Sunscreen (2014)

CHAPTER 25
SNE RCSNU
Guido Bens
Departmn o f ,ygol tamreD Orleans Rgio ,latipsoH ,snaelrO .ecnarF
Email: rjsnael o-rhc@sneb.odiug
Abstrac : Sunscre have becom since more than 40 years the most poular means of
aginstproec UV raditon(UVR) Westrncoui. Oga d inorgac
exist.flrThywpcum abond r UVR.scateProin
from UVB is quantifed as a minal erythma dose-ba sun protecin factor.
A tesing UVproc les :dezi radn ts and pigmetcrlk Psn
htgnel vaw are yltner uc used .sdohtem gnitekraM of andlbeig sne rcsnu yalrednu
natiol regu whc explains mjor diferncsbtw h European d the
US market.sunc So inperfmg Boadvt.sub
spectrum UVB and A UV protecin and regula aplicton in suficent amounts
are esntial for prevntio of skin caners, -induce UV ,nois erp uson m i
and skin agin. A signfcat benfit from regula suncre use has not yet ben
demonstra for primay prevntio of basl cel carinom and melano.
Concerig the prevntio of actin keratos, squamo cel ,samonicra and
skin agin, the efct of suncre i signfcat, bu it remains .et lpmocni Some
UVorganic fltes(PAB ,sevita red ,setam n ic ,seno hpozneb and )en lyrcot
have ben describ to cause .ygrel aot hp Percutanosbpi d endocri
disruptng acvy of smal-izedorgnc ad nao-sized rgc UV filters have
ben repotd. On lesiona skin and in pediatrc seting, thes products should be
used with caution. Cutaneos vim D synthei dpg on cinego icra -niks
UVB raditon, the potenial risk of vitamn D deficny by suncre use has
becom a major subject of public healt debat. Sunscre id impar vitamn
D synthei if they are used in the recomnd aut of ,-mc/gmZ but not in
lesr thicknes below 1.5 ?mc/gm tha corespnd betr to what user aply in
real life condits. Large molecuar last genratio UV B- Abroad spectrum
suncre have a betr benfit-rsk ratio than forme organic filters: They ofer
betr protecin in the A UV band, they are no toxic and no alergnic. A betr
outcme of suncre eficay espcialy in primay skin caner prevntio may
be achievd with thes molecus.
Sunlight, Vitamn D and Skin Cancer, Second Editon, edit by Jorg Reichrat.
©20 14 Landes Bioscen ad Springe s eni uB+ecn i S Media.
429
430 SUNLIGHT, VITAMIN D AND SKIN CANCER
INTRODUCTION
Sunscre ns rea organic or inorganic filter sub tances for topical ap lication ont the
skin. heyT have orig nal y be n dev loped for prev ntion of solar erythema. Since other
detrimental ef cts o f ultraviolet radi t on (UVR) have be n identif ed such as skin agin,
cutaneous im unosup res ion and car inoge si , sun cre n user and dermatol gist
exp ct sun cre ns ot be ef ic ent also ag inst thes problems. Howev r, a crit cal review
o f het pres nt litera u e shows that thes exp ctancies are only partial y true. More v r,
ther has be n omes con ern about safety of sun cre ns. With increasing evid nce of
anti- inflam tory nda anti- umor ef cts o f vitam in D that is p h o t s y n t h e s i z e d in the skin,
a poten ial iskr o f inducing vitamin D defic en y by sun cre n use has be n discu ed.
The fol wing revi w details chemical and phot biol gical pro e ti s of dif er nt
ultraviolet (UV) ilters,f labe ing, regulation and marketing aspect, and it discu e the
perfo mance o f sun cre ns gainst dif er nt efcts ofUVR as wel as their ben fit-r sk ratio.
UV RADI T ON
Natural y oc ur ing UVR from the sun has be n div de into two broad band regions:
low-en rgy UV A (with wavel ngths of320 to 40 nm) and hig -en rgy UVB (280-320
nm). Relative ef ctiven s of dif er nt wavel ngths in producing a biol gic reaction is
cal ed action spectrum for this particular reaction. The most obvious acute reaction of
white skin to UVR is e r y t h e m a which is c o m o n l y ad res d to as "sunburn." The action
spectrum of solar erythema lies mainly in the UVB band region, with a peak at 295 nm,
and rapide decline toward the UV A region ( F i g . 1 ): 295 nm UVB radi t on (UVBR) is
about 10 times more erythemogenic than short-wave UV ~R. U n d e r normal condit ons,
10
80
90
,
~. 70
c
.~ 60
t;:
a; 50
. .~
. 40
sa
3G 30
0:
20
. -
10
O+- - . . - .. - . - .. -~-----;;;;:=
280 290 30 310 320
Wavel ngth [nm]
1-.· .-.- .• Br ehtyrE- * .*.v~mn03sYnthes~J

Figure 1. Action spectrum of naturl tersic UVR for solar erythma and vitamn D 3 synthei.
(adpte from ref. 3).
SNE RCSNU 431
mid le and long-wave UV AR do not induce sunb rn. UV AR has ther fore be n further
broken down into two bands UV Al (340-40 nm) and UV A2 (320-340 nm) because of
the increased erythemogenic activ ty ofUVA2 compared with UVAI.
Solar radi t on is sign f cantly modif ed by the arth'se atmospher with ozne in the
stra ospher being the major phot protec ive agent tha absor al hig -en rgy cosmic
radi t on, UVCR (20 -280 nm) and short-wave UVBR up to 290 nm. Clouds, pol utan s,
and fog furthe mor decr ase UVR by scat ering and absorpti n. Howev r, UV AR and
visble light (VL, 40 -760 nm) are much les af ect d by the way through the atmospher .
Les than 5% o f het sunlight tha reach s the earth's surface is U V R , with a ratio ofUV A to
UVB of about 20: 1, dep ndi g on geo raphical latiude, altiude, sea on of the year, time
o f day, and met or l gical condit ons.' UV AR but not UVBR trave s window glas and
is ther fo e pres nt also indor. UV exposure does not only oc ur by direct sun hi e on the
skin, but also by difuse ir ad tion, or by light refl ction on the ground. Direct sun exposure
may rep sent more than 50% of UV ir ad tion in very specif condit s, e.g, around
mid ay on a cloud es sum er day. utB ti amounts to les than a quarte of cum lative
yearly UV exposure, dep ndi g on the an tomical region (15% for het face, 9%1 for the
neck, 24% for horiz ntal body surfaces such as the vertx). Dif use ir ad tion on cloudy
days or in the hades is with 80% the main contributor to the yearly exposure dose, althoug
this type of ir ad tion is not consider d to be sun exposure by m o s t ind viduals.' Dif use
and refl cted ir ad tions contain mainly wavel ngths in the UV A band.
EF ECTS OF UV RADI T ON IN HUMAN SKIN
UV A pen tra es de per into the skin than UVB does ( F i g . 2 ): heT major part (70%)
ofUVB is a b s o r b e d or scat er d by the stratum corneum. Twenty percent ofUVB reaches
Figure 2. Pentraio of UV raditon into the skin.

Delayed tan ing

VitaminD3
synthesis
.ni aleM
t synthei
DP
IPD (10min
(>2h)
~ 2h)
293
t
Figure 3. Biolgc efcts of UVR in human skin.
liv ng cels in the epidermal spinous layer and 0%1 superfic al dermis. UV AR and vis ble
light are les filter d by stra um corneum, but after absorption by melani , 30% ofUV A
hits bas l cels of epidermis and stil 20% reaches reticular dermis. One percent ofUV Al
pen tra es up to the imtsl o f subc tis.'
Posit ve and harmful ef cts ofDVR in the skin are tightly woven as they contribute
to the natural mechanism o f phot protec ion. UVR that is not scat er d by the superfic al
horny layer is absorbed yb endogenous chrom phores. Phot chemical reactions of thes
absorbing biom lecules result in altera ions of skin biol gy tha lead to the im ediate
or d e l a y e d UV ef cts rep sent d in F i g u r e 3 .
Epidermal chrom phores with absorption spectra within the DVB range are urocanic
acid, melani , arom tic amino acids such as tryp o hane and tyrosine in epid rmal proteins,
and nuclear DNA.4 A major target for UVB and UVA2 are nucleotides. Absorption of
UVR yb p y r i m d i n e and purine base result in DNA phot product formati n, mainly
pyrim dine dimers, but also pyrim dine (6-4) pyrim done phot products. Thes DNA
phot products rea conti uo sly excised by DNA repair enzymes. I f repair fails, they
can lead ot p53-mediated apo t si or, after replicat on, to DNA muta ions.' C®T and
C ®T muta ions are consider d as a nuclear fmgerp int ofUVB-induced phot dam ge.
DVB-gen rated thymine dimers induce p53 which is a pro-apo t ic protein that helps
to elim nate cels in which DNA is to heavily dam ged to eb repaired.' DVB trig ers
in the skin het production of cholecal iferol (vitamin D 3 ) romf 7-dehydroch lest rol
(DHC). heT action spectrum for hist synthesi is nearly identical to the one for solar
erythema ( F i g . 1 .) UV A alone does not permit cutaneous vitamin D 3 synthe is." DVB
exposure stimulates mito ic activ ty in epidermis and, to a les r extn, also in pa il ary
dermis that persi t from aysd to we ks. This result in ac nthosi and hyperk atosi
with na ap roximate 2-fold thickeni g of thes skin layers that is b e s t char cterized by
SNE RCSNU 43
the German t "Lichtswel (g-ndu calosity"). Th penomrvids

suplemntary UV protecin to the underlyig livng cels. A UV does not induce such
epidrmal thickeng.
While UVB efcts in the skin ocur by direct UVB photn absorptin y the targe
,seluc om UVA efcts ar mostly mediat by the noitamrof of :slacidar 1
Absorptin f
AR byUV etairpo a serohp morhc sucha NADH,idurocn ,snivalf and ustre
lipds promtes thes molecus into an excitd stae. Dispaton of this enrgy ocurs
eithr by interal covswhi may genrat organic dl, or, more ,yltneuq rf
by reaction wh tisular oxygen r gni atnoc- egyxo molecuswhi leads to noitamrof
of so-caled rtiv oxygen speci (ROS). 7
ROS are unstable d extrmly chia
reactiv molush can cause lipd neroxat plasm, nucer ad lairdnohc tim
.senarbme They can dmgecluarpotins e DNA strandbek oxidatn
of nuclei ".sdica heT gnid opser oc cits re ca h DNA tnirp egnif is eni augyxordyh-8
whic genrats G:C®TA mutaions by ero pairng of eni augyxordyh-8 with adeni
instead of cytosine during gniwol f .noitac lper Thes mutaions gerd by oxidatve
stre do not induce p53 nda escap therfo more easily to apotic contrl than
decu ni-BVU ",snoita um setyconaleM sem to be more senitv o A-induce UVDN
damge thn ?'.setyconitarek Pyrimdne s are not only formed by direct UVBR but
also by oxidatve sr after A UV .noita d r i DNA repai of pyrimdne s induce
by AR UV is les efctiv han excison rpa ofUVB-induce DNA damge."
In respon to -induceUV damge to DNA and other chrompes, ytkin and
inflamtory eds are relasd into the skin folwing 2I.RVU This is responibl
for sunbr as acute clina efct of overxpsu t sunlight.
DNA damge by UVB or A2 UV triges a tanig respon in human skin."
Nucleotid fragmns eovd frm the DNA after pi active mlnoy rs,
the key enzym in melanogsi. 13.4 UVBR sem to be most efctiv in stimulang de
nov melanogsi from pre-xistng melani moners and precuso. Melanocyt
denrits loga nd branch, melos nubr ad size ncra, d their ansf
from melanocyts to keratinocys is enhacd. This result in delay tanig tha
becoms visble withn 3 days after UV exposure." Melani is a large opaque molecu
absoring throug the UV and visble light band. It is photsable, i.e, it converts
the absored enrgy into heat rathe than into chemial enrgy.' Both constiuve and
induce mla pigento rc aginst -duceUV DNA damge. A-inuc UV
tan sem to be les proteciv than the one induce by 5I.BVU This may be explaind
by the more basl locaiztn ofUV A2-induce pigmentao d the lack of epidrmal
thickeng afr AR. UV A2,UV AI, UV and short-wave ibl light also induce another
kind of pigment reaction after exposur: In lite dose, thes wavelngths genrat
a greyish skin colr withn 15 min after exposur tha is caled imedat pigment
darkenig 21.)DPI( tI progesivly declins and disaper wthn 2 hours. Higher A UV
dose induce a longer-stadi pigmentao of more brownish colr caled persitn
pigment darkenig (PD) tha persit after 2 hours. IPD and PD do not repsnt de
nov melani synthei, bu they are a product of phot-xidan f pre-xistng mla
and precuso in presnc of oxygen. Neithr IPD nor PD provide protecin aginst
UV-induce skin damge.
Pentraig up to the dermis, AR UV is responibl for photagin changes: The
action spectrum for thes degrain mechanis lies mainly in the UV A 1 band. UVB
alone ds not induce photag.AUV induces a seri of matrix helopns
degrath dermal cogn ",krowemarf The prsnc of colagen dtrius hb emal
43 SUNLIGHT, VITAMIN D AND SKIN CAN ER
proc l agen synthesi and ther by ag r vates the deg n rative proces ." UV A-induced
oxidat ve stre also increas elastin mRNA levs in dermal fibro last whic explains
the elasto ic changes tha are char te is c of phot aged skin.'?
Both UV A and UVB aveh im unos p res ive poten ial evn at suberythemal
doses:" After UV ir adi t on Langerhans cels in the skin are dim n shed in number, and
their morphol gy and functio are alterd. This ef ct is used for therap utic pur ose
in dermatol gic phot erapy. UV A sup res delay d-t pe contac hypers n it v y 91.
Nghiem et al. showed in a mouse model tha evn established sy temic im une respon e
is impaired by short-wave UV 02.A Dami n et al. studie a nickel model of recal contac
hypers n it v y in humans tha was explored with a seri o f nar owband UV ir ad tions.
They found two peaks of im une-sup res ive ef ctiven s : the most importan one was
situa ed with n the UVB waveband (30 m),n the other one in the UVAI band region
(370 nm). As UV A lR rep s nt a far great r amount o f sunlight than UVBR, the authors
con lude tha wavel ngths around 370 nm are respon ible for most of UV-induced
im unos p res ion by natur l light. 12
The 20- fold increas d risk o f skin in therap utical y can er im unos p res d organ
transplant patien s sug e ts a role o f het im une sy tem in prev nti g those skin tumors.
Phot -induced im unos p res ion is ther fo e thought to contribu e to the car inoge ic
ef ct of UVR. The mutagenic action of UVR is physiol gical y contr l ed yb sev ral
mechanism : DNA repair enzymes in first line, pro-ap to ic regulation, .g,e by p53, in
second line, and cel u ar im une defns in third line. UVR anc afect each one o f thes
thre defns lines: UV AR ash enb shown ot inh b t DNA repair enzymes."! henW
muta ions con er the p53 gen, apo t si contr l si impared, nda actin keratose ,
squamo s and basl elc car inomas may arise." When UV - induced DNA muta ions hit
the patched gen, this can contribu e to the car inoge si ofbas l elc car inom ." Final y
the UVR-induced cutaneous im unos p res ion proba ly con er s in the same way
loca anti- umor im un ty, althoug this has not be n demonstra ed in h u m a n skin so ar.f
DETRIMENTAL EF ECTS OF SOLAR RADIATION BEYOND

