Kemikalije v okolju in rak

&,3.DWDORåQL]DSLVRSXEOLNDFLML

1DURGQDLQXQLYHU]LWHWQDNQMLåQLFD/MXEOMDQD 616-006-02:661(082)

6(0,1$5,QPHPRULDPGU'XãDQD5HMH/MXEOMDQD

.HPLNDOLMHYRNROMXLQUDN;;,9VHPLQDU,QPHPRULDPGU'XãDQD5HMH YRUJDQL]DFLML=YH]HVORYHQVNLKGUXãWHY]DERMSURWLUDNX>LQ@2QNRORãNHJD LQãWLWXWD/MXEOMDQD>LQ@1DFLRQDOQHJDLQãWLWXWD]DMDYQR]GUDYMH>XUHGQLãNL RGERU%UDQLVODYD%HORYLüHWDO@/MXEOMDQD=YH]DVORYHQVNLKGUXãWHY]D ERMSURWLUDNX

,6%1

%HORYLü%UDQLVODYD=YH]DVORYHQVNLKGUXãWHY]DERMSURWLUDNX 2QNRORãNLLQãWLWXW/MXEOMDQD1DFLRQDOQLLQãWLWXW]DMDYQR]GUDYMH/MXEOMDQD 286625280

6/29(1,-$3527,5$.8

'HVHWOHWQL]GUDYVWYHQRY]JRMQLSURJUDP]D]PDQMãDQMH]EROHYQRVWLLQXPUOMLYRVWL]DUDNRP .(0,.$/,-(92.2/-8,15$.

;;,9VHPLQDUª,QPHPRULDPGU'XãDQD5HMH©

YRUJDQL]DFLML=YH]HVORYHQVNLKGUXãWHY]DERMSURWLUDNX2QNRORãNHJDLQãWLWXWD/MXEOMDQDLQ 1DFLRQDOQHJDLQãWLWXWD]DMDYQR]GUDYMH

=ERUQLNMHSULSUDYLODLQ]DORåLOD=YH]DVORYHQVNLKGUXãWHY]DERMSURWLUDNX ,]GDMR]ERUQLNDLQL]YHGERVHPLQDUMDVRRPRJRþLOL

0LQLVWUVWYR]D]GUDYMH562QNRORãNLLQãWLWXW/MXEOMDQDLQVSRQ]RUMLJOVWU

=ERUQLNMHEUH]SODþHQ1DPHQMHQMH]GUDYQLNRPLQGUXJLP]GUDYVWYHQLPGHODYFHP SURIHVRUMHPLQSUHGDYDWHOMHP]GUDYVWYHQHY]JRMHLQYVHPGUXJLPNLGHODMRQDSRGURþMX ]GUDYVWYHQHY]JRMH

2GJRYRUQDXUHGQLFD GU0DMD3ULPLFäDNHOMGUPHG 8UHGQLãNLRGERU SULPPDJ%UDQLVODYD%HORYLüGUPHG

SURIGU0DMDýHPDåDUXQLYGLSOELRO

GU/XFLMD3HUKDULþGUPHG

GU0DMD3ULPLFäDNHOMGUPHG

L]USURIGU9HVQD=DGQLNGUPHG

$PDOLMD=GHãDUVHNUHWDUND

5HFHQ]HQWND SURIGU0DMDýHPDåDUXQLYGLSOELRO 2EOLNRYDQMHQDVORYQLFH PDJ7MDãDäXUJDäDENDU

/HNWRULQWHKQLþQLXUHGQLN 7RQHäDNHOM

7LVN 6WXGLR1/MXEOMDQD

1DNODGD L]YRGRY

/MXEOMDQDRNWREHU

KAZALO

UVODNIK

0DMD3ULPLFäDNHOM RAZISKOVANJE VPLIVA OKOLJA NA ZBOLEVANJE ZA RAKOM IN OCENJEVANJE TVEGANJA

9HVQD=DGQLN RAKOTVORNO DELOVANJE KEMIKALIJ IZ OKOLJA

0HWND)LOLSLþ HORMONSKI MOTILCI

/XFLMD3HUKDULþ 8ý,1.,5$.279251,+.(0,.$/,-9=5$.81$='5$9-(

$QGUHMD.XNHF$QMD-XWUDå=DOD-DQ$Q*DOLþLþ ZDRAVA TLA – ZDRAVI LJUDJE

0DUNR=XSDQ KEMIKALIJE V PITNI VODI

,YDQND*DOH RAKOTVORNE KEMIKALIJE V HRANI

8UãND%OD]QLN0RMFD)XDUW*DWQLN KLIMATSKE SPREMEMBE IN ZDRAVJE

/XþND.DMIHå%RJDWDM DRUGI VIRI IZPOSTAVLJENOSTI KEMIKALIJAM IZ OKOLJA:

NADZOR IN OMEJEVANJE TVEGANJ ZA ZDRAVJE

$ORM]*UDEQHU KOMUNIKACIJA O OKOLJSKIH TVEGANJIH

'DULQND3HN'UDSDO SEZNAM IN NASLOVI AVTORJEV

XXIV. seminar “In memoriam dr. 'XãDQD5HMH´VRILQDQþQRSRGSUOL

$675$=(1(&$8./WG3RGUXåQLFD/MXEOMDQD/MXEOMDQD (/,/,//<)DUPDFHYWVNDGUXåEDGRR/MXEOMDQD

)XQGDFLMDª'RFGU-&+2/(:$©/MXEOMDQD -2+1621 -2+1621GRR/MXEOMDQD

0$5,7,0GRR/MXEOMDQD

0(',/,1(0HãDQDWUJRYVNDGUXåEDGRR.DPQLN 0(5&.GRR/MXEOMDQD

52&+(IDUPDFHYWVNDGUXåEDGRR/MXEOMDQD

UVODNIK

Zveza slovenskih društev za boj proti raku je bila ustanovljena 1. marca 1984 in danes povezuje 11 regijskih društev. Je naslednica Društva za boj proti UDNXNLMHQDVWDORDSULODQDSREXGRSURIHVRULFHGU%RåHQH5DYQLKDU Njegov namen je bil zmanjšati zbolevnost in umrljivost za rakom v Sloveniji ter gmotno pomagati pri opremljanju Onkološkega inštituta. Ministrstvo za ]GUDYMH5HSXEOLNH6ORYHQLMHMH=YH]LSRGHOLORVWDWXVKXPDQLWDUQHRUJDQL]D cije in status društva, ki deluje v javnem interesu. Zveza slovenskih društev za boj proti raku si z regijskimi društvi prizadeva postati prepoznaven GHOHåQLNYFHORYLWHPSURJUDPXREYODGRYDQMDUDNDY6ORYHQLML

2VQRYQR SRVODQVWYR ]YH]H LQ GUXãWHY MH SULVSHYDWL N XVWYDUMDQMX WDNH VOR YHQVNHGUXåEH YNDWHULQHELQLKþH ]EROHODOLXPUO]DUDNRP]DUDGLODVWQH QHYHGQRVWLDOL]DUDGLEUH]EULåQRVWLGUåDYH

1DãD QDMSRPHPEQHMãD QDORJD MH ]GUDYVWYHQR RVYHãþDWL LQ L]REUDåHYDWL MDYQRVW SUL þHPHU VR Y YHOLNR SRPRþ NUDWND LQ MDVQD L]KRGLãþQD SULSRURþLOD Evropskega kodeksa proti raku. Vsako od postavk Kodeksa OMXGHP SRMD snjujemo z dodatnimi informacijami in razlagami, ki jih podajamo v pisnih JUDGLYLK SRVHEHM L]GHODQLK ]D UD]OLþQH FLOMQH VNXSLQH LQ RUJDQL]LUDPR GRGDWQD L]REUDåHYDQMD 2VQRYQRãROFL VR RGOLþQR VSUHMHOL QDã YVHGUåDYQL SURJUDP NL PHG QMLPL åH GROJR YUVWR OHW VSRGEXMD ]GUDY åLYOMHQMVNL VORJ QDPUHþåLYOMHQMHEUH]NDMHQMD3URJUDPVHLPHQXMHäLYOMHQMHMHOHSR±VNUELP ]D VYRMH ]GUDYMH 8þHQFH YDEL N SRGSLVX VORYHVQH REOMXEH GD Y WHNRþHP ãROVNHP OHWX QH ERGR ]DþHOL NDGLWL 0HG SRGSLVQLNL YVDNR OHWR L]åUHEDPR EOL]X XþHQFHY NL MLK QDJUDGLPR ] HQRGQHYQLP L]OHWRP Y ]DEDYLãþQL park Gardaland.

Druge naše naloge so zagovorništvo, zbiranje sredstev za akcije, s katerimi SRVNXãDPR GRVHþL HWDSQH FLOMH ]DVWDYOMHQH Y OHWQLK QDþUWLK SRYH]RYDQMH regijskih društev za boj proti raku, sodelovanje z drugimi sorodnimi društvi in organizacijami doma, v Evropi in v svetu.

3ROHJ]GUDYVWYHQRY]JRMQLKDNFLMNLMLKSULUHMD=YH]DYWHVQHPVRGHORYDQMX z regijskimi društvi, si društva v svojem okolju prizadevajo za skupne cilje še z lokalnimi akcijami.

3UL ]GUDYVWYHQHP RVYHãþDQMX ODLþQH MDYQRVWL LPDMR ]HOR SRPHPEQR YORJR vsi zdravstveni delavci na primarni ravni zdravstvenega varstva in zaposleni YãROVWYX=DWRVL=YH]DåHYHþOHWSUL]DGHYDVSRPRþMRXYHOMDYOMHQLKVWUR NRYQMDNRY GRGDWQR SULEOLåDWL ]QDQMH R YVHK PRåQRVWLK REYODGRYDQMD UDND GUXåLQVNLP]GUDYQLNRPGUXJLP]GUDYVWYHQLPGHODYFHPLQXþLWHOMHP]GUDY stvene vzgoje, ki naj to znanje predajajo ljudem, za katere skrbijo. Letos ]DWRåHãWLULLQGYDMVHWLþSULUHMDPRVHPLQDUYVSRPLQGU'XãDQD5HMHWRNUDW

je namenjen pregledu morebitnih zdravstvenih posledic, med njimi tudi UDNDYLKEROH]QL]DUDGLNHPLþQLKRQHVQDåHYDOYRNROMX

=QDQRMHGDELELORPRJRþHVNRUDMSRORYLFRYVHKUDNDYLKEROH]QLSUHSUHþLWL ] ]GUDYLP åLYOMHQMVNLPVORJRPUHGQRXGHOHåER Y SUHVHMDOQLKSURJUDPLK]D UDNDSDWXGL]åLYOMHQMHPYþLPPDQMRQHVQDåHQHPELYDOQHPLQGHORYQHP RNROMX

.HU MH QD WHP SRGURþMX ãH YHOLNR ]PRWQLK SUHGVWDY LQ QHMDVQRVWL WRNUDWQL seminar namenjamo pregledu znanstvenih dognanj o povezanosti med NHPLNDOLMDPLYRNROMXLQUDNDYLPLEROH]QLPL

=YH]DVORYHQVNLKGUXãWHY]DERMSURWLUDNXVH]DKYDOMXMHYVHPSUHGDYDWHOMHP LQ VSRQ]RUMHP NL VRGHOXMHWH SUL SULSUDYL LQ L]YHGEL 5HMHYHJD VHPLQDUMD WHUYVHPNLVWHQDPVVYRMRXGHOHåERGRND]DOLGDQDãHGHORVSUHMHPDWHLQ FHQLWH

0DMD3ULPLFäDNHOM

predsednica Zveze slovenskih društev za boj proti raku

RAZISKOVANJE VPLIVA OKOLJA NA ZBOLEVANJE ZA RAKOM IN OCENJEVANJE TVEGANJA

Vesna Zadnik

Povzetek7DNRQDJOREDOQLNRWWXGLQDORNDOQLUDYQLVRYHOLNHUD]OLNHYRQHVQDåHQRVWLRNROMD VNODGQR V WHP SD VH UD]OLNXMHWD WXGL L]SRVWDYOMHQRVW LQ RJURåHQRVW ]GUDYMD ]DUDGL ELYDQMD Y RQHVQDåHQHP RNROMX 9 0HGQDURGQL DJHQFLML ]D UD]LVNRYDQMH UDND VR GR NRQFD OHWD LGHQWLILFLUDOLNHPLNDOLMR]LURPDRNROLãþLQ]QDþLOQLK]DRQHVQDåHQRRNROMHNL]DJRWRYRYHþDMR WYHJDQMH UDND SUL OMXGHK 0HG QMLPLN EUHPHQX UDND QDMYHþSULVSHYD RQHVQDåHQ ]XQDQML ]UDN NRWFHORWDNLMHELOPHGGRND]DQHNDQFHURJHQHXYUãþHQOHWDâWHYLOQLVWURNRYQMDNLGDQHV PHQLMRGDMHEUHPHUDND]DUDGLGHMDYQLNRYL]ELYDOQHJDRNROMDSUHFHMYHþMHRG

9 RFHQMHYDQMX RJURåHQRVWL ]GUDYMD OMXGL ]DUDGL QMLKRYH L]SRVWDYOMHQRVWL NHPLNDOLMDP Y RNROMX XSRUDEOMDPR ]QDQVWYHQH PHWRGH .OMXE ]QDQVWYHQRVWL SRVWRSNRY SD QH GRORþDPR NDNãQR WYHJDQMHMH]DSUHELYDOFHVSUHMHPOMLYRLQNDNãQRMHLQGLYLGXDOQRWYHJDQMH2FHQMHYDQMHWYHJD QMD SRWHND Y ãWLULK VWRSQMDK LGHQWLILNDFLMD QHYDUQRVWL RFHQD XþLQND RFHQD L]SRVWDYOMHQRVWL LQ GRORþLWHYWYHJDQMD6NOHSQL GHORFHQMHYDQMD MH SULSUDYD NRQNUHWQLK]DNOMXþNRYLQSULSRURþLOWHU QMLKRYDSULPHUQDSUHGVWDYLWHYFLYLOQLGUXåELLQSROLWLNL

UVOD

3RMDYNDWHUHNROLUDNDYHEROH]QLMHNRQþQLUH]XOWDWGHORYDQMDYVHKãNRGOMLYLK LQ]DãþLWQLKGHMDYQLNRY]DNDWHUHVPRRGJRYRUQLERGLVLVDPLVVYRMLPL]GUD YLPL DOL QH]GUDYLPL åLYOMHQMVNLPL QDYDGDPL ERGLVL MH SRMDY SRVOHGLFD L]SR VWDYOMHQRVWLNHPLNDOLMDPIL]LNDOQLPLQELRORãNLPGHMDYQLNRPYRQHVQDåHQHP GHORYQHPDOL ELYDOQHPRNROMXRGORþLOQD SDMHWXGL GHGQDQDJQMHQRVW3UDY ]DWR YVL NL VR L]SRVWDYOMHQL NDNHPX ãNRGOMLYHPX GHMDYQLNX QH ]EROLMR ]D UDNRP 3UL UDNX WDNR QH JRYRULPR R SRY]URþLWHOMLK SDþ SD R QHYDUQRVWQLK GHMDYQLNLKNHUL]SRVWDYOMHQRVWNDWHUHPXRGQMLKãHQHSRPHQLGDERYVDN L]SRVWDYOMHQL]DJRWRYR]EROHODPSDNOHGDMHYHUMHWQRVWR]QHYDUQRVWGD ER]EROHOYHþMDNRWSULWLVWHPNLWHPXGHMDYQLNXQLL]SRVWDYOMHQ

=LQGXVWULDOL]DFLMRVRVH]DþHOHYQDãHPELYDOQHPRNROMX±]UDNXYRGLSUVWL±

QDODJDWL ãWHYLOQH RUJDQVNH LQ DQRUJDQVNH NHPLMVNH VSRMLQH 7HP VQRYHP VPRL]SRVWDYOMHQLYVLYYVHKåLYOMHQMVNLKREGREMLKMLKYRUJDQL]HPYQDãDPR ] YGLKDYDQMHP XåLYDQMHP KUDQH LQ SLMDþH WHU WXGL RE QHSRVUHGQHP VWLNX 6OHGRYH RNROMVNLK RQHVQDåHYDO ODKNR GRNDåHPR åH SUL QRYRURMHQþNLK 9 PHGLFLQVNLVWURNLMH]QDQLKSUHFHMEROH]QLLQVWDQMNLVRSRVOHGLFDL]SRVWDY OMHQRVWLQHYDUQLPVQRYHPYRNROMX9HþLQRPDJUH]DDNXWQH]DVWUXSLWYHNL VR SRVOHGLFD QHQDPHUQH L]SRVWDYOMHQRVWL OMXGL YLVRNLP NRQFHQWUDFLMDP QHYDUQLK VQRYL YHþLQRPD GHODYFHY QD GHORYQLK PHVWLK ODKNR SD WH VQRYL RQHVQDåLMR WXGL RNROMH LQ VR QHYDUQH ]D L]SRVWDYOMHQR SUHELYDOVWYR 'ROJR WUDMQHMãD L]SRVWDYOMHQRVW QLåMLP NRQFHQWUDFLMDP QHNDWHULK VQRYL ODKNR SRY]URþLNURQLþQHVSUHPHPEH=MDYQR]GUDYVWYHQHJDYLGLNDVRSRPHPEQH

zlasti bolezni dihalnih poti, alergije in rak [1]. Med rake, ki lahko nastanejo tudi kot posledica izpostavljenosti kemikalijam v delovnem ali bivalnem RNROMX XYUãþDMR UDNH SOMXþ NRåH VHþQHJD PHKXUMD SRSOMXþQLFH LQ SRWUH bušnice (npr. mezoteliom zaradi delovanja azbesta), bezgavk, jeter, ledvic, levkemije ter, manj pa še nekatere druge vrste rakov [2].

