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ACTUALITI N FOTOPROTECIE

ADVANCES IN SUNSCREEN PRODUCTS INDUSTRY

ANA-MARIA DRGNI, G.-S. IPLICA

* Clinica Dermatologie II, Spitalul Clinic Colentina, Bucureti.Clinic of Dermatology II, Colentina Clinical Hospital, Bucharest.

Rezumat

Utilizarea n mod constant a produselor defotoprotecie are o importan dubl att pentru evitareatoxicitii acute la radiaii UV, ct i pentru efectele petermen lung mbtrnirea pielii i apariia cancerului depiele. Eficiena produselor de fotoprotecie este susinut decalitatea substanelor active, care se regsesc n acesteproduse. Din pcate, o parte din ingredientele coninute nprodusele de protecie solar strbat epidermul i ajung ncirculaia sangvin. Unele produse pot conine ingredientecare pot produce importante efecte adverse. Oxybenzone

(benzophenone-3) este un compus prezent n jumtate dincremele de fotoprotecie i care poate determina un efectfoto-sensibilizant, carcinogen, cu creterea produciei deradicali liberi. Compuii anorganici, cum ar fi oxidul dezinc i dioxidul de titan s-au dovedit a face mai sigureprodusele de fotoprotecie. Oxidul de Zinc ofer o proteciefa de radiaiile UVA foarte bun, n timp ce dioxidul detitan asigur o protecie mai bun pentru UVB. FDA(Foodand Drug Administration) a anunat n iunie 2012 noilereglementri n domeniul fotoproteciei. Astfel, un produseste considerat rezistent la ap dac FPS (factorul deprotecie solar) este meninut dup imersia de 40 minute(2 imersii a cte 20 minute), iar un produs este foarterezistent la ap dac menine FPS dup imersia de 80minute (4 imersii a cte 20 minute). Numai cremele defotoprotecie cu un FPS de minim 15 sau mai mare s-audovedit a fi eficiente n reducerea riscului de cancer de pielei a fotombtrnirii cutanate.

Cuvinte cheie: fotoprotecie , oxibenzon, benzo-fenon-3, oxid de zinc, dioxid de titan, factor de proteciesolar.

Summary

Consistently use of sunscreening products has adouble importance - both to avoid acute toxicity of UVradiation, to reduce long-term effect - skin aging and skincancer. The efficiency of photoprotection products issupported by the quality of the active substances that arefound in these products. Unfortunately, some of theingredients contained in sunscreens cross the epidermisand reach the blood stream. Some products may containingredients that can produce significant side effects.

Oxybenzone (benzophenone-3) is a compound present in ahalf of photoprotection creams which could result in photo-sensitivity effect, carcinogenic effect, with increasedproduction of free radicals. Inorganic agents such as zincoxide and titanium dioxide are more safe for thesunscreening products. Zinc oxide offers better UVAprotection, whereas titanium dioxide provides superiorUVB protection. FDA (Food and Drug Administration)announced on june 2012 new rulles for sunscreen creams.Thus a product is considered waterresistant if SPF (sunprotection factor) is maintained after immersion for 40minutes (2 immersion of 20 minutes), and it is verywaterresistant if maintain SPF after immersion for 80minutes (4 immersion of 20 minutes). Only photo-

protection creams with a minimum SPF 15 or higher werefound to be effective in reducing the risk of skin cancer andskin aging.

Keywords: photoprotection, oxybenzone, benzo-phenone-3, zinc oxide, titanium dioxide, sun protectionfactor (SPF).

REFERATE GENERALEGENERAL REPORTS

Intrat n redacie: 4.07.2012

Acceptat: 12.09.2012

Received: 4.07.2012

Accepted: 12.09.2012

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DermatoVenerol. (Buc.), 57: 273-284

adjuvani: substane anti-radicali liberi(vitamina C, vitamina E, flavonoide),

substane emoliente, excipieni cu urmtoarele roluri princi-

pale: limitarea riscului de penetrarecutanat a substanelor active; permitereaaplicrii uniforme a produsului; conferireade rezisten la ap i transpiraie.

Substanele active care se gsesc n cremelede fotoprotecie confer caracteristica esenial aeficienei gradului de protecie solar inclusiv ncondiii de efort, transpiraie abundent, expu-nere repetat la ap sau chiar not.

Clasificarea substanelor active

1. Compui anorganici reprezentai deblocanii fizici

2. Compui organici reprezentai defiltrele chimice2 a. substane organice cu efect de pro-

tecie fa de UVA2 b. substane organice cu efect de pro-

tecie fa de UVB

1. Compuii anorganici

n prezent, cei mai utilizai compuianorganici care se regsesc n cremele defotoprotecie sunt reprezentai de oxidul de zinci dioxidul de titan. Aceti blocani fizici oferprotecie fa de radiaiile UVA i UVB prinabsorbia sau prin reflectarea luminii.

