4. Integración conceptual de elementos teóricos y caso de estudio
4.2 Caso de estudio El AMM
4.2.1 Antecedentes de desarrollo urbano en el AMM
RELEASING PRESERVATIVES Formaldehyde and formaldehyde-releasing preserva- tives are second only to fragrances as the most common sources of cosmetic-asso- ciated contact dermatitis.20 In order to
decrease sensitization rates and ulti- mately lower the concentration of formaldehyde in products, it is common
for manufacturers to use formaldehyde- releasing-preservatives (FRPs) instead of formaldehyde. Examples of FRPs are listed in Table 18-4. It is important to note, however, that the FRPs are the most sensitizing of the preservative class. Cases of contact dermatitis to formaldehyde/FRPs commonly present as eyelid dermatitis, which is often asso- ciated with the use of nail hardeners/lac- quers/cosmetics that contain formalde- hydes. Several mascaras, blushes, eye shadows, foundations, and shampoos also contain the FRPs that can contribute to the development of eyelid and facial dermatitis in the areas of sensitization. Other important potential sources of exposure to formaldehyde and FRPs include permanent press clothing, clean- ing agents, baby wipes, disinfectants, cigarette smoke, and the sweetener aspartame.21 It is worth noting that
formaldehyde is sometimes included in products touted as “natural.”
METHYLDIBROMO GLUTARONITRILE AND PHENOXYETHANOL (EUXYL K400) Methyl- dibromo glutaronitrile (MDGN), first introduced in the cosmeceutical industry in 1985, is a preservative used in a wide variety of toiletry and industrial products. Of note, contact allergy to this chemical is markedly on the rise, with this preserv- ative ranking second only to FRPs (Table 18-3). Initially, the maximum allowable concentration was 0.1% in both leave-on and rinse-off cosmetic products, with one exception—sunscreens, for which the maximum allowable concentration was 0.025%.22 However, by compounding
the MDGN with phenoxylethanol in a ratio of 1:4 (Euxyl K400, Schulke & Mayr Inc., Hamburg, Germany), the manufac- turer was able to make a highly effective and stable preservative at even lower concentrations (0.05%–0.02% depend- ing on the product).3A higher concentra-
tion would be more likely to cause sensitization.
Contact sensitization to Euxyl K400 does occur, however, and is usually due to the MDGN component. Allergy to MDGN has been reported in association with the use of makeup removal wipes, moistened toilet tissue, cucumber eye gel, barrier creams, ultrasonic gel, and makeups.23,24High sensitization rates led
the European Commission for Cosmetic Products to recommend a ban on the use of MDGN in leave-on products in 2003 and, likewise, in 2005 recommend that MDGN be banned from rinse-off products.25,26Products containing these
preservatives are still used in the United States and the provider and consumer should be aware of the potential for sensitization.
METHYLCHLOROISOTHIAZOLINONE AND METHYLISOTHIAZOLINONE (EUXYL K100) In 1977, methylchloroisothiazolinone (MCI, 5-chloro-2-methyl-4-isothiazolin-3-one) and methylisothiazolinone (MI, 2-methyl- 4-isothiazolin-3-one) were first registered in the United States as Kathon CG and Euxyl K100.27These two chemical preser-
vatives are combined in a ratio of 3:1 (MCI:MI) and have been extensively added to bubble bath preparations, cos- metics, and soaps.28,29Because of their
chemical nature of having polarity (being lipophilic at one end and lipophobic at the other), MCI and MI are compatible with a large number of surfactants and emulsi- fiers. Furthermore, the isothiazolinones are biocidal, as they interact and oxidize accessible cellular thiols on microbials.30
In a multicenter study including 15 different countries, MCI was identified as the culprit contact allergen in 2.9%
141
CHAPTER 1
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CONT
ACT DERMA
TITIS
(TYPE 4 SENSITIVE SKIN)
(Finland), 3.6% (United States), 5.7% (Germany), and 8.4% (Italy) of the cases.31 The rinse-off products (i.e.,
shampoos and soaps) were less likely to provoke dermatitis when compared to leave-on formulations (i.e., moisturizers and cosmetics). Of note, there may be a potential for MCI or MI to cross-react with metronidazole, as the chemicals have similar molecular structures.32
Thus, the provider may need to be aware of this when prescribing formulations for rosacea, such as Noritate and Metrogel in an MCI- or MI-allergic patient.
