or wash-off products, which must be washed off with water within a few minutes.The widespread use of cosmetics and skin care products worldwide increases the possibility of exposure to irritants and contact allergens.Patch tests have been widely used in the determination of the aetiology of some hypersensitivity skin reactions attributed to contact with agents that may cause allergy. Such tests are used to assess the potential of some ingredients and finished cosmetic products to cause acute local dermal irritation. The epicutaneous test originated in 1895 when the German physician Joseph Jadassohn, after extensive empirical practice to establish which agents triggered dermatitis in healthy volunteers, presented a diagnostic tool for skin allergy.This technique makes it possible to assess the safety of cosmetic ingredients or products, to establish their irritant and allergenic potential. Our genes determine the characteristics of our skin (colour, texture, predisposition to certain dermatological conditions or diseases, etc.), the way it evolves over time, as well as its ageing process.However, external factors such as the climate, pollution or the lifestyle of each person (inadequate rest, stress, smoking, inadequate diet or bad cosmetic habits, among others) affect the state of the skin. This is why it is necessary for a specialist to make a medical diagnosis of the state of the skin.Adverse skin reactions to cosmetics, or increased symptoms such as fever, pain, or general malaise, may occur. The possible reactions and/or risks foreseen will most frequently manifest themselves on the skin, in the form of redness (redness), inflammation (hives) or slight itching in the area of application. Mild and transient irritant reactions, reactivation of a previous dermatitis, angry back syndrome may also occur. Occasionally, more significant reactions may occur, such as active sensitisation, hypo- or hyperpigmentation, persistent positive reactions, keloid formation, scarring or granulomas, Koebner's phenomenon and, rarely, systemic reactions.The dermatologist should be aware of these possible skin reactions and try to identify the causative agents and other contributing factors. Most of these reactions can be treated without sequelae, once the causative agent is recognised and avoided.Is there such a thing as reactivity and allergy to cosmetics?Cosmetic "allergy" does exist. We speak of "allergy" in inverted commas because it is a general term, but we are referring to dermatitis or eczema that occurs when a substance, in contact with the skin, inflames it. This inflammation can occur in two ways, either through excessive contact with an irritant substance (known as irritant dermatitis) or because the consumer has a reaction to the agent that contacts the skin (allergic dermatitis). Phototoxic dermatitis and contact urticaria are also common adverse reactions.It is estimated that 0.01 to 0.03% of the population is allergic to cosmetics. This prevalence is estimated, as only 15-30% of consumers visit a dermatologist and most of them avoid the "suspect" product without going to a doctor.e majority, avoid the suspicious "product" without attending to the doctor.Which cosmetic ingredients have the highest irritant and allergenic potential?High irritant potentialThe components are used to treat acne, hyperpigmentation and photoageing, and must take into account the depth of penetration, which varies according to the agent, the concentration of the agent and the exposure time."Exfoliating" components include retinoic, glycolic, trichloroacetic and salicylic acids, resorcinol and phenol. Irritation and photosensitivity reactions may also occur following the use of topical retinoids, manifesting as erythema, scaling and irritation. Reducing the frequency of application and the use of a barrier moisturiser, together with a sunscreen, may improve tolerance.Subjective irritation or intolerance causes as a tingling, burning, stinging or itching sensation without visible skin alteration, which is also observed after application of topical medications. Propylene glycol, hydroxy acids and ethanol are capable of causing sensory irritation in susceptible individuals.Benzoic acid, azelaic acid, sorbic acid, lactic acid, benzoyl peroxide, and tretinoin, for example, can cause sensory irritation.High allergenicity potentialFragrances are a basic ingredient in the manufacture of cosmetics. A perfume is composed of between 10 and 300 fragrances. Fragrances represent the second most frequent cause of contact allergy in our environment, after metal allergy, with a positivity in contact tests varying between 1.7 and 15% and are the most frequent cause of cosmetic allergy.The cosmetic products most commonly associated with fragrance allergy, in descending order, include deodorants, scented lotions and perfumes.The prevalence of sensitisation to fragrances has been estimated to be 7.6%, with leave-on products being a more frequent cause of fragrance allergy than rinse-off products.Hydroxycitronellal and geraniol are the most common fragrances contained in perfumes, while linalool, limonene and citronellol are the most common in daily hygiene and moisturising products. An allergen of importance in deodorant CAD is Lyral®.Preservatives are a common cause of allergy to skin care products. The preservatives with the highest prevalence of sensitisation are euxylK400® (with its components methyldibromoglutaronitrile and to a lesser extent phenoxyethanol) formaldehyde and Kathon CG®, while parabens are the least prevalent.The widespread use of botanicals in topical cosmetics increases the likelihood of exposure to a variety of potential plant allergens. Botanicals commonly implicated include plants of the Compositae family, tea tree oil, propolis (derived from bee hives), peppermint, lavender or lichens, among others.In which cosmetic products should we be particularly careful about skin tolerance?Body and facial cleansing products include fragrances, preservatives, surfactants (cocamidopropylbetaine) and vehicle components (lanolin alcohols). Allergic reactions are less common compared to leave-on products, due to the limited amount of time the substance is in contact with the skin.Moisturisers are a major source of sensitising allergens due to their widespread use, distribution over large areas of the body, repeated exposure and increased penetration. Common allergens include fragrances, preservatives, vitamin E, essential oils, benzyl alcohol, propylene glycol and lanolin.Skin whitening agents contain a variety of active ingredients including hydroquinone, mercury and others such as arbutin, kojic acid, licorice, ascorbic acid, soy and retinoids, among others. Known side effects are irritant and allergic reactions, hypopigmentation and hyperpigmentation. Hair dyes are classified as semi-permanent and permanent. Semi-permanent dyes are derived from nitroanilines, nitrophenylenediamines and nitroaminophenols, which use low molecular weight elements that penetrate the hair cuticle. Permanent dyes work through primary intermediates (p-phenylenediamine [PPD]), which are oxidised with hydrogen peroxide and react with different couplers to produce a wide range of colours.Oxidative hair products often contain other potent skin sensitisers.Hair bleaches include hydrogen peroxide solutions that oxygenate melanin and ammonium persulphate. Direct contact with these oxidising agents can cause irritant dermatitis and, in rare cases, chemical burns.Nail polishes and hardeners contain nitrocellulose, resins, plasticisers, solvents and thinners, colours and suspending agents. Sensitisers in nail products include additives, impurities, by-products formed during polymerisation or degradation and residual monomers. The most common allergen in nail polishes and hardeners is tosylamide formaldehyde resin, closely followed by acrylics.ConclusionCosmetic products are widely used and reactions to these products are frequently observed in daily dermatological practice.Rapid recognition with identification and removal of the offending agent are key elements for the successful management of such reactions.Patch test, Open test, HRIPT, Photopatch, etc., allow the formulator of cosmetic products to know and establish a preliminary safety profile of the cosmetic ingredients to be used and to establish a possible safety profile of the cosmetic product to be designed with these ingredients and to make variations in concentration and even the elimination of the ingredient or ingredients that were positive, with the aim of minimising the variables that lead to increased risk.