THE UV SPECTRUM
VL and near infra ed radi t on (IRA, A = 760-14 0 nm) ac ount resp ctively for
4 nda 30% of solar radi t on reaching the skin, thus for much more hant UVR. VL and
IRA pen tra ion reach s dermal struc res.' VL has be n shown to induce ROS and
matrix-degrading enzymes but no thymin dimer formation." It stimulates pigmenta ion
in darke phot ypes, but cel transforming ef cts have not be n document d evn
in fair-sk n ed people." IRA gen rates dermal mitoch ndrial ROS leading to matrix
metal opr teinase activation." VL and IRA thus sem to contribu e to skin agin but
not to skin can er formatin.
TOPICAL PHOTOPROTECTION AGENTS
The numerous del t rious efcts ofUVRmake protec ive measures nec s ary. Total
avoidance and protec ive clothing are withou any doubt the most ef ctive methods but
they rea not practi able for daily consequ nt protec ion. For this reason topical y ap lied
sun cre ns are since more than 40 years the most used phot protec ive means.
SNE RCSNU 435
Suncare products are av il b e as ils,o creams, lotins, spray, els,g and ticks.
The prays form is les recom end as it leads to unequal and insuf ic ent ap lic t on.
Sunscre ns are comp sed o f dif er nt UV filter agents and, dep ndi g on their galenic
pres nta io , o f moistur ze s, conservati es, and often altern ive phot r ectan s such as
antiox dants. UV protec ion increas with filter con e tra ion ni sun cre ns, but toxic ty
and po r cosmetic ac eptance limt UV filter con e tra ion for in vio use in human beings.
Clas ic recom endation orf sun cre n use is to aply 15 to 30 min befor sun exposure
and to rep at ap licat on ev ry two hours. The product has to be reap lied earlier after
activ y tha aym wash or rub o f the sun cre n, i.e, after swim ng, sweating or t o w e l
drying. "Water- esi tan " suncare products are defm d sa maintain g intac protec ion
after two 20 min exposure to w a t e r wher as "very water- si tan " sun cre ns protec
after four 20 min water im ersions." For water resi tance tes ing, subjects do not towel
tes site after water exposure so tha a main factor o f ef ica y los by bathing in the
real life is not as e s d by this prot c l. The term "remane ce" describes a sun cre n's
resi tance to ext rnal elim nation by water, sweat or rub ing. Tightly related to reman ce
is a p r o d u c t ' s "sub tan iv ty" tha char cteriz s the cap ity o f a filter sub tance to fix to
struc es in the up er epid rmis whic ensur a long lasting action.
MEASURING PHOT PROTECTION
The sun protecin factor (SPF) o f suncre exprs their capity o f protecin from
eryth ma after UV exposur. SPF therfo sentialy ranslte rotecinp from UVBR.
For SPF tes ing, erythema is induced by a xeno lamp solar simulator. The smal est
dose causing a min mal y perc ptible erythema with wel -defm d borde s at 24 hours
after neo single ir adi t on is cal ed min mal erythema dose (MED). Basic MED mainly
dep n s on the ind v ual's natur l phot protec ive poten ial provide by consti u ve
and ad ptive pigmenta ion and skin thicken g, but lsoa on vari ble par met rs such as
nutri on and drug intake. The stand r product dose for SPF tes ing is 2 mg of malized
sun cre n per em? of skin. The amount of 2 mg/cnf is an industrial stand r without
scient fic basi. SPF is a ratio cal u ated from the fol wing formula:
MED with the tes d sun cre n

SPF=
MED without sun cre n
This MED-related procedure has the advantage compared with in vitro

spectroph tome ry ot be directly related to the biol gic consequ nces of UV exposure
in a given ind v ual. tI is based on the ind vi ual sen it v y to UVR at a given mo ent.
At least theor tical y, PFS permits ot estima e the factor by which sun exposure can be
ext nde in daily practi e until erythema thres old: I f het recom end dose of2 mg/cm-
is ap lied (whic si in gen ral otn the case!) and no ext rnal elim nation oc urs, a SPFIO
suncare product permits to stay ten times longer in the sunlight without erythematous
reaction than without this protec ion. Howev r, DNA dam ge and im unosup res ion
oc ur ven below het erythema threshold dose. Thes harmful ef cts are not consider
by SPF cal u tion." A second pitfal of the MED-based SPF labe ing is the fact that
erythema prev ntion by com ercial sun cre n products is not only due to filterng and
scat ering yb UV filters but lsoa due to inflam tory efcts of other ingredi nts such
10 0k
90%
:;i.
g 80%
'to ~ 70%
o uc
c'- 40° 6
8'~
U • (I> 0/ 5
6- .• .>g 40%
~ •e
.! 30%
~ 20 (I)
0k
10%
4.0 .. - -r- - - -r- - ---_--_
o 20 40 60 80 10
SPF
Figure 4. Reduction of eryth mogenic UVR by suncre.
as al ntoi , o-bisa ol , and 18-f3glycrhetin acid. The lat er anti- nflam tory
sub tances do not protec s from other harmful UV ef cts and may mi c a great r SPF
than the one the product would have achiev d based on tsi UV iltersf only."
The relation betwe n the perc ntage. o f filter d UVBlUVA2 radi t on and SPF is
a logarithm c and not a linear one ( F i g . 4 ). B e t w e n 195 and 052 cosmetic industry
gave a race to higher and higher SPFs, and great SPF numbers have become for the
consumer the first criterion of choi e betwe n dif er nt sun cre n products. Inde d UV
absorption increas from 0% to 90% betwe n a moisturizer without SPF nda a SPF10
sun cre n, but only romf 97% to 9% betwe n a SPF30 and a SPF10 product. To lim t
the implic t dec ption of the consumer by high SPF numbers which can lead to a false
hope of "complet " protec ion and sub equ nt over xposure to harmful phot dam ge,
sev ral countries have regulated sun cre n labe ing.
UVA protec ion is more dif cult to quantify than UVB-SPF, because UV A is
few erythemog nic. Cur ently ther is no inter ational y ac ept d stand r method for
measuring UV A protec ion by sun cre ns. The most com only used methods are in vio
PD measured by a stand r ized phot est" and crit cal wavel ngth (CW) as e s d in
vitro by spectroph tome ry. CW is d e f m e d as the wavel ngth below which 90% of the
sun cre n's UV absorbency oc urs as m e a s u r e d in the band region from 290 to 40 nm."
REGULATIONS AND MARKETING
Sunscre n marketing is submit ed to national legis at on. Thes regulations are

harmonized among the me ber stae of the European Union (ED) wher ap roved UV
filters are listed as cosmetics. Ef ica y requirem nts and labeling are regulated by the
European Com is on." In the United Staes, in contras , sun cre ns are consider d as
over-th counter drugs tha are subj ect o Fod and Drug Admin stra ion (FDA) regulation."
They must ther fore undergo considerable safety and al ergy tes ing in clin cal trials that
is respon ible for high cost to the manufacture s and importan delay before marketing
as c o m p a r e d with the ED wher new filter products can enter the market more rapidly.
SNE RCSNU 437
Especial y the last gen ration broad spectrum UVA-UVB filters are av ilab e in the EU
and other parts of the world since many years. In the US only one filter of this group,
Mexoryl SX, was ac epted in 20 6 as a comp ne t of certain sun cre n formulations,
but it is not ap roved as an ind vidual UV filter.
In het EU market d sun cre n products have to provide both a min mal UVB-SPF
of 6 and a broad spectrum protec ion covering the VU A and.b UV A broad spectrum
protec ion is d e f m e d as a "UV A protec ion factor" o f ta least 1/3 o f het SPF as obtained by
the PD method, and a CW of370 nm or more," The SPF values to be used in sun cre n
labe ing are lim ted to 6, 10, 15,20,25, 30, 50, and 50+. Products with an SPF of60 and
more have to eb label d "SPF50+." ef ica y The ofUV protec ion must furthe more be
ind cated on the labe by ref renc to the categories "low," "medium," "high," and "very
hig ." Thes categories are defined as a stand r ized degr e of protec ion ag inst UVB
and UV A ( T a b l e 1 .) UV A protec ion is ind cated on the labe by het acronym "UV A"
enclosed with n a cirle.
In the US the FDA put forwa d in 201 a new final rule on labeling and ef ctiven s
tes ing of sun cre n drugs which has become ef ctive June 18,2012: SPF labe ing in the
US is not lim ted to 8 values as in Europe. The FDA pro se to cap het maximu SPF
labe at "50+" as in the EU, but this is only a recom endation and not part of the fmal
rule. UV A protec ion is ind cated by the term "broad spectrum" tha has be n precised to
require a CW o f at least 370 DI. The PD method is not ap roved for VU A protec ion
tes ing in the us. " B r o a d spectrum" and SPF labes should be printed in the same font and
col r and ap ear in the same line, or im ediately next to ache other.f Only sun cre ns
with broad spectrum and SPF :2 15 are al owed to claim protec ion from skin can er and
early skin agin. Other products may only claim sunb rn protec ion.
In both the EU and the US, claims such as "to al sun protec ion" or "sun block" are
forbid en on sun cre n products. To date, 29 UV filters are ap roved in the UE and 17
in the us. T a b l e 2 gives an over iew of thes sub tances that wil be discu sed in the
fol wing sections.
ORGANIC UV FILTERS
Organic UV filter sub tances mainly act by absorption of phot ns in the UV

wavel ngth band. They are aromatic molecules conjugated with carbonyl groups. Thes
chrom phores absorb UV phot ns through el ctron resona ce de loca iz t on in het
arom tic comp unds tha raise the molecule from the el ctronic ground singlet stae
So into an excited el ctronic stae SI or hig er. In most clas ic UVB absorbe s such as
PAB this leads to a transitory polarization of the organic molecule ( F i g . 5 ). Organic
UV filter molecules capture phot ns of a more or les specif wavel ngth A around their
absorption maximu . No organic UV filter, esp cial y not the "clas ic molecules," cover
the entire UV spectrum. For this reason, fmalized sun cre n products are in gen ral an
as ociat on of sev ral filter sub tances. The absorbed en rgy is dis pated by vibronic
relax tion tha deliv rs heat via col is on with het sur oundi g medium." A minor part
o f en rgy may also be emit ed in ormf of fluoresc nt radi t on (A = 4 0 - 7 6 0 nm), e.,L
VL, with wavel ngths that are longer than those of the in t al phot n. Although this kind
o f radi t on is harmles , it has to be lim ted for the cosmetic ac eptance of the UV filter.
Energy rel ase permits the excited filter molecule to return to its ground stae wher it
is a g i n av ilab e to absorb ad it onal phot ns. Filters that rep at perf ctly this cy lical
Table 1. Sun protec ion categori s of sun cre ns as defm d by the European Com is ion"
In Vivo Minmu UVA-PF as Measurd
Labeld Category Labeld SPF Measurd SPF by the PD Protcl Minmal Critcal Wavelngth
"Low protecin" 6 6 to 9. 1/3 of labed SPF ~ 370 nm
10 10 to 14.9 for al categoris for al categoris
"Medium protecin" 15 15 to 19.
20 20 to 24.9
25 25 to 29.
"High protecin" 30 30 to 49.
50 50 to 59.
"Very hig protecin" 50+ 60 and more
SNE RCSNU 439
Excited stae
Intramolecular
elctron· transfer Relaxtion
t
Ground stae
HO. ~-D-{
. -/
RBVU
PAB
Figure 5. Mechanism of UVB absorptin by the "clasi UV filter PAB.
proces without undergoing sign f cant chemical change are clas if ed as phot s able.
Phot s able filters can retain their UV -absor ing potency during long exposure .
The excited form of filter molecu s after UV absorption has to be very short-lived
in orde to prev nt chemical reactions betw en the filter and tis ular proteins or
oxygen whic could lead to phot al ergic or phot xic reaction. Unfortuna ely such
reactions, mainly phot al ergy, have be n described rep atedly with PAB derivat es,
cin am tes, and benzopheno es.": Sev ral molecu s have enb withdrawn. The
phot sen it za ion to benzopheno -3 (oxybenzo e) is particular y sevr, because
phot al ergic cros - eactions are known with benzopheno -4 (another broad spectrum
filter), topical y ap liedk topr fen, and evn with sy temical y admin ster d fenofibrate."
In rec nt years oct rylen , a cin am te derivat e tha is frequ ntly incorp ated into
sun cre n formulations for both its UVB-UVA2 filter pro e ty and tsi phot s abil z ng
ef ct on other filters, has em rged as a new phot al ergen." In detail, thre dif er nt
pat erns of skin reactions to oct rylen have be n identif ed;" (1) young children
with alergic contac dermati s to oct rylen without phot reactiv y, (2) adults with
phot al ergic contac dermati s to oct rylen and history o f phot al ergy to ketopr fen,
and (3) asympto a ic adults with history of phot al ergy to ketopr fen and posit ve
phot pa ch tes from oct rylen withou clin a counterpa . The phot al ergic poten ial
o f oct rylen is not explained by chemical struc e sim larit es with ketopr fen but
rather by a phot induced reactiv y of oct rylen toward primary amines and alcoh s.
Octo rylen amides and estr may cros react with phot products of benzopheno e
derivat es such as ketopr fen or oxybenzone."
UV filters ap roved as active ingredi nts in sun cre n products in the European Union 901,)UE( in the United
Australia 01 )UA(
Max.
Auth. Abs. Permit ed
INCIName Abreviaton IUPACName Cone. Trade Name(s) Max. In Com ents
filters
PAB 4-Aminobenzoic acid 5% in @AB P 283nm EU,US, Bind g
EU; Au stratum
15% in god sub tan iv ty
US, Au god reman ce.
dimethyl PAB OD-PAB 2-Ethyl exyl 8% Eusolex @70 6 31 nm EU,US, Phot al ergic
p-dimethylamino-benzoate Escalo @705 Au
PEG-25 Polyeth l ne glyco 25 10% Uvinul @52P 310nm EU,Au
PAB aminobenzoate Unipabol ®71U
ethyl-4 benzoic acid
OMC 2-Ethyl ex -3 (4 10%; Escalo ®75 31 nm EU,US, Lipo hil c
Methoxycin am te methoxyphenyl) 7.5% in Uvinul @08CM Au used in
Octinoxate pro -2 enoate US Eusolex @29 with other
Neo eliopanH not phot s able
®VA pre ar tions
ParsolMCX@
- 2-Ethoxyeth l 3% 310nm US,Au
p-Methoxycin am te 3-( 4-methoxyphenyl)
pro enoate
IMC 3-Methylbutyl 10% Neo Heliopan 289nm EU,Au