Parabens
The para-hydroxybenzoic acids (parabens) are a family of five alkyl esters that differ in para-position chemical composition substitutions on the benzene ring (methyl paraben, ethyl paraben, propyl paraben, butyl paraben, and benzyl paraben). These chemical substitutions impart on each paraben ester a different solubility and antimicrobial activity spectrum. Frequently, manufacturers take advantage of this and use the parabens in conjunc- tion with each other to enhance antimi- crobial efficacy.33In the United States, the
average total paraben exposure per indi- vidual is estimated to be approximately
76 mg/d (1.3 mg/kg/d for a person weighing 70 kg) with the majority (50 mg/d) derived from cosmetics and per- sonal hygiene product exposure. Notably, food preparations (e.g., mayonnaise, jams, salad dressings, etc.) are thought to account only for approximately 1 mg/d.33
The parabens, when absorbed through the skin, are partially metabo- lized by carboxyl esterases in the skin, liver, and kidney.34Recently, it has been
demonstrated that a portion of parabens may be retained in human body tissues without hydrolysis by tissue esterases, which has raised concern over the potential for adverse side effects.35
Special regard has been given to the estrogen-like effects, which were first described by Routledge et al. in 1998 and have been further substantiated by several studies.36–39
Since estrogen is a major etiologic fac- tor in the development of human breast tissue and breast cancers, Darbre et al. proposed that parabens and other chem- icals that are used in underarm cosmetics may have contributed to what was then, in 2003, the increasing incidence of breast cancer.40In an uncontrolled study
of 20 patients with breast tumors, parabens were found in 90% of the
TABLE 18-1
Cosmetic Implications of Top Allergens 2001–200254
ORDER SUBSTANCE POSITIVEREACTIONS(%) POTENTIALCOSMETICIMPLICATIONS
1 Nickel sulfate (2.5%) 16.7 Metal: eyelash curlers, razors,
tweezers, mineral makeup
2 Neomycin (20%) 11.6 Antibiotic
3 Balsam of Peru (25%) 11.6 Fragrance & Flavorant—perfume,
cosmetics, lotions, makeup removers
4 Fragrance mix (8%) (␣-amyl 10.4 Fragrance & Flavorant
cinnamic aldehyde, cinnamic alcohol, cinnamic aldehyde, eugenol, geraniol,
hydroxycitronellal, isoeugenol, oak moss absolute)
5 Thimerosal (0.1%) 10.2 Preservative—mascara
6 Sodium gold thiosulfate (0.5%) 10.2 Metal: Secondary effect,
titanium dioxide and zinc oxide abrade gold jewelry during make up application, resulting in gold particle transfer to face
7 Quaternium-15 (2%) 9.3 Preservative—mascara,
foundation, eye shadow, blush, cleansers
8 Formaldehyde (1% aqs) 8.4 Preservative—cleansers,
cosmetics
9 Bacitracin (20%) 7.9 Antibiotic—Obagi Nuderm step 7
10 Cobalt chloride (1%) 7.4 Metal—eyelash curlers, razors,
tweezers, mineral make up
TABLE 18-2
Fragrance-Based Allergens3,54–57
ALLERGENMIX ALLERGEN ESTIMATEDSENSITIZATIONRATES
Balsam of Perua,d 11.6%54
Fragrance Mix 1b,d 11.4%55–10.4%54
Fragrance Mix 2c,d
Cinnamic alcohola,b 7.6%3
Eugenola,b 5.4%3
Cinnamic aldehydea,b 4.9%3
Isoeugenola,b 3.1%3
Geraniolb 2.8%3
Lyralc 2.7%57–0.4%56
Ylang-ylang 2.6%55
Hydroxycitronellalb 2.1%3
Oak moss absoluteb 1.8%3
Benzyl Alcohola,d 1.3%3
Narcissus 1.3%55 Jasmined 1.2%55–0.4%56 Citralc 1.1%57 Sandalwood 0.9%55 Farnesolc 0.5%57 Citronellolc 0.4%57 Tea treed 0.3%56 a-Hexyl-cinnamic aldehydec 0.3%57 Coumarinc 0.3%57
␣-amyl cinnamic aldehydeb 0.2%3
aIndicates component/cross-sensitization with balsam of Peru. bIndicates component of Fragrance Mix 1.
cIndicates component of Fragrance Mix 2. dCurrent inclusion on 2007 NACDG screening panel.
