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Effects of Cosmetic Formulations Containing Hydroxyacids on Sun-Exposed Skin

Effects of Cosmetic Formulations Containing Hydroxyacids on Sun-Exposed Skin

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This paper describes recent data on the effects of various skin formulations containing hydroxyacids (HAs) and related products on sun-exposed skin. The most frequently used classes of these products, such as α- and β-hydroxyacids, polyhydroxy acids, and bionic acids, are reviewed, and their application in cosmetic formulations is described. Special emphasis is devoted to the safety evaluation of these formulations, particularly on the effects of their prolonged use on sun-exposed skin. We also discuss the important contri- bution of cosmetic vehicles in these types of studies. Data on the effects of HAs on melanogenesis and tanning are also included. Up-to-date methods and techniques used in those explorations, as well as selected future developments in the cosmetic area, are presented.
This paper describes recent data on the effects of various skin formulations containing hydroxyacids (HAs) and related products on sun-exposed skin. The most frequently used classes of these products, such as α- and β-hydroxyacids, polyhydroxy acids, and bionic acids, are reviewed, and their application in cosmetic formulations is described. Special emphasis is devoted to the safety evaluation of these formulations, particularly on the effects of their prolonged use on sun-exposed skin. We also discuss the important contri- bution of cosmetic vehicles in these types of studies. Data on the effects of HAs on melanogenesis and tanning are also included. Up-to-date methods and techniques used in those explorations, as well as selected future developments in the cosmetic area, are presented.

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Hindawi Publishing CorporationDermatology Research and PracticeVolume 2012, Article ID 710893, 6 pagesdoi:10.1155/2012/710893
Review Article
EffectsofCosmeticFormulationsContaining HydroxyacidsonSun-Exposed Skin:CurrentApplicationsandFutureDevelopments
 AndrijaKornhauser,
1
SergioG.Coelho,
2
and VincentJ. Hearing 
2
1
O
 ffi
ce of Cosmetics and Colors, Center for Food Safety and Nutrition, US Food and Drug Administration,4517 Pinecrest Heights Dr, Annandale, VA 22003, USA
 2
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Correspondence should be addressed to Andrija Kornhauser, akornhause@aol.comReceived 6 December 2011; Accepted 20 March 2012Academic Editor: Bruno A. BernardCopyright © 2012 Andrija Kornhauser et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Thispaperdescribesrecentdataonthee
ff 
ectsofvariousskinformulationscontaininghydroxyacids (HAs)andrelatedproductsonsun-exposedskin.Themostfrequentlyusedclassesoftheseproducts,suchas
α
-and
 β
-hydroxyacids,polyhydroxyacids,andbionicacids,arereviewed,andtheirapplicationincosmeticformulationsisdescribed.Specialemphasisisdevotedtothesafetyevaluationof these formulations, particularly on the e
ff 
ects of their prolonged use on sun-exposed skin. We also discuss the important contri-bution of cosmetic vehicles in these types of studies. Data on the e
ff 
ects of HAs on melanogenesis and tanning are also included.Up-to-date methods and techniques used in those explorations, as well as selected future developments in the cosmetic area, arepresented.
1.Introduction
The cosmetic market is growing rapidly internationally andshows no sign of slowing in the foreseeable future. Withinskin care products, antiaging and sun protection productsare the main driving forces in this trend. Contemporary cos-metics contain a large number of active ingredients, such asbotanicals, antioxidants, hormones, and hydroxyacids (HAs)to name just a few. In this paper, we focus on the role thatHAs play in cosmetic/skin care products, their safety evalua-tions, and their e
ff 
ects on sun-exposed skin. This paper cov-ers selected new developments in the field which appearedsince our previous review of this topic, and it also includesselected topics not covered in that paper [1].
2.Presentationof HAsStructureandClassification
HAs have significantly influenced skin care since their intro-duction to dermatology about 40yrs ago [2]. Since theirinclusion in cosmetic formulations, they have been used totreat acne, ichthyosis, keratoses, psoriasis, photoaged skinand other disorders [3]. Following these developments, HAshave been gradually added into a variety of cosmetic pro-ducts for daily use and over extended time periods [4]. Atpresent, glycolic acid, lactic acid, and salicylic acid are themost frequently used HAs in cosmetics. One of the mostcited beneficial e
ff 
ects of HAs is the reported improvementof photoaged skin. The driving force behind the increase inHAs use in cosmetic dermatology and skin care systems hasbeen their antiaging e
ff 
ects [5]. Based on their structure andfunction, HAs can be classified as
α
-HAs,
 β
-Has, and salicylicacid (SA) and its derivatives. The most common representa-tiveofan
α
-HAisglycolicacid,whichwasoneofthefirstHAsto be incorporated into cosmetic formulations [4]. Another
α
-HAbeingusedinvarioustopicalformulationsislacticacid(L-form).Representatives of 
 β
-HAs are hydroxybutanoic acid,malic acid, and citric acid. Citric acid is presently widely used in various cosmetic formulations as an antioxidant [6].
 