p-Methoxycin am te 3-(4 methoxyphenyl) pro- @0 IE
2-enoate
continued
Table 2. Contiued
Max.
filters (conti ued)
CBM 3-(4'Trimethylam onium)- 6% Mexoryl @KS 295nm EU God phot s abil ty,
benzyliden-borna -2 also permit
on-methylsu fate other UV
BC 3- Benzyliden -borna - 2% Mexoryl @02-DS 295nm EU cin am tes
2-one Ultren @K9
Unisol @2 -S
Camphor BCSA Alpha-(2-0xob rn- 6% Mexoryl @LS 295nm ED
3 -yliden )toluen -4
sulphonic acid
4-Methylbenzyliden MBC 3 -(4' Sulfo )-benzyliden - 4% Eusolex @0 36 305nm EU,Au
borna -2 on Neo Heliopan
Enzac men @CBM
Parso150@
Polyacr -Amido ethyl - N-[2(and 4)-(2 ox b rn- 6% Mexoryl @WS 295nm EU
Camphor 3-yliden m thyl)-benzyl]-
acrylamide polymer
salicy te HMS 3, 3, 5-Trimethyl- 10% in Eusolex @SMH 306nm EU,US, Can reduc
cy lohexyl-sa icylate EU; Neo Heliopan Au phot degrad tion
15% in @SMH of oxybenzo e
US,Au avobenzo e
Octylsa icylate OS 2-Ethyl exylsa icylate 5% Escalol58~ 307nm EU,US,
Eusolex @SO Au
Neo Heliopan @SO
Uvinul @81-0
continued
Table 2. Contiued
Max.
filters (conti ued)
Triethanolamine TS Tris(2-hydrox ethyl) 12% US, Au UVB-absorbing
am onium an lgesic
salicy ate 2-hydroxybenzoate
Phenylbenzim dazole PBSA 2- Phenylbenzim dazol-5 8% in Eusolex @23 308nm EU,US, Hydrophil c
sulfonic acid EU; Neo Heliopan Au can improve
Ensulizole 4% in Hydro" phot s abil ty
US, Au Parsol @SH filters
Dimethicod ethyl- DBM Benzyliden malon te 10% Parsol @XLS 31 nm EU,Au Phot s able,
benzalm onate polysi oxane stabil ze
Polysi c ne-15
Triazone OT 2,4 6-tris[p-(ethyl exyl- 5% Uvinul @051T 314nm EU,Au
oxycarbonyl)anil o ]-
1,3 5-triaz ne
OC 2-Ethyl ex -2 cyano-3, 10% Eusolex @RCO 30 nm EU,US, Phot s able
diphenylacrylate Neo Heliopan Au to stabil ze
@30 Phot al ergic
Uvinul N-539 @T
Benzophen UVB-A2 broad spectrum filters
Benzoph ne-3 BENZ-3 2-Hydroxy-4 methoxy- 10% in Escalo @765 28 nda EU,US, Phot labie,
Oxybenzo e benzopheno e EU,Au; Eusolex @0634 325nm Au importan
6% in Neo Heliopan @B poten ial;
US UVAsorb @TEM "contains
Uvinul @04M to be printed
continued
Table 2. Contiued
Max.
INC Name Abreviaton IUPACName Cone. Trade Name(s) Max. In Com ents
UVB-UVA2 broad spectrum filters (continued)
Benzopheno e-4 BENZ-4 2-Hydrox -4 methoxy- 5% in Escalo57f) 28 and EU,US, God phot s abil ty,
Sulisobenz benzopheno -5 sulfonic EU; UVAsorb ®5S 36 nm Au phot al ergic
acid 10% in Uvinul MS40® reaction
US, Au
Benzopheno e-8 - (2-Hydrox -4 methoxy- 3% 352nm US, Au
Dioxybenzo e phenyl)-(2 hydrox phenyl)
methano e
filters
Methoxy- BMD 1-( 4-ter .Butylphenyl)-3 5% in Eusolex 02®9 356nm EU,US, Por phot s abil ty
Dibenzoylmethane (4-methoxyp en l)-pro an- EU,Au; Parsol ®9871 Au its pure form,
1,3-dion 3% in to eb stabil zed
US as ociat on
filters such as BC,
Polysicne-15
Butamido DBT 4,'-[(6«1 I-Dimethyl- 10o~ UVAsorb ®BEH 345nm EU
ethyl )-amino-carbonyl)-
phenylaminoj-I, 3,
5-triaz ne-2, 4-yl)
di m no]-bis (benzoic acid-
2-ethyl x est r)
Disodum Phenyl Dibenz- DPT 2,'-(1 4-Phenyl )-bis 10% Neo Heliopan 345nm EU,Au hydros lub e
Tetrasulfonate (IH-benzim dazol-4,6- Ap®
Bismdazylte disulfonic acid)
continued
Table 2. Contiued
Max.
INC Name Abreviaton IUPACName Cone. Trade Name(s) Max. In Com ents
filters (continued)
Hydroxy- DHB 10% Uvinul A @sulP 30 and EU phot s able
Benzoate 370nm
anthranilate - 5% 340nm US, Au
Meradimate
generation UVB-UVA2-UVAI broad spectrum filters
Terephthalidene MSX 3, '-(1,4 Phenyl edim th- 10% Mexoryl @XS 345nm EU,US, Hydros lub e,
Sulfonic yliden )bis-(7, 7-dimethyl- Au phot s able
2-ox bicy lo-
Ecamsule (2.- 2.1 )heptane-l methane-
sulfonic acid
MXL 2-( H benzotriazol-2 yl)- 15% Mexoryl @LX 30 and Eu,Au Lipos lub e,
4-methyl-6 (2-methyI3- 34 nm
(1,3- te ramethy 1-
1-( t r i m e t h y lsiy ox)-
dis loxany phenol ry 1)-
MBT 2, '-Methylen -bis 6- 10% Tinos rb @M 306 and Eu,Au Very phot s able,
Benzotriazolyl (2H-benzotriazol-2 yl)-4 360nm absorption
ethylbutylphenol (1, 3 -te ram thylbu )- hydros lub e
Bisoctrizole phenol
Bis-Ethyl exylo phenol BEMT 2,4-Bis [4-(2 ethyl exy- 10% Tinos rb @S 305 and Eu,Au Excel nt
Methoxyphenyltriazine loxy)-2 hydrox phenyl]-6 345nm oil solube,
Anisotriazine (4-methoxyphenyl)-I,3 5- resi tan
Bemotriz nol triazine
continued
Table 2. Contiued
Max.
filters
Dioxde Ti0 2 25% 307 nm EU, US, Excel nt
Au UVA2 coverag ,
UVAI
(micronized) ZnO 25% 360 nm EU, US, Go dUVA
inEU, Au ef ctive
US; Not explic t y
No the EC -ap roved
lim t in comp unds.
Au
INC = Inter ational Nomenclature of Cosmetic Ingredi nts; IUPAC = Inter ational Unio of Pure and Aplied Chemistry;
Maximu authorized filter con e tra ions; Abs. Max. = Wavelngth at whic maxi um absorpti n oc urs with the filter; USAN
Consider ng the large use of sun cre s, howevr, phot c ntac al ergi s to UV
filters remain relatively rae evnts. In the case of eczma in sun-expos d skin ares
tha aveh ben trea d with sun cre s, not UV -relat d contac sen it za on to UV
filters as wel as contac and phot c n a t alergy to other comp ne ts of sun cre s
besid the filters have to be elim nat d.
Some UVB filters such as cinamtes undergo after UV absorptin an intramolecu r
trans to cis isomer zation. Others exp ri nce defin t v struc al transformation whic
alters their protec iv capity. This is a major problem with the cur ently used UVA
filter avobenz whic lose considerably of its phot r ectiv poten ial after
ir ad tion in tsi pure form." As phot r ection by sun cre s is tesd by single
ir ad t on, the phot uns able char te of the con er d molecu s is not as e d
by stand r tes prot c ls. Phot uns able filters can be stabil zed by as oci t n with
other organic UV filters (se T a b l e 2 ) or with norgaic ilters.f
Clasic organic UV filters are lit e-siz d more ro les lipo h c molecu s. Thes
chemi al pro e ti s alow pen tra ion at least ntoi the de p r layers of the epid rm s
wher the filters may encou ter livng cels whic explains the inc de o f phot al ergy
as a clin a manifesta ion o f im unol gic reaction to filter molecu s having formed
haptens after phot ac iv t on. Percutaneo s sytemic absorpti n of organic UV filters
has ben repo ted for sevral ilterf molecu s: Sarveiya et al. found % 1 of topical y
ap lied oxybenzo in the urine o f 48 hours after sun cre use." Janju et al. det c d
oxybenz , octyl-methoxycin am te (OMC), and 4-methylbenzyliden camphor
(MBC), i.e, rep s nta ive molecu s o f 3 dif er nt familes of organic UVB filters,
in plasm and urine o f healthy volunte rs." In the US National Health and Nutri on
Examin t o Survey 20 3-20 4, benzoph -3 asw det c d in 96% ofurine sample
from the gen ral po ulation, with con e tra ions eingb hig er in women than ni men
and hig er in no -Hispan c whites than in no -Hispan c blacks." One or more organic
UV filter has ben det c d in 85% o f human milk sample in Switzerland betw n
204 and 206. 3 4 heT det c ion o f organic UV filters in urine and human milk was
only in a part o f case actuly relat d to the use o f sun cre s. UV filters are pres nt
in sevral cosmetic products such as shampo, hair spray, lipst ck , and make-up, as
wel as in clothes, washing powder, and evn in furnite. In al thes products, UV
filters may be ade as pres vati es aginst 4 .RVU heT pen tra ion of sy temical y
absor ed sun cre s into the organs nda heirt clear nce have nev r ben ased.
Ther is confli t g dat con er i g the existnc o f endocri e disrupt ng pro e ti s
o f suncre: Sevral ni vitro and animl in vio tudies staed estrog n-like or
anti- drogen activy, efct on rep oductive organs, on dev lopment, and on the
hypot al mic-p tu ary-th oid axis ofbenzopheno - 3, 3-benzy liden camphor, MBC,
OMC, hom sal te, aD-PABA, and PAB. 4
Thes result are not confirmed by other
authors (revi wed in ref. 4). In particul , estrogen-like activ y was not found ni
human adults." Sunscre absorpti n and endocri e activ y have nev r ben examined
in pre ub rtal children who are not only more prone to sy temic absorpti n than adults
but are also more sen it ve to low levs of horm ne action due to their low levs of
endog us rep oductive horm nes.
For thes pentraio problems, the use of the above mentiod organic UV filters
is otn recomnd for young children who have an imature straum corneum and
for patiens with pre-xistng skin lesion tha may go along with an imparent of the
epidrmal barie functio. In thes two groups o f user, pen tra io o f tradionl organic
filters is probaly yet more importan than for the genral skin-healty adult poulatin.
SNE RCSNU 47
Besid their pro er dermal pen tra ion, organic UV filters have ben shown to
enha ce topical pen tra ion o f herbic des and insect id s. This has ben demonstra ed
for the herbic des 2,4-dichlor p enoxyaceti acid and par qu t, and for the insect d s
par thion and mal thion. 45 The filters 0 D- PAB, 0 MC, hom sal te, octy I salicy late,
oct rylen , oxybenzo e, and benzopheno -4 (molecu s from 5 dif er nt chemical
subgro ps of organic UVB filters) wer tes d in a mouse model and ni human split
skin in vitro:" Al but oct ylen wer found to increas cutaneous pen tra ion of
the ap lied herbic des and insecti des. This findg is particular y al rming for
agricult ra worke s using pestic des who are encouraged to wear sun cre ns for their
outd or work, and orf fair-skin ed ind v uals from the temp rate zone who sek
to protec thems lves during a stay in tropical countries from both inte s sunlight
and insect atck.
By reaction with tis ular proteins, DNA or oxygen, phot uns able UV filters may
cause harmful or evn pro-ca inoge c efcts in the skin: In vitro studie found DNA
nucleotid dimer ormatinf to be enha c d under PAB treatment," UVR-induce
mutageni y to be increasd by isoamyl p-methoxycin am te (IMC), and tis ular radicls
to be formed by phot -degra d avobenz. Howevr, the in vio sign f ca e o f thes
findgs is doubtfl, and a reviw of avilbe clina dat con lude tha UV filters,
at least when used oc asi n l y, do not pose a human healt concern."
The first sun cre in the world aperd in 1928 in the US with het com er ial
introduc i n o f an emulsion tha contai ed the two organic UVB filters benzyl salicy te
and enzylb cin am te.' PAB was paten d in 1943. The main coner when the
first topical suncre wer dev lop d was to provide protec i n from UVB-induce
sunbr. During the folwing decas new chemi al filter familes with more and more
derivats wer devlop, and optim za on of their con e tra ion and combinat o
o f sevral filters with comple ntary absorpti n peaks alowed hig er SPFs. Up to
the 1980s, hig SPFs in a cosmeti al y pleas nt galenic pres nta io wer suf ic ent
to satify suncre user worldie. Absenc of UVA protec ion was tolerat d as it
provide desirabl ant withou risk of sunbr. With increasg evidnc about the
role of VU AR in the long-term eltriousd efcts of sun exposur, organic filters
with absorpti n maxiu in the UVA band range and benzoph nes being the irstf
VBIUA2 broad spectrum filters wer marketd. But benzoph nes provide only
insuf c ent protec i n in the ong-wavel UVAI band region. For phot labi ty and
dermal pentraio o f clasi organic filters, the above describ advers events-mostly
phot al ergy and conta dermatitis-were suc e iv ly repotd. Resarch ther fo
focused on the dev lopm nt of filter subtance provid ng both a maxiu o f product
safety and an absor ing coverag of the entir UV spectrum, but permit ng on the
other hand an as oci t n with clasi UV filters in finalzed products.
In 193 L'Oreal (Clichy, France) introduce the first rep senta ive of a new
gen ration of organic broad spectrum UV filters: ter pht aliden dicamphor sulfonic
acid (Mexoryl" SX, MSX). SXM is a water-solub e filter tha is suitable for day
wear sunscre n formulations including sun cre n-contain g moisturizers and
facil formulations. In 198 the ames manufacture complet d its range of products
by an oil-so uble sub tance: drometrizole tris loxane (Mexoryl" XL, MXL), a
hydrox benzotria le derivat. This molecu is comp sed o f two dif er nt chemi al
sub nit : heT 2-hydroxyphenyl benzotriazole sub nit contai s the UV -absor ing
poten ial over het whole UVB, UVA2, and UVAI wavel ngth spectrum with two
dif er nt absorption peaks, one in the UVB band (Iv = 30 nm) and another one at
the imtl betw n UVA2 and UVA1 34 m).n The