5DYHQ L]SRVWDYOMHQRVWL MH QDMEROM RGYLVQD RG JHRJUDIVNHJD REPRþMD NMHU SRVDPH]QLNSUHåLYLYHþLQR þDVD7DNRQDJOREDOQLNRWWXGLQD ORNDOQLUDYQL VRQDPUHþYHOLNHUD]OLNHYRQHVQDåHQRVWLRNROMDVNODGQR]QMLPLSDVHUD]OL NXMHWDWXGLL]SRVWDYOMHQRVWLQWYHJDQMHGDERNGR]DUDGLELYDQMDYRQHVQD åHQHP RNROMX ]EROHO 2QHVQDåHQMH MH QD JOREDOQL UDYQL QDMEROM NULWLþQR Y YLVRNR DOL SD QD QRYR LQ KLWUR LQGXVWULDOL]LUDQLK GUåDYDK SUHGYVHP Y PDQM UD]YLWLK GHOLK VYHWD NMHU VWD ]DNRQRGDMD LQ QDG]RU SRPDQMNOMLYD DOL SUHYHþ ohlapna [2].

7XGLY6ORYHQLMLVRREPRþMDNMHUVRSUHELYDOFL]DUDGLRQHVQDåHQRVWL]UDND YRGHLQSUVWLEROMRJURåHQL]QHNDWHULPLUDNL=GRND]DQRDOLYHUMHWQRUDNRWYRU QLPLVQRYPLRQHVQDåHQRRNROMHMHSULQDVSRVOHGLFDSUHWHNOLKLQGXVWULMVNLK L]SXVWRYLQRGODJDOLãþ$QKRYR±D]EHVW%HODNUDMLQD±SROLNORULUDQLELIHQLOL

=DVDYMH±SUDãQLGHOFL EHQ]HQ&HOMVNDNRWOLQD±WHåNHNRYLQHUXGDUMHQMD ,GULMD±åLYRVUHEURäLURYVNLYUK±XUDQ0HåLFD±VYLQHF.RþHYMH±UDGRQ LQWHQ]LYQHJDNPHWLMVWYD'UDYVNRSROMH±SHVWLFLGLDOLSURPHWDYHþMHFHVWH LQPHVWQDVUHGLãþD±SUDãQLGHOFLEHQ]HQåHOH]QLãNHSURJH±SHVWLFLGL9 strokovnih krogih, predvsem pa v raznih skupinah s civilnimi iniciativami, pa RVWDMDMRRGSUWDYSUDãDQMDRYHþMHPWYHJDQMXUDNDSUHELYDOFHYWXGLãWHYLOQLK GUXJLKREPRþLM1DGUåDYQLUDYQL]DHQNUDWQLPDPRVHVWDYOMHQHJDSUHJOHGD REPRþML NMHU MH ]DUDGL L]SRVWDYOMHQRVWL RQHVQDåHYDORP Y ELYDOQHP RNROMX ]GUDYMHSUHELYDOFHYRJURåHQR1DMEROMVPRVHWDNHPXVH]QDPXSULEOLåDOL]

Y]SRVWDYLWYLMR GHJUDGLUDQLK RNROLM NLMLK ODKNR QD SRGODJL=DNRQDR YDUVWYX RNROMD 8U O 56 ãW GRORþL YODGD SRYVRG WDP NMHU VR NHPLþQD DOL PLNURELRORãNDRQHVQDåHYDODYRNROMXYNRQFHQWUDFLMDKNLSRPHQLMRJURåQMR ]D]GUDYMHOMXGLR]LURPDSUHVHJDMRYUHGQRVWLGRORþHQHYSUHGSLVLKþH]PHUQR REUHPHQMHQDREPRþMDDOLSDVHNRQFHQWUDFLMHNHPLþQLKDOLPLNURELRORãNLK RQHVQDåHYDOYRNROMX]DUDGLYSOLYDPHWHRURORãNLKLQGUXJLK]XQDQMLKGHMDYQL NRYREþDVQRWDNR]YLãDMRGDSRPHQLMRJURåQMR]D]GUDYMHOMXGLSRWHQFLDOQR REUHPHQMHQDREPRþMD

'2/2ý$1-(5$.279251267,21(61$ä(9$/

0RUHELWQRUDNRWYRUQRVWNDNHVQRYLXJRWDYOMDMR]ED]LþQLPLLQHSLGHPLRORãNLPL UD]LVNDYDPL 3UL ED]LþQLK ODERUDWRULMVNLK UD]LVNDYDK JUH ]D NUDWNRWUDMQH SRVNXVH QD FHOLþQLK NXOWXUDK LQ EDNWHULMDK WHU ]D GROJRWUDMQH QD åLYDOLK = DQDOLWLþQLPL HSLGHPLRORãNLPL UD]LVNDYDPL SUHYHUMDMR SRYH]DQRVW PHG L]SR VWDYOMHQRVWMR LQ UDNRP SUL þORYHNX 2 WHP DOL MH WD ]YH]D SUL þORYHNX UHV

Y]URþQD YHþLQRPD SUHVRMDMR VNXSLQH VWURNRYQMDNRY NL VQRYL SR VWURJR GRORþHQLK PHULOLK UD]YUãþDMR Y YHþ VNXSLQ JOHGH QD VWRSQMR GRND]DQH SRYH]DQRVWL]UDNRP

(GHQQDMREVHåQHMãLKLQQDMNDNRYRVWQHMãLKVH]QDPRYQDVWDMDY0HGQDURGQL DJHQFLML ]D UD]LVNRYDQMH UDND L] /\RQDInternational Agency for Research on Cancer,$5&NLMHSRVHEQDDJHQFLMD6YHWRYQH]GUDYVWYHQHRUJDQL]D FLMH >@9 VH]QDPX WH DJHQFLMH VR NHPLNDOLMH QMLKRYH ]PHVL DOLSURL]YRGQL SRVWRSNLSDWXGLYLUXVLLQIL]LNDOQLGHMDYQLNLUD]YUãþHQLYãWLULVNXSLQH9SUYL VNXSLQLVNXSLQDVRWLVWL]DNDWHUHMHGRYROMGRND]RYRNDUFLQRJHQRVWL]D OMXGLPHGQMLPLVRQDMEROM]QDQLD]EHVWWREDþQLGLPDONRKROQHSLMDþHLWG Y GUXJL VNXSLQL VR WLVWL ]D NDWHUH Y]URþQD ]YH]D ãH QL GRND]DQD MH SD YHUMHWQD7RVNXSLQRGHOLPRQDSRGVNXSLQR$NDPRUVRXYUãþHQLYHUMHWQL NDQFHURJHQLSULNDWHULK LPDPRRPHMHQHGRND]HSULOMXGHKLQSUHFHM ]DQH VOMLYH GRND]H L] HNVSHULPHQWDOQLK UD]LVNDY R]LURPD SR]QDPR PHKDQL]PH QDVWDQNDUDNDWHUSRGVNXSLQR%NDPRUVRXYUãþHQHPRåQHNDQFHURJHQH VQRYL9SULPHUMDYLVVNXSLQR$LPDPR]DVQRYLYVNXSLQL%PDQMGRND]RY R NDQFHURJHQRVWL R]LURPD QH PRUHPR L]NOMXþLWL GUXJLK PRåQLK UD]ODJ 9 WUHWML VNXSLQL VR NHPLNDOLMH LQ GUXJL GHMDYQLNL NL VR MLK VLFHU åH SURXþHYDOL YHQGDUMLK]DHQNUDWãHQLPRJRþHXYUVWLWLYQREHQRRGSUHMRPHQMHQLKVNX SLQLQWXGLQHYþHWUWRNDPRUVRGLMRNHPLNDOLMHNL]DþORYHNDQLVRNDUFLQRJHQH 6H]QDPQDRVQRYLQRYLKVSR]QDQMVWDOQRSRVRGDEOMDMRLQGRSROQMXMHMRYVHP MHGRVWRSHQQDPHGPUHåMXKWWSZZZLDUFIU

'RNRQFDOHWDVR Y ,$5& LGHQWLILFLUDOLNHPLNDOLM R]LURPDRNROLãþLQ ]QDþLOQLK ]D RQHVQDåHQR RNROMH 7DEHOD NL ]DJRWRYR YHþDMR WYHJDQMH UDNDSULOMXGHK,$5&VNXSLQDâWHYLOQLGUXJLGHMDYQLNLNLVRWXGLYRQH VQDåHQHP RNROMX QSU ãWHYLOQD REVWRMQD RUJDQVND RQHVQDåHYDOD SD VR UD]YUãþHQLYVNXSLQRPHGYHUMHWQHR]LURPDPRåQH NDQFHURJHQH>@=D SUDYLOQRRYUHGQRWHQMHGHOHåDUDNRYNDWHULKSRMDYPRUDPRSULSLVDWLELYDQMX Y RQHVQDåHQHP RNROMX MH ELOD NOMXþQD XYUVWLWHY RQHVQDåHQHJD ]UDND NRW FHORWHPHGJRWRYHNDQFHURJHQHYVNXSLQR>@2GOHWDNRVWD'ROO LQ3HWR>@REMDYLODSRHQRVWDYOMHQVH]QDPRGSUDYOMLYLKGHMDYQLNRYWYHJDQMD NLQDMYHþSULVSHYDMRNXPUOMLYRVWL]DUDGLUDNDMHQDPUHþYVWURNRYQLKNURJLK YHOMDOR GD YHþ NRW SRORYLFR VPUWL ]DUDGL UDND SRY]URþLMR GHMDYQLNL NL VR SRYH]DQL]åLYOMHQMVNLPVORJRPRNURJYVHKUDNRYQDMELELODSRVOHGLFD L]SRVWDYOMHQRVWLUDNRWYRUQLPVQRYHPQDGHORYQHPPHVWXPHGWHPNRMHELO GHOHå SULSLVDQ L]SRVWDYOMHQRVWL Y ELYDOQHP RNROMX RFHQMHQ QD ± 3R RFHQDK,$&5L]OHWD>@SDQDMELOHWQR]DUDGLYGLKDYDQMDRQHVQDåHQHJD ]XQDQMHJD ]UDND VDPR ]DUDGL SOMXþQHJD UDND XPUOR YHþNRW OMXGL NDU MH VNRUDM YVHK VPUWL ]DUDGL UDND >@ âWHYLOQL VWURNRYQMDNL GDQHV PHQLMRGDMHEUHPHUDND]DUDGLGHMDYQLNRYL]ELYDOQHJDRNROMDSUHFHMYHþMH RG>@

7DEHOD=QDQH]DJRWRYRUDNRWYRUQHVQRYL,$5&VNXSLQDNLVHQDKDMDMRYRQHVQDåHQHP RNROMXRUJDQQDNDWHUHJDGHOXMHMRLQQDMSRJRVWHMHRQHVQDåHQLPHGLMSRY]HWRSR>@

6QRY 2UJDQDOLPDOLJQRP 1DMSRJRVWHMHRQHVQDåHQLPHGLM

Arzen in njegove

anorganske spojine SOMXþDNRåDPHKXU YRGD

$]EHVWYVHKREOLN JUORSOMXþDPH]RWHOLRP

MDMþQLN zrak

Benzen DNXWQDQHOLPIRFLWQD

OHYNHPLMD ]UDNL]SXãQLSOLQL

±EXWDGLHQ OHYNHPLMDOLPIRP ]UDN

(ULRQLW PH]RWHOLRP ]UDNJHRJUDIVNRWRþNRYQR

(WLOHQRYRNVLG GRMNDOLPIRLGQLWXPRUML ]UDNQRWUDQML

)RUPDOGHKLG QRVQRåUHOROHYNHPLMD ]UDNQRWUDQMLLQ]XQDQML ,QGLYLGXDOQDNXULãþD

SUHPRJ SOMXþD ]UDNQRWUDQML

,]SXãQLSOLQLGL]HOVNLK

PRWRUMHY SOMXþD ]UDN

.URP9, SOMXþD YRGDSUVW

2QHVQDåHQ]XQDQML]UDN SOMXþD ]UDN

3UDãQLGHOFLY

RQHVQDåHQHP]XQDQMHP zraku

SOMXþD ]UDN

3ROLNORULUDQLELIHQLOL NRåD KUDQD]UDNQRWUDQML 5DGRQLQQMHJRYLUD]SDGOL

SURGXNWL SOMXþD ]UDNQRWUDQML

6LOLFLMHYSUDK SOMXþD ]UDN

7&'' YVLUDNL KUDQDSUVW

7REDþQLGLP±SDVLYQD

izpostavljenost SOMXþD ]UDNQRWUDQML

7ULNORUHWLOHQ OHGYLFD YRGDKUDQD

OCENJEVANJE TVEGANJA

3ULSUHSR]QDYDQMXGRORþDQMXLQQDG]RURYDQMXQHYDUQRVWLNLVRMLSRGYUåHQL OMXGMH]DUDGLL]SRVWDYOMHQRVWLãNRGOMLYLPGHMDYQLNRPYRNROMXJUH]DVRRGYLVQR GHORYDQMH UD]QLK GUXåEHQLK VWUXNWXU >@ &HORWQL SURFHV NL JD LPHQXMHPR DQDOL]D WYHJDQMD MH VKHPDWLþQR SULND]DQ QD 6OLNL 6HVWDYOMHQ MH L] WUHK ORþHQLKSURFHVRYNLVHPHGVHERMYVHVWUDQVNRSUHSOHWDMRLQSRYH]XMHMR9 RFHQMHYDQMX WYHJDQMD ] ]QDQVWYHQLPL PHWRGDPL RFHQMXMHPR PRåQH SRVOH GLFHL]SRVWDYOMHQRVWLQD]GUDYMHOMXGL3URFHVSRWHNDYãWLULKVWRSQMDKLGHQ WLILNDFLMDQHYDUQRVWLRFHQLXþLQNDLQL]SRVWDYOMHQRVWLWHUGRORþLWHYWYHJDQMD NLVRSRGUREQHMHSUHGVWDYOMHQHYQDGDOMHYDQMX>@2EYODGRYDQMHWYHJD QMD MH SROLWLþQR YRGHQ LQWHUGLVFLSOLQDUQL SURFHV Y NDWHUHP VH SUHGODJDMR L]ELUDMR LQ L]YDMDMR RGORþLWYH V NDWHULPL VH SRVNXãD ]PDQMãDWL WYHJDQMH SUL OMXGHKLQYHNRVLVWHPLK,]YDMDMRJDSROLWLNLVQRYDOFL]DNRQRYJRVSRGDUVWYHQLNL QDUDYRYDUVWYHQLNL LQ RVWDOL ]DLQWHUHVLUDQL SRVDPH]QLNL ,]ELUD SRVWRSNRY MH RGYLVQDRG]D]QDYDQMDQHYDUQRVWLYSUHELYDOVWYXGUXåEHQLKQRUP]DNRQRY LQ VWDQGDUGRY WHU QH QD]DGQMH RG VWURãNRY LQ XþLQNRY 0HG ]QDQVWYHQLP RFHQMHYDQMHP RJURåHQRVWL LQ SROLWLþQLPL SUL]DGHYDQML ]D QMHQR REYODGDQMH SD MH WUHED XJRWRYLWYH ]DNOMXþNH WHUSUHGYLGHQHXNUHSH SUHGVWDYOMDWLRJUR åHQLPSUHELYDOFHPWHUSRVNUEHWLGDMLKSUDYLOQRUD]XPHMRLQXSRãWHYDMR

6OLND6KHPDWLþQLSULND]SURFHVRYYDQDOL]LWYHJDQMD

Identifikacija nevarnosti

9 SUYHP NRUDNX RFHQMHYDQMD WYHJDQMD L]YHGHPR SRVWRSHN LGHQWLILNDFLMH QH YDUQRVWL 9 QMHP XJRWDYOMDPR NDWHULP VQRYHP VR ELOL OMXGMH L]SRVWDYOMHQL GRORþLPRYLUHL]SRVWDYOMHQRVWLLQRJURåHQRVNXSLQRQDNDNãHQQDþLQNDNR MHVQRYYVWRSLODYWHORLQNDNRVHMHELRWUDQVIRUPLUDODLQNDNRELODKNRL]SR

stavljenost škodovala njihovemu zdravju. V ocenjevanju tveganja ne ugotavljamo morebitne rakotvornosti snovi po postopkih, opisanih v prej- ãQMHPSRJODYMX=DYHþLQRNHPLNDOLMQMLKRYLK]PHVLSURL]YRGQLKSRVWRSNRY ELRORãNLK DJHQVRY IL]LNDOQLK GHMDYQLNRYDOL SD NDU VNXSNRY RNROLãþLQ NL VR ODKNR SUREOHPDWLþQL Y ELYDOQHP RNROMX VR NRQþQH RFHQH V NULWLþQLPL YUHG QRVWPL åH GRVWRSQH Y SRGDWNRYQLK ]ELUNDK ãNRGOMLYLK VQRYL 0HG QMLPL MH QDMSRSROQHMãD åH RPHQMHQD ]ELUND NL MR REOLNXMH ,$5& >@ NRULVWQH RFHQH SD VR GRVWRSQH WXGL QD VSOHWQLK VWUDQHK DPHULãNLK $JHQFLMH ]D ]DãþLWR okolja (Environmental Protection Agency(3$KWWSVZZZHSDJRYLULVLQ