COSMETIC DERMA
TOLOGY
:
PRINCIPLES
AND PRACTICE
142
breast tumor samples; however, it has been suggested that there may have been “contamination” of the glassware that the samples were processed in from the detergents used by the technicians.37,41
The close proximity of the axilla and the breast has further fueled queries as to the possibility of an association of parabens with breast cancer.42This led the
Cosmetic Ingredient Review Board to reevaluate the safety of parabens in 2005.43 The panel determined that the
original conclusion on the safety of parabens in cosmetics withstood, and that parabens were shown to have much less estrogenic activity than the body’s natu- rally-occurring estrogen.44 Nevertheless,
lack of information on the effects of long- term exposure to low levels of parabens and subsequent accumulation in the body
tissues suggests the need for prospective longitudinal studies.37
With regard to topical adverse effects from cosmetic preparations, the parabens have caused both irritant and allergic type contact dermatitis.45–48 For example,
paraben allergy has been described in asso- ciation with facial cosmetics, ultrasound gels, topical steroid creams, and food additives.49–52A recent meta-analysis by
Krob et al. revealed that despite widespread use of this preservative class, the overall prevalence and relevance of paraben allergy was remarkably low (0.5%), when com- pared to other preservative chemicals.53 IODOPROPYNYL BUTYL CARBAMATE In 1996, iodopropynyl butyl carbamate (IPBC) was approved for use in the United States by the Cosmetic Ingredient Review at an allowable level of up to 0.1% in topical formulations.3
Testing for this allergen began in Denmark in 1996 and in the United States in 1998, with current data suggest- ing that the sensitization potential is rel- atively low when compared to the other preservative allergens.54(See Chapter 37
for further discussion of preservatives.)
OTHER ALLERGENS IN SKIN, HAIR, AND NAIL CARE PRODUCTS (TABLES 18-5 TO 18-8)
Skin reactions have been described with hair care products as well as hair
TABLE 18-5
Other Sensitizers Found in Skin and Hair Care Products 2,6-Ditert-butyl-4-cresol (BHT) 2-tert-Butyl-4-methoxyphenol (BHA) 4-Chloro-3-cresol (PCMC) Benzyl alcohol Benzyl salicylate Cetyl alcohol Chloracetamide Chlorhexidine digluconate Isopropyl myristate Lanolin alcohol Propyl gallate Sorbic acid
Sorbitan monooleate (Span 80) Sorbitan sesquioleate Stearyl alcohol tert-Butylhydroquinone Triclosan (Irgasan DP 300) Triethanolamine Benzoyl peroxide Cocamide DEA Cocamidopropyl Betaine
Di-alpha-tocopherol acetate (vitamin E) Methyl methacrylate
Potassium dichromate
TABLE 18-6
Botanicals That Can Cause Allergy in Skin and Hair Care Products
Aloe vera Angelica Arnica
Balsam of Peru (Myroxylon pereirae) Beeswax Bladderwrack Catnip Chamomile Colophony (rosin) Compositae Mix Coriander Cucumber Dog rose hips Echinacea Ginkgo Goldenseal
Gotu kola (Centella asiatica) Green tea Hops Kelp Lavender Licorice Marigold
Propolis (bee’s glue) Rosemary Sage
Sesquiterpene lactone St. John’s wort Tea tree oil Witch hazel Ylang-ylang oil
TABLE 18-7
Products in Hair Coloring and Processing that Can Cause Skin Sensitization
2,5 Diaminotoluene sulfate 2-Nitro-P-phenylenediamine 3-Aminophenol 4-Aminophenol Ammonium persulfate Ammonium thioglycolate Glyceryl thioglycolate Hydrogen peroxide Hydroquinone Paraphenylenediamine (PPD)⫹ Resorcinol