(A = siloxane sub nit of MXL
confers to the molecu a lipo h c char te tha rends it suitable for water- si tan
sun cre n formulati ns, includ g those worn on the beach and during vigorus
physical exrcis. 1
Another hydrox benzotriazole derivat e was com ercial zed in
19 by Ciba Specialty Chemicals (Basel, Switzerland): The hydros lub e methyl ne
bis- enzotriazoly te ram thylbut phenol (MBT, Tinos rb" M) covers, with two
absorpti n peaks, the ntire VBU and UV A spectrum. hisT organic ilterf has het
particularity to asocite orf its UV -protec iv action both absor ing and refl cting
pro e ti s. UV refl ction si normal y only sen ithw inorga c UV filters. MBT
consi t of microf ne rganico particles tha are disper d in the aqueos phase of
sun cre n emulsion .
The lates oil-sube UV filter is bis-ethyl x o phen l methoxyp n ltriaz e
(BEMT, Tinosrb" S). It was introduce in 20. The mechanis of action ofBEMT
is ilustraed in F i g u r e 6 : BEMT is a large polyarmtic molecu. The asymetric
intramolecular vibronic
H+.transfe noitax ler Phot -Tautomerism
r
Duration 10- 21 sec
(tlb$opi>n peal a t 305

UVB
» 6 OCH 3
~ ij dQ~
~ > 6,&
·· 'o l~
H
NI~
Ji
/"
.• Q·d •.
.)
UVA
(abSorptin peak at342nm)
BEMT
Figure 6. Mechanism of UV A and UVB absorption by bis-ethyl exylo phenol methoxyphenyltriaz ne
(BEMT, inosrb"T S).
SNE RCSNU 49
struc re of the molecule harbo s separ te absorption site for UVBR and UV AR.
After absorption of UV phot ns the molecule is prom ted into an excited stae that
undergoes phot - automerism with intramolecular prot n transfer. The duration of this
isomerization is in the order of 10- 21
second. This extrem ly short time span does otn
permit any ext rnal chemical reaction to be trig er d. This prev nts the formation of
radic ls or haptens from the phot excited BEMT molecu . BEMT returns by vibronic
relax tion with heat rel ase into its en rgetic ground stae in chemical y unchanged
form and is ag in ready to absorb UVR. 3
Mexoryls and tinos rbs provide strong absorbency up to the UVAI range and
exc l ent phot s abil ty. Their use in com ercial sun cre n pre ar tions permits
to achiev sign ficantly bet er UV A protec ion as measured yb the PD prot c l.
In order to obtain high UVB-SPF and UVA-PF whic can ot be a c h i e v d with one
filter alone, they are nev rthel s as ociated with clas ic organic filters and inorganic
pigments in com ercial zed sun cre ns. They can stabil ze phot labi e filters uchs as
cin am tes or avobenzone." The large molecular size of thes last gen ration organic
filters (molecular weight> 50 Da) prev nts percutaneous absorption. Phot al ergic
and phot oxic reactions have nev r be n reported for thes ilters.f Both MB T and
BEMT do not have estrogenic or androgenic activ y in vitro. 50
INORGANIC UV FILTERS
Inorganic UV filter sub tances are chemical y inert pigments that stay in the up er
layers of the epid rmis and stra um corneum. In their tradit onal no micronized form,
they refl ct or scat er radi t on. The degr o f refl ction and scat ering by thes pigments
is strongly dep nde t on their particle size and shape. Two inorganic oxides are used
for UV protec ion in humans: zinc oxide (ZnO) and ti anium diox de (Ti0 2 ). In their
no micronized form, with a particle size of20 to 50 nm, inorganic filters act as opaque
radi t on blockers that refl ct not only UVR in b o t h the UVB and the UV A spectrum, but
also VL and IRA. In this form they are particular y suitable for protec ion in V L - i n d u c e d
phot sen it vity disea s such as porphyrias." Howev r, the refl ction o f vis ble light
makes inorganic sun cre ns vis ble to the eys and thus cosmetical y les ac eptable.
Iron oxide, a red ish pigment with absorbing cap city in the UV A range, is sometimes
ad e to large-sized particle inorganic filter pre ar tions to cor ect their "white lo k."
Cosmetic ac eptabil ty of inorganic UV filters si improved by micronization of the
particle size to 10-50 nm. Decr asing the particle size reduces refl ction, mainly of
longer wavel ngths, and shifts protec ion toward shorte
wavel ngths. Micronization
increas absorbency by inroganic filter particles ( F i g . 7 ) 1. Microfine ZnO protec s over
a wide range ofUVA, including UVAl, but is les ef ctive ag inst UVBR. It si very
phot s able and does not react with organic UV filters. 52 Micronized Ti0 2 provides
go d protec ion in the UVB and UV A2 range, utb is insuf ic ent for UV AI. ZnO
and Ti0 2 are ther fore perf ctly complem ntary in one sun cre n pre a tion. They
are frequ ntly as ociated to organic UV filters for their phot s abil zing pro e ti s.
Although the particle size of micronized Ti0 2 is s m a l e r than the one of ZnO, it has a
hig er refl ctive index and ap ears ther fore whiter than nO.Z l 52
• Micronized Ti0 2 is
also more phot reactive than ZnO by UV absorpti n: The crystal ine forms of Ti0 2 are
semiconductors. UVB ro UV A2 phot ns can prom te el ctrons from the valenc band
to the conduction band, gen rating simple el ctrons and posit vely charged spaces cal ed
1,2
Non microfine
-. inorganic filter
i 0.., . •.
.2
c 0,8 · · · ·t· \
,,
-S"
o \
~ ,60
lJ
~ ,,
li
"" , ,
CI)
0: 0,4
0,2 . Microf ne Ti02 ' '"

. ..
O+-----r-------r-----s:-------r----~---~~.-....--
280 30 320 340 360 380 40 1\ [nm]
___ UrB ~ AVU 2 ~~~~~~~~::~~~~W~~M~~ttt~m~t:t:~~:::::::~ww~:::~mtl~:~~~~ AVU I · :::~:~ttm:~:~m~~:mmm~m~tMtfftlmWMl
Figure 7. Micron zat of inorgac UV filters shift absorptin spectra toward shorte wavelngths.
holes. After formati n, el ctrons and holes either recombine or migrate rapidly in about
10- 1
second to the particle surface wher they react with het sur o ndi g mediu . In
aqueos enviro ment, this can lead to formati n ofROS, and in vitro genot xic ty has
ben described in some studie. As evn na o-sized inorga ic filters do not pen tra e
into layers o f epid rmis contai ng livng cels, this phenomeno does not sem to play
a sign ficant role in clin al use of sun cre s. 53 As for organic UV filters, ther is few
dat no the poten ial transdermal absorpti n of na o-sized inorganic filters through
lesiona, esp cial y sun burnt skin, nda on use in pediatr c seting. Ther si also omes
con er about inhal tion and pulmonary absorption of such na op rticles. Micronized
inorga ic filters should ther fo e be used with caution on lesional skin and in young
children, and sun cre n spray contai ng such micronized filters should be avoide .
Nev rthel s , evn subc taneous and intravenous admin stra ion of na o-sized Ti0 2
and ZnO di not show sign ficant toxic ty in mice (revi wed in ref. 53).
The phot reactiv y of inorga ic UV filters reduc s their protec ive ef ica y. For
this eason,r Ti0 2 and ZnO particles are often coated with dimethicone or sil ca whic
stabil zes the filter sub tances. Coated inorga ic UV filters are char cteriz d by god
sub tan iv ty by fixaton to stra um corneum proteins, and lite or no pen tra ion into
the skin. ZnO in a phenyl trimethicone solution was evn shown to inh bit transdermal
pestic de pen tra ion, wher as Ti0 2 alone had no efct. 45 Im unol gic sen it za ion
to inorga ic filter pigments has not ben repo ted so far."
EF ICA Y OF SUN CRE NS
Sunscre SPF is defin by the capity o f protec ing from UV -induce erythma.
I f aplied coretly, suncre rea therfo by definto efctiv aginst unbr.s
But today, consumer expct from unscre use also protec i n from the other
harmful efcts of UVR tha have ben dev lop d above. It is difcult to com ent on
SNE RCSNU 154
the "real" ef ica y of sun cre ns for other ind cations, esp cial y for tumor prev ntion,
for two major reason :
Studies on the protec ive ef ica y o f sun cre ns ag inst skin agin and cutaneous
car inogen si often use animal models in which thes changes are induced
with n we ks after UV ir ad tion. Howev r, in human beings, cutaneous
car inogen si is a multi-step proces dev loping over sev ral deca s. As kins
tumor formation in humans sem to be a much more complex scenario than in
mouse models, the observations obtained in t h e s models can be transfer d to
the situa ion in humans only with great caution. nI the same ay,w murine skin
agin models do not nec s arily refl ct the condit ons in human skin.
Skin tumors aris ng a very ongl time after ir ad tion, up to 40 years, the
entir epidemiol gic dat av ilab e today was obtained with sun cre n agents
com ercial zed befor the introduc i n ofUV A l/UV A2 filters and last gen ration
broad band filters. Although sun cre n use was alre dy wide-spread in the 1980s,
the adv nces in sun cre n dev lopment achiev d since that time con erni g the
coverage of the entire UV A spectrum and ilterf phot s abil ty do without any
doubt contribute to the long-term ef ica y of sun cre ns.
Factors af ecting the ef ica y of sun cre ns are es ntial y inadequate ap lication
and ext rnal elim nation.
Wher as SPF tes ing prot col is b a s e d on an ap lication of2 rug/em' of sun cre n,
under real- ife condit ons user wer found to ap ly rather amounts about 0.5 ,"me/gur
45
Under thes ap lication condit ons, a SPF50 sun cre n provides a SPF of only 5.
Inde d protec ion increas expone tial y with increasing sun cre n con e tra ion. 5
Some site such as back, later l side of the neck, and arse are regular y mis ed during
sun cre n ap licat on. Not only toweling after a bath but also simple clothing after
sun cre n ap lication reduces the protec ion factor of sun cre s." Because of their
white ap e rance, inorganic sun cre ns are often ap lied in les r amounts than organic
filters which obviously ev n more decr ase their ef ica y compared with the one that
75
could be e x p c t e d from their UVB-SPF/UV A_PF.
Most people ap ly sunscre ns only oc asional y for important and plan ed
sun exposure, mostly during leisure time nda holidays. Both cel transforming and
im unosup res ive ef cts of UVR are already det c able after suberythemal UV
iradton. The great s part o f cum lative lifetm UV exposure is suberyth mal, oc ur ing
outside peak periods, Le., through short- ime but rep ated daily outdo r stay, by dif use
UVR under cloudy sky, and by UVAR indor. As sun cre ns at enuate the detrimental
ef ct evn of sub erythemal UVR, it is not surp is ng that daily use o f a sun cre n is m o r e
protec ive ag inst UV - induced skin changes than intermit ent use o f het same product. 58,9
When cor ectly used, sun cre ns provide a sati factory but not complet protec ion
ag inst phot dermatose : Light forms of polymorph light dermati s, actin c herp s
labi s, solar urticar , and actin c reticuloid can be prev nted by sun cre ns covering
both UVB and UVB wavel ngths.v? Broad spectrum sun cre ns with high UVB-SPF
also protec lups erythematosu patients from flares."
UV AR is the princ pal responsible for UV -induced skin agin. For this reason, only
studies tha as e dermal changes after solar simulating ir ad tion, Le., contain g
UV A, are rep senta ive o f the skin agin proces in humans. Only sun cre ns with high
protec ion factors in both the UVB and the UV A spectrum wer found to dim nish skin
agin ef ects." But ev n with MXS the protec ion remained incomplet although the test
was perfo med with lite UV A dose, and after rep ated long-term exposure, elasto ic
changes ap ear d evn in sun cre n-protec d skin ares. Phil ps et al. emphasized the
importance o f consequ nt daily ap licat on in p r e v n t i o n o f kins agin: heyT showed tha
forget ing sun cre n ap lication only ev ry fourth day sign ficantly impa rs treatment
ben fits in long-term use." But the ef ica y and safety o f sun cre ns in kins agin
prev ntion has not be n established for long-term use over sev ral years. Both organic
and micronized inorganic filters are inef ctive in filter ng VL and IRA that contribute
to the skin agin proces .
To prev nt cutaneous phot - im unos p res ion, sun cre ns must provide protec ion
ag inst both UVBR and UV AR. But evn broad spectrum sun cre ns can only partial y
restore Langerhans cel numbers, delayed-type hypers n it vity to recal antigens, and
contac hypers n it vity (CHS) response to chemical al erg ns. 2 46,3 8 A nearly complet
conservation of CHS is only obtained with sun cre ns of ering high UVA-PF with a
superio ty ofmexoryls compared with avobenzone." In humans, sun cre n protec ion
ag inst phot induced im unosup res ion is not cor elated with SPF, and it is inferio
to protec ion from erythema. 82
The protec ive value of sun cre ns ag inst phot car inogen si is dif cult to ac es
because o f het long time span betwe n the begin g ofUV exposure and the ap ear nce
o f a clin cal y perc ptible skin tumor in humans. Although sun cre ns are widely used
since the 1960s, het inc denc of melanoma and no melanoma skin cancer (NMSC) is
steadily increasing. This raise some doubt about the cap city of sun cre ns to prev nt
cutaneous phot car inoge si .
Sev ral studies in m i c e " and in humans 76, 46 have shown an inh bit on by sun cre ns
o f p53 expres ion increas after UV ir ad tion, consider d as a marker of DNA dam ge,
but no impact on the ap ear nce o f p53 muta ions. In thes studies, Ti0 2 asw superior
to OMC. A product contain g MSX, MXL, avobenzo e, and Ti0 2 ithw an UV A-PF
(P D) of 14 complet ly sup res d p53 expres ion in h u m a n s wher as another sun cre n
having a UV A-PF of 7 and contain g only avobenzo e and Ti0 2 as UV A filters di
not. 46 The use of reduced p53 expres ion as ef ica y marker of sun cre ns is subject of
contr ve sy: Inde d p53 is a pro-apo t ic protein that interv nes in the organism' natural
anti- umor def ns . Its sup res ion is ther fore not an ideal criterion for the evalu tion
o f anti-phot car inoge ic activ y.
MSX and OMC wer found to provide equal protection ag inst pyrim dine dimer
formation in m i c e that wer ir adiated with a solar simulator. But when polychromatic
light was used that contained only UV A and vis ble light, MSX protected bet er than
86.CMO The same workgroup reported that MSX complet ly abrogated UV-induced
DNA fragmenta ion in a comet as ay." In vi o they described a superiority ofMSX
compared with OMC in p r e v n t i n g tumor formation in m i c e after UV ir adiation." One
should notice, howev r, that al cited studies on MSX 96,8 46ytiv tca have be n done at
the res arch center o f L'Oreal (Clichy, France) who is the manufacture ofmexoryls.
Another workgroup confr med that com ercial European UVB-UV A broad spectrum
sunscre ns reduce thymine cy lobutane dimer formation in ir adiated skin explants.?
In vio, two randomized case-control studies, one conducted over only six months"
and another one conducted over 4.5 years," found a reduced number of new actin c
keratose (AK) and a higher number of remis on of pre- xist ng AK in the group treat d
with daily sun cre n compared with the placebo group. The ben fit of daily sun cre n
SNE RCSNU 453
aplicton was in the orde o f an averg o f one AK avoide per person over the 4.5-year
study period. 27
The Nambour (Que nsla d, Australi ) Skin Cancer Prev ntio Trial examined
162 partic pants in a randomized contr l ed seting: for a 4.5 year eriod,p one group
aplied evry morni g a broad spectrum sun cre (OMC and avobenz , SPF 16), and
a contr l group practi ed discret onary sun cre n use. This trial found a sign f cantly
reduc inc de of squamo s cel car inomas (SC) in the trea m nt roup,g but no
dif er nc betw n the two roupsg ni inc de o f basl cel car inomas 37.)C B( For
reduction of overal melanom inc de , het rialt failed to achiev the thres old of
sign fican e." Ulrich et al. confirmed a sign f ca tly reduc inc de of AK and
SC in organ transplant recip nts after 2 years nceo daily ap licat on of an SPF50+ /
UVA-PF20+ sun cre n (Tinos rb Sand M, octyl riazone, OMC, IMC, avobenz )
but only a no sign f cant reduction ofBC.75
Althoug suncre sem to have some delaying efct on AK and SC, a complet
protecin canot be achievd evn by daily aplicton. The lack to protec from BC
incde in adults may be explaind by the fact tha BC is probaly induce by sun
exposur during childo and adolesc n e" wheras SC incde is relatd to
cumlative UV dose includg chroni exposur during later phase of life.
The posit ve or negative role of sun cre s in the dev lopment of melanom has
produce major contr ve sy: Some ret ospectiv studie published in the atel 190s
con lude tha melanom inc de was hig er among sun cre n user, and tha,
par doxical y, sun cre s may induce melanoma.F'" Thes studie wer crit c zed for
conf u di g, e.g, peol who are at most risk of burni g and ostm likey to devlop
melanom are also most likey to use sun cre ns." Two meta- n lyse on al dat
published betw n 196 and 203 di not confrm any relation betw n sun cre n use
and melanom inc de , neith r in posit ve nor in negative sen. 8 .2 83 The rec ntly
published folw-up anlysi for melanom in the Nambour Skin Cancer Prev ntio
Trial only found a tend cy toward reduc prima y melanoma ten earsy after trial
ces ation in the group tha had aplied an as ociat on of 2 UV filters." The ben fit of
long-term sun cre use in this study was sign f cant only for prev ntio of invas e
melanom on any body site. The type o f tumor invasion was not part o f het intal study
critea but only a secondary, explorat y fmding tha has ther fo to be interp ted with
caution. The valid ty o f the melanoma dat from this study is also questionable because
o f the findg tha sun cre s di not sign f ca tly reduc melanoma inc de in the
body ares wher the study product was ap lied but only when cal u ated for invas e
melanom on the toal body surface. More v , the prot c l (sun cre n ap licat on
evry morni g for 4.5 years) was design d to reduc rather long-term cum lative UV
exposure than interm nt hig dose rate sun exposure whic is the exposure pat ern
consider as most importan for melanoma induction and prom ti n.
How to explain this confusion? Wavel ngths tha induce melanoma are not
know. The litera u e emphasize the role of acute-intermit en sun exposure with
sunb r , esp cial y during child o and adolesc n e.v-" whic sug e ts a role of
UVBR in m e l a n o m a induct on. On the other hand, the augment d melanoma inc denc
among forme PUV A patients" demonstra es tha UV AR proba ly also contributes
to melanoma in t a ion. Gen tic su ceptib l ty tha si not contr l ed by sun protec ion
habits may play a more importan role in melanoma induction and prom tion than
previously su pect d.
In sumary, het to ated avilbe epid m ol g c dat do not formaly prove a