$JHQFLMH]DVWUXSHQHVQRYLLQUHJLVWHUEROH]QLAgency for Toxic Substances and Disease Registry$76'5KWWSZZZDWVGUFGFJRY

2FHQMHYDQMHXþLQND

9RFHQMHYDQMXXþLQNDNLMHGUXJDVWRSQMDRFHQMHYDQMDWYHJDQMDXJRWDYOMDPR NDNãQH SRVOHGLFH SUL þORYHNX SRY]URþDMR UD]OLþQH VWRSQMH L]SRVWDYOMHQRVWL NDNLVQRYL=D VDPR SRãNRGER RUJDQL]PD MH QDPUHþSRPHPEHQ RGPHUHN VQRYL NROLþLQDþDV NL SULGH Y WHOR 9 RFHQMHYDQMX XþLQND WRUHM XJRWDYOMDPR kakšen je odnos med odmerkom in pojavljanjem bolezni pri ljudeh. Pri ne- UDNRWYRUQLKVXEVWDQFDK YSRGDWNRYQLK]ELUNDKãNRGOMLYLKVXEVWDQF SRLãþHPR SRGDWHNRQDMYHþMLGR]LSULNDWHULKXþLQNRYQD]GUDYMHãHQH]D]QDPRR]LURPD R QDMPDQMãL GR]L SUL NDWHUL VH XþLQNL SRMDYLMR 1D WHM SRGODJL L]UDþXQDPR NDNãQD MH QDMYHþMD GQHYQD GR]D VQRYL NL ãH QH SUL]DGHQH ]GUDYMD SRVD PH]QLND3RVDPH]QLNMLMHODKNRL]SRVWDYOMHQGQHYQRFHORåLYOMHQMH

6OLND6KHPDWLþQLSULND]RFHQMHYDQMDXþLQNDSRSUDåQHPVLYDNULYXOMDLQEUH]SUDåQHP SULVWRSXþUQDNULYXOMD

Zaradi predpostavke o majhnih dozah, ki na zdravje nimajo vpliva, se tak SULVWRS N RFHQMHYDQMX XþLQND L]SRVWDYOMHQRVWL LPHQXMH SUDåQL SULVWRS ãH YDUQDGR]DSDSUDåQDGR]DDOLNDUSUDJ1D6OLNLMHSUDåQLSULVWRSSULND ]DQVNULYXOMRYVLYLEDUYL=DUDNRWYRUQHVQRYLSULGHSUDåQLSULVWRSUHGNRY SRãWHY 1DPHVWR QMHJD Y RFHQMHYDQMX XþLQND XSRUDEOMDPR WL EUH]SUDåQL SULVWRS 6OLND þUQD NULYXOMD 9 QMHPSUHGSRVWDYOMDPR GD YHþMD GR]DQH SRPHQL KXMãHJD HIHNWD KXMãH UDNDYR EROH]HQ SDþ SD YHþMR YHUMHWQRVW EROH]QL YHþ ]EROHOLK ]D UDNRP PHG L]SRVWDYOMHQLPL VDM SRVDPH]QLN UDNDYREROH]HQODKNRGRELDOLSDQH1DPHVWRSUDåQLKGR]VHYRFHQMHYDQMX XþLQNDGRORþDVSUHMHPOMLYRWYHJDQMH

Ocenjevanje izpostavljenosti

9 WUHWMHP NRUDNX RFHQMHYDQMD WYHJDQMD SULSUDYLPR RFHQR L]SRVWDYOMHQRVWL To je postopek, pri katerem ocenjujemo dejansko izpostavljenost ljudi v FLOMQHP SUHELYDOVWYX ãNRGOMLYL VQRYL R]LURPD RFHQMXMHPR NROLNR VQRYL MH RUJDQL]HP GHMDQVNR DEVRUELUDO 0HWRGH ]D GRORþDQMH L]SRVWDYOMHQRVWL VR ãWHYLOQHLQMLKJOHGHQDQDþLQPHUMHQMDGHOLPRQDGLUHNWQHLQLQGLUHNWQH3UL GLUHNWQLKPHWRGDKVSRVHEQLPLQDSUDYDPLQDG]RUXMHPRGHMDQVNRL]SRVWDY OMHQRVWOMXGLDOLSDPHULPRNRQFHQWUDFLMRELRORãNLKND]DOQLNRYL]SRVWDYOMHQRVWL YRUJDQL]PX8SRUDEDGLUHNWQLKPHWRGMHRUJDQL]DFLMVNRLQþDVRYQR]DKWHY QD LQ ]DWR SUHFHM GUDåMD UH]XOWDWL SD VR VHYHGD YHOLNR EROM YHURGRVWRMQL Y SULPHUMDYL]LQGLUHNWQLPLPHWRGDPLSULNDWHULKYRFHQMHYDQMXXSRUDELPRWL nadomestne mere izpostavljenosti, ki dejansko izpostavljenost odrazijo bolj DOLPDQMQDWDQþQR

3ULUD]LVNRYDQMXYSOLYDRQHVQDåHQHJDRNROMDQD]EROHYDQMH]DUDNRPVH]D oceno izpostavljenosti direktne metode uporabijo le izjemoma, saj smo ]DUDGLGROJHODWHQþQHGREHYHþLQRPDSULPRUDQLYUHWURVSHNWLYQRRFHQMHYDQMH L]SRVWDYOMHQRVWL ãWHYLOR ]EROHOLK SD MH WXGL PHG L]SRVWDYOMHQLPL UHODWLYQR PDMKQRNDUSRPHQLGDPRUDPRþHVHåHOLPRYUH]XOWDWLKL]RJQLWLYSOLYRP QDNOMXþMD Y DQDOL]H YNOMXþLWL GRYROM YHOLNR ãWHYLOR OMXGLPHULWHY NDU VHYHGD UD]LVNDYRWDNRRUJDQL]DFLMVNRNRWILQDQþQRRWHåL

9 SRSXODFLMVNLK UD]LVNDYDK NMHU YSOLY ELYDOQHJD RNROMD QD SRMDYOMDQMH UDND RFHQMXMHPR QD SRGODJL UXWLQVNR ]EUDQLK SRGDWNRY Y UHJLVWULK UDND VH NRW QDGRPHVWQDPHUDL]SRVWDYOMHQRVWLQDMSRJRVWHMHXSRUDEOMDJHRJUDIVNDORND FLMDVWDOQHJDELYDOLãþDREGLDJQR]LEROH]QL96ORYHQLMLMHWDSRGDWHNGRVWRSHQ QDUDYQLJHRJUDIVNLKNRRUGLQDWNDURPRJRþDDQDOL]HQDSROMXEQRGRORþHQLK JHRJUDIVNLKHQRWDKDOLFHORQDLQGLYLGXDOQLUDYQL

3ULJHRJUDIVNLDQDOL]LMH NOMXþQD GRORþLWHYQDMSULPHUQHMãH YHOLNRVWLRVQRYQH HQRWH R]LURPD PLQLPDOQHJD ãWHYLOD SUHELYDOFHY Y WHM HQRWL .DNRYRVWQL SRGDWNLR GHMDYQLNLK WYHJDQMD NL ELMLK åHOHOL YNOMXþLWL YDQDOL]RVR UXWLQVNR

QD YROMR ]D YHþMH XSUDYQRDGPLQLVWUDWLYQR GRORþHQH HQRWH ± Y 6ORYHQLML QDMYHþNUDW SR UHJLML UHGNR QD UDYQL REþLQ *ODYQL SUREOHP YHOLNLK HQRW MH QMLKRYDKHWHURJHQRVW9UHGQRVWLXSRUDEOMHQLKVSUHPHQOMLYN]DL]EUDQRHQRWR QDPUHþ]UFDOLMR SRYSUHþMH GHMDQVNLKYUHGQRVWLSRVDPH]QLKGHORYWH HQRWH (QRWD NL LPD QD HQHP GHOX YHOLN SUHVHåHN WYHJDQMD EROH]QL QSU ]DUDGL WRþNRYQHJDLQGXVWULMVNHJDRQHVQDåHQMDVLFHUSDMHWYHJDQMHSRGSRYSUHþQR VHERYDQDOL]LSRMDYLODNRWHOHPHQWVSRYSUHþQLPWYHJDQMHP3RGURþMHNMHU MHWYHJDQMHYSUHVHåNXVHERYWHPSULPHUX]DNULOR

+HWHURJHQRVWL YHOLNLK HQRW VH L]RJQHPR ] L]ELUR PDQMãLK REPRþLM = L]ELUR PDQMãHRVQRYQHHQRWHVLFHU]YHþDPRORþOMLYRVWDKNUDWLSULUHGNLKEROH]QLKLQ PDMKQLK REPRþMLK ]YHþDPR SUREOHP YHURGRVWRMQRVWL VWDWLVWLþQLK SRGDWNRY 9HUMHWQRVW SRMDYOMDQMD UHGNH EROH]QL QD PDMKQHP REPRþMX DOL QD YHOLNHP REPRþMX ] PDMKQLP ãWHYLORP SUHELYDOFHY MH QDPUHþ PDMKQD LQ V WHP ]HOR YDULDELOQDWDNRGDVRRELþDMQRUH]XOWDWLQDGDOMQMLKDQDOL]SRVOHGLFDQDNOMXþMD VR VWDWLVWLþQR QH]QDþLOQL 6WDWLVWLþQR YHURGRVWRMQRVW ODKNR ]YHþDPR V SRGDOMãDQMHPRSD]RYDQHJDREGREMDDOLSD]XSRUDERHQHRGWHKQLNJODMHQMD NMHUQDSRGODJLGHMDQVNHJDãWHYLOD]EROHOLKYSRVDPH]QLHQRWLWHUSRGDWNRY R LQFLGHQFL Y VRVHGQMLK REPRþMLK R]LURPD GUXJLK SRPHPEQLK LQIRUPDFLM RFHQLPRRJURåHQRVW]EROH]QLMRYHQRWLNLQDV]DQLPD>@

=XSRUDERSRGDWNDRVWDOQHPSUHELYDOLãþXREGLDJQR]LNRWQDGRPHVWQHPHUH SULRFHQMHYDQMXL]SRVWDYOMHQRVWLVH YDQDOL]R ODKNRSULNUDGHMRQHNDWHUHGR GDWQHSULVWUDQRVWL9DQDOL]LVKHPDWLþQRSULND]DQLQD6OLNLVPRRFHQMHYDOL YSOLYWRþNRYQHJDLQGXVWULMVNHJDRQHVQDåHYDOFDQDSRMDYOMDQMHUDNDWDNRGD VPRL]UDþXQDOLLQPHGVHERMSULPHUMDOLWYHJDQMHUDNDSUHELYDOFHYNLåLYLMRY REPRþMXRGGDOMHQHPGRNPRGYLUDYSULPHUMDYLVWLVWLPLNLåLYLMRYSDVX

±NP RGGDOMHQHPRG YLUD WHU WLVWLPLNL åLYLMR Y RGGDOMHQRVWL ±NP RG YLUD >@ 2VQRYQD SRGPHQD MH ELOD GD Y NROLNRU WRþNRYQL LQGXVWULMVNL YLU YHþDEUHPHUDNDERGRLPHOLSUHELYDOFLYSUYHPREPRþMXQDMYHþMHWYHJDQMH YWUHWMHPSDQDMPDQMãH2EWHPVPRPHGGUXJLPSUHGSRVWDYLOLWXGLGDVR RVWDOL QHYDUQRVWQL GHMDYQLNL HQDNRPHUQR UD]SRUHMHQL Y SURVWRUX WHU GD VH ãNRGOMLYL GHMDYQLN ãLUL NRQFHQWULþQR RG WRþNRYQHJD YLUD 2EHK SUHGSRVWDYN QDMYHUMHWQHMHVNRQNUHWQLPLPHULWYDPLQHELPRJOLSRWUGLWL

'RORþLWHYWYHJDQMD

9]DGQMLID]LRFHQMHYDQMDWYHJDQMD]GUXåLPRSRGDWNHNLVPRMLKSULGRELOLY SUYLK WUHK VWRSQMDK 'RYROMHQH R]LURPD ]GUDYVWYHQR ãH VSUHMHPOMLYH L]SR VWDYOMHQRVWL SULPHUMDPR ] GHMDQVNLPLL]SRVWDYOMHQRVWPLFLOMQHJD SUHELYDOVWYD 7YHJDQMHGRORþLPR]DUD]OLþQHSRGVNXSLQH]GUDYHRGUDVOHRWURNHVWDURVW QLNHNURQLþQHEROQLNHLGU

6OLND*HRJUDIVNDDQDOL]DYSOLYDLQGXVWULMVNHJDRQHVQDåHYDODQDSRMDYOMDQMHUDND Povzeto po [13]

1DNRQFXGRORþDQMDWYHJDQMDVHPRUDPRRGORþLWL]DHQHJDL]PHG]DNOMXþNRY D GRSXVWQRWYHJDQMHMHSUHVHåHQR±SRWUHEQLVRGRGDWQLRNROMVNLLQMDYQR

]GUDYVWYHQLXNUHSLLQQMLKRYDHYDOYDFLMD

E WYHJDQMHQLYHþMHRGGRSXVWQHJD±WUHQXWQLXNUHSL]DGRãþDMR

F ]DGRORþLWHYWYHJDQMDVR SRWUHEQH GRGDWQHUD]LVNDYH±GRNRQþQHUD]

MDVQLWYHVYHWXMHPRXSRãWHYDQMHSUHYLGQRVWQHJDQDþHOD

9VSRURþLOLK]DVWURNRYQRLQODLþQRMDYQRVWPRUDPRYHGQRUD]NULWLGDVPR PHG FHORWQLP SURFHVRP RFHQMHYDQMD WYHJDQMD QDUHGLOL YHOLNR SUHGSRVWDYN ]DUDGLNDWHULKMHNRQþQDGRORþLWHYWYHJDQMDEROMDOLPDQM]DQHVOMLYD

0HGQDMSRJRVWHMãLPLY]URNLQH]DQHVOMLYRVWLGRORþLWYHWYHJDQMDVR

x UD]OLNH Y WRNVLþQRVWL LQ ELRNLQHWLþQLK PHKDQL]PLK SUL UD]OLþQLK åLYDOVNLK YUVWDK

x HNVWUDSRODFLMD]YLVRNLKQDQL]NHGR]H

x XSRUDED SRGDWNRY L] UD]LVNDYHNMHUMH SRW YQRVD ãNRGOMLYHJD GHMDYQLND GUXJDþQDNRWMHRELþDMQRSULþORYHNX

x UD]OLNH PHG VNXSLQR YNOMXþHQR Y UD]LVNDYR LQ VNXSLQR NL MH UHVQLþQR L]SRVWDYOMHQDRWURFL]GUDYLGHODYFL

x L]SRVWDYOMHQRVWGRGDWQLPGHMDYQLNRPWYHJDQMDQHVDPRSURXþHYDQHPX x QDSDþQDUD]YUVWLWHY]GUDYVWYHQLKSRVOHGLF

.OMXEXSRUDELYVHKXVWUH]QLK]QDQVWYHQLKSRVWRSNRYSDSULRFHQMHYDQMXWYH JDQMD QH GRORþLPR LQ VH QD SRGODJL GRORþLWYH WYHJDQMD QH RSUHGHOMXMHPR NDNãQRWYHJDQMHMH]DFLOMQRSUHELYDOVWYRãHVSUHMHPOMLYRDOLREVWDMDMRUD]OLNH ]QRWUDMSURXþHYDQHSRSXODFLMHR]LURPDNDNãQRMHLQGLYLGXDOQRWYHJDQMH

=$./-8ý(.