2 Dermatology Research and Practice
Coumaric acid Citric acid GluconolactoneGlycolic acid Lactic acid Lactobionic acidMalic acid Salicylic acid Tropic acidOOO OOOOOOOOO O O OOHOHOHOHOHOH OHOHOHOHOHOHOHOHOHOHOH OHOH OHOHOHHOHOHOHOHOHOHOHHO
Figure
 1: Structures of selected
 α
-HAs,
 β
-HAs, salicylic acid, and coumaric acid and two representatives of polyhydroxy acids, lactobionicacid, and gluconolactone.
SA and its derivatives are widely used in contemporary cosmetic formulations. In the cosmetic and dermatologicliterature, SA is frequently described as a
 β
-HA. As presentedin a paper by Yu and van Scott, this classification is incorrect[7]. SA does not function as a
 β
-HA according to its chemicalstructure or by its biological or physiological function [7].Polyhydroxy acids (PHAs) and polyhydroxy bionic acids(PHBAs) constitute more recent arrivals into the cosmeticdomain. They constitute a new generation of HAs with mul-tiple skin benefits, making them very popular in cosmetic/skin care products. Structures of selected HAs are presentedin Figure 1.
3.Effects ofFormulations ContainingHAs
Due to the rapid proliferation of HAs into the cosmeticworld, safety evaluations of these products have became acrucial public health issue. As an important contribution tothis problem, the Cosmetic Ingredient Review (CIR) ExpertPanel assessed the available evidence and determined that
α
-HA ingredients are not reproductive or developmentaltoxins, mutagenic or carcinogenic, and skin sensitizers [8].Furthermore, the CIR Panel recommended concentration (amaximum of 10%) and pH (at or above 3.5) in cosmeticformulations containing
 α
-HAs. In addition, the CIR PanelrecommendedthatHA-containingproductsshouldbeform-ulated to avoid enhancing sun sensitivity and that consumersshould be advised to use daily sun protection [8]. Several yearslater,thesameCIRPanelevaluatedproductscontainingSA and salicylates and recommended that sensitivity tosunlight be taken into account when developing cosmeticformulations which was also the same recommendation pro-vided in the initial assessment of 
 α
-HA-containing products[8, 9]. Knowledge of the involvement of any cosmetic/skin careproduct in the induction of photocarcinogenesis is still inits infancy. The largest and most comprehensive study sofar, sponsored by the National Toxicology Program (NTP),reported on the photocarcinogenic potential of HAs [10].The authors reported that glycolic acid did not modify thephotocarcinogenesis induced by SSR, while SA (4%, cos-metic concentration) was photoprotective.An important contribution to this field was recently pub-lished by Lu et al. [11]. They tested four commercially avail-able moisturizing creams in their mouse model and foundthat, when applied topically to the mice, all the productshad tumorigenic activity. This paper presents an importantfindinganddeservestobediscussedherebriefly.Theconcernabout various e
ff 
ects of cosmetic creams on the skin is notentirely new. A number of published papers and clinicalstudies, including the above-mentioned NTP study, havesuggested that there is a measurable influence of variousapplied cosmetic vehicles on cutaneous responses to UVR exposure. The protocol applied by Lu et al. di
ff 
ers signifi-cantly from previously reported approaches. Lu and his teamapplied the four selected creams to mice with a high risk of developing skin tumors without UVB exposure (termedhigh-risk mice) after the initial 3 months of exposure. In thiscase, the observed results cannot be explained by a vehiclee
ff 
ectontheopticalpropertiesofskin.Theirpaper,therefore,raises the question of whether these agents are more activecompounds (tumor promoters). It was expected that such
 