proteciv oler of suncre gainst melanom and BC, althoug othb tumors are at
least parti l y UV-induce, and they show only an incomplet efct aginst AK, SC,
and skin agin. This may have sevral easonr tha are inkedl under each ther:o
The use of suncre with insuf c e t UVB-SPF and lack of coverag ni the
UV A spectrum: Most dat wer coletd befor last gen ration broad spectrum
filters wer avilbe. Based on the result o f preclin a studie and prelim na y
clina dat with the new filters, we can expct betr protec i n perfo mance
with thes suncre. But as the time span betw n UV exposur and skin
caner manifest on in humans is extrmly long, incde numbers wil not
decras befor sevral decas.
The inadequt choie o f study poulatin for pros ectiv epidmolgc studie:
For both BC and melano, the role ofUV exposur specialy during the
early years of life has ben emphaslzed.r-" tudiesS houlds therfo focus on
protec iv interv on during this period whic makes them yet more difcult
to realiz as the cor esp ndi g tumors arise up to 04 earsy after crital sun
exposur. Gal gher et al. repotd a randomized contr l ed interv ion trail on
white children in whic the trea m nt group tha aplied a broad spectrum SPF30
suncre befor each sun exposur over thre years dev lop d fewr nevi than
the unprotec d group. The difernc asw particul y sign f ca t in freckld
white children who dev lop d 30% to 40% fewr nevi in the sun cre -p otec d
group than freckld children asigned to the contrl group." As hig nevus
density is recognized as a iskr actorf of melano, this study may indcate a
protec iv potenial o f broad spectrum unscre i f they are used regula y
during childo.
The inducto of over xp su e behavior by suncre protec ing ef ctively
aginst erythma: Autier et al. confirmed tha sun cre user usaly stay longer
in the sunlight than unprotec d peol. 8 Many user abuse suncre to extnd
direct sun exposur, esp cial y during holidays. High SPFs supre the alrm
signal ofUVB-induced sunbr and give a false hope o f "complet " protec i n
to tsi user. Especial y i f UV A protec i n of the employ d sun cre is not
perfct, over xp su e can induce sevr phot dam ge tha is not im ed at ly
obvius to the sun cre user.
The sup res ion of natural phot protec ion mechanism by the cur ently
market d sun cre ns: Melani e synthesi , rel ase of melanos mes, and
thickeni g of stra um corneum are mainly trig er d by UVBR that is
ef ctively blocked by modem sun cre ns. In the case o f rep ated sun exposure
with a topical phot protec ion having an el vated PFS / PD (UVB / UV A
protec ion) ratio, the sun cre n user is thus more submit ed to the harmful
epidermal and dermal ef cts o f UV AR than an unprotec d ind vidual who
wil undergo natural ad pta ion tha protec s ag inst both UVBR and UV AR.
This is consi ten with the observation tha peo le with importan chronic
UV exposure by oc upational outdo r activ y, e.g, agricult ral worke s,
who typical y have tan and skin thickeni g in sun-exposed site, rea at a
sign ficantly reduced risk of melanoma compared with indo r worke s with
intermit ent UV exposure. 84,5
SNE RCSNU 45
SUN CRE NS AND VITAMIN D 3 SYNTHESI
Besid t wel-kno y role in skelta homi, vtan D has ben rpotd

to have anti-croge ps. nimat vyxord hi -52,1 D deficny and low solar
UVB exposur inca mortly f caners, includg o, breast, prostae, ovarin
caner, and evn melano. An antiprolfev efct of vitamn D is also suported
by cel cultre and animl model exprimnts. Mov, vitamn D deficny has ben
asocited with the incde of type 2 diabets, and with the incde or sevrity of
cardiovsul disore and sevral inflamtory, autoimne, and conetiv tisue
diseauch mltp arhis,ceoud ,su otameh yr and sytemic
scleroi (vwd in refs. 6 and 89). Most of thes repots failed to contrl confudig
by georaphic varitons in relation to skin photye, lifesty behaviors, diet, and
socienm tau of the examind poult. The "vitamn D question" has becom
a dilema of public healt debat: Large studie have shown tha vitamn D deficny
is a frequnt fmding in adults in Westrn countries.v"? I thes countries, it is espcialy
prevalnt in peol with dark skin photye, in indor workes with por casul UV
exposur (i.e, the majority of active adult poulatin), and in eldr peol becaus of
los of skin thicknes and conseutivly dmh capity of vitamn D synthei. As
the cutaneos synthei of choleaifr (vitamn D 3 ) from 7-DHC in cel mebrans
is exclusivy triged by UVR in the UVB-spectrum ( F i g . 1 ), an interfc of hig
SPF suncre with vitamn D 3 synthei is posible. Sunscre use in a contrled
adminstro seting has inde ben shown to supre vitamn D synthesi .":
On the other hand, vitamn-D producing UVB wavelngths are at the same time the
most cinego cra -niks ones. Cutaneos chlifrpd is satured 10% to
20% of the orignal epdm7-DHC conetrai." This thresold amount is achievd
by far suberythmal UVB dose in the orde of 0.25% DEM to the face and backs of
hands 3 times Aditonalweky." UVBR transfom i vtampre D 3 into the biolgcay
inactve metabolis tachyserol and lumistero." Morev, evn phot-syneizd
vitamn D is photlabie. Ts means tha the vitamn D amount tha canot be evacutd
shortly from the skin into the blod cirulaton is degra in the epidrms by furthe
sun exposur." Field studie with personal UV dosimetr done in difernt countries of
North Ameica nd NorthEupacnlde iy UV exposurfbth adolescnt
and indor workes was suficent for adequt vitamn D synthei (reviwd in ref.
95). Satisfcory vitamn D levs wer detc in indor workes with regula modest
sun exposur in Denmark" and in suncre user up to 70 years and older in Australi
(latiude 79)S°73 and Spain (41 89.)N° The American Academy of Dermatolgy does not
recomnd unprotecd exposur to sunlight or to artifcl UV devics in inteo to
bost vitamn D synthesi ."
In this contex of conflitg scientf dat and divergnt recomndatis, the
answer to the "vitamn D question" has probaly ben given by Faurscho et al.:?' In an
exprimntal seting, they iradte with a standrize UVB dose healty volunters
tha wer protecd with difernt amounts ofa previously aplied suncre (0 to 2 mg!
.)"me Serum vitamn D levs wer monitred befor and after 4 UVB iradtons. The
investgaor fud tha the recomnd 2 em- g!dose of suncre do inde block
vitamn D synthei, wra dose of 1.5 mg/c' and below do not do so. The thicknes
of suncre aly aplied by user being rathe betwn 0.5 and 1 mg/cm-" this study
may explain the divergn result betwn previous studie using contrled aplicton
seting and those under real- ife condit s. In con lusi , perf ct sun cre n use does
impa r vitam n D ynthesi. But as protec ion by sun cre s is cur ently incomplet ,
thes products do not sem to contribu e sign f ca tly to vitam n D insuf cien y in the
gen ral po ulati n.
More v , alimentary intake of vitamn D 3 , e.g, in form of fortied milk, rangeo
juice, or faty fish (salmon, macker l) can help to maint suf ic ent plasma levs. 6,95 For
patien s at risk for vitam n D defic n y, dietary sup lem nta ion is efica ous and safe.
ALTERNATIVE PHOT PROTECTIVE AGENTS
A great number of sub tances for topical ap licat on have enb pro sed for
phot r ectiv purose, e.g, antiox dants acting as radicl scaveng rs, DNA repair
enzyms, olig nucleotid s stimulating natur l melanog esi , vitam n A derivat s,
and active otanicb comp ne ts. In exp rimental seting, they aveh anti-eryth mogenic
efct. Some o f them protec skin from UV -induce im unos p res ion or carinoge si
(revi wed in ref. 10). Especial y a-toc pherol (vitam n E), L-ascorbi acid (vitam n C),
and ferulic acid rea someti s ade to sun cre n pre a tions. Transfer from in vitro
antiox dant activy to neutraliz t on of UVA-induce ROS in het skin under real- ife
condit s remains, howev r, a major pharm col gical chaleng: ostM antiox dants are
inher tly unstable. heT stabil y problem of antiox dants is evn great r in the condit on
of UVR xposure and ni pres nc of absor ing UV filters. More v , hydrophil c
antiox dants such as vitam n C have to be chemi al y modif ed to pen tra e beyond the
straum corneum bar ie in contac to livng cels wher OSR are gen ral y encou t red.
Such chemi al modif cation reducs antiox dant pro e ti s of some sub tances. On the
other hand, UV filters should eb kept no the skin surface and should not pen tra e into
the epid rmis.'? This limts the usef ln s o f incorp ating antiox dants into sun cre n
formulatins: angW et al. showed tha sun cre n products contai ng antiox dants di
inde hardly provide any protec ion aginst fre radic ls. In the tes d products, the
radic l protec ion was entir ly due to UV A filters.'?
Other topical phot protec ive sub tances are prop sed as after sun NAD repair
agents: nI a group of XP patients, topical ap lication of phage T 4 endo ucleas V
(dimeric ne) for one year resulted in a 30% decr ase of BC inc denc and a 70%
decr ase of AK inc de .I'" Such sign ficant ef ica y of dimeric ne has not be n
demonstra ed so far in ind vi uals without XP. heT repair enzyme phot lyase was
found to restore UVB-induced DNA-dam ge ni h u m a n skin when used encapsulated
into lipos me in a topical y ap lied formulation. Topical phot lyase ev n prev nted
UVBR-induced im unosup res ion in vi o.'?
Antiox dants have also ben tesd for phot r ection in oral admin stra ion. But
oral antiox dant sup lem nta ion di not show any impact on het inc de of NMSC
in a randomize , double- ind , placebo- ntrol ed prima y prev ntio trial on 1307
ind v uals sup lem nt d for 7.5 years with eith r an as ociat on of vitam ns C and E,
,en torac-31 selnium, nda zinc, ro a matching placebo.'? In the emalf subgro p the
incde o f melanoma was ven hig er in the antiox dant group than in the placebo
po ulati n. An increas d al -c use mortali y o f adults sup lem nted with the above cited
antiox dants was found in a meta- n lysi o f prima y and secondary prev ntio trials. 105
Pro- xidant activy, hepatic and gastroin est al toxicy, and poten ial DNA dam gin
efcts have also ben repo ted for dietary poly henols such as gren tea extrac s.'?
SNE RCSNU 457
In sumary, the role of antioxs in skin caner prevntio is rathe doubtfl: In