6WURNRYQMDNRPVSRGURþMDMDYQHJD]GUDYMDNRWWXGLMDYQR]GUDYVWYHQLSROLWLNL ]DVNUEOMHQDODLþQDLQVWURNRYQDMDYQRVWUHGQR]DVWDYOMDYSUDãDQMDDOLQLPRUGD QD REPRþMXNMHUåLYL YHþUDNDNRWGUXJMH9VOXåEL (SLGHPLRORJLMD LQUHJLVWHU UDNDQD2QNRORãNHPLQãWLWXWX/MXEOMDQDåHYHþNRWGHVHWOHWGHODPRDQDOL]H R UDNX QD PDQMãLK REPRþMLK Y 6ORYHQLML 3RGDWNL 5HJLVWUD UDND 5HSXEOLNH 6ORYHQLMHQDPUHþRPRJRþDMRXPHVWLWHYSRVDPH]QHJDEROQLNDQD]HPOMHYLG GR UDYQL JHRJUDIVNLK NRRUGLQDW WDNR GD ODKNR ] XSRUDER XVWUH]QLK PHWRG SURVWRUVNHJD JODMHQMD RFHQLPR PRUHELWQR ]YHþDQR WYHJDQMH UDND QD SROMXEQHPREPRþMX.RWRPHMLWYHQLIDNWRUSULSRVNXVLKSRMDVQMHYDQMDPRUH ELWQLKSUHVHåNRYQDMYHþNUDWXJRWDYOMDPRGDSULPDQMNXMHQDWDQþQLKSRGDWNRY R VWDQMX LQ SURVWRUVNL UD]SRUHMHQRVWL GHMDYQLNRY WYHJDQMD VDM MH R]HPOMH 6ORYHQLMH ]DJHRJUDIVNRDQDOL]R YSOLYD RNROMVNLKIDNWRUMHYQDSRMDYEROH]QL ]DUDGL UD]JLEDQHJD WHUHQD LQ VSHFLILþQLK PHWHRURORãNLK SRJRMHY L]UHGQR ]DKWHYQR>@

*HRJUDIVNH DQDOL]H SUHVHåNRY UDND QD PDQMãHP SRGURþMX QLVR UXWLQVNH QDORJHQDãHHSLGHPLRORãNHVOXåEH3ULSUDYOMDPRMLKYVNORSXSRVHEQLKSUR MHNWRY QDMYHþNUDW QD SREXGR GUåDYQH DOL SD UHJLRQDOQH MDYQR]GUDYVWYHQH VWURNH LQ SROLWLNH 9VH SRJRVWHMãD VR WXGL YSUDãDQMD LQ ]DKWHYH UD]OLþQLK FLYLOQLK LQLFLDWLY LQ PHGLMHY 3UHGYVHP UXPHQL WLVN ] DODUPDQWQL SULVSHYNL Y VPLVOX ,] 6WUDVERXUJD RSR]RULOL QD VNUE ]EXMDMRþR XJRWRYLWHY 7UHWMLQD 6RþDQRY XPUOD ]DUDGL UDND >@ VHMH PHG OMXGPL EROM DOL PDQM XSUDYLþHQ

strah. Nedostopnost ustreznih informacij ali pa neprimerno oziroma QHSUDYRþDVQR SRGDMDQMH VH SUDYLORPD NRQþD V VSORãQLP QH]DXSDQMHP Y SRREODãþHQH GUåDYQH XVWDQRYH WHU ] YHþDQMHP YSOLYD NYD]L ]QDQVWYH QLNRY NDWHULK FLOM GHORYDQMD QL UD]MDVQLWHY SHUHþHJD SUREOHPD WHPYHþ ODVWQDSURPRFLMDLQILQDQþQDGREURELW

6WURNRYQMDNL ODKNR Y SURFHVX RFHQMHYDQMD WYHJDQMD ] ]QDQVWYHQLP SULVWR SRP NYDQWLILFLUDPR WYHJDQMH NL JD LPDMR L]SRVWDYOMHQL SUHELYDOFL GD ERGR ]EROHOL ]D NDNR EROH]QLMR 6NOHSQL GHO MH SULSUDYD NRQNUHWQLK ]DNOMXþNRY LQ SULSRURþLOWHUQMLKRYDXVWUH]QDSUHGVWDYLWHYFLYLOQLGUXåELLQSROLWLNL9HVþDV VHMHWUHED]DYHGDWLGDMH]D]QDYDQMHWYHJDQMDYODLþQLMDYQRVWLRGYLVQRRG ãWHYLOQLK IDNWRUMHY LQ WLSLþQR L]NOMXþXMH QXPHULþQH UH]XOWDWH ]QDQVWYHQLK DQDOL] >@ 0HG QDMSRPHPEQHMãH IDNWRUMH NL RE UHDOQR QL]NL QHYDUQRVWL YHþDMRREþXWHNRJURåHQRVWLVR

x L]SRVWDYOMHQRVWRWURNLQGUXJLKUDQOMLYLKVNXSLQ x QHSURVWRYROMQDL]SRVWDYOMHQRVW

x QH]PRåQRVWQDG]RUDQDGL]SRVWDYOMHQRVWMR x SULVWUDQRVWYUD]SRUHGLWYLL]SRVWDYOMHQRVWL x XPHWQLYLULRQHVQDåHQMD

x QHSR]QDYDQMHYLUDRQHVQDåHQMD

x RQHVQDåHQMHMHVWUDQVNLSURGXNWGHMDYQRVWLNLNRULVWLOHRQHVQDåHYDOFX 3R]QDYDQMH LQ XSRãWHYDQMH WHK IDNWRUMHY MH Y YVHK RNROMVNRMDYQR]GUDY VWYHQLKSURMHNWLKNOMXþQDþHåHOLPRGDERGRSUHGORJLVOLãDQLLQVSUHMHWL

LITERATURA

.UHLQEURFN/(QYLURQPHQWDOHSLGHPLRORJ\,Q$KUHQV:3LJHRW,HGLWRUV+DQGERRN RIHSLGHPLRORJ\%HUOLQ6SULQJHU±

&RKHQ$-&DQWRU.33ROOXWLRQRIDLUZDWHUDQGVRLO,Q6WHZDUW%::LOG&3HGLWRUV :RUOGFDQFHUUHSRUW/\RQ,$5&±

,$5&3UHDPEOHWRWKH,$5&PRQRJUDSKV/\RQ,$5&3ULGREOMHQRV VSOHWQHVWUDQLKWWSPRQRJUDSKVLDUFIU(1*3UHDPEOHLQGH[SKS

(VSLQD & 6WUDLI . )ULLV 6 .RJHYLQDV 0 6DUDFFL 5 9DLQLR + HW DO (XURSHDQ FRGH DJDLQVWFDQFHUWKHG(QYLURQPHQWRFFXSDWLRQDQGFDQFHU&DQFHUHSLGHP 6XSSO6±

6WUDLI.&RKHQ$-6DPHW-0HGLWRUV$LUSROOXWLRQDQGFDQFHU/\RQ,$5&

'ROO53HWR57KHFDXVHVRIFDQFHUTXDQWLWDWLYHHVWLPDWHVRIDYRLGDEOHULVNVRIFDQFHU LQWKH8QLWHG6WDWHVWRGD\-1DW&DQFHU,QVWLWXWH±

)HUOD\ - 6RHUMRPDWDUDP , (UYLN 0 'LNVKLW 5 (VHU 6 0DWKHUV & HW DO */2%2&$1 Y&DQFHULQFLGHQFHDQGPRUWDOLW\ZRUOGZLGH,$5&&DQFHU%DVH1R/\RQ ,$5&3ULGREOMHQRVVSOHWQHVWUDQLKWWSJORERFDQLDUFIU

.HVVOHU53UHYHQWLRQ$LURIGDQJHU1DWXUH6±

'XIIV-+3DUN09&KHPLFDOULVNDVVHVVPHQW81(3,3&6:+2

10. EPA. Human health risk assessment. Pridobljeno 25. 8. 2016 s spletne strani https://www.

epa.gov/risk/human-health-risk-assessment.

=DGQLN9äDJDU7'UREQH63ULPLFäDNHOM0(VWLPDWLRQRIFDQFHUEXUGHQLQ%UHåLFH PXQLFLSDOLW\ D FRPPXQLW\ QHLJKERULQJ .UãNR QXFOHDU SRZHU SODQW LQ 6ORYHQLD &URDW 0HG-±

äDJDU7=DGQLN93ULPLFäDNHOM0/RFDOVWDQGDUGL]HGLQFLGHQFHUDWLRHVWLPDWLRQDQG FRPSDULVRQZLWKRWKHUPDSSLQJPHWKRGVIRUVPDOOJHRJUDSKLFDODUHDVXVLQJ6ORYHQLDQ EUHDVWFDQFHUGDWD-$SSO6WDWL±

=DGQLN93ULPLFäDNHOM0äDJDU75D]ãLUMHQRVWUDNDYLKEROH]QLY6ORYHQLMLLQ=DVDYMX /MXEOMDQD2QNRORãNLLQãWLWXW/MXEOMDQD

=DGQLN9*HRJUDIVNDDQDOL]DYSOLYDVRFLDOQRHNRQRPVNLKGHMDYQLNRYQDLQFLGHQFRUDND Y 6ORYHQLML Y REGREMX ± 'RNWRUVNR GHOR /MXEOMDQD 0HGLFLQVND IDNXOWHWD 8QLYHU]DY/MXEOMDQL

.XNHF$%RåQDU0=0ODNDU3*UDãLþ%+HUDNRYLþ$=DGQLN9HWDO0HWKRGRORJLFDO DSSURDFKLQGHWHUPLQDWLRQRIVPDOOVSDWLDOXQLWVLQDKLJKO\FRPSOH[WHUUDLQLQDWPRVSKHULF SROOXWLRQ UHVHDUFK WKHFDVH RI =DVDYMH UHJLRQ LQ6ORYHQLD*HRVSDWLDO +HDOWK

±

6WDPHMþLþ ' ,] 6WUDVERXUJD RSR]RULOL QD VNUE ]EXMDMRþR XJRWRYLWHY 7UHWMLQD 6RþDQRY XPUOD]DUDGLUDND'HOR

6DQGPDQ30/DQDUG-&ULVLVFRPPXQLFDWLRQ*XLGHOLQHVIRUDFWLRQSODQQLQJ:KDWWR VD\ZKHQWHUURULVWVHSLGHPLFVRURWKHUHPHUJHQFLHVVWULNH$PHULFDQLQGXVWULDOK\JLHQH DVVRFLDWLRQ

RAKOTVORNO DELOVANJE KEMIKALIJ IZ OKOLJA

0HWND)LOLSLþ

POVZETEK. 1DVWDQHN LQ UD]YRM UDND MH NRPSOHNVHQ YHþVWRSHQMVNL SURFHV 9 SULVSHYNX VR RSLVDQH ODVWQRVWLLQ RVQRYQLPHKDQL]PL UDNRWYRUQHJD GHORYDQMD NHPLNDOLM 5D]OLNXMHPR JHQR WRNVLþQHLQ QHJHQRWRNVLþQHNDUFLQRJHQHSULþHPHUJHQRWRNVLþQL SRY]URþLMR JHQHWVNHVSUHPHPEH SRWUHEQH ]D LQLFLDFLMR LQ QDSUHGRYDQMH UDND PHGWHP NR QHJHQRWRNVLþQL SRVSHãXMHMR FHOLþQR SUROLIHUDFLMR LQ YSOLYDMR SUHGYVHP QD SURPRFLMR UDND 9HþLQD RUJDQVNLK NDUFLQRJHQRY GHOXMH LQGLUHNWQRLQSRWUHEXMHMRSUHVQRYRYYPHVQHSURGXNWHNLWYRULMR'1.DGXNWHNLYNROLNRUVHQH SRSUDYLMR SRY]URþLMR PXWDFLMH LQ NURPRVRPVNH DEHUDFLMH 1HNDWHUL NDUFLQRJHQL SUHGYVHP NRYLQH LPDMR JHQRWRNVLþQH XþLQNH SUHN SRY]URþDQMD WYRUEH SURVWLK NLVLNRYLK ]YUVWL .HPLMVNL NDUFLQRJHQL SRY]URþDMR WXGL HSLJHQHWVNH VSUHPHPEH L]UDåDQMD WDUþQLK JHQRY 1D RVQRYL SR]QDYDQMHYVHKWHKODVWQRVWLODKNRVNOHSDPRGDMHL]SRVWDYOMHQRVWNHPLMVNLPNDUFLQRJHQRP SRPHPEHQQHYDUQRVWQLGHMDYQLN]DQDVWDQHNUDND

UVOD

5D]YRMUDNDMHYHþVWRSHQMVNLSURFHVYNDWHUHPVHNRSLþLMRJHQHWVNHLQHSL JHQHWVNH VSUHPHPEH NL QD NRQFX SULYHGHMR GR QDVWDQND FHOLF NL QHQDG ]RURYDQRUDVWHMRLPDMRVSRVREQRVWYGLUDQMDYVRVHGQMDWNLYDLQ]DVHYDQMD LQSRVWDQHMRNOLQLþQRSUHSR]QDYQHNRWEROH]HQ6OLND

9VWRSQMLLQLFLDFLMHQDVWDQHSRãNRGED'1.NLSULYHGHGRPXWDFLMHLQVWHP VSUHPHQLJHQHWVNL]DSLVFHOLFHQRYHMãHUD]LVNDYHSDVRSRND]DOHGDODKNR GRLQLFLDFLMHSULYHGHMRWXGL HSLJHQHWVNHVSUHPHPEHL]UDåDQMD JHQRY)D]D SURPRFLMHUDNDREVHJDVHOHNWLYQRNORQDOQRUDVWLQLFLLUDQLKFHOLFLQODKNRWUDMD YHþOHW1DVWDQHMRWXGLQDGDOMQMHJHQHWVNHVSUHPHPEHNLYID]LQDSUHGRYDQMD SULYHGHMRGRWUDQVIRUPDFLMHSUHGUDNDYLKFHOLFYPDOLJQHUDNDYHFHOLFH +DQDKDQLQ:HLQEHUJ>@VWDRSLVDODãHVWNOMXþQLKODVWQRVWLNLVRSRWUHEQH za nastanek raka:

WUDMQRVLJQDOL]LUDQMH]DFHOLþQRSUROLIHUDFLMR QHRG]LYQRVWQD]DYLUDOFHUDVWL

RGSRUQRVWQDFHOLþQRVPUW

Y]SRVWDYLWHYQHRPHMHQHVSRVREQRVWLUHSURGXNFLMHQHVPUWQRVWFHOLF VSRVREQRVWVSURåLWYHDQJLRJHQH]HWYRUEHQRYLKåLOLQ

VSRVREQRVWLQYD]LMHLQ]DVHYDQMD>@

7HVSUHPHPEHYYHOLNLPHULQDVWDQHMRNRWUH]XOWDWDNWLYDFLMHRQNRJHQRYLQ LQDNWLYDFLMH WXPRUVXSUHVRUVNLK JHQRY 2QNRJHQL UDND LQGXFLUDMR >@ FHOLFL RPRJRþDMR SURLIHUDFLMR LQ SUHåLYHWMH 1DVSURWQRSDWXPRUVXSUHVRUVNLJHQL FHOLFH ãþLWLMR SUHG VSUHPHPEDPL NL YRGLMR Y QDVWDQHN UDND >@ QD SULPHU WDNRGDSUHSUHþXMHMRSUROLIHUDFLMRDOLSDVSURåLMRSURJUDPLUDQRFHOLþQRVPUW DSRSWR]R

6OLND9HþVWRSHQMVNLPRGHOQDVWDQNDUDNDNLREVHJDLQLFLDFLMRSURPRFLMRLQQDSUHGRYDQMH

2QNRJHQL YHþLQRPD GHOXMHMR NRW GRPLQDQWQL =YHþDQD DNWLYQRVW R]LURPD L]UDåDQMHHQHJDDOHOD]DGRVWXMH]DDNWLYDFLMRVLJQDOL]LUDQMD]DYHþMRUDVWLQ SUHåLYHWMH2QNRJHQLVHDNWLYLUDMR]DUDGLQDVWDQNDWRþNRYQHPXWDFLMHSRPQR åHYDQMD VHJPHQWD NURPRVRPD NL YVHEXMH WH JHQH DOL SD WUDQVORNDFLMH QD PHVWRNLMHSRGQDG]RURPPRþQHJDSURPRWRUMD=D LQDNWLYDFLMR WXPRUVX SUHVRUVNLKJHQRYSDVHVPDWUDGDMHSRWUHEQDL]JXEDIXQNFLMHREHKDOHORY>@

=DUDGLWHJDVWDQDYDGQRSRWUHEQLGYHVWRSQML1DMSRJRVWHMHQDVWDQHWRþNRYQD PXWDFLMDYHQHPDOHOXLQL]JXEDYGUXJHP]DUDGLGHOHFLMHDOLUHNRPELQDFLMH

MEHANIZMI DELOVANJA RAKOTVORNIH KEMIKALIJ

*OHGH QD PHKDQL]HP GHORYDQMD ODKNR NHPLMVNH NDUFLQRJHQH GHOLPR QD JHQRWRNVLþQH LQ QHJHQRWRNVLþQH NDUFLQRJHQH 7DEHOD 3UYL SRY]URþDMR SRãNRGEH '1. LQ PXWDFLMH LQLFLDFLMR WHU QDSUHGRYDQMH UDND GUXJL SD VSRGEXMDMR FHOLþQR GHOLWHY Y WDUþQHP WNLYX SULVSHYDMR N ILNVDFLML PXWDFLM SRY]URþDMRVSUHPHPEHYL]UDåDQMXJHQRYLQVSUHPHPEHQDG]RUDUDVWLFHOLF SUHNGHORYDQMDQDUD]QHFHOLþQHUHFHSWRUMHQSUKRUPRQVNH$K533D5LQ SULVSHYDMRNSURPRFLMLUDND