Pentru o asigurare adecvat a fotoprotecieiaceste ingrediente necesit aplicarea unui stratmai gros de crem de fotoprotecie, conferind unaspect opac al pielii [3]. Oxidul de zinc confer oprotecie fa de radiaiile UVA foarte bun, ntimp ce dioxidul de titan asigur o protecie mai

bun pentru UVB [4]. n momentul aplicriiprodusului, particula de oxid de zinc rmne lanivelul stratului cornos, de unde absoarberadiaiile UV.

Oxidul de fier, un alt compus anorganic, estemai apropiat de culoarea natural a pielii datoritnuanei roiatice, motiv pentru care este adugatfrecvent n compoziia produselor de foto-protecie, cu scopul reducerii opacitii oxiduluide zinc i a dioxidului de titan [5]. Din consi-derente estetice, aceti compui nu au fost

adjuvants: free anti-radicals (vitamin C,vitamin E, flavonoids), emollient

substances, excipients with the following main roles:

to limit the risk of skin penetration byactive substances; to allow uniformapplication of the product; to conferresistance to water and perspiration.

The active substances which are found insunscreen creams bestow upon them an essentialfeature: the efficacy of the degree of sunprotection, measured under all conditions,including effort making, abundant perspiration,

repeated water exposure or even swimming.

Classification of active substances

1. Inorganic compounds represented byphysical blockers

2. Organic compounds represented bychemical filters2 a. UVA-protection organic compounds2 b. UVB-protection organic substances

1. Inorganic compounds

Presently, the inorganic compounds mostfrequently used in sunscreen creams are zincoxide and titanium dioxide. These physicalblocking factors offer protection against UVA andUVB radiations by absorption or by lightreflection.

In order to assure adequate photoprotection,these ingredients imply application of a thickerlayer of sunscreen cream, confering an opaqueaspect to the skin [3]. Zinc oxide confers verygood protection against UVB [4]. When theproduct is applied, the zinc oxide particle

remains at the level of the skin, where it absorbsthe UV radiations.Another inorganic compound, iron oxide, is

more similar to the natural colour of the skin,owing to its reddish hue, reason for which it isfrequently added in the composition of sunscreenproducts in order to reduce the opacity of zincoxide and titanium dioxide [5]. Out of cosmeticconsiderations, these compounds have not beenpromoted until recently, when sunscreen creamswith microparticles have been developed.

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promovai pn de curnd cnd au fost introduseformele de creme ecran solar cu microparticule.

Microparticulele de oxid de zinc i dioxid detitaniu (10-50nm) prin micorarea dimensiunii lorreduc difuzia luminii vizibile i mbuntescaspectul estetic al tegumentului. De asemeneaabsorb radiaiile UV, dar n cazul acestor formede microparticule absorbia este ndreaptat maimult spre gama de radiaii cu lungimi de undmai scurte (UVB).

Datorit fotostabilitii compuii anorganicisunt preferai pentru uz pediatric sau pentrupersoanele alergice la produsele de fotoprotecie[6]. Ca urmare a opacitii oferite, oxidul de zinci dioxidul de titan s-au dovedit a fi eficiente i ncazul persoanelor cu boli fotosensibile, prinprotecia mpotriva luminii vizibile [7].

2. Compuii organici

2 a. Substane organice cu efect de proteciefa de UVA

Apariia filtrelor noi cu protecie puternicfa de UVA reprezint un progres major ndezvoltarea produselor de protecie solar ireducerea efectelor cauzate de radiaiile UVAcum ar fi eritemul, mbtrnirea prematur a

pielii, fotosensibilizare i apariia cancerului depiele. Radiaiile UVA cu un spectru de aciunecuprins ntre 320-400 nm sunt mprite n 2 cate-gorii: UVA tip 1 (320-340 nm) i UVA tip 2 (340-400 nm).

FDA (Food and Drug Administration) aconceput un sistem de msurare a radiaiilorUVA bazat pe teste in vivo i in vitro (tabel 1).Pentru testele in vivo a fost utilizat factorul deprotecie UVA (UVA-PF) care determin capa-

By reducing their size, zinc oxide andtitanium dioxide particles (10-50nm) deplete the

diffusion of the visible light and improve theesthetic aspect of the tegument. They also absorbUV radiations, although in these microparticlesabsorption is moreover directed to the range ofrays with shorter wavelengths (UVB).

Owing to their photostability, inorganiccompounds are the treatment of choice inpediatric use as well as in patients allergic tosunscreen products [6]. As a result of the opacitythey confer, zinc oxide and titanium dioxide havealso proven efficacious in persons withphotosensible conditions, by way of theprotection against the visible light [7].

2. Organic compounds

2 a. UVA-protection organic compounds

The development of new highly UVA-protective filters is a breakthrough in sunscreenproducts industry, with major consequences inthe abatement of effects caused by UVAradiations, such as erythema, untimely skinageing, photosensitisation and skin cancer. UVAradiations with wavelengths of 320-400nm aredivided into two categories: type I (320-340 nm)

and type II (340-400 nm).The Food and Drug Administration hasconceived a new system for measuring UVAradiations based on in vivo and in vitro tests(Table 1). For in vivo tests the UVA protectionfactor (UVA-PF) has been used, that determinesthe capacity of the photoprotection product toprevent the basking process. For in vitro tests, theratio between UVA/UVA1 radiations has beenused.