topical ,snoitalumrof their eficay undr real-if condts, epialy whn combined
with suncre, is not .dehsilbatse Their long-term oral intake in pharmcolgi
snoitar nec o does not prevnt skin caner. None of thes subtance h so far proved
an activy in prevntio of sunbr, UV-induce ,nois erp uson m i or skin caner
prevntio on a lev comparble to what is know for benfit from suncre, and
ther are seriou safety coners about .stnadixo tna Topical DNA endouclas are,
howevr, promisng in after sun .sdnuopm c But alterniv photreciv agns are
far from being ready to replac suncre in UV protecin straegi.
CONCLUSION AND DISCU SION
Eighty years after their comerial introduc, suncre remain tils most
efctiv for what they have orignaly ben made for, Le., protecin aginst sunbr
and other short-em UV efcts such as .se otamredot hp They have limted efct in
prevntig sk agin, AK, and SC. Also in some particul condits uh as gentic
disore or post-ranl iatrogenc nois erp uson m i tha expos to importan
risk of mret- aidemr tni devlopmnt of multipe skin caners, benfit from regula
suncre has ben clinay .dehsilbatse Howevr, basd on this reviw of clina
and lacigo medip dat, today's suncre snoitalumrof canot pretnd to provide
protecin from suoma qs-no cel skin caner for the enralg adult poulatin. The
gentic part in the etiolgy of thes tumors is not suficent to explain their stil risng
incde worl despit wide-spra suncre .
This gnit op asid lack of eficay may partily be due to etauqedani seu of
suncare :stcudorp serU do genraly ot aply them for daily short-em outdr stay
and indor exposur to AR UV travesing windo glas, althoug thes condits are
elbisnop er of the major part of evitalum c ife-tml UV dose in the genral poulatin
having rte indor .noitapuc o Howevr, ecnavresbo-n of daily noitac lp a has ben
shown t canel th benfit o sne rcsnu in long-termus. Even for planed UV exposur,
sne rcsnu are usly apied n tneic f usni uantiyq compredwh t protecinfa
tesing condits whic ylbaredisnoc reducs the efctiv 5 ,45.FPS ,revo r M seru
often omit noitac lp a-er evry two hours tha is de n m ocer to compensat extrnal
product .noitan mile nO the other and, andcosequt lifeongus of sne rcsnu in the
de n m ocer isamount fre pcibl and exps,fmcilro:aty
In sumer 201, the price of a god quality brod spectrum n with SPF50+ and
an UVA-PF ~ 20, and CW ~ 370 nm is about 250 € / gk in France. Befor sun exposur
on the beach, a man with a body surface are of 1.8 m 2
who respct the de n m ocer
suncre amounts has to aply 36 g for toal body protecin whic cause cost of
9 € for only one coret .noitac lp a nO the other hand, the s en uo c n i fo suncre
mret-gnol use in the de n m ocer mountsa has nevr ben examind with regad to
their irtaon potenial, interaco wh toxic secnatsbu in the ,tnem orivne sytemic
,noitprosba endocri activy and clearn." Such mret-gnol suncre 2 mg/c- use
probalyeds t vitamnD ,ycnei f usni at least in the tempra cli zon." Another
reason for suncre yca if eni my be the actul use of etauqedani ficaye markes for
potency:Bhri sumag SPF andA- UVcuretlysmpo
are not relatd to ,ytil batso hp ,ecn amer genom ,noitce orp and noitce orp num i
whic are howevrcital pmsf caner .noit ev rp orF the ,remusnoc unscre
choie is no easy deal: For lack of standrizo A UV protecin tesing, A-PF UV