*HQRWRNVLþQH NHPLMVNH UDNRWYRUQH VQRYL DOL NHPLMVNH NDUFLQRJHQH ODKNR UD]GHOLPR QD WLVWH NL QHSRVUHGQR UHDJLUDMR ] PROHNXOR '1. LQ WLVWH NL SRWUHEXMHMR SRSUHMãQMR SUHVQRYQR DNWLYDFLMR 3ULPHUL QHSRVUHGQLK NDUFLQR JHQRY NL QH SRWUHEXMHMR SRSUHMãQMR SUHVQRYQH DNWLYDFLMH VR HWLOHQ RNVLG IRUPDOGHKLG WHU ãWHYLOQL NHPRWHUDSHYWLNL >@ ,QGLUHNWQL NDUFLQRJHQL DOL SURNDUFLQRJHQLSDVHPRUDMRQDMSUHMSUHVQRYLWLGDQDVWDQHMRUHDNWLYQLYPHVQL SURGXNWL NL UHDJLUDMR ] '1. LQ SRY]URþLMR SRãNRGEH 2FHQMHQR MH GD MH RNURJþHWUWLQDNDUFLQRJHQRYWDNãQLKNLGHOXMHMRQHSRVUHGQRWULþHWUWLQHSD MHSURNDUFLQRJHQRY>@

7DEHOD=QDþLOQRVWLJHQRWRNVLþQLKLQQHJHQRWRNVLþQLKNDUFLQRJHQRY

*HQRWRNVLþQLNDUFLQRJHQL x UHDJLUDMR]'1.

x VRPXWDJHQL

x ODKNRGHOXMHMRNRWSRSROQLNDUFLQRJHQL x WXPRULJHQRVWMHRGYLVQDRGRGPHUND

x QLPRJRþHGRORþLWLPHMQHYDUQHGR]HL]SRVWDYOMHQRVWLQLPDMRSUDJDGHORYDQMD x GHOXMHMRYYVHKID]DKQDVWDQNDLQUD]YRMDUDND

1HJHQRWRNVLþQLNDUFLQRJHQL x QHUHDJLUDMR]'1.

x QLVRPXWDJHQL

x YSOLYDMRQDL]UDåDQMHJHQRY x LPDMRSUDJGHORYDQMD

x XþLQNLVRUHYHU]LELOQLRGYLVQLRGRGPHUNDLQWUDMDQMDL]SRVWDYOMHQRVWL x WXPRULJHQRVWMHRGYLVQDRGRGPHUND

x GHOXMHMRYID]LSURPRFLMHUDND

.HPLMVNLNDUFLQRJHQLSRY]URþDMRSRãNRGEH'1.SUHNNRYDOHQWQHYH]DYHQD UHDNWLYQD PHVWD PROHNXOH '1. SUHN RNVLGDWLYQLK SRãNRGE '1. ]DUDGL SRY]URþDQMD WYRUEH SURVWLK NLVLNRYLK ]YUVWL 526 LQDOL SUHN SRY]URþDQMD HSLJHQHWVNLKVSUHPHPE>@.HPLMVNLNDUFLQRJHQLR]LURPDQMLKRYLSUHVQRYNL PRUDMR ELWL WXGL VSRVREQL YVWRSLWL Y RUJDQL]HP LQ FHOLFH NDU SRPHQL GD PRUDMR ELWL DOL OLSRILOQL GD MH RPRJRþHQ SDVLYQL WUDQVSRUW DOL SD PRUDMR Y FHOLFH YVWRSLWL ] DNWLYQLP WUDQVSRUWRP .RPSOHNVQRVW GHORYDQMD NHPLMVNLK NDUFLQRJHQRYYSURFHVXQDVWDQNDLQUD]YRMDUDNDMHSULND]DQDQD6OLNL

*HQRWRNVLþQLNHPLMVNLNDUFLQRJHQLVHNRYDOHQWQRYHåHMRQDQXNOHRWLGH'1.

SULþHPHUQDVWDQHDGXNW'1.DGXNWHODKNRUD]GHOLPRYGYHJODYQLVNXSLQL L PDMKQH ] QDMKQR PROHNXOVNR PDVR LQ LL ]DMHWQH PDNURPROHNXODUQH DGXNWH 6DP '1.DGXNW QH SRY]URþL PXWDFLMH UD]OLþQL DGXNWL SD LPDMR UD]OLþQRVSRVREQRVWSRY]URþDQMDPXWDFLM9HþLQDNHPLNDOLMNLWYRULMRDGXNWH MH PRþQR HOHNWURILOQLKQHSRODUQH PROHNXOH V SR]LWLYQLP QDERMHP HOHNWURILO QHJDFHQWUDNLWYRULMRQHUHYHU]LELOQHVWDELOQHDGXNWHQDPRþQLKQXNOHRILOQLK PHVWLK QHSRODUL]LUDQD PHVWD ] PRþQLP QHJDWLYQLP QDERMHP Y PROHNXOL '1. âLENLHOHNWURILOLSRODUL]LUDQH PROHNXOH ] GHOQLPSR]LWLYQLP QDERMHP NRW VR DOGHKLGL LQ NHWRQL SD UHYHU]LELOQR UHDJLUDMR V ãLENLPL QXNOHILOQLPL PHVWLYPROHNXOL'1.>@7HNHPLMVNHUD]OLNHVRSRPHPEQHVDMVRVWDELOQL DGXNWL SRYH]DQL ] YHþMR PXWDJHQRVWMR =D UDNRWYRUQL SRWHQFLDO SD MH SR PHPEQRWXGLYH]DYQRPHVWRDGXNWDQDQXNOHRWLGVDMVRGRORþHQDYH]DYQD PHVWDEROMPXWDJHQD

Absorpcija

6OLND0HWDEROLþQDDNWLYDFLMDNHPLMVNLKNDUFLQRJHQRYLQQMLKRYLJHQRWRNVLþQLLQ QHJHQRWRNVLþQLXþLQNL

Majhni, nizkomolekularni DNK-adukti najpogosteje nastanejo po alkilaciji kovalentne vezave funkcionalne alkilne skupine na molekulo DNK. Na splošno je alkilacija dušika nukleinske baze manj mutagena od alkilacije NLVLND7LDGXNWLODKNRGHVWDELOL]LUDMR'1.WDNRGDQDVWDQHMRQHNRGLUDMRþD DED]LþQD PHVWD DOL SD ODKNR SRY]URþLMR YJUDGQMR QDSDþQH ED]H >@ 9 WR skupino spadajo N-nitrozo spojine in nitrozamini, ki nastajajo tudi endogeno, SD WXGL ERMQLVWUXS LSHULW 1HNDWHUH DONLOLUDMRþHNHPLNDOLMH SD SRY]URþLMR QD VWDQHNSUHþQLKYH]LPHGYHULJDPD'1.NL]DYUHMRWUDQVNULSFLMRLQUHSOLNDFLMR '1. >@ LQ ODKNRPHG SRSUDYOMDQMHPSRY]URþLMR QDVWDQHNGYRYHULåQLK SUH ORPRY'1.>@7DNRGHOXMHQDSULPHUNHPRWHUDSHYWLNFLVSODWLQ

9HOLNLDGXNWLSDYHþLQRPDXVWDYLMRWUDQVNULSFLMRLQUHSOLNDFLMR'1.LQSRY]UR þDMRSUHORPHNURPRVRPRYLQYHOLNHGHOHFLMHNDUSULYHGHGRL]JXEHKHWHUR]L JRWQRVWL>@(SLGHPLRORãNHLQHNVSHULPHQWDOQHUD]LVNDYHSRWUMXMHMRSRYH]DYH PHG WYRUER '1.DGXNWRY LQ QDVWDQNRP UDND >@ 9 WR VNXSLQR VSDGD YHþLQD JHQRWRNVLþQLK RUJDQVNLK NDUFLQRJHQRY WLSLþQL SULPHUL VR EHQ]RD SLUHQ LQ GUXJL SROLDURPDWVNL RJOMLNRYRGLNL KHWHURFLNOLþQL DURPDWVNL DPLQL DIODWRNVLQ%LGU

1HNDWHUH NHPLNDOLMH DOL QMLKRYLSUHVQRYNLSRY]URþDMR RNVLGDWLYQH SRãNRGEH '1. NL VR SRJRVWR SRVOHGLFD GHORYDQMD VWUDQVNLK UHDNWLYQLK SURGXNWRY NL QDVWDMDMR Y SUHVQRYL 2NVLGDWLYQH SRãNRGEH VR RGJRYRUQH ]D YHOLN GHO PXWDFLM >@ 3UHWHåQR MLK SRY]URþDMR SURVWH UHDNWLYQH ]YUVWL UHDNWLYQH PROHNXOH DOL LRQL ] QHSDUQLPL HOHNWURQL NRW VR UHDNWLYQH NLVLNRYH ]YUVWL Reactive Oxygen Species 526 >@ 1DVWDQHN 526 MH SRVOHGLFD QHSR VUHGQHJD GHORYDQMD NHPLNDOLM DOL SD SRVUHGQHJD SUHN SRY]URþDQMD YQHWLM 526SRY]URþLMRUD]QHPROHNXODUQHSRãNRGEHYNOMXþQRVSUHORPLYHULJ'1.

LQNRYDOHQWQLPLYH]PLQDQXNOHLQVNH ED]H>@'LRNVLQL LQ SROLNORULUDQLELIHQLOL VRSULPHUNDUFLQRJHQRYNLSRY]URþDMRPXWDFLMHVWYRUMHQMHP526>@

3ROHJ ãWHYLOQLK RUJDQVNLK VQRYL VR UDNRWYRUQH WXGL QHNDWHUH NRYLQH NL MLK 0HGQDURGQDDJHQFLMD]DUD]LVNRYDQMHUDND,$5&XYUãþDPHGNDUFLQRJHQH LQ YHUMHWQR NDUFLQRJHQH ]D OMXGL 0HGQMH VSDGDMR NDGPLM QLNHOM NREDOW VYLQHF YDQDGLM EHULOLM DU]HQ LQ NURP 0HKDQL]PL UDNRWYRUQHJD GHORYDQMD NRYLQ VR PDQM UD]LVNDQLNRW PHKDQL]PL GHORYDQMD RUJDQVNLK VSRMLQ 0HKD QL]PLGHORYDQMHNRYLQVHVLFHUUD]OLNXMHMRYHþLQRPDSDSRY]URþDMRJHQHWVNH LQ HSLJHQHWVNH VSUHPHPEH VSUHPHPEH FHOLþQH SUROLIHUDFLMH LQ SUHVQRYH VSUHPHQMHQHVLJQDOQHSRWLWHUWYRUER526>@.DGPLMDU]HQQLNHOMNREDOW LQVYLQHFSDWXGLNRPSHWLWLYQRLQKLELUDMRHQFLPHVFLQNRYLPREURþHPPHG NDWHUHVSDGDMRãWHYLOQLHQFLPLYNOMXþHQLYSRSUDYOMDQMHSRãNRGE'1.>@

3RVOHGLFDMHLQKLELFLMDSRSUDYLODSRãNRGE'1.LQVWHPYHþMDYHUMHWQRVWGD SRãNRGEHSULYHGHMRGRPXWDFLM

9QDVWDQHNLQUD]YRMUDNDQLVRYNOMXþHQHOHPXWDFLMHWDUþQLKJHQRYNLL]YLUDMR L] SRãNRGE '1. 1RYHMãH UD]LVNDYH NDåHMR GD LPDMR SUL WHP SURFHVX SRPHPEQR YORJR HSLJHQHWVNH VSUHPHPEH (SLJHQHWVNH VSUHPHPEH VR VWDELOQHGHGQHLQSULYHGHMRGRVSUHPHPEYL]UDåDQMXJHQRY>@9HOLNRMH GRND]RY GD L]SRVWDYOMHQRVW RNROMVNLP GHMDYQLNRP VSUHPHQL HSLJHQHWVNR UHJXODFLMRJHQRPDþHSUDYPHKDQL]PLãHQLVRSRYVHPUD]LVNDQL(SLJHQHW VNHVSUHPHPEHGHOXMHMRQDL]UDåDQMHJHQRYSULþHPHU]DSRUHGMD'1.QLVR VSUHPHQMHQD=DVHGDMVWDQDMEROMHUD]LVNDQDPHKDQL]PDPHWLODFLMD'1.LQ PRGLILNDFLMDKLVWRQRY

0HWLODFLMD'1.MHQRUPDOHQIL]LRORãNLSURFHVSULNDWHUHPVHPHWLOQDVNXSLQD

&+NRYDOHQWQRYHåHQDSHWLRJOMLNRYDWRPSLULPLGLQDSULþHPHUQDVWDQH PHWLOFLWR]LQPH&5HDNFLMRNDWDOL]LUDHQFLP'1.PHWLOWUDQVIHUD]D>@

3UHWHåQRVRPHWLOLUDQL&S*GLQXNOHRWLGLNLVRSRJRVWRORFLUDQLYSURPRWRUVNLK UHJLMDKJHQRYWDNRLPHQRYDQL&S*RWRNLCpG islands&*,0HWLOLUDQL&*, SUDYLORPD ]DYUHMR WUDQVNULSFLMR JHQD 6SUHPHQMHQL Y]RUFL PHWLOLUDQRVWL VR ]QDþLOQL]DYVHYUVWHUDND0HWLODFLMD'1.GHOXMHQDUD]YRMUDNDQDWULJODYQH QDþLQHLVSORãQDKLSRPHWLODFLMDLLKLSHUPHWLODFLMDSURPRWRUMHYLQLLLLQGXN FLMD WRþNRYQLK PXWDFLM >@ 6SORãQD KLSRPHWLODFLMD MH ]JRGQML GRJRGHN SUL UD]YRMXUDNDNLODKNRSRY]URþLYHþMHL]UDåDQMHRQNRJHQRYSRYH]DQDSDMH WXGL]L]JXERJHQRPVNHVWDELOQRVWL>@0HWLODFLMDSURPRWRUMDMHSRYH]DQD]

XWLãDQMHPL]UDåDQMD JHQRY LQ VHVPDWUD GDMH JODYQL PHKDQL]HPLQDNWLYD FLMH WXPRUVXSUHVRUVNLK JHQRY >@ 2FHQMHQR MH GD LPD YHþLQD WXPRUMHY

± KLSHUPHWLOLUDQLK SURPRWRUVNLK UHJLM >@ âWHYLOQH RNROMVNH LQ SRNOLFQH L]SRVWDYOMHQRVWL VR SRYH]DQH V VSUHPHPEDPL PHWLODFLMH '1.

3RY]URþDMR MLK WDNR LRQL]LUDMRþD VHYDQMD NRW ãWHYLOQH RUJDQVNH LQ DQRUJDQ VNH NHPLNDOLMH RG NDWHULK LPDMR ãWHYLOQH SOHLRWURSQH XþLQNH ýH PHWLOLUDQL

&S*QLVRSRSUDYOMHQLODKNRSRY]URþLMRWXGLWRþNRYQHPXWDFLMH

1DL]UDåDQMHJHQRYGHOXMHMRWXGLVSUHPHPEHKLVWRQRYNDWHULKSRVOHGLFHVR VSUHPHPEH]JUDGEHNURPDWLQDNLQHSRVUHGQRYSOLYDQDWUDQVNULSFLMRJHQRY UHSOLNDFLMR'1.SRSUDYOMDQMH'1.LQRUJDQL]DFLMRNURPRVRPRY>@+LVWRQL VRSURWHLQLNLMLKVHVWDYOMDRVHPSRGHQRWRNURJNDWHULKMHRYLWD'1.LQWYRUL ]JUDGER NL VH LPHQXMH QXNOHRVRP >@ 6SUHPHPEH ODKNR QDVWDQHMR QD UD]OLþQLK SRGHQRWDK LQ YNOMXþXMHMR DFHWLODFLMR PHWLODFLMR IRVIRULODFLMR DOL JOL NR]LODFLMR QD 1NRQFLK SURWHLQRY NL ãWUOLMR L] QXNOHRVRPD >@ $FHWLODFLMD KLVWRQRY MH SRYH]DQD ] DNWLYDFLMR WUDQVNULSFLMHPHGWHPNR VR GUXJH VSUH PHPEHPDQMUD]LVNDQH5D]LVNDYHVRSRND]DOHGDVRRNROMVNHLQSRNOLFQH L]SRVWDYOMHQRVWLSRYH]DQHVVSUHPHPEDPLKLVWRQRYSUHGYVHPL]SRVWDYOMH QRVW NRYLQDP .URP QD SULPHU SRY]URþL XWLãDQMH JHQRY ] GHORYDQMHP QD HQFLPHNLNDWDOL]LUDMRDFHWLODFLMRKLVWRQRY>@

RAKOTVORNO DELOVANJE KADMIJA

.DGPLM&GMHYVHSRYVRGQDY]RþHRQHVQDåHYDORRNROMD1DMGHPRJDY]UDNX ]HPOML LQ YRGL ]DUDGL ]HOR GROJHJD UD]SRORYQHJD þDVD SD VH DNXPXOLUD Y UDVWOLQDKLQYWNLYLKåLYDOLLQOMXGL0HGQDURGQDDJHQFLMD]DUD]LVNRYDQMHUDND JD NODVLILFLUD NRW NDUFLQRJHQHJD ]D OMXGL 6NXSLQD SRY]URþD SOMXþQHJD UDNDSRYH]XMHMRSDJDWXGL]QDVWDQNRPOHGYLþQHJDLQMHWUQHJDUDNDUDND PHKXUMDSURVWDWHVOLQDYNHLQKHPDWRSRHWVNHJDVLVWHPD0ROHNXODUQHUD]L VNDYHPHKDQL]PRYUDNRWYRUQHJDGHORYDQMDVRSRND]DOHQMHJRYRNRPSOHNVQR GHORYDQMHNLVHL]UDåDYYVHKVWRSQMDKQDVWDQNDUDND6OLND1HSRVUHGQLK SRãNRGE '1. NDGPLM QH SRY]URþD VSURåD SD WYRUER 526 NL SRY]URþLMR SRãNRGEH '1. LQ SRVOHGLþQR PXWDFLMH âH SRPHPEQHMãL PHKDQL]HP MH ]DYLUDQMH SRSUDYOMDOQLK PHKDQL]PRY '1. LQ DSRSWR]H 3RVOHGLFD MH NRSL þHQMHQHSRSUDYOMHQLKSRãNRGE '1.NDU]YHþD SRJRVWRVWPXWDFLMLQ YRGL Y JHQRPVNRQHVWDELOQRVW9ID]LSURPRFLMHNDGPLMVSUHPLQMDL]UDåDQMHJHQRY WDNR SUHN HSLJHQHWVNLK PHKDQL]PRY YSOLYD QD PHWLODFLMR '1. NRW WXGL ] GHORYDQMHPQDVLJQDOQHSRWLNLXUDYQDYDMRFHOLþQRSUROLIHUDFLMR>@

Slika 3. Mehanizem karcinogenega delovanja kadmija prek indukcije poškodb DNK, inhibicije SRSUDYOMDOQLKPHKDQL]PRY'1.QDG]RUDFHOLþQHUDVWLLQDSRSWR]HVWLPXODFLMHFHOLþQH

SUROLIHUDFLMHLQHSLJHQHWVNLKVSUHPHPEL]UDåDQMDJHQRY>@

=$./-8ý(.

