COSMETIC DERMATOLOGY: PRINCIPLES AND PRACTICE
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CHAPTER 37 Preservatives
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Edmund Weisberg, MS Leslie Baumann, MD
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Preservatives are integral ingredients in various food, pharmaceutical, cosmetic, and skin care formulations As water is included in the majority of such products, preservatives are added to prevent the growth of microorganisms and the resultant rapid deterioration or decomposition of the product Indeed, without preservatives, which are biocidal chemicals, these items important to daily life would exhibit little to no shelf life and become quickly invaded and permeated by numerous bacteria, fungi, and molds As such, preservatives are intended to maintain the integrity of the product and protect the user from infection1 While antimicrobial preservatives are essential components in the majority of cosmetics and skin care products, these ingredients have been cited frequently as causes of allergic contact dermatitis1 3 Such occurrences are most often associated with topical application on damaged or broken skin Of greater concern in recent years has been the reports linking the use of some skin care products with cancer incidence This chapter will focus on the most frequently used class of preservatives, recent data regarding the estrogenic potential of these compounds, and the controversy regarding possible associations between the chronic use of chemical preservatives that make contact with the skin and cancer the strong record of efficacy, safety, and stability exhibited by this group of compounds The frequency of inclusion of these ingredients has not markedly changed during the last quarter of a century despite the introduction or synthesis of new substances The use of parabens in pharamaceutical products as preservatives actually dates back to the 1920s8 These chemicals have been generally regarded as safe because they are quickly absorbed and hydrolyzed into the less toxic PHBA3 It is also worth noting that the metabolism of parabens is influenced by the inclusion in cosmetic preparations of penetration enhancers, which facilitate the rapid absorption of parabens through intact skin9,10 There have been several reports of contact sensitivity associated with cutaneous exposure to parabens, but while this mechanism has not yet been fully elucidated, such occurrences, as stated above, are linked to contact with damaged or broken skin The family of parabens include methyl paraben (MP), ethyl paraben, butyl paraben, isobutyl paraben, propyl paraben, isopropyl paraben, and benzyl paraben11 Methyl, ethyl, propyl, and butyl paraben are the most frequently used parabens in cosmetic formulations12 (Table 37-1) Notably, these chemicals can be absorbed through the skin and migrate into the bloodstream and bodily tissues review conducted by Soni et al in 2002 suggested that MP is thought to be absorbed totally and avidly through the skin as well as gastrointestinally metabolized into PHBA, before it is conjugated and eliminated through the urine Notably, Soni et al found no evidence of cutaneous or systemic accumulation13 In the wake of the reports postulating a relationship between the chronic use of parabens-containing deodorant and breast cancer incidence (see Parabens and Breast Cancer section), some investigators have undertaken longer-term examination of parabens exposure to the skin In particular, Ishiwitari et al considered the effects of daily MP use on human skin They measured the concentrations of the preservative in the stratum corneum of the human forearm in 12 volunteers after 1 month of twice-daily applications of MP-containing formulations, and also investigated the long-term effects of exposure on keratinocytes in vitro The investigators found that MP was not completely metabolized, with significant increases in concentrations in the stratum corneum measured after 1 month MP was also found to have reduced the proliferating capacity of keratinocytes and altered cell morphology They speculated that the accumulation of MP may be coordinated with the differentiation and aging of keratinocytes, and suggested that further research, especially in vivo study, is warranted to obtain a better understanding of the effects of daily use of MP3 In another recent study, Handa et al evaluated the effects of ultraviolet-B (UVB) exposure on human keratinocytes treated with MP Their approach was to culture HaCaT cells in MP-containing medium for 24 hours before exposing the medium to 15 or 30 mJ/cm2 of UVB, and then culturing for an additional 24 hours While a 0003% concentration of MP exhibited no impact on HaCaT cell viability and UVB irradiation alone induced little or no necrosis of keratinocytes, a 0003% MP concentration was found to significantly enhance UVB-induced apoptosis as well as oxidative stress, nitric oxide synthesis, lipid peroxidation, and transcription factor activation of the keratinocytes The investigators concluded that the combination of MP and UV may impose deleterious effects on human skin Consequently, they are investigating
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