values are not indcate evn for suncre with proteciv activy in this band region.
The eficay of suncre i most of al detrmin by their UV filter .noit sopm c But
for ingredt list, the manufctre can use INC, IUPAC, and trade names of filters
whic makes it difcult to the user to identfy the respctiv .secnatsbu In Europe the
consumer i erom ehtruf confrted confusig egau n l-it um labeing d ingredt
list contaig snoita verb a in foreign langue.
With regad to this reviw, physican should omit mesag to their atiensp
sugetin ha suncre a protec from BC and melano. Drtgis hould
be conerdt presv ou discplne' crediblty n a contex whr public informat
is to much dominate by comerial inters of cosmeti and pharmceutil ndsy.
Sunscre in their curent form are probaly not the key to skin caner prevntio in
the genral poulatin. On the other hand, it would be iresponbl not to recomnd
their use.'? More basic, but higly efctiv measur should stil be encouragd. This
includes sun avoidnce espcialy during peak UVR betwn 10: a.m and 4:0 p.m,
windoclthg,a-bsrfeUV.pv winbroad-m
Sunscre a perfctly complet hs ,snoitad em oc r but they should nevr canel
them. Much educationl wrk is yet to be done to overcm th poularity of sunbathig
and the tanig ideal th are stil wide-spra n our society pal in adolescnt
young adults. After 30 years, primay and secondary prevntio progams now begin to
show positve outcmes in Australi, espcialy in melano incde and survial. 108
,s el htrev N the benfit o sne rcsnu aginst hrmful ects ofUVR is .elbained u
God pructsne afod bth hig SPF and a A wel balncedprotiUVBI
ratio. In the ,erut f more poten A UV filterng may becom .elbis op Regular suncre
use at least for elbadiovanu tne imretni UV exposur sem to be safe and .suoica f e
Major proges ha ben made during the past 30 years in the suncre domai with the
tnempolev d of poten A UV ,sretlif noitaz norcim of inorgac ,sne rcsnu and synthei
of new elbatso hp and detar lot- ew organic flte .seluc om Thes rcnt su proteciv
products wil improve the ecnatpec a of sne rcsnu and therby the observatin of
.snoitadnem ocer Last genrioAbad spectrumUVB- fil have a betr nfi
/ risk ratio than forme ganic UVB :sretlif They protec us probaly et from sunlight
than forme molecus tha wer used in most cigol imed p studie avilbe today on
suncre .yca if e They are not absored throug the skin, they do not have endocri
gnitpursid ,seitr po andAtheir osUVgnDvitambrp cueos
more thansyi flerUVBomd. nawb gnired snoC the slow tnempol ved
of skin caner in humans, the benfit of our actul suncre market wil take years to
becom clinay and yl acigol imed p .suoivbo This reviw wil probaly have to be
revisd whn the outcme f mret-gnol studie wh recnt sne rcsnu wil be .elba i va
REFNCS
1. Kul av nijay P, Lim HW. Phot protec ion. J Am Acad Dermatol 205; 52:937-58, quiz 95 -62;
PMID: 159286; ht p:/ dx. oi. rg/l0. 16/j. a d.20 4.07 63.
2. Vem z D, Milon A, Vuil eumier L, Bul iard JL. Anatomical exposure pat erns of skin to sunlight: relative
contribu ons of direct, ifused and refl cted ultraviolet radi t on. Br J Dermatol 201; 167:38 -90;
PMID:2 3561 ; ht p:/ dx. oi rg/l0.1 j.1365-213 .201 . 089 .x
3. Kochevar IE, Taylor CR, KrutIna 1. Fundamentals of cutaneous phot biol gy and phot im unol gy.
In: WolfK, Goldsmith LA, atzK SI et al (editors). Fitzpatrick's Dermatol gy in Genral Medic ne, 7th
editon, McGraw-Hil , New York, 208, p 79-80.
SNE RCSNU 459
4. Young AR. Chrompesin human ski. Phys Med Bio 197; 42:8-0 ;952 719:DIMP .iod x / :pt h
0.1 org/ .40 /5 24/5 19- 30 /8 0
5. GoukasinDA,ElerMSthmc YB. efdinulot Thym solar iuted
on iradt p53 andproteis.J 53-gul Invest Drmaol 19; 2:5-3 ;95268 9:DIMP htp:/
dx.oirg/l01 .x 8640 .9 1 74 -3251.j/640
6. Wolpwitz D, Gilchrest BA. The vitamn D question: hw much do you ned and how should you get it?
J Am Acad Dermatol206; 54:301-7; ;16034 61:DIMP .7501 .50 2 da j. /610 . /groL d.x / :pt h
7. PinelSR.Cutaos ,egam dot hp JAm stre,pocin.adxvl AcDermto
203; 48:1-9, quiz 20-; ;5632 5 1:DIMP .6l 30 2 djm/7 l. 1 groL d x / :pt h
8. Wenczl E, Pol S, Timeran AJ, van der Schans GP, Roza L, Schotrs A. Physiolgca dose of
ultravioe dn iuce DNA strand breaks in cultred human melanocyts, detc by means
of an lacimehconum i asy. Photcem Photbil 197; 6:82-30; ;96 1249:DIMP htp:/dx.oi
org/10.l j 75 - 9 .tb032 x
9. Parson PG, Haywrd IP. Inhibto of DNA repai synthei by sunlight. Photcem Photbil 1985;
42:87-93; ;5639 04:DIMP htp:/dx.oirgIOl1j75-098b4
10. Marot L, Belaid JP, Meunir JR, Perz P, Agapkis-Cue . The human melanocyt as a particul
targe for A UV raditon and an endpoit for photrecin asm. Photce Photbil 19;
69:8-3;107 PMID .x 743 0bt.9 l 7 01- 5 .j/1 0 /gro.i d x / :pt h
I . Mouret S, Baudoin C, Charveon M, Favier A, Cadet J, Douki T. Cyclobutane pyrimdne dimers are
predominat DNA lesion in whole human skin exposd to A UV raditon. Proc Nat! Acad Sci USA
206; ;07-56731: 01 ;8 145961:DIMP htp:/dx.oirgl073nas6421
12. Honigsma . Erythema and .noita nemgip Photdermal Photimunl Photmed 20; 18:75-;
;04 7 12 :DIMP .x 402 81. 0 2 1870- 61.j/4301. /gro.i d x / :pt h
13. ElerMS, Ya ndDNAGilchrestB.mg .si en gonalem Nature 372:41-; 9 ;3 24897:DIMP
.Oa314273/8 01. /gro.i d.x / :pt h
14. ParkHY, GilchestBA EMS .Yar sm inahceM of ultravie decu ni-thgil .noita nemgip Photcem
Photbil196; 63:1-0; ;0687 5 :DIMP ht p:/ dx. oi rg/10.l j 751- 09 .l 6 tb0298 .x
15. GangeRW,ofADEBlcktiyMI.przKhevaSund Comti
A- UV and ts UVB-induce agst eryhm and formatin evit sne - a lcunod e site in DNA by
UVB inhuma skin. JlnvestD rma ol1985; 85:362-4; ;98104 3:DIMP -3251/ .01/groL d.x / :pt h
I 74.ep26983
16. Varni J, Spearmn D, Peron P, Flige SE, Dat SC, Wang ZQ, et al. Inhibto of type I proclagen
synthei b damge colagen in photaged skin and by de arg d-esan g l oc colagen in vitro. Am J
Patho120; ;24-139:851 ;1408321 :DIMP .0- 4 6) 1( 9-20 S/61 l. gro i d x / :pt h
17. KawguchiY, TankH, Okad T, Konish H, TakhsiM, Ito M, et al. Efect o reactiv oxygn speci
on the elastin mRNA exprsion in cultred human dermal .st albor if Fre Radic Bio Med 197;
23:16-5; ;9035619:DIMP .9-075 )69( 485-19 0S/61 .0 /gro.i d x / :pt h
18. Kely DA, Young AR, McGregoJ, et al. Sensitvyo sunbr i asocitedwh suceptibly UVR-
of supreincl-mdato .ytinum i J Exp Med 10628;PID:5- 19:
.165 3.19 mej/4801. /gro.i d x / :pt h
19. Bestak R, Halidy GM. Chronic low-dse UVA iradton induces loca supreion of conta
,ytiv sne r pyh angerhsL cl depltion a supreo cl activon JeH1 3C mice. Photcem
Photbil196; 64:9-7; ;0462798:DIMP .x 368IObt. 9 1 7 0 - 5 1.j/ l 0 groL d.x / :pt h
20. Nghiem DX, Kazim N, ClydesaG, HN, Anathswmy Kripke ML, Ulrich SE. Ultravioe raditon
supre an establihd mun respo: implcatonsfr suncre dig. J Invest Dermatol 201;
;9-3 1 :71 ;239017 :DIMP .x 3051 2.x 0 - .j/640l 1 gro.i d x / :pt h
21. Damin DL, Mathews YJ, Phan TA, Halidy GM. An action spectrum for ultravioe decu ni- o taid r
nois erp uson m i in humans. Br J Dermatol201; 164:57-9; .815 7312:DIMP
2. HV,DeBuysLv S, MurayJC deDL, Pinl SR. Modemt aprchs .noitce orp tohp Dermatol
Clin 20; 18:57-90; ;5639 01 :DIMP .4-802 7)5 ( 368- 70S/61 l.0 /gro i d.x / :pt h
23. Lacour JP. Carcinoges f basl cel :samonicra gentics and molecuar mechanis. Br J Dermatol
20; 146(SupI):7-9; ;72 6 91 :DIMP .x 5 16s 4l 3 2-5 1.j/640 l gro i d.x / :pt h
24. Liebl F, Kaur S, Ruvol E, Kolias N, Southal MD. Iraditon f skin with visble light induces ratv
oxygen speci and gnidarge -xirtam enzyms. J Invest Dermatol201; ;7-109 :231 ;8 3 1 2 :DIMP
.674 1 02.dij/8301. /gro.i d x / :pt h
25. MahmoudBH, Ruvol E, Hexsl CL, Liu Y, Owen MR, Kolias N, et aI. Impact of A UV long-waveth
and visble ght on tne pmoc nalem skin. J Invest Drmaol20 1 0; ;7-290 : 31 1402:DIMP 0914; htp:/
dx.oirg/10I38j295
26. Schroed P, Haendlr J, Krutman J. The role of near infraed raditon in photagin f the skin. Exp
Gerontl208; 43:629-; ;9 743581:DIMP .01 4 8 2.regx j/610l. groL d x / :pt h
27. Wang SQ, Lim HW. Curent sa of the suncreglatio the United Staes: 201 Fod and Drug
Adminstrao' fl rule on labeing d s en vitcef tesing. JAm Acad Dermatol201; ;9-368:56
;213 281 :DIMP .520 7 .1 02 da j. /610 . /groi d.x / :pt h
28. Kely DA, Sed PT, Young AR, Walker SL. A laicrem oc suncre' protecin aginst ultravioe
decu ni- o taid r nois erp usonum i is morethan isub50%glower ptcn .snamuh
J Invest lotamreD 203; .30 2.74 1-3251.j/6401. /gro.i d.x / :pt h;9 153 21:DIMP;17-56:021 .x 50 21
29. C, outeaEhv Ppris Cfd . 1 L of Inluecrtai stneid rgni on the SPF denimret d in vo.
Arch Dermatol Rs 201; ;12-7 8:403 ;05270 2 :DIMP .x-7521- 0-3 40 s/70 1.0 /groL d.x / :pt h
30. Moyal D, iksworhciW K, Tricaud C. In vio persitn pigment darkenig :dohtem a noitar snomed of
the ytil b cudorpe of the A UV protecin fas result at sevral tesing .seirotarobal lotamredot hP
Photimunl Photmed 206; 2: 14-8; PMID: 167984; ht p:/ dx. oi rg 10 /j. 6 -
.x 32 0 .60 2.1870
31. DifeyBL, TanrPR J,Mts Nah JF. In vitro tnems e sa of the murtceps-daorb fo prtecin ulavo
suncre .stcudorp J Am 20;cad Dermtol ;810 I:D MP;53-4201: /7601. /gro.i d x / :pt h
.192 01. 0 2.djm
32. The nois m oC of the European .seit num oC nois m oC noitadnem ocer of2 206Septmbr on
the eficayo suncrepodt a the claims de rlating heo. Ofc Journal f the European
Unio, L265/39 .60 2.9 62
3. Ciba Specialty .slacimehC Ciba Tinosrb" pduct brohe. Basl, 20.
34. C,ASzcurko Dmpatin Mchel, MoreauA, Leroy D. cntalg o Ph :enoz ebyxo ten years
of .ecn irepx lotamredot hP lonum iot hP Photmed 194; ;7-4 1:01 .42 3087:DIMP
35. Journe F, Marguey C, yfaz rdnot kaR J, EI Sayed F, Bazex 1. Sunscre :noitazit sne a 5-year stud.
.59 01 579 10 / 8 1.0 /gro.i d x / :pt h;91 4830 :DIMP;3-1 2:97; Iloer n Vm eDatcA
36. TestPhopac MulinrE Stdy )STP CME( .ecrofksaT A photacEurenmli
tes study. Br J Dermatol 201; 16:02-9; ;234 8 2 :DIMP -5631.j/ 01 gro.i d x / :pt h
.x 75801.2 0 .3 12
37. narduA-len vA M, Dutare H, Gosen A, JeanmougiM, Comte C, Berni C, et al. ,en lyrcot O an
emrgin .negr l aot hp Arch Dermatol201; ;7-357:641 ;6304 602:DIMP /10 . groi d.x / :pt h
.231.01 2.1otamredhcra
38. Karlson I, Person E, nos netraM ,J Borje A. noitag sevnI fo the suncre octrylen's noitcaretni
with amino acid anlogs in the presnc of UV .noita d r hotcemP Photbil 201; ;21-409:8
;478 24 :DIMP .x 241 0.21 .7901- 571.j/ 1 .01/gro.i d x / :pt h
39. C. Bouiln Rect advs un .noitce orp J SciDermatol 20; 61;- PMID:7 S5)(upl1 23 ;49 46701
.0-78 0 )9 (1 8 -3290S/610 . 1/gro.i d x / :pt h
40. V, Sarveiy Rsk S, BensoRAE. Liqud cihpargotam rhc asy for gent:sucm noitac lp a
to in vio asemnt of skin pentraio d sytemic absorptin human .sre tnulov J Chromatg
B Analyt Technol Biomed Life Sci 204; ;13-52 :308 ;923 6051:DIMP .j/610 . 1/gro.i d x / :pt h
.2 0 1.30 2.bmorhcj
41. Janju NR, Mogens B, Anderso AM, Petrsn JH, Henriks ,M Skaeb NE, et al. Systemic
absorptin f the sne rcsnu ,3-eno hpozneb ,etam n icyxohtem-lytco and )en dilyzneb-lyhtem-4( 3
camphor after whole-bdy topical noitacilp a and evitcudorpe hormne evls in .snamuh J Invest
Dermatol204; ;16-75:321 ;24519 51:DIMP .x 527 .40 2 X 0 -2 0.j/1 .0l/gro.i d x / :pt h
42.Y, eXWongL CalftAM,Ridy .L mahde N,AJ 3-eno hp znebt gane rcsnu ehtfosn itar nec oC
in of residnt h United NaolHhSs:urvy ExmintNo .40 2- 30 2 Enviro
Health Perspct 208; ;7-398:61 PMID: ;1 392681 9621 .phe/9821.0 /groi d.x / :pt h .
43. SchlumpfM, Kypke K, Witasek M, Anger J, Mascher H, Mascher D, et al. Exposure atn ofUV
filters, ,secnarg f parbens, ,setal ht p organchl pesticd, PBDEs, and PCBs in human milk:
ofUV crelatin filters wh use of .scitemsoc er hpsomehC 201; 8: ;38-17 1 ;460 3 12:DIMP htp:/
1/gro.i d.x 0 .1 02.er hpsomehc.j/61 1 .970.9 0
4. Krause M, Klit A, Jens BlombrgM, Seborg T, H, Frediksn SchlumpfM, et al. :sne rcsnuS are they
benfical or healt? An overiw f endocri suptg roei fUV-l. Int J ;210 ordnA
35:42-6; ;874216 2:DIMP .x 0821 . 02 5 6 - 31.j/ 1 .0l/gro.i d x / :pt h
45. Brand RM, Pike J, Wilson RM, Charon AR. sne rcsnuS contaig physl UV blockers can increas
lamredsnart absorptinf .sedic tsep Toxicl Ind ealthH 203; ;61-9: 1 ;235 6451:DIMP .iod.x / :pt h
.a096Iht307 28470/19 .01/gro
46. Pont AR, Charon Brand RM. Active stneid rgni in sne rcsnu act as forenhacstpil
.dica tecayxonehpor lhcid-4,2edic breh t ;40 2locamr hPlp A ocix T ;79102 51:DIMP;45-843:591
0 16/j. dxoirgl htp:/ .30 2.pa t 09.21
47. Sutherland JC, Grifn KP. cioznebonimA-P acid can senitz the formatin of pyrimdne dimers in
DNA: direct chemial evidnc. Photcem loib tohP 1984; 40:391-; ;3 05836:DIMP .iod x / :pt h
0.1/j org 1- 571. .4891.790 .x 406 bt
SNE RCSNU 461
48. Gaspro FP, Mitchnk M, Nash JF. A reviw of unscre safety and eficay. Photcembil
198; 68:243-5; ;18574 9:DIMP .x 7 690bt.8 91 7 0 -157 .j/1 .0l/groL d.x / :pt h
49. ChatelinE, GbrdB. noitaz l b tso hP of butyl enaht mlyoznebidyxohtem andethylx (Avobz)
etam n icyxohtem by lonehpyxl ehyt-sib methoxypnl triazne (Tinosrb S), a new UV
-130 /265 . l gro i d x / :pt h;25049 1 :DIMP;6- 04 7 1 2Ioib t hPme c o .r tlifdnab or
10 2(5 68 104 < 70) .2;OC.0 2>A MBOP:
50. Ashby J, Tinwel H, Plautz J, Twomey K, Lefvr PA. Lack of bindg to isolated estrogn or androge
and recptos, ivy the ra sy,imtueofphc te filrsuncTobav
M-active and Tinosrb S. Regul Toxicl I aco Phrm 201; 34:287-91; ;2354 71 :DIMP .iod x / :pt h
1.5 org/l 06/rtph.2 1
T, ClarkNewRD51.HFgusonJMcLd Camr, ely sne rcsnu protecin improvedcnf
for photseniv a in the blue light region. Br J Dermatol201; ;49- 87:541 ;3096 71 :DIMP
.x 924 0.1 2 3 -56 1.j/ 40 l/gro.i d x / :pt h
52. Mitchnk MA, Fairhust D, Pinel SR. Microfne zinc oxide (Z-cote) as a photsable BVUIAVU
sunblock agent. J Am Acad Dermatol 9;1 40:85-9; ;7102 9 :DIMP htp:/dx.oirgl016
.3-2 507)9 (2 69-0 IOS
53. Nohynek GJ, Dufor EK. Nano-sized cosmeti formulatins solid naoprticles in suncre: a risk
to human healt? Arch Toxicl201; 86:103-75; ;760 42 :DIMP htp:/dx.oirgl07s24-
.5-1380-210
54. J WulfHC,sedLock-AnrS at1M edh beach do nt proec aginstyhm: new
defintoSPFspr.hmaluI97;13:2-MD4508
.x 5120 bt.79 1 8 0- 61.j/ 0l/gro.i d x / :pt h
5. A,Faurscho WulfHC. The relation bw sun protecinfa nd amount f suncre aplid n vio.
Br J Dermatol207; ;9-617:651 174930; PMID: .x 48670 2.3 1 -56 .j/1 0l gro.i d x / :pt h
56. Beyr DM, AaurschoF M,Haedrsl WufC. Clothing reducs sun protecinfa suncre.
Br J Dermatol201; 162:45-9; ;6 54891:DIMP .x 87490 2.3 1 -56 .j/1 0l gro.i d x / :pt h
57. Difey BL, Grice 1. The influec o suncre typ on .noitce orp t h Br J Dermatol197; 137:0-5;
PMID:927 634; 1 .0l/gro i d.x / :pt h /j .79 1.3 2-5631. .x 709tb3
58. PhilpsTJ, Bhawn J, Yar M, Belo Y, DLopicl Nash JF. Efect o daily versu nc iterm
on aplict sor UVimulated decu ni- o taid r skin repoin humas.JA Acad Dermtol20;
43:610-8; PMID ;51640 1 .4 2701 .djm/7601. l gro i d.x / :pt h
59. Seit S, Fourtanie A, Moyal D, Young AR. Photdamge human skin by suberythmal xpo to
solar ultravioe raditon can be atenud by suncre: a reviw. Br J Dermatol201; ;41-309:361
;14 7 902:DIMP .x 810 2.3 -56 1 j/ l.0 gro i d x / :pt h
60. Beani JC. Photprecin x. In: ocietS Francise de ,eigol tamredot hP ed. .eigol tamredot hP
:nosiaml M- ieuR Arnet, 203: 13-46.
61. Kuhn A, Gensch K, Haust M, Meuth AM, Boyer F, Dupy P, et al. Photpreciv fs of a broad-
in suncre spectrum decu ni-teloivartlu suoenatuc lups :su otamehtyre a ,dezimodnar ,del ortnoc-elcihev
study.oble-in JAm cadDermtol201;A 64:37-8; ;40 761 2:DIMP htp:/dx.oirgl016j
.350 21.9 0 da j
62. Seit S, Moyal D, Richard S, de Rigal J, Levqu JL, Hoursea C, et al. Mexoryl SX: a broad absorptin
A UV filter protecs human skin from the efcts of repatd suberythmal do of A. UV J Photcem
Photbil B 198; 4:6-7 ;92754 9:DIMP .5-2 10 )89(4 31- 0 S/61 .0l/gro i d.x / :pt h
63. Ser I, Cano JP, Picot MC, eynadirJ MeunirL. nois erp uson m I induce by acute solr-imd
ultravioe exposur in humans: prevntio by a suncre with a sun protecin factor of 15 and hig
UVA .noitce orp J Am Acad Dermatol 197; 37:18-94; ;205 729:DIMP htp:/dx.oirgl016
OS 08)79(2 69-0 1 123-5.
64. Fourtanie A, Bemrd F, Bouiln C, Marot L, Moyal D, Seit S. Protecin f skin biolgca tres by
types difrno .sne rcsnu 643178; PMID:2-hotmed0 Piunl hotderma
.x 8 10 .6 2 1870- 61.j/ 0l/gro.i d x / :pt h
65. AnathswmyHN, Loughlin SM, Cox P, Evans RL, Ulrich SE, Kripke ML. Sunlight and skin caner:
inhbto of p53 mutaions in UV-iradte mouse skin by suncre. Nat Med 197; :510-4;3
;81 24 9:DIMP .015-79 mn/8301. l gro i d.x / :pt h
6. Krekls G, Vorte C, Kuik F, et al. noitce orp-AND by :sne rcsnu .gni atsonum i-35p Eur J Dermatol
197; 7:259-6. dm.elcitra/87 9 lO/0 scod-e/tnirp e/moc. lj w / :pt h
67. Bern , Ponte J, Ponte F. Decrasdp53 xion humans-expodcrilyk after opicl
.noitce orp tohp lotamredot hP lonum iot hP 48-53;1 9Photmed: ;48 6289:DIMP .iod.x / :pt h
.x 3 0 bt.89 1 70- 61.j/ 0l gro
68. Ley RD, Fourtanie A. Sunscre protecin aginst ultravioe decu ni- o taid r pyrimdne dimers
in mouse epidrmal DNA. Photcem Photbil 197; 65:107-; ;082 19:DIMP .iod x / :pt h
org/lj 0.1 .79 1.7901- 571. b07961.xt
69. Fourtanie A. Mexoryl SX protecs aginst solar-imuted UVR-induce photcaringes in mice.