1DVWDQHNUDND MH SRVOHGLFD LQWHUDNFLMPHG JHQL LQ RNROMHP (SLGHPLRORãNH UD]LVNDYH VR SRND]DOH GD QD QMHJRY QDVWDQHN YSOLYDMR RNROMH åLYOMHQMVNL VORJLQJHQHWVNHSUHGLVSR]LFLMHSRVDPH]QLND9HQGDUSDNHPLMVNLLQIL]LNDOQL UDNRWYRUQLGHMDYQLNLYHGQRSULVSHYDMRNYHþMLJURåQMLEROH]QLQHJOHGHQDWR DOL MR SRYH]XMHPR ] JHQWVNR SUHGLVSR]LFLMR åLYOMHQMVNLP VORJRP SRNOLFQR L]SRVWDYOMHQRVWMR DOL GHMDYQLNL RNROMD 9 ]DGQMLK GHVHWOHWMLK MH SR]QDYDQMH PHKDQL]PRY QDVWDQND UDND LQ UDNRWRYRUQHJD GHORYDQMD NHPLNDOLM PRþQR QDSUHGRYDORNDUMHSUHFHM GRSULQHVORNEROMãLGLDJQRVWLNLLQ ]GUDYOMHQMXãH YHGQR SD SURFHVRY QDVWDQND UDND LQ PHKDQL]PRY GHORYDQMD NHPLNDOLM QH SR]QDPRGRYROMGREURGDELODKNREROH]HQXVSHãQHMHSUHSUHþHYDOL

/,7(5$785$

+DQDKDQ ' :HLQEHUJ 5$ +DOOPDUNV RI FDQFHU 7KH QH[W JHQHUDWLRQ &HOO

±

:HLQEHUJ5$7KHELRORJ\RIFDQFHU1HZ<RUN*DUODQG6FLHQFH

3. Knudson Jr AG. Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68 (4): 820–3.

4. NTP Report on carcinogens. 12^th edition. Research Triangle Park, NC: US Department of health and human services, Public health service, National toxicology program, 2011.

5. Irigaray P, Belpomme D. Basic properties and molecular mechanisms of exogenous chemical carcinogens. Carcinogenesis. 2010; 31 (2): 135–48.

6. Gates KS. An overview of chemical processes that damage cellular DNK: Spontaneous hydrolysis, alkylation, and reactions with radicals. Chem Res Toxicol 2009; 22 (11): 1747–60.

7. Hlavin EM, Smeaton MB, Miller PS. Initiation of DNK interstrand cross-link repair in mammalian cells. Environ Mol Mutagen 2010; 51 (6): 604–24.

8. Sczepanski JT, Jacobs AC, Van Houten B, Greenberg MM. Double-strand break formation during nucleotide excision repair of a DNK interstrand cross-link. Biochemistry 2009; 48 (32): 7565–7.

9. Wiencke JK, McDowell ML, Bodell WJ. Molecular dosimetry of DNK adducts and sister chromatid exchanges in human lymphocytes treated with benzo[a]pyrene. Carcinogenesis 1990; 11 (9): 1497–502.

10. van Schooten FJ, Hillebrand MJ, van Leeuwen FE, Lutgerink JT, van Zandwijk N, Jansen HM, et al. Polycyclic aromatic hydrocarbon-DNK adducts in lung tissue from lung cancer patients. Carcinogenesis 1990; 11 (9): 1677–81.

11. Lu AL, Li X, Gu Y, Wright PM, Chang DY. Repair of oxidative DNK damage: Mechanisms and functions. Cell Biochem Biophys 2001; 35 (2): 141–70.

12. Klaunig JE, Wang Z, Pu X, Zhou S. Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 2011; 254 (2): 86–99.

13. Schiestl RH, Aubrecht J, Yap WY, Kandikonda S, Sidhom S. Polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin induce intrachromosomal recombination in vitro and in vivo. Cancer Res 1997; 57 (19): 4378–83.

14. Galanis A, Karapetsas A, Sandaltzopoulos R. Metal-induced carcinogenesis, oxidative stress and hypoxia signalling. Mutat Res 2009; 674 (1–2): 31–5.

15. Witkiewicz-Kucharczyk A, Bal W. Damage of zinc fingers in DNK repair proteins, a novel molecular mechanism in carcinogenesis. Toxicol Lett 2006; 162 (1): 29–42.

16. Calvanese V, Lara E, Kahn A, Fraga MF. The role of epigenetics in aging and age-related diseases. Ageing Res Rev 2009; 8 (4): 268–76.

17. Gronbaek K, Hother C, Jones PA. Epigenetic changes in cancer. APMIS 2007; 115 (10):

1039–59.

18. Esteller M. Epigenetics in cancer. N Engl J Med 2008; 358 (11): 1148–59.

19. Weidman JR, Dolinoy DC, Murphy SK, Jirtle RL. Cancer susceptibility: epigenetic mani- festation of environmental exposures. Cancer J 2007; 13 (1): 9–16.

)LOLSLþ00HFKDQLVPVRIFDGPLXPLQGXFHGJHQRPLFLQVWDELOLW\0XW5HV±

HORMONSKI MOTILCI

/XFLMD3HUKDULþ

POVZETEK +RUPRQVNL PRWLOHF R]LURPD NHPLþQL SRY]URþLWHOM KRUPRQVNLK PRWHQM .3+0 MH RG ]XQDM YQHVHQD VQRY R]LURPD ]PHV VQRYL NL SUHN VSUHPHPE Y GHORYDQMX KRUPRQVNHJD VLVWHPD SRY]URþL ãNRGOMLYH XþLQNH QD ]GUDYMH Y LQWDNWQHP RUJDQL]PX QMHJRYHP SRWRPVWYX R]LURPD VXESRSXODFLMLMDK =D VNRUDM NHPLNDOLM MH ELOR SRWUMHQR GD SUHN KRUPRQVNHJD QDþLQD GHORYDQMD ODKNR ãNRGLMR ]GUDYMX Y LQWDNWQHP RUJDQL]PX .3+0 QDMGHPR Y åLYLOLK ]GUDYLOLKSUHGPHWLKVSORãQHUDEHNHPLþQLKSULSUDYNLK]D]DWLUDQMHãNRGOMLYFHYJRULYLKSUHPD]LK SURGXNWLKJRUHQMD.3+0SULSLVXMHMRãWHYLOQHãNRGOMLYHXþLQNHQD]GUDYMHRGEROH]QLUHSURGXN WLYQLKRUJDQRYLQ]PDQMãDQHSORGQRVWLPRWHQMGHORYDQMDãþLWQLFHLQUD]YRMåLYþHYMDVODGNRUQH EROH]QLLQPHWDEROQHJDVLQGURPDGRSRUDVWDKRUPRQVNRRG]LYQLKUDNRY1DUD]YRMKRUPRQVNR RGYLVQLKUDNRYYSOLYDMRãWHYLOQLQHYDUQRVWQLGHMDYQLNLYNOMXþQRV.3+06OHGQMLPSULSLVOMLYHJD GHOHåDUDNRYWUHQXWQRQLPRJRþHGRORþLWL]DUDGLSRPDQMNDQMDYHURGRVWRMQLKUD]LVNDYSULL]SR VWDYOMHQLK SUHGYVHP Y NULWLþQLK UD]YRMQLK REGREMLK 3ULþDNXMHPR GD VH ER WHåLãþH SULKRGQMLK UD]LVNDY SUHPDNQLOR UDYQR Y VPHUL SRVOHGLF ]DUDGL L]SRVWDYOMHQRVWL Y UD]YRMQLK REGREMLKin utero Y RWURãWYX LQ DGROHVFHQFL =DUDGL REãLUQRVWL LQ NRPSOHNVQRVWL WHPH VH Y SULVSHYNX RVUHGRWRþDPR QD GHILQLFLMH SRWUHEQH ]D UD]XPHYDQMH .3+0 WHU SRJODYLWQH QHJRWRYRVWL LQ NRQWURYHU]QRVWL 1DVHPLQDUMX ERPR SUHGVWDYLOL WXGL QHNDM NRQNUHWQLK SULPHURY SRYH]DY PHG .3+0LQKRUPRQVNRRG]LYQLPLUDNL

UVOD

,]UD] KRUPRQVNL PRWLOHF DQJendocrine disruptor VR SUYLþ XSRUDELOL OHWD ]DKRUPRQVNRDNWLYQHRNROMVNHNHPLNDOLMHY]YH]LVNDWHULPLVRSRYH ]RYDOL ãNRGOMLYH YSOLYH QD VSROQL UD]YRM SUL OMXGHK LQ GUXJLK RUJDQL]PLK >@

2GWOHM]DY]HPDMRSRPHPEQRPHVWRPHGUD]LVNRYDOQLPLLQMDYQR]GUDYVWYHQLPL SULRULWHWDPLLQVRSRVWDOHSRJRVWDWHPDYQHWLKUD]SUDYYVWURNRYQLKLQODLþQLK NURJLK

96ORYHQLMLVHSROHJL]UD]DKRUPRQVNLPRWLOHFXSRUDEOMDWDWXGLL]UD]DNHPLþQL SRY]URþLWHOM KRUPRQVNLK PRWHQM in NHPLþQL KRUPRQVNL PRWLOHF 2ED VWD QDWDQþQHMãD RG L]UD]DKRUPRQVNL PRWLOHF VDM JUH ]D NHPLþQH VQRYL NL ODKNRPRWLMRGHORYDQMHKRUPRQVNHJDHQGRNULQHJDVLVWHPD1HUDYQRYHVMH KRUPRQVNHJD VLVWHPD ODKNR ]PRWLMR WXGL ãWHYLOQL GUXJL GHMDYQLNL NRW VR VYHWOREDKUXSþXVWYDEROH]HQVNDVWDQMDLWG9QDGDOMHYDQMXWHJDSULVSHYND ERPR XSRUDEOMDOL Y MDYQR]GUDYVWYHQLK NURJLK XGRPDþHQL L]UD] NHPLþQL SRY]URþLWHOMLKRUPRQVNLKPRWHQM.3+0

1D 1DFLRQDOQHP LQãWLWXWX ]D MDYQR ]GUDYMH SRGURþMH .3+0 VSUHPOMDPR Y RNYLUXWRNVLNRYLJLODQFHåHGREULKSHWQDMVWOHW=HSLGHPLRORãNHJDLQNOLQLþQHJD YLGLNDVHV.3+0XNYDUMDMRNROHJL]2QNRORãNHJDLQãWLWXWDLQ8QLYHU]LWHWQHJD NOLQLþQHJD FHQWUD /MXEOMDQD 7HPHOMQLP UD]LVNDYDP .3+0 VH SRVYHþDMR Y DNDGHPVNLKNURJLKSUHGYVHPQDIDNXOWHWL]DIDUPDFLMRYHWHULQDUVNLPHGL FLQVNLLQELRWHKQLþQLIDNXOWHWLWHUQDUD]LVNRYDOQLKLQãWLWXWLKNRWVR1DFLRQDOQL

LQãWLWXW]DELRORJLMR.HPLMVNLLQãWLWXW,QãWLWXW-RåHI6WHIDQLQGUXJLPHGWHP NR RUJDQL Y VHVWDYL PLQLVWUVWHY ]D ]GUDYMH NPHWLMVWYR LQ RNROMH VNUELMR ]D ]DNRQRGDMRLQQDG]RU>@

=DUDGL REãLUQRVWL LQ NRPSOHNVQRVWL WHPH VH Y SULVSHYNX RVUHGRWRþDPR QD GHILQLFLMHSRWUHEQH]DUD]XPHYDQMHQDþLQHGHORYDQMD.3+0WHUQDSRJOD YLWQHQHJRWRYRVWLLQNRQWURYHU]QRVWLNLãHYHGQRGHOLMRVWDOLãþDVWURNRYQMDNRY RGORþHYDOFHYLQVSORãQHMDYQRVWLPHGWHPNRSRJODYLWQHSRVOHGLFHL]SRVWDY OMHQRVWL.3+0OHSRY]HPDPR

./-8ý1('(),1,&,-(

,QWHUSUHWDFLMHSRGDWNRYR.3+0VRSRJRVWRSUHYHþSRHQRVWDYOMHQHSRYUãQH QHFHORYLWHLQ]DYDMDMRþHQHOHYPHGLMLKLQYVSORãQLMDYQRVWLDPSDNWXGLY VWURNRYQLKNURJLK=DWR]DEROMãHUD]XPHYDQMHQDYDMDPRNOMXþQHGHILQLFLMH

.HPLþQLSRY]URþLWHOMKRUPRQVNLKPRWHQM

2EVWDMDYHþGHILQLFLM.3+0YHQGDUMHQDMãLUãHVSUHMHWDGHILQLFLMD6YHWRYQH ]GUDYVWYHQHRUJDQL]DFLMH6=2L]OHWD.HPLþQLSRY]URþLWHOMKRUPRQ VNLKPRWHQMMHRG]XQDMYQHVHQDVQRYR]LURPD]PHVVQRYLNLSUHNVSUHPHPE Y GHORYDQMX KRUPRQVNHJD VLVWHPD SRY]URþL ãNRGOMLYH XþLQNH QD ]GUDYMH Y LQWDNWQHP RUJDQL]PX QMHJRYHP SRWRPVWYX R]LURPD VXESRSXODFLMLMDK 0RUHELWQL.3+0MHRG]XQDMYQHVHQDVQRYR]LURPD]PHVVQRYL]DNDWHUR VH SULþDNXMH GD EL ]PRJOD SRY]URþLWL KRUPRQVNH PRWQMH Y LQWDNWQHP RUJDQL]PXQMHJRYHPSRWRPVWYXR]LURPDVXESRSXODFLMLMDK>@

9 VNODGX ] GHILQLFLMR 6=2 MH ]D XPHVWLWHY HNVRJHQH NHPLNDOLMH R] ]PHVL PHG .3+0 SRWUHEQD Y]URþQD SRYH]DYD PHG L]SRVWDYOMHQRVWMR LQWDNWQHJD RUJDQL]PDNHPLNDOLMLLQãNRGOMLYLPXþLQNRPSRKRUPRQVNHPQDþLQXGHORYDQMD

+RUPRQVNRDNWLYQDVQRY

3RPHPEQR MH GD UD]OLNXMHPRPHG .3+0 LQ KRUPRQVNRDNWLYQLPLVQRYPL +$6 +RUPRQVNR DNWLYQD VQRY DQJ endocrine active substance MH NDWHUD NROL NHPLNDOLMD NL ODKNR ] QHSRVUHGQR DOL SRVUHGQR LQWHUDNFLMR V KRUPRQVNLPVLVWHPRPSRY]URþLXþLQHNQDKRUPRQVNLVLVWHPWDUþQHRUJDQH LQ WNLYD 9HQGDU þH VR ELRORãNH VSUHPHPEH WRYUVWQH LQWHUDNFLMH Y RNYLUX KRPHRVWDWVNLKR]LURPDGHWRNVLILNDFLMVNLKNDSDFLWHWRUJDQL]PDQLQXMQRGD ERGRSRVOHGLFHãNRGOMLYH>@

âNRGOMLYLXþLQHN

âNRGOMLYL XþLQHN DQJadverse effect MH VSUHPHPED Y PRUIRORJLML UDVWL UD]YRMXUD]PQRåHYDQMXDOLåLYOMHQMVNLGRELRUJDQL]PDDOLVXESRSXODFLMHNL PDQMãD IXQNFLRQDOQR NDSDFLWHWR DOL NRPSHQ]DFLMVNR UH]HUYR RE GRGDWQHP VWUHVXDOLYHþDREþXWOMLYRVW]DGUXJHYSOLYH>@