Protecia UVA Categoria UVA-PF UVA1/UV(in vivo) (in vitro)

Fr protecie < 2 < 0,20UVA

Sczut 2 - 4 0,20 - 0,39

Medie 4 - 8 0,40 - 0,69

Crescut 8 - 12 0,70 - 0,95

Foarte crescut > 12 > 0,95

Tabelul 1. Sistemul de 4 stele de msurare a proteciei fa deradiaiile UVA

(dup Sambandan DR, Ratner D. Sunscreens:an overview and update. J Am Acad Dermatol.2011;64:748758)

Table 1. The four-star system of measuring protection againstUVA radiations (according to Sambandan D.R., Ratner D.,Sunscreens: an overview and update. J Am Acad Dermatol.2011;64:748758)

UVA Protection Category UVA-PF UVA1/UV(in vivo) (in vitro)

Without UVA < 2 < 0.20protection

Low 2 - 4 0.20 - 0.39

Medium 4 - 8 0.40 - 0.69

Increase 8 - 12 0.70 - 0.95

Very high > 12 > 0,95

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Benzophenone is an organic compound witha wide protection spectrum both for UVA and

UVB rays. In UVA rays this spectrum ranges from320 to 350nm.It is a photolabile preparation and its

oxidation can interrupt the antioxidation process.FDA has approved three types of benzo-phenones: oxybenzone, sulisobenzone anddioxybenzone. Oxybenzone is the mostcommonly used of them, although its incidencein photoallergic contact dermatites is the highest[6].

Avobenzone (butyl-methoxydibenzoylme-thane, Parsol 1789), a powerful UVA filter, was

the first organic agent approved by FDA thatensures protection against type 1 UVA rays.

Nevertheless, it is highly photolabile, so thatafter one hour of sun exposure its photo-protection qualities diminish up to 60 per cent [8].Avobenzone can also affect the stability of otheractive substances present in photoprotectionenzymes [9].

Ecamsule (terephthalylidene dicamphorsulfonic acid; Mexoryl SX - LOreal, Paris, France)is the latest FDA approved compound (2006)offering a broad protection spectrum.

This UVA protection organic compound hasproven efficacious in the prevention and evenreduction of UV-induced pigmentation, of p53protein accumulation, of the alteration ofLangerhans cells and in the prevention ofphotodermatoses [10].

2 b. UVB-protection organic substances

Organic substances, and UVB filters inparticular, act by absorption of UV rays and theirconversion into thermal energy. The p-amino-

venzoic acid (PABA) is the compound that offersthe highest UVB protection.Owing to its capacity to bind with

keratinocytes, it favours skin pigmentation, whileincreasing UV resistance to water immersion andto perspiration [6]. When applied on the skin,PABA can penetrate the skin, thereby increasingthe risk of contact dermatitis.

Due to the higher incidence of contactdermatites caused by PABA, this compound hasbeen replaced by PABA derivatives.

citatea produsului de fotoprotecie n prevenireaprocesului de bronzare. n cazul testelor in vitro a

fost folosit raportul dintre radiaiile UVA/UVA1.Benzofenona este un compus organic cu unspectru larg de protecie att pentru radiaiileUVA ct i pentru radiaiile UVB. Spectrul deprotecie n cazul radiaiilor UVA este cuprinsntre 320-350nm.

Preparatul este fotolabil iar oxidarea sa poatentrerupe sistemul de antioxidare. FDA a aprobat3 tipuri de benzofenone: oxibenzona, suliso-benzona i dioxibenzona. Oxibenzona este celmai utilizat compus dei are cea mai mareinciden a producerii dermatitelor de contact

fotoalergice [6].Avobenzona (butil-metoxi-dibenzoil-metan,Parsol 1789), un filtru puternic UVA, a fostprimul agent organic aprobat FDA care asigurprotecie mpotriva radiaiilor UVA tip 1.

Cu toate acestea, este foarte fotolabil, astfel cdup 1 or de expunere la soare proprietile salede fotoprotecie scad pn la 60% [8]. Avo-benzona poate de asemenea s afecteze stabili-tatea altor ingrediente active, prezente n cremelede fotoprotecie [9].

Ecamsula (acid tereftaliden-dicamfor-sul-

fonic; Mexoryl SX - LOreal, Paris, Frana),aprobat de FDA n 2006, este cel mai noucompus care ofer un spectru larg de protecie.

Acest compus organic cu protecie fa deUVA s-a dovedit a fi eficient n prevenirea ichiar reducerea pigmentrii induse de radiaiileUV, acumulrii proteinei p53, alterrii celulelorLangerhans i a prevenirii fotodermatozelor [10].

2 b. Substane organice cu efect de proteciefa de UVB

Substanele organice, n special filtrele UVB

acioneaz prin absorbia radiaiilor UV iconversia acestora n energie termic. Acidul p-aminobenzoic (PABA) este compusul care ofercea mai mare protecie fa de UVB.