processing and coloring chemicals. Toluene sulfonamide formaldehyde resin in nail polish is such a common cause of contact dermatitis that compa- nies such as Sally Hansen and Revlon have developed “formaldehyde- and toluene-free” nail polish. In fact, in some countries such as Switzerland, “formaldehyde resins” are banned in nail care products. Sunscreen ingredients
TABLE 18-3
Preservatives Found in Cosmetic Products with Estimated Sensitization Rates 3,53,54
Thimerosal (merthiolate) 10.2% Quaternium 15 (Dowicil®) (FRP) 9.3% Bronopol (Bronopol®) (FRP) 3.3% DiadUrea (Germall 11®) (FRP) 3.2% Imidurea (Germall 115) (FRP) 3.0% DMDM Hydantoin (Glydant®) (FRP) 2.8%
Methyldibromo glutaronitrile and 2.7% phenoxyethanol (Euxyl K 400) Methylchloroisothiazolinone and 2.3% Methylisothiazolinone (Euxyl K100) Benzyl alcohol 1.3% Parabens 0.6%
Iodopropynyl butyl carbamate 0.3%
TABLE 18-4
Preservatives That Can Cause Contact Dermatitis
Benzoic acid Benzyl alcohol
Euxyl K 400 (Methyldibromo glutaronitrile and phenoxyethanol)
Formaldehyde
Formaldehyde-releasing-preservatives (FRPs):
Quaternium 15
Imidazolidinyl urea (Germall) Diazolidinyl urea (Germall II) Bromonitropropane diol (Bronopol) DMDM hydantoin
Methylchloroisothiazolinone (MCI) P-tert-Butylphenol formaldehyde resin Parabens
Propylene glycol Sodium benzoate
Toluenesulphonamide Formaldehyde Resin (tosylamide)
143
have also been reported to cause skin allergy. In order to elucidate the cause of contact dermatitis in most patients, a thorough history is crucial. Having the patients bring in the offending skin care products, when known, is also neces- sary.
TREATMENT
The first step in the treatment of any contact dermatitis is to identify the offending agent, whether an allergen or a caustic irritating chemical. Once identifi- cation has been made, the subsequent step is avoidance of the culprit com- pound and, in the case of ACD, all cross- reactive substances. Alternative product substitution is imperative for the well- being of the patient. Furthermore, mea- sures should be taken to ensure barrier integrity (i.e., decreased hand washing with soaps and increased emollient use) for both allergic- and irritant-based der- matoses. The use of emollients to help heal the skin is important, especially with regard to reactions that are irritant in nature (see Chapter 31).
In the interim, while the avoidance regimen is being instituted and the immune system is being given a chance to “forget” the sensitization, sympto- matic treatment in ACD and CU may consist of topical corticosteroids or topi- cal immunomodulators. At times, with severe acute or chronic extensive
involvement, the use of systemic agents such as prednisone, cyclosporine, or ultraviolet light treatments may be indi- cated. The use of ICD corticosteroids is controversial, but seems to be advanta- geous if applied early.
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CONT
ACT DERMA
TITIS
(TYPE 4 SENSITIVE SKIN)
TABLE 18-8
Sunscreen Ingredients that Can Cause Sensitization
2-Ethylhexyl-4-dimethylaminobenzoate (Eusolex 6007) (Padimate O) (Octyl Dimethyl paba) 2-Ethylhexyl-4-methoxycinnamate
(Parsol MCX) 2-Hydroxy-4-methoxy-4-
methylbenzophenone (Mexenone) 2-Hydroxy-4-methoxy-benzophenon- 5-sulfonic acid (Sulisobenzone) 2-Hydroxy-4-methoxybenzophenone
(Eusolex 4360)
3-(4-Methylbenzyliden)camphor (Eusolex 6300)
4-Aminobenzoic acid (PABA)
4-tert-Butyl-4’-methoxydibenzoylmethane (Parsol 1789) (Avobenzone)
Benzophenone-3 (oxybenzone) Homomenthylsalicylate (Homosalate) Isoamyl-p-methoxycinnamate Octyl salicylate (Octisalate) Phenylbenzimidazol-5-sulfonic acid
144
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