1DþLQLQPHKDQL]HPGHORYDQMD

1DþLQ GHORYDQMD DQJmode of action MH ] UREXVWQLPL HNVSHULPHQWDOQLPL RSD]RYDQML LQ PHKDQLVWLþQLPL SRGDWNL SRGSUWR ELRORãNR YHUMHWQR VRVOHGMH NOMXþQLKGRJRGNRY]DþHQãL]LQWHUDNFLMRNHPLNDOLMHVFHOLFRNLSUHNIXQNFLR QDOQLKLQDQDWRPVNLKVSUHPHPEYRGLYRSD]RYDQHXþLQNH.OMXþQLGRJRGHN DQJkey event MH GHILQLUDQ NRW HPSLULþQR RSDåHQL SUYL NRUDN NL MH QXMQL HOHPHQWQDþLQDGHORYDQMDR]LURPDMHR]QDþHYDOFHQXMQHJDHOHPHQWD>@

=DUD]OLNRRGQDþLQDGHORYDQMDLPSOLFLUDPHKDQL]HPGHORYDQMDDQJmechanism of actionQDWDQþQHMãHUD]XPHYDQMHPROHNXODUQLKRVQRYWRNVLþQHJDXþLQND>@

+RUPRQVNLHQGRNULQLVLVWHP

+RUPRQMHVQRYNLL]YLUDL]GRORþHQHJDWNLYDLQXþLQNXMHQDGUXJDWNLYDGR NDWHULK SULVSH V NUYMR +RUPRQVNL HQGRNULQL VLVWHP YNOMXþXMH HQGRNULQH RUJDQH LQ WNLYD NL XUDYQDYDMR SUHVQRYR UDVW UD]YRM WHU GHORYDQMH WNLY LQ RUJDQRYLQWDNRYSOLYDQDSUDNWLþQRYVDNRFHOLFRRUJDQL]PD3ULWHPVRGHOX MHMRãWHYLOQHWHOHVXODVWQHNHPLþQHVQRYLPHGWHPNRVHIL]LRORãNRUDYQRYHVMH Y YHþLQL SULPHURY Y]GUåXMH ] QHJDWLYQLPL SRYUDWQLPL ]DQNDPL 9H]DYD QD KRUPRQVNHUHFHSWRUMHSRY]URþLVSUHPHQMHQRL]UDåDQMHJHQRYDOLVSUHPHPEH Y EHOMDNRYLQDK NDU YSOLYD QD GHORYDQMH FHOLF ýH MH KRUPRQRY SUHYHþ DOL SUHPDORR]LURPDþHQLGRYROMUHFHSWRUVNLKYH]DYQLKPHVWODKNRQDVWDQHMR KRUPRQVNRQHUDYQRYHVMHLQ]QMLPSRYH]DQHPRWQMHLQEROH]QL>@

7ULSRPHPEQH HQGRNULQH RVLVR KLSRWDODPLþQRKLSRIL]QRJRQDGQD KLSRWD ODPLþQRKLSRIL]QRQDGOHGYLþQD LQ KLSRWDODPLþQRKLSRIL]QRãþLWQLþQD RV Y]GROå NDWHULK SRWHNDMR NRPSOHNVQH YHUWLNDOQH NRPXQLNDFLMH NRW WXGL QDY]NULåQH KRUL]RQWDOQH NRPXQLNDFLMH PHG HQGRNULQLPL åOH]DPL LQ GUXJLPL RUJDQVNLPL VLVWHPL9QHNDWHULKSULPHULKNRWVRL]ORþDQMHLQ]XOLQDL]WUHEXãQHVOLQDYNH PLQHUDORNRUWLNRLGRY L] QDGOHGYLþQH åOH]H R]LURPD SDUDWKRUPRQD L] REãþLW QLþQLKåOH]YKRPHRVWDWVNLK]DQNDKQHVRGHOXMHWDKLSRWDODPXVLQKLSRIL]D DPSDN MH UDYHQ QDãWHWLK KRUPRQRY RGYLVQD RG NRQFHQWUDFLMH JOXNR]H QDWULMDLQNDOLMDR]LURPDNDOFLMDLQIRVIRUMDYVHUXPX>@=YVHYHþMLPUD]X PHYDQMHP UHFHSWRUVNHJD VLJQDOL]LUDQMD LQ PROHNXODUQH ELRORJLMH VH EULãHMR PHMHPHGKRUPRQVNLPåLYþQLPLQLPXQVNLPVLVWHPRP=DWRVHYGRORþHQLK NRQWHNVWLK N HQGRNULQHPX VLVWHPX SROHJ NODVLþQR GHILQLUDQHJD SULãWHYDMR

tudi druge vrste signaliziranja, ki poteka prek receptorjev [9], kar dodatno zapleta interpretacijo vplivov KPHM in HAS.

1$ý,1,'(/29$1-$KPHM,1HAS

.HPLNDOLMH LPDMR ODKNR UD]OLþQH QDþLQH GHORYDQMD QD KRUPRQVNL VLVWHP = vezavo na hormonske receptorje lahko delujejo kot agonisti ali antagonisti.

Poleg tega lahko vplivajo na:

x GHMDYQLNH NL SRVUHGXMHMR XþLQNH DNWLYLUDQLK KRUPRQVNR UHFHSWRUVNLK kompleksov;

x FHOLþQLSULY]HPVQRYLSRWUHEQLK]DVLQWH]RKRUPRQRY

x GHORYDQMHHQFLPRYYSOHWHQLKYVLQWH]RSUHVQRYRLQRþLVWHNKRUPRQRY x L]ORþDQMHKRUPRQRYL]HQGRNULQLKWNLY

x YH]DYRKRUPRQRYQDWUDQVSRUWQHEHOMDNRYLQH

x nevro-endokrino signalizacijo in uravnavanje endokrinih funkcij [3, 9].

1HJOHGHQDQDþLQGHORYDQMDMHSRPHPEQRGDUD]OLNXMHPRKRUPRQVNRDNWLY QRVWRGKRUPRQVNHPRWQMH+RPHRVWDWVNDNDSDFLWHWDNLY]GUåXMHIL]LRORãNR GLQDPLþQRUDYQRYHVMHMHSRPHPEQD]QDþLOQRVWKRUPRQVNHJDVLVWHPDýH NDNãQD HNVRJHQD NHPLNDOLMD ]DþDVQR VSUHPHQL GHORYDQMH KRUPRQVNHJD VLVWHPD]QRWUDMKRPHRVWDWVNHNDSDFLWHWHRUJDQL]PDSRVOHGLFDQHERãNRG OMLYLXþLQHNDPSDN]JROMVSUHPHPED]QRWUDMIL]LRORãNHJDUD]SRQD>@

1$ý,1,,=3267$9/-(1267,,1326/(',&(

Pri ljudeh in drugih organizmih so raziskovalci v raznih predelih sveta XJRWRYLOL VSUHPHPEH ãWHYLOD LQ NYDOLWHWH VHPHQþLF SRQHNRG VR XJRWRYLOL XSDG GUXJRG SRUDVW VSUHPHQMHQR UD]PHUMH PHG VSRORPD SUL QHNDWHULK YUVWDKYSULGPRãNLKSRWRPFHYSULGUXJLKåHQVNLKSRUDVWSRMDYOMDQMDDQR PDOLM VSROQHJD WUDNWD SUL PRãNLK SRUDVW EROH]QL UHSURGXNWLYQHJD WUDNWD SUL åHQVNDKSRUDVWQHSORGQRVWLPRWHQMGHORYDQMDãþLWQLFHPRWHQMQHYURORãNHJD razvoja in delovanja imunskega sistema ter porast hormonsko odvisnih UDNRY NRW VR UDN GRMNH SURVWDWH PRG LQ ãþLWQLFH >@ =DUDGL XJRWRYOMHQLK SRYH]DY PHG QDãWHWLPL XþLQNL LQ L]SRVWDYOMHQRVWMR NHPLþQLP VQRYHP VH MH razmahnilo intenzivno raziskovanje z namenom, da se pojasnijo vzroki in SULGRELMRGRGDWQLSRGDWNLLQ]QDQMHRPHKDQL]PLKXþLQNRYGDVHL]EROMãDMR PHWRGRORãNL SULVWRSL UD]ãLUL LQ L]EROMãD VSUHPOMDQMH GD VH QDGDOMXMH LGHQWLILNDFLMD .3+0 Y]SRVWDYLMR PHGQDURGQL VH]QDPL LQ ED]H SRGDWNRY RFHQLWYHJDQMHLQVSUHMPHMRXVWUH]QLXNUHSL]D]PDQMãHYDQMHWYHJDQMD 3UYRWQH UD]LVNDYH VR VH RVUHGRWRþDOH QD YSOLYH QD VSROQH LQ ãþLWQLþQH KRUPRQHWHUVWHURLGRJHQH]R>±@PHGWHPNRMHY]DGQMHPGHVHWOHWMX YVHYHþUD]LVNDYWXGLRYSOLYXNHPLNDOLMQDGUXJHKRUPRQVNHSRWLLQ]QMLPL

SRYH]DQH PRWQMH NRW VR PRWQMH GHORYDQMD QDGOHGYLþQH åOH]H VODGNRUQD EROH]HQWLSD,,PHWDEROQLVLQGURPXþLQNLQDNRVWLLQ]REH>±@

3ROHJ ãWHYLOQLK ]GUDYLO GLHWLOVWLOEHVWURO SHURUDOQL NRQWUDFHSWLYL KRUPRQVND QDGRPHVWQD WHUDSLMD Y PHQRSDY]L NRUWLNRVWHURLGL ]GUDYLOD ]D ]YHþDQR SURVWDWRQHNDWHULDQWLDULWPLNLQHNDWHULDQWLSVLKRWLNLSDUDFHWDPROLWGODKNR KRUPRQVNR UDYQRYHVMH PRWLMR ãWHYLOQH NHPLNDOLMH NL VR ERGLVL Y QDUDYL RG QHNGDMERGLVLQDPHUQRDOLQDNOMXþQRGRGDQHåLYLORPR]LURPDVRVHVWDYLQH ãWHYLOQLKSUHGPHWRYVSORãQHUDEHRGWHNVWLODREODþLOHOHNWULþQLKLQHOHNWURQ VNLK QDSUDY JUDGEHQLK PDWHULDORY GR SDSLUMD RWURãNLK LJUDþ NR]PHWLNH LQ HPEDODåH 3RMDYOMDMRVH PHG SURGXNWL]JRUHYDQMDLQ VR VHVWDYLQH ãWHYLOQLK NHPLþQLK L]GHONRY RG UD]NXåLO GR VUHGVWHY ]D ]DWLUDQMH SOHVQL åXåHON JOR GDYFHYLQSOHYHODYGRPDþHPRNROMXLQYNPHWLMVWYX6H]QDP.3+0LQ+$6 MHL]MHPQRSHVWHU0HGQMHVSDGDMRYVDNGDQMHVHVWDYLQHåLYLONRWVRQDPL]QL VODGNRU NXKLQMVND VRO UDVWOLQVNL HVWURJHQL NRIHLQ HWLOQL DONRKRO JOLKLUL]LQ VHVWDYLQH SODVWLNH QSU ELVIHQRO $ LQ IWDODWL VHVWDYLQH GHWHUJHQWRY QSU QRQLOIHQRO VHVWDYLQH JRULY QSU SHUNORUDW NRQ]HUYDQVL QSU SDUDEHQL REVWRMQDRUJDQVNDRQHVQDåHYDODGLRNVLQLIXUDQL SROLNORULUDQLELIHQLOLSROL EURPLUDQL ELIHQLO HWUL NRYLQH DU]HQ NDGPLM VYLQHF åLYR VUHEUR SHVWLFLGL QSUDWUD]LQD]ROIXQJLFLGLPDQHERUJDQRNORUQLSHVWLFLGLSURNORUD]RUJDQVNL VWDQDWL YLQNOR]ROLQ SURGXNWL JRUHQMD QSU SROLDURPDWVNL RJOMLNRYRGLNL LQ ãWHYLOQH GUXJH NHPLNDOLMH NL VPR MLP L]SRVWDYOMHQL Y YVDNGDQMHP åLYOMHQMX 3RGUREQHL]VOHGNHLQUD]SUDYHRXþLQNLKSRVDPH]QLK.3+0LQ+$6QDOMXGL LQ GUXJH RUJDQL]PH SRGDWNH R L]SRVWDYOMHQRVWL LQ QDþLQLK GHORYDQMD MH PRåQRSUHEUDWLYãWHYLOQLK]QDQVWYHQLKVWURNRYQLKLQSUHJOHGQLKþODQNLKWHU PRQRJUDILMDK>±@

9]YH]L]YVHELQRGDQDãQMHJDVHPLQDUMDåHOLPRSRVHEHML]SRVWDYLWLQHGDYQL SUHJOHGQLþODQHN=DGQLNRYHLQ.UDMþHYHRHSLGHPLRORãNLKWUHQGLKKRUPRQVNR RGYLVQLK UDNRY WR MH UDND GRMNH HQGRPHWULMD MDþQLNRY SURVWDWH PRG LQ ãþLWQLFH Y 6ORYHQLML 'HOHå SULPHURY KRUPRQVNR RGYLVQLK UDNRY GRVHJD þHWUWLQR YVHKUDNRYY6ORYHQLMLLQVR± ]L]MHPRUDNDMDMþQLNRY±YSRUDVWX

$YWRULFLUD]SUDYOMDWDR]QDQLKQHYDUQRVWQLKGHMDYQLNLKYNOMXþQRV.3+0LQ ]DNOMXþLWDGDVOHGQMLPSULSLVOMLYHJDGHOHåDUDNRYWUHQXWQRQLPRJRþHGRORþLWL ]DUDGL SRPDQMNDQMD YHURGRVWRMQLK UD]LVNDY SUL L]SRVWDYOMHQLK SUHGYVHP Y NULWLþQLKUD]YRMQLKRGEGREMLK>@

KONTROVERZNOSTI IN NEGOTOVOSTI

ýHSUDY Y QDGDOMHYDQMX QDYHGHQH NRQWURYHU]QRVWL LQ QHJRWRYRVWL QLVR HNV NOX]LYQH ]D .3+0 LQ +$6 VH R QMLK QDMLQWHQ]LYQHMH UD]SUDYOMD UDYQR Y SRYH]DYL V ãNRGOMLYLPL YSOLYL NHPLNDOLM QD KRUPRQVNR UDYQRYHVMH ]DWR MLK SUHGVWDYOMDPRQHNROLNRSRGUREQHMH

3UDJXþLQND

3UDJXþLQNDMHYRGLOQDNRQWURYHU]QRVWY]YH]LV .3+0LQ+$66OREUD]OL NXMHELRORãNLHNVSHULPHQWDOQLLQPDWHPDWLþQLSUDJ%LRORãNLSUDJMHRGPHUHN SRGNDWHULPVQRYQHSRY]URþLQREHQLKãNRGOMLYLKXþLQNRY(NVSHULPHQWDOQL SUDJ MH RGPHUHN SRG NDWHULP XþLQNL QLVR RSDåHQL 0DWHPDWLþQL SUDJ MH RGPHUHN SRG NDWHULP MH XþLQHN PDWHPDWLþQR QLþ 9HQGDU Y åLYLK VLVWHPLK RGPHUHN SUL NDWHUHP MH XþLQHN PDWHPDWLþQR YHþML RG QLþ QL DYWRPDWLþQR ELRORãNRUHOHYDQWHQR]LURPDMHELRORãNDUHOHYDQWQRVWSUHML]MHPDNRWSUDYLOR

>@ 7R SRWUMXMHMR ERJDWH L]NXãQMH ] ]GUDYLOL åLYLOL LQ ãWHYLOQLPL GUXJLPL NHPLNDOLMDPL SUL NDWHULK MH ]D GRVHJR åHOHQLK R]LURPD WRNVLþQLK XþLQNRY WUHEDY]GUåHYDWLGRYROMYHOLNRNRQFHQWUDFLMRVQRYLGRYROMGROJR7UDGLFLRQDOQR VHSULVWRS GRORþLWYH HNVSHULPHQWDOQHJD SUDJD XþLQNDXSRUDEOMD ]DQHUDNR WYRUQH VQRYL 9 SRVNXVLK XJRWRYOMHQL RGPHUNL EUH] ãNRGOMLYHJD XþLQND RE XSRUDELXVWUH]QLKIDNWRUMHYRFHQMHYDQMDNLXSRãWHYDMRQHJRWRYRVWLY]YH]L]

UD]OLNDPL PHG SRVNXVQLPL åLYDOPL LQ OMXGPL VR L]KRGLãþH ]D NYDQWLILNDFLMR QHYDUQRVWL NHPLNDOLMH LQ GRORþLWHY YDUQLK RGPHUNRY 1DUDãþDMRþD XSRUDED JHQRPVNLK RURGLM MH SRND]DOD GD MH SUDJ ]D QDVWDQHN NOMXþQHJD GRJRGND QDUDYQLRGPHUNDSULNDWHUHPMHPRåQRRSD]LWLWXGLKLVWRORãNHVSUHPHPEH QH VDPR SULQHUDNRWYRUQLK SURFHVLKDPSDNWXGL SULUDNRWYRUQLK 8þLQNLSUL QLåMLK RGPHUNLK VR QDMYHUMHWQHMH SULODJRGLWYHQL RG]LYL QD VSORãQHGHMDYQLNH VWUHVDNLSDVHQHRGUDåDMRQDUDYQLUHJXODFLMHJHQRY2SD]RYDQLRG]LYLQD VSRGQMHP GHOX VSHNWUD HNVSHULPHQWDOQLK RGPHUNRY VR SRJRVWR HQDNL RG]LYRP Y SULPHUMDOQLK VNXSLQDK LQ VR YHUMHWQR SRVOHGLFD GHMVWYD GD MH HNVSHULPHQWDOQLRGPHUHNQLåMLRGSUDåQHJDDOLSDSRVOHGLFDSRPDQMNOMLYRVWL HNVSHULPHQWDOQLKSURWRNRORY>@