Datorit capacitii sale de a se lega dekeratinocite, favorizeaz pigmentarea pielii ipermite n acelai timp rezisten UV la imersia nap sau n caz de transpiraie [6]. n momentulaplicrii la nivelul pielii PABA poate penetrastratul cornos, crescnd astfel riscul apariieidermatitei de contact.


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Datorit frecvenei mari a dermatitelor decontact cauzate de PABA a fost nlocuit cu

derivai de PABA.Padimate O este un derivat care nupenetreaz stratul cornos, determin foarte rarpigmentarea pielii i ofer o siguran superioarfa de PABA. Acesta este folosit n general ncombinaii cu alte ingrediente, pentru a creteFPS (factorul de protecie solar) [5].

Cinamatele, incluznd octinoxatul icinoxatul, sunt n prezent cele mai utilizate filtreUVB n Statele Unite, deoarece nu determinpigmentarea pielii i foarte rar pot induce iritaii[6]. Fiind mai puin poteni dect Padimate O,

acetia reduc rezistena la ap a cremeifotoprotectoare, motiv pentru care produsele careconin cinamate necesit reaplicare.

Totodat, aceti compui organici prezintriscul fotodegradrii, ceea ce duce la scdereaeficienei lor [11].

Salicilaii, cei mai slabi compui organici anti-UVB, au un spectru de absorbie cuprins ntre 300i 310 nm. Acetia sunt importani mai multdatorit fotostabilitii pe care o confer celorlaltesubstane active prezente n produsele deprotecie solar. Din categoria salicilailor facparte octisalatul, homosalatul i salicilatul detrolamin. Aceste ingrediente ofer o sigurancrescut a utilizrii produselor de fotoprotecie,datorit efectelor adverse aproape absente cumar fi reaciile de fotosensibilitate. Din acestemotive sunt adugate n concentraii relativcrescute pentru a ridica nivelul proteciei fa deradiaiile UVB.

Octisalatul i homosalatul sunt compui cu ofotostabilitate foarte mare, fiind utilizai pentru areduce fotodegradarea altor substane active. Deasemenea sunt i hidrofobi, putnd fi folosii casolveni pentru alte ingrediente prezente n

cremele de fotoprotecie [6]. Salicilatul detrolamin este solubil n ap i este folositfrecvent n produsele destinate ngrijirii prului.

Octocrilena este un filtru UVB slab. Deicontribuie la creterea fotostabilitii, includereasa n produsele de fotoprotecie este dificil ipresupune costuri ridicate [6].

Ensulizolul este un filtru UVB solubil n ap,avnd o consisten mai uoar i mai puin grascomparativ cu alte ingrediente, este folositfrecvent n cremele de hidratare zilnice [12].

Padimate O is a derivative that does notpenetrate the skin, very seldom inducing skin

pigmentation and thereby offering superiorsafety as compared to PABA. It is mainly used incombinations with other ingredients, in orderto increase the SPF (sun protection factor)[5].

Cinnamates, which include octinoxate andcinoxate, are presently the most frequently usedUVB filters in the USA, since they do notdetermine skin pigmentation and only veryrarely induce irritations [6]. Less potent thanPadimate O, they reduce the water resistance ofphotoprotective creams, reason why cinnamate-containing products need application.

These organic compounds present the risk ofphotodegradation, which leads to a decrease intheir efficacy [11].

Salicylates, the weakest anti-UVB organiccompounds, have an absorption spectrumranging from 300 to 310 nm. They are importantonly due to the photostability they confer to theother active substances present in sunscreenproducts. Salicylates include octisalate,homosalate and trolamine salicylate. These

ingredients confer higher safety in the use ofphotoprotection products due to almost absentadverse effects such as reactions tophotosensitivity. Therefore, they are added inrelatively high concentrations, in order toincrease the UVB-protection level.

Octisalate and homosalate are compoundswith very high photostability. They are used toreduce the photodegradation of other activesubstances. They also are hydrophobe and areused as solvents for other ingredients present inphotoprotection creams [6]. Trolamine salicylateis water soluble and is frequently used in haircare products.

Octocrylene is a weak UVB filter. Although itcontributes to photostability increase, itsinclusion in photoprotection products is difficultand implies high costs [6].

Ensulizole is a water soluble UVB filter witha lighter and less fatty consistency as comparedto other ingredients. It is mainly used inhydrating day creams [12].

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Compuii organici i cei anorganici potaciona sinergic pentru a crete FPS [13].

Eficiena produselor de fotoprotecie

Tipul produsului de protecie solar (crem,gel, spray, stick) determin de multe ori eficienafotoproteciei. Pentru meninerea proprietilorde fotoprotecie i a fotostabilitii filtrelor UVeste recomandat ca produsul s asigure ominimalizare a interaciunii dintre ingredienteleactive i cele inactive. Tipul produsului deter-min de asemenea durabilitatea fotoproteciei irezistena la ap. O protecie solar ineficientpoate fi rezultatul unei aplicri insuficiente sau a

unei reaplicri rare [14].Utilizarea constant a produselor de protecie

solar s-a dovedit a fi eficient n prevenirea ireducerea riscului de dezvoltare a keratozeloractinice i a cancerelor non-melanotice [15].