Photcem Photbil 196; 64:8-93; PMID:863475; .69 1 7 0 - 5 1.j/ 01/gro.i d x / :pt h
tb03125.x
70. Mouret S, Bogdanwicz P, Haure MJ, Castex-Riz N, Cadet J, Favier A, et al. Asemnt of the
photrecin proetis of suncre by chromatgpi measurnt of DNA damge in skin
explants. Photcem Photbil 201; 87:109-6; PMID:210948; -157 .j/ 1 0 gro.i d x / :pt h
.x 4380 . 1 2 7901
71. Thompsn SC, Joley D, Marks R. Reduction of solar keratos by regula suncre use. N Engl J Med
193; 329:147-5; PMID8 .20619 34 IMJEN/6501. gro i d.x / :pt h
72. Darlingto S, Wilams G, Neal R, Frost C, Gren A. A randomize contrled trial to ase suncre
aplicton d beta caroten suplemntaio the prevntio f solar keratos. Ach Dermatol 203;
139:45-; PMID270 htp:/dx.oirglacem13945
73. Gren A, Wilams G, Neal R, Hart V, Lesli D, Parson P, et ela Daily suncre aplicton and
betacron suplemntaio in prevntio of basl-ce and squamo-cel carinoms of the skin:
a randomise contrled trial. Lancet 19; 354:72-9; PMID:0475183; /610 . gro i d.x / :pt h
.2-861 )89(637 -04IOS
74. Gren AC, Wilams GM, Logan V, Struon GM. Reduc melano after regula suncre use:
randomize tl folw-up. J Clin Onco120; 29:57-63; PMID:21356; htp/dx.oirgl0
708. 2 JCO.01
75. Ulrich C, Jurgens S, Degn A, Hackethl M, Ulrich M, Patel MJ, et ela Prevntio f no-melaski
caner in organ transpl patiens by regula use of a suncre: a 24 months, prosectiv, a-nl
study. Br J Dermatol 209; 16(Supl 3):78-4; PMID:197536; htp:/dx.oirgl01j365-
.x 35490. 2 3 1
76. GalgherRP,Hi BjdkCD FinchamS, ColdAJ McLeanDI,t. pigmentaryxosu,Slh
factors, and risk ofnmelacyti skin caner. I. Basl cel carinom. Ah Dermatol195; 157- 3:
63; PMID:7851; htp/dx.oirgl0acem964
7. Westrdahl J, Olson H, Masbck A, Ingvar C, Jons N. Is the use of suncre a risk factor for
Res Mlanom 5:9-6; 1e? malignt ;759437 :DIMP -0938 /7901. l gro i d.x / :pt h
.70 -0 2 59 1
78. Whiteman DC, Valery P, McWhirte W, Gren AC. Risk factors for childo melano in Quenslad,
Australi. Int J Cancer 197; 70:26-31; PMID:89506; ht p:/ dx. oi rg/l0.1 2 (SIC )1097-
:07)6 1079 (5120 1 .8-2;OC.0 3>4CJI-D A: 62<
79. WolfP, Quehnbrg F, Mulegr R, Stranz B, Kerl H. Phenotypic marks, sunlight-readfco and
suncre in patiens wh cutaneos ml: an Austrian ce-olstudy. Melanom Rs 198;
8:370-; PMID:976481; .210 - 8 9 1 0 3 /79 1.0l gro i d x / :pt h
80. Westrdahl J, Ingvar C, Masbck A, Olson H. Sunscre use and malignt melano. Int J Cancer
20; 87:145-0; PMID:08614; htp:/dx.oirgl02197-5()8<4AID
.3-2;OC.0 3>2 CJI
81. Difey BL. Sunscre and melano: the futre loks bright. Br J Dermatol 205; 153:78-;
PMID:1608753; .x 92760 5 .3 12- 6 j/ l.01 gro i d x / :pt h
82. Huncharek M, Kupelnick B. Use of topical suncre ad the risk of malignt eo: a meta-nlysi
of 9067 patiens from 1 case-ontrl studie. Am J Public Health 20; 92:173-; PMID:120847;
.371 29 HPJA/501 . l gro i d x / :pt h
83. Denis LK, Bean Freman LE, VanBek MJ. Sunscre use and the risk for melano: a quantive
reviw. An Inter Med 203; 139:6-78; .61987641:DIMP
84. Elwod JM, Jopsn .1 elanomM and sun exposur: an overiw of published studie. Int J Cancer 197;
73:198-20; PMID:93542; htp:/dx.oirgl02(SIC)197-53<8AD
.R-2;OC.0 3>6CJI
85. Walter SD, King WD, MaretL. ofAsciatn whmelocutansig xpr intem
to ultravioe dn: result of a case-ontrl udy in Ontario, Cand. Int J Epidemol19; 28:41-
27; PMID:104583; .814 3 2/eji 901. l/groL d x :pt h
86. Stem RS; PUVA Folw up Study. The risk of melano in asocitn wh long-term xpsu to PUVA.
JAm Acad Dermatol201; 4:75-61; PMID:13240; .67541 0 2 djm/76 1. l gro i d x / :pt h
87. GalgherRP, Rivers JK, Le TK, Bajdik CD, McLean DI, Coldman AJ. Broad-spectumn and
the devlopmntf new nevi in white children: A randomize ctl ria. JAM 20; 283:95-60;
PMID:0865273; ht p:/ dx. oi rg l0 jam 283 95 .
8. Autier P, Dore JF, Negri S, Lienard D, Panizo R, Lejun FJ, et ela Sunscre use and duration of sun
exposur: a double-in, ramz til. JNatl Cancer Inst 19; :304- PMID:043619; htp:/
15.304dxoirg/l 1093/jnci.
SNE RCSNU 463
89. GodarDE, Ppe SJ, Grant WB,HolickMF. Sar UV dosef andult Americsv Or.) .noitcudorp
;1 02lonirc d eotamr D 3:24-50; ;2569 2 :DIMP .29 51 4.3 mred/16 4.0l/gro.i d x / :pt h
90. E,Hypone Power C. si on mativopyH D in Britsh adul t age 45 y: ediwnoitan cohrt sudy of dietary
and lifesty .srotciderp Am J Clin Nutr 207; 85:60-; .0154 371:DIMP
91. Matsuok LY, Ide L, Wortsman J, nilhguaLc M JA, Holick MF. sne rcsnuS supre ctanovim
D3 .si ehtnys J Clin lonircodnE Metab 1987; 64: ;8-561 ;80 3 0 :DIMP htp:/dx.oirgl021
.561 - 46-mecj
92. Matsuok LY, Wortsman J, Holis BW. Use of topical suncre fo the evalution f regional syth
of vitamn D3. J Am Acad Dermatol190; 2:7-5; ;63416 2:DIMP htp:/dx.oirgl0169-
.S-701 7)09(2 69
93. nilhguaLc M JA, Anderso R, Holick MF. Spectral charte of sunlight modulates si ehtnysot hp of
previtamnD3 and its sremosi tohp in human skin. Scien 1982; ;3-10 :612 ;48 1 26:DIMP htp:/
.48 1 26.ecn i s/621 .0l/gro.i d x
94. Web AR, DeCostaBR, Holick MF. Sunlightreas ofprductinaes vitamn D 3 by causing
bateMlonirc d E lCJ.noitad rge ohpsti /012 . l gro i d.x / :pt h;851 4 2:DIMP;7-28 : 6;9 1
.28 -5 86-mecj
95. BA,KDLimCoperHWGlchst ira eF-f ohcsiB HA, RigelDS Cyr WH, et bohsanigl. Suht,
and vitamn D. J Am Acad Dermatol 205; ;67-86 :25 ;084 58 1:DIMP htp:/dx.oirgl016j
03.15 jad.205
96. Thiedn E, Philpsen PA, Heydnrich J, Wulf HC. Vitamn D lev in sumer and winter relatd to
UVRmeasurd xpo n .roivaheb Photbil209;cem MID:148-5 ;28390791 htp:/
dx.oirg/l0j175-926
97. Marks R, Foley PA, Joley D, Knight R, Harison J, Thompsn SC. The efct of regula suncre
on vitamn D levs in an Australin .noitalupo Result of a dezimodnar trial.coned Arh Dematol
195; ;12-514: 31 ;285627 :DIMP .60 34 1 9 .5 l mredhc a/ 0 l. groL d x / :pt h
98. Fareons J, Barnds M, Rodriguez J, Renau A, Yoldi B, da iv N-zep6L A, et al. Clincay presbd
suncre( protecinfa 15) does not decrasum vitan D noitar nec o eithrsufcnly
to induce changes in parthyoid functio or in metabolic markes. Br J Dermatol 198; ;7-2 4:931
;68276 9:DIMP .x 5042 .89 1 3 2-56 1.j/ 40l /gro.i d x / :pt h
9. A, Faurscho Bey DM, A Schmeds Bogen MK, PAhilps WufHC. The rlation bewsuc
layer thicknes and vitamn D productin after ultravioe B :erusopxe a randomize cl trial. Br
J Dermatol201; ;5-193:761 ;578215 2:DIMP htp:/dx.oirgl01j365-24
10. Chen L, Hu JY, Wang SQ. The role of stnadixo tna in :noitce orp tohp A crital reviw. J Am Acad
Dermatol201; ;42-310 :76 ;90 .2 1 da j. /610l gro.i d x / :pt h .1326042 :DIMP
10. Wang SQ, StanfieldJW, U.Osterwald In vitro stnems e sa of A UV protecin by poular suncre
avilbe n the United Staes. J Am Acad Dermatol 208; ;24- 39: 5 PMID: ;460538 1 .iod x / :pt h
.340 7 .8 02 da j. /610 . l/gro
02. 1 D, Yarosh KleinJ O'Conr A, HawkJ Rafl E, WolfP; musotnemgiPa redo X StudyEfecoGrp.
4 T aplied tocy esa lcunod e V on i sklpmencar xod :musotnemgip arndomise
study. Lance 201; 357:926-; PMID ;0539821 .8-412 0) (637 -041 S/6 0l. /gro i d.x / :pt h
103. Steg H, Roza L, Vink A, Grew M, Ruzicka T, kceB-r hterG S, et al. Enzyme plus light therapy to
repai DNA damge in detai r -B teloivartlu human ski. Proc Natl Acad Sci USA 20; 97:10-5;
PMID: ;7860 601 l/groL d.x / :pt h 0.1 .798 2503 .sanp/370
104. Hercbg S, Ezedin K, Guinot C, Prezios P, Galn P, Bertais S, et al. Antioxda noita nem lp us
the incras k of skin caer in wome but not in men. J Nutr 207; 137 ;501-8902: PMID: .94 907 1
105. GludL,RBjeakovicNDC.trsnSmf Moaliy rndzetx
stnem lp us for primay nd secondary :noitnev rp sytemaic rvw and .si ylan -atem JAM 207;
;75-248:792 PMID: ;6257 3 1 .248 792.am j/10 . l/gro.i d x / :pt h
106. Lambert JD, Sang S, Yang CS. Posible ysrevortnoc over dietary :slonehpylop benfits vs risk. Chern
Res Toxicl207; 20:583-; ;3 026371:DIMP .51 0 7xt/120l.OI/gro.i d x / :pt h
107. Difey BL. Sunscre as a evita nev rp measur in :amonalem an desab-ecn dive aproch or the
yranoituacerp princle? Br J Dermatol 209; 16(Supl 3):25-7; ;35 7 91:DIMP Lod.x / :pt h
org/I0.l j 1365-2 . 0 9 4 x
108. McCarthy oHW The Australin expc in sun protecin ad screnig fo .amonalem J Surg Oncol
204; ;54-632:68 ;03912 51:DIMP .680 2.osj/20 1. /groL d.x / :pt h
109. ofCuncilDretv the EC. .)CE /867/ ( List of the UVpermitd fls whic produtsmaye
.niatnoc Anex VI. 205; .4-201: 0
10. cituepar hT Gods .noitar sin mdA Australin regulatoy guidelns for OTC medicns .)MOGRA(
.mth sne rc us-0l mogra-ct /yr sudni/ a.vog t.w / :pt h.sne rc uS.210 rebotc021.3 noisreV

Sunscreen (2014)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Sunscreen (2014)

Uploaded by

Copyright:

Available Formats

CHAPTER 25

1-.· .-.- .• Br ehtyrE- * .*.v~mn03sYnthes~J

EF ECTS OF UV RADI T ON IN HUMAN SKIN

Figure 2. Pentraio of UV raditon into the skin.

Delayed tan ing

Figure 3. Biolgc efcts of UVR in human skin.

the German t "Lichtswel (g-ndu calosity"). Th penomrvids

DETRIMENTAL EF ECTS OF SOLAR RADIATION BEYOND

TOPICAL PHOTOPROTECTION AGENTS

MEASURING PHOT PROTECTION

MED with the tes d sun cre n

This MED-related procedure has the advantage compared with in vitro

Figure 4. Reduction of eryth mogenic UVR by suncre.

REGULATIONS AND MARKETING

Sunscre n marketing is submit ed to national legis at on. Thes regulations are

Organic UV filter sub tances mainly act by absorption of phot ns in the UV

Figure 5. Mechanism of UVB absorptin by the "clasi UV filter PAB.

IMC 3-Methylbutyl 10% Neo Heliopan 289nm EU,Au

the imtl betw n UVA2 and UVA1 34 m).n The

(tlb$opi>n peal a t 305

0,2 . Microf ne Ti02 ' '"

EF ICA Y OF SUN CRE NS

In sumary, het to ated avilbe epid m ol g c dat do not formaly prove a

SUN CRE NS AND VITAMIN D 3 SYNTHESI

Besid t wel-kno y role in skelta homi, vtan D has ben rpotd

ALTERNATIVE PHOT PROTECTIVE AGENTS

In sumary, the role of antioxs in skin caner prevntio is rathe doubtfl: In

CONCLUSION AND DISCU SION

choie is no easy deal: For lack of standrizo A UV protecin tesing, A-PF UV

69. Fourtanie A. Mexoryl SX protecs aginst solar-imuted UVR-induce photcaringes in mice.

You might also like