OPINION
peptide in question, which should include the reputed biological action of the molecule under evaluation.
Enzyme 5-α reductase inhibitors
Other new cosmetic ingredients with interesting biological properties that are now coming to the fore as cosmetic ingredients include those that are purported to inhibit key mammalian enzyme processes. Examples of such materials are those that act as inhibitors of the enzyme 5-α reductase in the skin. The enzyme 5-α reductase is of interest to cosmetologists in the light of its role in male and female pattern hair loss, where the product of the enzyme plays a key role in the maintenance of hair follicle integrity. 5-α reductase metabolises the androgen testosterone to the more potent hormone dihydrotestosterone (DHT). One effect attributed to DHT is shrinkage of the hair follicle, resulting in the production of smaller and finer hair fibres, eventually leading to hair breakage and shedding. With this knowledge, cosmetic ingredients have been developed whose action, in vitro, is to inhibit 5-α reductase. Such materials are gaining prominence as ingredients in cosmetic products designed to both stimulate eyelash growth and prevent lash shedding, for example. However, the inhibition of this enzyme results in a concomitant elevation of local testosterone levels in the tissue where the material is applied. And it is this secondary effect of the 5-α reductase inhibitors that needs to be taken in to account when considering the safety of such ingredients. Generally, this is rarely done as the published guidance for the safety assessment of cosmetic ingredients essentially drives consideration primarily of toxicity end-points such as skin and eye irritation, skin sensitisation and genotoxicity and not the biological activity of the molecule under assessment. So, in the case of the 5-α reductase inhibitors, reductions in DHT biosynthesis, while leading to beneficial effects on localised hair growth, can also result in reduced levels of other DHT metabolites, some of which are hormones with important antiproliferative activity. Other DHT metabolites include hormones which play an important role in stress response modulation in the brain.
The secondary elevation in local skin testosterone levels could also lead to more immediately obvious effects such as excessive oiliness and acne in the skin of affected individuals, for example.14,15
These
would clearly be unacceptable sequelae of the usage of a 5-α reductase inhibitor as a cosmetic ingredient. In addition, elevated
Enzyme 5-αreductase inhibitors stimulate eyelash growth and prevent lash shedding.
circulating androgen levels in women are reported to result in hirsutism in affected individuals.16
Although there is no prevailing
evidence that this clinical picture arises as a result of elevated, localised skin androgen levels, it cannot be discounted as a hypothetical secondary effect of artificially perturbing skin androgen metabolism.
Conclusion
In conclusion, the introduction of cosmetic ingredients with novel biological activities, such as proteolytic enzymes, peptide growth factors and enzyme inhibitors should be viewed as challenging the established dogma of the toxicological evaluation of cosmetic ingredients and finished products. In the case of peptide growth factors and enzyme inhibitors for example, in the absence of firm evidence to the contrary, perturbing such natural processes must surely be viewed as having potential negative effects on the normal homeostatic mechanisms of the skin. This is the great challenge for the safety assessment of cosmetic ingredients and finished products in the 21st century.
Bibliography Scientific Committee on Consumer Safety. The SCCS’s notes of guidance for the testing of cosmetic ingredients and their safety evaluation. 7th Revision. Adopted 14 December 2010. SCCS/1416/11
References 1 Anon. 15th Report of the Joint FAO/WHO Expert Committee on Food Additives. WHO Technical Report Series No 488. FAO Nutrition Meetings Report Series No 50. 1972. Evaluation of Food Additives. Some enzymes, modified starches and certain other substance: toxicological evaluations and specifications and a review of the technological efficacy of some antioxidants. WHO. Geneva.
2 Kelling CK, Bartolo RG, Ertel KD, Smith LA, Watson DD,Sarlo K. Safety assessment of enzyme-containing personal cleansing products: Exposure characterization and development of IgE antibody to enzyme after a 6-month use test. J Allergy Clin Immmunol 1998: 101: 179-87. 3 Sarlo K, Adamson GM, Hollis VL, Innis JD,
Babcock LS, Kirchner DB. Development of allergic antibody to an enzyme in a body lotion: Results of an 18-month clinical study. J Immunotoxicol 2004; 1: 71-7.
4 Gailhofer G, Wilders-Truschnig M, Smolle J, Ludvan M. Asthma caused by bromelain: an occupational allergy. Clin Allergy 1988; 18: 445-50.
5 Baur X and Fruhmann G. Allergic reactions, including asthma, to the pineapple protease bromelain following occupational exposure. Clin Allergy 1979; 9: 443-50.
6 Hart-Davis A. Cream of the crop. London Evening Standard; 19 January 2011: 34.
7 Berlanga-Acosta J, Gavilondo-Cowley J, Lopez- Saura, Gonzalez-Lopez T et al. Epidermal growth factor in clinical practice – a review of its biological actions, clinical indications and safety implications. Int Wound J 2009; 6: 331-46.
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11 Maraschin R, Bussi R, Conz A, Orlando L et al. Toxicological evaluation of u-hEGF. Toxicologic Pathology 1995; 23: 356-66.
12 Mehta RC, Smtih SR, Grove GL, Ford RO et al. Reduction in facial photodamage by a topical growth factor product. J Drugs Dermatol 2008; 7: 864-71.
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14 Wiegratz J, Kuhl H. Managing cutaneous manifestations of hyperandrogenic disorders: the role of oral contraceptives. Treat Endocrinol 2002; 1: 372-86.
15 Thiboutot D. Acne: hormonal concepts and therapy. Clin Dermatol 204; 22: 19-28.
16 Karrer-Voegeli S, Rey F, Reymond MJ, Meuwly JY, Gaillard RC, Gomez F. Androgen dependence of hirsutism, acne and alopecia in women: retrospective analysis of 228 patients investigated for hyperandrogenism. Medicine (Baltimore) 2009; 88: 32-45.
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