Expunerea la soare accelereaz procesul defotombtrnire prin apariia la nivel cutanat aradicalilor de oxigen, generai de radiaiileultraviolete. UVA i UVB ptrund n derm,distrugnd fibrele elastice i reeaua de colagen[16]. Un studiu realizat recent a demonstrat cutilizarea zilnic a produselor de protecie solar

poate preveni modificrile aprute n cadrulprocesului de fotombtrnire, cum ar fihiperplazia epidermic i afectarea reelei decolagen [17].

Efectele adverse ale produselor de foto-protecie

PABA i oxibenzona sunt compuii cel maifrecvent implicai n generarea efectelor adversen timp ce avobenzona, sulisobenzona,octinoxatul i Padimate O induc rareori reaciiadverse. Oxibenzona (benzofenona-3) este un

ingredient activ care se regsete n mai mult dejumtate din toate produsele de protecie solar.S-a dovedit a avea un efect foto-sensibilizant,carcinogen, cu creterea produciei de radicaliliberi i potenial risc de a afecta ADN-ul celular[18]. Salicilaii, compuii anorganici i ecamsulanu pot penetra stratul cornos astfel cfotosensibilitatea n cazul acestor compui esteextrem de rar ntlnit [19]. Microparticulele dedioxid de titaniu pot trece prin membranacelular i pot afecta funcia fibroblatilor.

Organic and inorganic compounds can actsynergically to increase SPF [13].

Photoprotection products efficacy

The type of sunscreen presentation (cream,gel, spray, stick) often determines the efficacy ofthe photoprotection. To maintain photoprotectionproperties and the photostability of UV filters it isrecommended that the product ensuresminimalising of the interaction between activeand inactive ingredients. The type of productpresentation also determines the duration ofphotoprotection and of water resistance. An

ineffective sun protection may be the result ofinsufficient application or of rare re-applications[14].

Consistent use of sunscreen products hasproven efficacious in the prevention andreduction of the risk of developing actinickeratoses and non-melanoma cancers [15].

Sun exposure accelerates the process ofphotoageing by the appearance of oxygenradicals at skin level, generated by ultravioletrays. UVA and UVB penetrate the skin,destroying elastic fibres and the collagen network

[16]. A recent study has demonstrated that theuse of sunscreen products can prevent changesoccurring within the photoageing process, suchas epidermic hyperplasia and the involvement ofthe collagen network [17].

Adverse effects of sunscreen products

PABA and oxybenzone are the compoundsthe most frequently involved in producingadverse reactions, while avobenzone, suli-benzone, octinoxate and Padimate O seldom

induce adverse reactions. Oxybenzone (benzo-phenone-3) is an active substance used in morethan half of all sunscreen products. Is has aphotosensitising and carcinogen effect andincreases the yield of free radicals and the risk ofaffecting the cell DNA [18]. Salicylates, inorganiccompounds and ecamsule cannot penetrate theskin, so that photosensitivity is very seldomencountered in such compounds [19]. Titaniumdioxide microparticles can penetrate the cellmembrane and affect the function of the

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Polimerii de acoperire ai acestor compui potmpiedica aderena lor la membrana celular,

meninnd astfel activitatea celular normal[20].Microparticulele de oxid de zinc i dioxid de

titaniu pot produce apoptoza celulelor neurale,acest efect fiind mai mult dependent de dozdect de mrimea particulelor [21].

Riscurile legate de absorbia sistemic asubstanelor active

Eficiena produselor de fotoprotecie estesusinut de calitatea substanelor active care seregsesc n aceste produse. Din pcate, o partedin ingredientele coninute n produsele deprotecie solar strbat epidermul i ajung ncirculaia sangvin. n cazul copiilor ptrundereaingredientelor n snge poate afecta sntatea.Dei riscul de absorbie al celor mai frecventutilizate filtre organice este redus, acest risc poateapare atunci cnd produsul este aplicat rapid peo suprafa mare de piele sau cnd ingredientulrespectiv se gsete n concentraii mari nprodus.

Absorbia sistemic a filtrelor organice nupresupune neaprat apariia efectelor adverse.

Pentru aprecierea corect a riscului sunt necesareteste de genotoxicitate, carcinogenicitate, toxici-tate reproductiv i fototoxicitate [22].

Unele ingrediente prezente n produsele defotoprotecie, ca benzofenona-3, 3-(4-metil-benziliden) camfor i octil-metoxicinamatul, aufavorizat creterea apariiei efectelor adverseendocrine, datorit prezenei activitii estro-genice. ntr-un studiu efectuat pe voluntarisntoi, a fost aplicat pe o suprafa mare depiele un produs coninnd 10% benzofenon-3,octil-metoxicinamat i 3-(4-metil-benzyliden).