Dermatology Research and Practice 3findings would result in immediate reactions. Two commen-taries on Lu’s paper were published in the same issue of the journal. The first commentary, by Staeb et al. [12], criticizedthe design of the experiments; the second commentary,by Ellefson [13], questioned the statistical approach. Bothgroups expressed some doubts about the validity of thefindings of Lu et al. A third commentary, by Forbes [14], dis-cussed the paper and provided a brief overview of the field.It is obvious that more studies of this kind are needed. Themost important question emerging from this challenginglaboratory data, however, is the relevance of these findings tohumans. The cosmetic market is by no means static, and new products, including HAs and their derivatives, are steadily entering into the already large cosmetic repertory. A few examples will be highlighted here. Seo et al. [15] examinedthe e
ff 
ects of p-coumaric acid (PCA), a hydroxy derivativeof cinnamic acid, on erythema and pigmentation in UV-exposed human skin. Twenty-one subjects, with the Fitz-patrick skin types III-IV, were included in the investigation.TheauthorsreportthattopicallyappliedPCApreventedUV-induced erythema and subsequent pigmentation in humanskin. The authors speculated that PCA may suppress theinduction of erythema by altering gene expression or by low-eringtheUV-inducedinflammation.Inaddition,theauthorssuggested that PCA also acts as a potent tyrosinase inhibitor.In conclusion, Seo et al. stated that the product showed noapparent adverse reactions and, therefore, may be a usefulactive ingredient in cosmetic formulations. Im et al. [16]investigated the physicochemical properties of fatty esterderivatives of SA for UV protection. Octanoyl, nonanoyl,decanoyl, laurel, myristoyl, and palmitoyl oxysalicylate(C16SA) were investigated. The authors concluded that theC16SAwasreadilyhydrolyzedtoitsparentcompoundinskinhomogenates, suggesting that it might be converted to SAafter topical administration. Furthermore, it showed thelowest permeation of SA in all types of skin and a loweraccumulation and smaller uptake in the lipid phase as com-pared with the other derivatives examined. On the basis of the reported findings, they suggested that C16SA could be apotential candidate for UV protection. Another applicationof a SA derivative was recently reported by Merinville et al.[17]. They provided evidence that sodium salicylate (SS)obtained from the neutralization of 1% SA with sodium hy-droxide can deliver satisfactory antiaging benefits, with sig-nificantly reduced skin irritation, which commonly occursfollowing application of SA to sensitive skin. They conductedthree clinical studies, and by measuring biological, optical,andobservationalbiomarkerstheycoulddemonstratesignif-icant anti-aging e
ff 
ects of SS, which is especially suitable forsubjects with sensitive skin.Recently, Tasic-Kostov et al. [18] conducted a study toassess the safety and e
cacy of lactobionic acid as comparedto glycolic acid. Seventy-seven volunteers participated in theproject, and skin color (erythema and melanin index), trans-epidermal water loss, electrical capacitance, and pH of theskin were measured. The authors confirmed that lactobionicacid resulted in improved skin benefits as compared withcorresponding glycolic acid formulations, particularly withrespect to skin irritation and barrier impairment.
4.PresentApplicationsandFutureDevelopments
Determining a person’s sensitivity to sunlight is critical tounderstanding the UV e
ff 
ects of formulations with HAs. TheMED is typically determined on each individual to assesstheir UV sensitivity in conjunction with knowledge of theFitzpatrick skin type [19]. The Commission Internationalede L´eclairage (CIE) currently has a technical committeeformed to address typical MEDs for individuals of all skintypes, and their technical report will be forthcoming withrecommendations and guidelines (http://div6.cie.co.at/?i caid
=
609&pubid
=
318). The MED parameter allows one tocomparebiologicallyequivalente
ff 
ectsresultingfrom1MEDto previous data in the literature. Typically, a series of ex-posures of increasing doses is used for MED determinationas described in previous studies [2024]. Subject photo- type, site area size, geographical skin location, site-specificmelanin content, and UV source vary by clinical study andpresent specific challenges when determining the MED. Toallow for comparison across clinical studies, UV doses mustbe wavelength weighted using the CIE reference actionspectrum for erythema [25]. Twenty-four hours after UVexposure, trained observers determine the MED by visualassessment using a scale where 1 MED is defined as pink erythema with at least one distinct border.Obviously, this determination can be subjective and ishighly dependent on a trained observer. There are a few limitations with assessing the MED visually especially whenconsidering varying illumination conditions, environmentaltemperatures, and viewing angles during the visual assess-ment at di
ff 
erent clinical sites. To address this issue, in thecase of sunscreens there are some standard requirementsregarding lighting conditions that have been set forth in theUS FDA Sunscreen Monograph [26] that can also be appliedto HA evaluation. In addition, increased melanin contentpresents a challenge when discriminating erythema, and thisisanareawheredi
ff 
usereflectancespectroscopy(DRS)excelsovervisualevaluation.Somepioneeringworkwasperformedover 2 decades ago that defined the use of CIE L
a
b
colorspace system variables and transformed them into a vectorrepresentationofskinpigmentationdefinedastheindividualtypologyangle(ITA
=
[arctan(L
50/b)]
×
180/Pi)[27,28]. However, this CIE L
a
b
system is inadequate to dis-criminate erythema masked by higher melanin content, andtherefore measuring skin chromophores, such as melanin,oxyhemoglobin and deoxyhemoglobin, by DRS is highly desirable for defining the MED noninvasively. Several studieshave been published on the use of DRS, which prove thatit can be applied as an adjunct to aid in the prediction andmeasurement of MEDs for HA UV e
ff 
ects [2931]. In the past decade, gene array technologies have changedthe way we evaluate skin biology responses by allowing usinsight into the global genome profile at particular momentsin time and under specific environmental conditions. Recen-ly through the use of microarrays the di
ff 
erent spectral res-ponses from repetitive UVA and/or UVB exposure of humanskin were characterized [32]. Further, acute doses withfull-spectrum solar-simulated radiation and solar-simulated

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