Dup o sptmn, toate substanele au fostgsite n cantiti variabile n urina i sngelepersoanelor testate. Ca urmare, s-a concluzionatc 3-(4-metil-benzyliden) nu ar trebui utilizat lacopiii cu vrsta sub 12 ani pn la apariia unoralte studii care s certifice sigurana acestoringrediente [23].

n cazul etilhexil-metoxicinamatului, unuldintre cele mai utilizate filtre UVB n produselede fotoprotecie, au fost observate reaciifotoalergice, reacii estrogenice i non-

fibroblasts. The covering polymers of thesecompounds can prevent their adherence to the

cell membrane, therefore keeping cell activitywithin normal limits [20].Zinc oxide and titanium dioxide micro-

particles can induce neural cells apoptose, aprocess more dependent on the dosage than onthe size of the particles [21].

Risks of active substances systemicabsorption

The efficacy of photoprotection products issupported by the quality of the active substances

that are found in these products. Unfortunately,some of the ingredients contained in sunscreenscross the epidermis and reach the blood stream.Penetration of these ingredients in the blood cancause diseases in children. Although the risk ofabsorption in the case of the most commonorganic filters is low, it may occur when theproduct is quickly applied on large skin areas orif the ingredient is present in high concentrationsin the product.

The systemic absorption of organic filtersdoes not necessarily trigger adverse reactions. In

order to correctly assess the risks, one should runtests of genotoxicity, carcinogenicity, re-productive toxicity and phototoxicity [22].

Some of the ingredients present in photo-protection products, such as benzophenone-3, 3-(4-methyl-benzylidene) camphor and octyl-methoxycinnamate, have fostered endocrineadverse effects, due to their estrogenic activity. Ina study performed on healthy volunteers, aproduct containing 10 per cent benzophenobe-3,octyl-methoxycinnamate and 3-(4-methyl-

benzylidene) was applied on large skin areas.One week later, all substances were found invariable quantities in the urine and blood of thetested persons. Henceforth, it was concluded that3-(4-methyl-benzylidene) should not be used inchildren less than 12 years old until moreelaborate studies certify its safety [23].

In the case of ethylhexyl-methoxycinnamate,one of the most common UVB filters inphotoprotection products, photoallergic, estro-genic and non-estrogenic reactions have been

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estrogenice, precum i producerea de radicaliliberi de oxigen [23].

Nouti

Factorul de protecie solar

FDA a definit FPS ca fiind raportul dintredoza de radiaie UV necesar pentru a produce odoz eritematoas minim (MED) n pieleaprotejat dup aplicarea unei cantiti de 2mg/cm2 de crem fotoprotectoare i doza deradiaie UV necesar pentru a produce MED npielea neprotejat [24].

Produsele cu SPF 50 ofer o protecie doar

uor mai bun dect cele cu SPF 30. De asemenea,pot induce consumatorilor un fals sentiment desiguran, determinndu-i s stea mai mult lasoare i astfel s creasc riscul arsurilor solare ial cancerului de piele [12].

Metoda COLIPA

Ca urmare a eforturilor depuse din ultimiiani de a include substane protectoare mpotrivaradiaiilor UVA n cremele de fotoprotecie i de adezvolta o metod de msurare a fotoprotecieiprin intermediul acestor produse, un grup de

cercettori au realizat o metod de msurare invitro a radiaiilor UVA denumit COLIPA(European Cosmetics Trade Association) [25].Metoda este folosit n prezent n Europa pentrutestarea i etichetarea produselor de proteciesolar.

Efectul utilizrii produselor de foto-protecie asupra nivelului de vitamina D

Radiaiile de tip UVB reprezint factorulbiologic cel mai activ implicat n carcinogenezapielii dar sunt utile pentru transformarea

provitaminei D (7-dihidrocolesterol) nprevitamina D la nivelul pielii [26]. Din aceastcauz a aprut ipoteza conform creia utilizareaproduselor de protecie solar poate predispunela apariia deficitului de vitamina D, n special ncazul persoanelor vrstnice.

Pentru studierea acestei ipoteze a fost realizatun studiu pe 2 loturi pe parcursul a 2 ani cuscopul determinrii nivelului vitaminei ipotenialul risc de apariie secundar ahiperparatiroidismului [27]. Vitamina D,

noted, alongside the yield of oxygen freeradicals [23].

Advances in photoprotective productsindustry

The sun protection factor

FDA has defined SPF as the ratio between theUV radiation dose necessary to produce aMinimal Erythemal Dose (MED) in the protectedskin after applying 2 mg/cm2 of sunscreencream, and the dose of UV radiations necessaryto produce MED on the unprotected skin [24].

Products with SPF equal to 50 offer protection

only slighly more effective than those with SPFequal to 30. Likewise, they can induce in patientsa false safety feeling, prompting them tosunbathe for a longer time, therefore increasingthe risk of sunburns and skin cancer [12].

The COLIPA method

As a result of efforts made in recent years toinclude UVA-protection substances in sunscreencreams and to develop means to assess thephotoprotection level of these ingredients, agroup of researchers has conceived a method

called COLIPA (European Cosmetics TradeAssociation) to measure in vitro sunscreen UVAprotection [25]. This method is presently used inEurope to test and label sunscreen products.

The effect of sunscreen application onvitamin D level

UVB-rays represent the biological factor mostactively involved in skin cancer, although theyhave proven to be useful in the transformation ofprovitamin D (7-dihydrocholesterol) into

previtamin D at skin level [26]. This is why ahypothesis emerged according to which the useof sunscreen products can predispose to vitaminD deficiency, especially in elderly patients.

To study this hypothesis, a study wasperformed on two groups for a period of twoyears, aiming at determining the vitamin leveland the risk potential in the appearance ofhyperparathyroidism as side effect [27]. VitaminD, parathormone and bone biological markershave been assessed every season. The level of 25-

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parathormonul i markerii biologici osoi au fostevaluai n fiecare sezon. Nivelul 25-

hidroxivitaminei D a crescut pe perioada verii,avnd o valoare semnificativ ridicat n grupulcontrol n al doilea an. De asemenea, pe perioadaiernii s-a observat o scdere a 25-hidroxivitaminei D n ambele grupuri, cu oscdere semnificativ n cazul utilizatorilorproduselor de protecie solar. Nu au fostsemnalate modificri semnificative aleparathormonului, fosfatazei alcaline totale,osteocalcitoninei, hidroxiprolinei urinare i acalciului urinar. Astfel n urma rezultatelorobinute s-a demonstrat c produsele defotoprotecie utilizate cu un FPS de 15 audeterminat o scdere minor a nivelului 25-hidroxivitaminei D, valoare care nu poate ficorelat cu inducerea secundar a hiper-paratiroidismului.

Trimiterea pacienilor la saloanele de bronzatartificial cu scopul de a preveni deficitul devitamina D nu este susinut tiinific. Pentru ceamai mare parte a populaiei, expunereaincidental la soare, combinat cu o dietechilibrat n vitamina D, ofer suficiente rezervede vitamina D pentru tot anul [28].

Persoanele care sunt predispuse deficitului

de vitamina D sunt vrstnicii, obezii, cei careprezint fotosensibilitate i cei care locuiesc nrile nordice.

Academia American de Dermatologierecomand o doz zilnic de vitamina D de1000UI, obinut din suplimente sau diet.Pentru evitarea supradozrii vitaminei D esteindicat s nu se depeasc o doz maxim pe zide 2000 UI.

Noile reglementri FDA

Un produs este considerat rezistent la ap

dac FPS este meninut dup imersia de 40minute (2 imersii a cte 20 minute), iar un produseste considerat foarte rezistent la ap dacmenine FPS dup imersia de 80 minute (4 imersiia cte 20 minute). De asemenea denumirile deimpermeabil la ap i impermeabil latranspiraie (engl. waterproof respectivsweatproof) sunt nlocuite cu rezistent la ap(engl. waterresistant). Pe ambalajul produselorde protecie solar se va specifica noiunea despectru larg (engl. broad spectrum) dac

hydroxyvitamin D has raised in summer, beingsignificantly higher in the control group in the

second year. Likewise, during winter time adecrease of 25 per cent of the level of 25-hydroxyvitamin D took place in both groups,with a significant decrease in users of sunscreenproducts. No significant changes were noted inparathormone, total alkaline phosphatase,osteocalcitonin, hydroxyproline and urinarycalcium. Therefore, the results of the studydemonstrated that products with SPF equal to 15determine a minor decrease of the level od 25-hydroxyvitamin D and this value cannot becorrelated with secondary inducement of

hyperparathyroidism.The method of sending patients to artificial

sunbathing solariums in order to prevent vitaminD deficiency is not scientifically supported. Formost part of the population, incident sunexposure, combined with a vitamin D-balanceddiet, ensures enough vitamin D reserves for therest of the year [28].

Persons most prone to vitamin D deficiencyare the elderly, the obese, people withphotosensitivity or originating from northerncountries.

The American Academy of Dermatologyrecommends a daily dose of vitamin D of 1,000UI, either as adjuvant or in the food diet. To avoidoverdose, a maximum daily quantity of 2,000 UIis indicated.

The new FDA regulations

A product is considered water-resistant if theSPF is maintained after immersion for 40 minutes(2 immersions of 20 minutes), and it is highlywater-resistant if the SPF is maintained after

immersion for 80 minutes (4 immersions of 20minutes). Phrases like waterproof andsweatproof, respectively, are replaced bywaterresistant. On the package of sunscreenproducts the label containing the phrase broadspectrum shall be applied in case of both UVA-and UVB-protection products.

Only photo-protection creams with aminimum SPF equal to or higher than 15 werefound to be effective in reducing the risk of skincancer and skin ageing. Non-broad spectrum

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protecia preparatului este att pentru UVA ct ipentru UVB.

Numai cremele de fotoprotecie care au unFPS cu o valoare de minim 15 s-au dovedit a fieficiente n reducerea riscului de cancer de pielei a fotombtrnirii cutanate. Produsele care nuau un spectru larg sau cele care au un spectrularg, dar un FPS cuprins ntre 2 14 ofer doar oprevenie a arsurilor solare i nu s-au dovediteficiente n reducerea risculi de cancer de pielesau a mbtrnirii cutanate [29].

O analiz recent ntre utilizarea produselorde protecie solar i expunerea la soare, a artato cretere a expunerii intenionate la soare ntre13% i 39% [30].

Academia American de Dermatologierecomand utilizarea cu regularitate a produselorde protecie solar pentru prevenirea canceruluide piele. Este important alegerea unui produscare s ofere un spectru larg de protecie, care saib un SPF 30 i s fie aplicat corect zilnic.Totodat este necesar educarea pacienilor ipromovarea unor metode de sntate publicprivind ncurajarea utilizrii produselor defotoprotecie.

Provocrile majore pentru viitor se refer lanecesitatea unei alinieri internaionale a regle-

mentrilor privind preparatele de fotoprotecie iinformarea pacienilor cu scopul utilizarriioptime a acestor produse.

products or broad spectrum products with SPF of2 to 14 only offer sunburns prevention and did

not prove efficacious in reducing skin cancer andskin ageing risks [29].One recent study on the use of sunscreen and

sunprotection products has shown an increase indeliberate sun exposure of 13 to 39 per cent [30].

The American Academy of Dermatologyrecommends consistent use of sunscreenproducts for the prevention of skin cancer. Thechoice and daily adequate application of a broadspectrum sunscreen product with an SPF of 30 isof great importance. It is also necessary toeducate the patients and promote public health

methods that encourage the use of photo-protection products.Major future challenges refer to the necessity

in our country to meet new internationalregulations regarding sunscreen products and toinform patients as to the adequate use of suchproducts.

Bibliografie/Bibliography1. Blasi P, Schoubben A, Giovagnoli S, Rossi C, Ricci M, The Real Value of Novel Particulate Carriers for Sunscreen

Formulation, Expert Rev Dermatol, 2011, 6 (5): 509-517.2. Jain SK, Jain NK. Multiparticulate carriers for sun-screening agents. Int. J. Cosmet. Sci, 2010, 32, 8998.3. Mitchnick MA, Fairhurst D, Pinnell SR. Microfine zinc oxide (Zcote) as a photostable UVA/UVB sunblock agent.

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4. Pinnell SR, Fairhurst D, Gillies R, Mitchnick MA, Kollias N, Microfine zinc oxide is a superior sunscreeningredient to microfine titanium dioxide. Dermatol Surg 2000; 26: 309-14.5. Kullavanijaya P, Lim HW. Photoprotection.J Am Acad Dermatol 2005;52:937-58, quiz 59-62.6. Palm MD, ODonoghue MN. Update on photoprotection, Dermatol Ther 2007; 20: 360-767. Moseley H, Cameron H, MacLeod T, Clark C, Dawe R, Ferguson J. New sunscreens confer improved protection

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Conflict de interese Conflict of interestNEDECLARATE NONE DECLARED

Adresa de coresponden: Clinica Dermatologie II, Spitalul Clinic Colentina, Bucuretios. tefan cel Mare nr. 19-21 Bucureti

Correspondance address: Clinic of Dermatology II, Colentina Clinical Hospital, Bucharesttefan cel Mare street no. 19-21

11. Perugini P, Simeoni S, Scalia S, Genta I, Modena T, Conti B, et al. Effect of nanoparticle encapsulation on thephotostability of the sunscreen agent, 2-ethylhexyl-p-methoxycinnamate. Int J Pharm 2002; 246: 37-45.

12. Sambandan DR, Ratner D. Sunscreens: an overview and update.J Am Acad Dermatol. 2011; 64: 748758.13. Lademann J, Schanzer S, Jacobi U, Schaefer H, Pflucker F, Driller H, et al. Synergy effects between organic and

inorganic UV filters in sunscreens.J Biomed Opt 2005; 10: 14008.14. Wright MW, Wright ST, Wagner RF. Mechanisms of sunscreen failure.J Am Acad Dermatol 2001; 44: 781-4.15. Ullrich SE. Photoimmune suppression and photocarcinogenesis. Front Biosci 2002; 7: d684-703.16. Yaar M, Gilchrest BA. Photoageing:mechanism, prevention and therapy. Br J Dermatol 2007; 157: 874-87.17. Seite S, Fourtanier AM. The benefit of daily photoprotection.J Am Acad Dermatol 2008; 58: S160-6.18. Darvay A, White IR, Rycroft RJ, Jones AB, Hawk JL, McFadden JP. Photoallergic contact dermatitis is uncommon.

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nanoparticles on human dermal fibroblasts and how to protect cells. Small 2009; 5: 511-20.21. Lai JC, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, et al. Exposure to titanium dioxide and other

metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts. Int J Nanomedicine 2008;3: 533-45.

22. Nash JF. Systemic effects of topically applied sunscreen ingredients. In: Clinical Guide to Sunscreens andPhotoprotection. Lim HW, Draelos ZD (Eds). Informa Healthcare, 2009, 139154

23. Janjua NR, Mogensen B, Andersson AM, Petersen JH, Henriksen M, Skakkebaek NE, et al. Systemic absorptionof the sunscreens benzophenone-3, octyl-methoxycinnamate, and 3-(4-methyl-benzylidene) camphor after whole-body topical application and reproductive hormone levels in humans.J Invest Dermatol 2004; 123: 57-61.

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