9QDVSURWMXVWRNVLNRORJL]DY]HPDMRHQGRNULQRORJLVWDOLãþHGDSUHGSRVWDYNH RSUDJXYSULPHUX.3+0LQ+$6QLVRQDPHVWX]DUDGLSRVHEQRVWLLQ]DSOH WHQRVWL KRUPRQVNHJD VLVWHPD (QGRJHQL KRUPRQL LQWHJUDOQR NRRUGLQLUDMR UD]YRM LQ GHORYDQMH WNLY LQ GHOXMHMR QD VSHFLILþQH UHFHSWRUMH SUL ]HOR QL]NLK RGPHUNLKWRMHYSLNRLQQDQRPRODUQLKNRQFHQWUDFLMDK$ILQLWHWD]DUHFHSWRUMH MHODKNRGUXJDþQDRGVSORãQHPRþLNHPLNDOLMHin vivo+RUPRQVNLUHFHSWRUML VR QDMREþXWOMLYHMãL QD VSRGQMHP GHOX NULYXOMH RGPHUHNXþLQHN LQ VH SUL UD]OLþQLK RGPHUNLK YHåHMR QD UD]OLþQH UHFHSWRUMH NDU VH ODKNR RGUDåD Y UD]OLþQLK RG]LYLK 8þLQNL VR RGYLVQL RG UD]YRMQH VWRSQMH L]SRVWDYOMHQHJD RUJDQL]PD YHþMLP SRWHQFLDO ]D UD]YRM WUDMQLK XþLQNRY LPDMR UD]YLMDMRþL VH RUJDQL]PL>@

(NVSHUWQDVYHWRYDOQDVNXSLQD(66NLMHYþDVX±GHORYDODNRW VWURNRYQD SRGSRUD ]D GRORþLWHY ]QDQVWYHQLK PHULO ]D .3+0 SUL (YURSVNL NRPLVLMLVHMHVWULQMDODGDMHRG]LYKRUPRQVNLKUHFHSWRUMHYRGYLVHQRGNRQ FHQWUDFLMHKRUPRQDLQUHFHSWRUMD7RSRPHQLGDMH]DRG]LYSRWUHEQDGROR þHQD ]DVHGHQRVW UHFHSWRUMHY 7HRUHWLþQR EL ODKNR HQD PROHNXOD RG ]XQDM YQHVHQHJDDJRQLVWDGRGDQDREVWRMHþLNRQFHQWUDFLMLHQGRJHQHJDKRUPRQD

DNWLYLUDOD GRORþHQL UHFHSWRU NDU EL SRPHQLOR GD Y SULPHUX +$6 LQ .3+0 SUDJD XþLQND QL 9HQGDU WR QH SRPHQL GD EL ELO RG]LY ãNRGOMLY þHSUDY GRSXãþDMR PRåQRVW L]MHP 9HþLQD HNVSHUWRY MH PHQLOD GD .3+0 LPDMR SUDJãNRGOMLYLKXþLQNRYNLSDMHSULQHNDWHULKYSRVDPH]QLKSULPHULKODKNR ]HOR QL]HN RGYLVQR SDþ RG QDþLQD GHORYDQMD LQ PRþL NHPLNDOLMH 3UDJ XþLQNDMHODKNRSRVHEHMQL]HNYþDVXIHWDOQHJDUD]YRMDNRKRPHRVWDWVNLLQ GHWRNVLILNDFLMVNLPHKDQL]PLãHQLVRGR]RUHOL>@

8þLQNLSULQL]NLKRGPHUNLK

8þLQNL SUL QL]NLK RGPHUNLK VR XþLQNL NL VH SRNDåHMR SUL RGPHUNLK NL VPR MLPOMXGMHL]SRVWDYOMHQLYYVDNGDQMHPåLYOMHQMXR]LURPDXþLQNLRGPHUNRYNL VRQLåMLRGWLVWLKXSRUDEOMHQLKYWRNVLNRORãNLKUD]LVNDYDK>@

9DQGHUEHUJLQVRGQL]DMRYUVWRSULPHURYXþLQNRYHQGRJHQLKKRUPRQRY($6 LQ.3+0SULQL]NLKRGPHUNLKLQSUHGODJDMRGDMH]DXJRWDYOMDQMHHQGRNULQLK XþLQNRYWUHED L]YDMDWLWHVWLUDQMH SULYHþQL]NLKRGPHUNLKQDPHQLWLSRVHEQR SR]RUQRVW L]LGRP SUL QHL]SRVWDYOMHQL SULPHUMDOQL VNXSLQL Y OXþL KLVWRULþQLK NRQWUROQLKSRGDWNRYLQL]YHVWLWHVWLUDQMHWXGL]XVWUH]QRSR]LWLYQRSULPHUMDOQR VNXSLQR >@ 9HQGDU MH ELO ]HOR REãLUHQ SUHJOHG 9DQGHUEHUJRYH LQ VRG GHOHåHQ NULWLN LQ VLFHU GD VR ELOH UHIHUHQFH VHOHNWLYQR L]EUDQH SUHVRMD UD]LVNDYQLELODQDUHMHQDXQLIRUPQRDPSDNVRDYWRUMLSULSLVDOLYHþMLSRPHQ UD]LVNDYDP ] XþLQNL SUL QL]NLK RGPHUNLK NRW WLVWLP NMHU WRYUVWQLK XþLQNRY QLVRXJRWRYLOLGDRGPHUNLQLVRYHGQRXVWUH]DOLGHILQLFLMLQL]NHJDRGPHUNDLQ GD VR DYWRUML Y]URþQRVW SRHQRVWDYOMHQR SULSLVDOL QD SRGODJL VWDWLVWLþQR SRPHPEQLKSRYH]DYNLSDQLVRQXMQRY]URþQRSRJRMHQHLQQLVRSRVOHGLFD KRUPRQVNHJDQDþLQDGHORYDQMD>@

3RPDQMNDQMH NRQVHQ]D PHG VWURNRYQMDNL JOHGH XþLQNRY QL]NLK RGPHUNRY .3+0MHELORHYLGHQWQRWXGLY(661HNDWHULHNVSHUWLVRPHQLOLGDMHGRND ]RY GRYROM GUXJL GD VR SRWUHEQH PHGODERUDWRULMVNH SULPHUMDYH ] XSRUDER REþXWOMLYLKPHWRGLQXVWUH]QRREþXWOMLYLKL]LGRYNDMWLL]LGLUD]LVNDYSULQL]NLK RGPHUNLKVRSRJRVWRWHåNRSRQRYOMLYL>@

= JOREDOQLP KXPDQLP ELRPRQLWRULQJRP >@ VH GR QHNH PHUH ]DSROQMXMH YU]HOY]YH]L]GHMDQVNLPLL]SRVWDYOMHQRVWPLOMXGLQL]NLPRGPHUNRPNHPLNDOLM YNOMXþQR V .3+0 +XPDQL ELRPRQLWRULQJ +%0 YVH SRJRVWHMH YNOMXþXMH WXGLELRPDUNHUMHXþLQNDLQREþXWOMLYRVWL]DWRSULþDNXMHPRGDERVSRPRþMR UH]XOWDWRY +%0 PRåQR SRMDVQLWL YVDM QHNDWHUH NRQWURYHU]QRVWL Y ]YH]L ] XþLQNL.3+0SULQL]NLKRGPHUNLKþHSUDYERLQWHUSUHWDFLMDUH]XOWDWRYHSLGHPLR ORãNLKUD]LVNDY]DUDGLãWHYLOLKEHJDYLKVSUHPHQOMLYNãHQDSUHMSUHFHMãHQL]]LY

1HPRQRWRQLRGQRVPHGRGPHUNRPLQXþLQNRP

1HPRQRWRQLRGQRVELID]LþQLYREOLNLþUNH8DOLREUQMHQHJD8PHGRGPHUNRP LQ XþLQNRP SRPHQL GD NULYXOMD XþLQND Y RGYLVQRVWL RG RGPHUND VSUHPLQMD VPHURGSR]LWLYQHNQHJDWLYQLDOLREUDWQR1HPRQRWRQLRGQRVPHGRGPHUNRP LQXþLQNRPMHGREURSR]QDQYIL]LRORJLMLIDUPDNRORJLMLLQWRNVLNRORJLMLLQMHELO RSLVDQSULYHþNRWVXEVWDQFDKPHGGUXJLPSULDQWLHSLOHSWLNLKDQNVLR OLWLNLK ELIRVIRQDWLK HQGRJHQLK KRUPRQLK NDURWHQRLGLK PLQHUDOLK VUþQLK JOLNR]LGLK VWDWLQLK WURSDQVNLK DONDORLGLK YLWDPLQLK MRKLPELQX NR WXGL SUL ãWHYLOQLK .3+01HPRQRWRQL RGQRVPHGRGPHUNRPLQXþLQNRPLPDODKNR UD]OLþQH Y]URNH ± RG QHSRVUHGQH VWLPXODFLMH EODJH KLSHUNRPSHQ]DFLMH RE ]DþHWQL PRWQML KRPHRVWD]H GR YSOHWHQRVWL SRGWLSRY UHFHSWRUMHY QD UD]QLK UDYQHKRUJDQVNHJDVLVWHPD>±@

0RUHELWQL QHPRQRWRQL RGQRV PHG RGPHUNRP LQ XþLQNRP LPD ODKNR ]D SRVOHGLFR GD VH SUL NRQYHQFLRQDOQHP WHVWLUDQMX QH XJRWRYLMR XþLQNL SUL RGPHUNLKQLåMLKRGHNVSHULPHQWDOQHJDRGPHUNDEUH]XþLQND3RVOHGLþQRMH L]UDþXQ YDUQLK RGPHUNRY ODKNR PDQM ]DQHVOMLY 9HQGDU QHPRQRWRQL RGQRV QHL]NOMXþXMHREVWRMDELRORãNHJDSUDJD>@

8þLQNL]PHVL

2FHQDXþLQNRY]PHVLSRSXODUQRWXGLªXþLQNLNRNWHMORY©MHYVHNDNRUSUREOHP VRGREQHWRNVLNRORJLMH9HQGDUMHELOQDYNOMXEYU]HOLPY]QDQMXQDWHPSRG URþMXY]DGQMLKOHWLKGRVHåHQSUHFHMãHQQDSUHGHNSULUD]YRMXXVWUH]QLKPHWRG LQQDYRGLO>±@

=DSOHWHQRVW SUHVRMH XþLQNRY ]PHVL QL VSHFLILþQD ]D .3+0 =D QDSRYHG XþLQNRY ]PHVL MH SRWUHEQR SR]QDYDQMH QDþLQD GHORYDQMD ãNRGOMLYLK L]LGRY WRNVLNRNLQHWVNLK LQ WRNVLNRGLQDPVNLK LQWHUDNFLM =DUDGL SHVWURVWL QDþLQRY GHORYDQMD PRåQRVWL ]HOR QL]NLK SUDJRY XþLQND LQ QHPRQRWRQHJD RGQRVD PHG RGPHUNRP LQ XþLQNRP MH QDSRYHG LQWHUDNFLM Y ]YH]L V .3+0 ãH EROM ]DKWHYQD>@

.ULWLþQDRNQDL]SRVWDYOMHQRVWLLQUD]YRMD

.ULWLþQD RNQD L]SRVWDYOMHQRVWL LQ UD]YRMD VR RG VWRSQMH UD]YRMD RGYLVQD REGREMD REþXWOMLYRVWL 2G VSRþHWMD GR RGUDVORVWL R]QDþXMHMR SRVDPH]QH UD]YRMQH VWRSQMH RUJDQL]PD ]QDþLOQL GLQDPLþQL SURFHVL QD UDYQL PROHNXO FHOLFWNLYRUJDQVNLKVLVWHPRYLQFHOHJDRUJDQL]PD5D]OLNHYWHKSURFHVLK VNXSDM ] L]SRVWDYOMHQRVWMR RNROMVNLP QHYDUQRVWQLP GHMDYQLNRP GRORþDMR QDUDYRLQVWRSQMRSRVOHGLF>@

,]SRVWDYOMHQRVW .3+0 Y þDVX NULWLþQLK RNHQ UD]YRMD MH ODKNR ELVWYHQD ]D XþLQNH Y NDVQHMãLK åLYOMHQMVNLK REGREMLK 3ROHJ WHJD VH ]DUDGL UD]OLN Y ]UHORVWL LQ IXQNFLRQDOQRVWL HQGRNULQHJD VLVWHPD XþLQNL ODKNR UD]OLNXMHMR Y RGYLVQRVWL RG UD]YRMQHJD R]LURPD åLYOMHQMVNHJD REGREMD Y NDWHUHP MH RUJDQL]HP L]SRVWDYOMHQ .3+0 9 ]JRGQMLK REGREMLK UD]YRMD KRPHRVWDWVNH SRYUDWQH]DQNHãHQLVRUD]YLWHSUDYWDNRMHQH]UHOSUHVQRYQLVLWHP0DMKQD VSUHPHPED UDYQL KRUPRQRY PHG UD]YRMHP LPD ODKNR WUDMQH LQ KXGH SRVOHGLFH>@

Pomanjkljivosti testnih metod

6HGDQMHWHVWQHPHWRGH]DXJRWDYOMDQMHXþLQNRY+$6LQ.3+0>@VHRVUH GRWRþDMRQDVWHURLGRJHQH]RWHUHVWURJHQVNRDQGURJHQVNRLQWLURLGQRRVSUL VHVDOFLK 3RPHPEQH SRPDQMNOMLYRVWL VR XJRWDYOMDQMH YSOLYRY VSUHPHPEin utero QD NDVQHMãD REGREMD åLYOMHQMD REþXWOMLYRVW PHWRG LQ PRUHELWQR QH YNOMXþHYDQMH L]LGRYVSHFLILþQLK ]D KRUPRQVNHPRWQMH.HUSD MH ]D.3+0 ]QDþLOQDSHVWURVWQDþLQRYGHORYDQMDYHUWLNDOQLKLQKRUL]RQWDOQLKNRPXQLNDFLM WHUãNRGOMLYLKXþLQNRYVH ODKNRSULþDNXMHGDERGR WLXþLQNLXJRWRYOMHQLVDM UD]OLþQHWHVWQHPHWRGHSRNULYDMRUD]OLþQHYLGLNHXJRWDYOMDQMDWRNVLþQRVWL=D ]DQHVOMLYHMãRSUHVRMRGUXJLKPRGDOLWHWERWUHEDPHWRGHXVWUH]QRGRSROQLWL>@

=$./-8ý(.

9 ]DGQMHP GHVHWOHWMX MH ELOR SULGREOMHQLK RJURPQR LQIRUPDFLM ]QDQMD LQ L]NXãHQM Y ]YH]LV .3+0 LQ+$6 =D VNRUDM NHPLNDOLM MH ELOR SRWUMHQR GDODKNRãNRGLMR]GUDYMXYLQWDNWQHPRUJDQL]PXSUHNKRUPRQVNHJDQDþLQD GHORYDQMD PHGWHPNR MH ELOR ]D QHNDM XJRWRYOMHQR GD VR KRUPRQVNR DNWLYQH3RWUMHQHVRELOHãNRGOMLYHSRVOHGLFHSULL]SRVWDYOMHQRVWLYLVRNLPLQY QHNDWHULKSULPHULKWXGLSULL]SRVWDYOMHQRVWLQL]NLPRGPHUNRP9HQGDURVWD MDMR ãWHYLOQH SRPDQMNOMLYRVWL QHJRWRYRVWL LQ NRQWURYHU]QRVWL 9HþLQD WHK QL HNVNOX]LYQD]D.3+0LQ+$6DPSDNWXGL]DGUXJHNHPLNDOLMHYHQGDUVHR QMLKQDMLQWHQ]LYQHMHUD]SUDYOMDSUDYY]YH]LV.3+0)L]LRORJLMDLQSDWRORJLMD HQGRNULQHJD VLVWHPD VWD QHGYRPQR VSHFLILþQL LQ SUHFHM ]DSOHWHQL NDU MH QHGYRPQRGRGDWHQ L]]LYSULRFHQLQHYDUQRVWLLQWYHJDQMD7RGDNOMXEWHPX SUHVHQHþD UD]JUHWRVW UD]SUDY Y ]YH]L V .3+0 LQ +$6 NL MLK PRUGD ODKNR SULSLãHPR SRG]DYHVWQLP LPSXO]RP ]DUDGL VWUDKX SUHG L]XPUWMHP JOHGH QD WRGD.3+0YSOLYDMRQDSORGQRVWLQUD]YRM3RPHPEQRMHGDVHSULREOLNR YDQMX ]DNOMXþNRY XSRãWHYD WHåD GRND]RY QD SRGODJL VLVWHPDWLþQH SUHVRMH ]DQHVOMLYRVWL UD]LVNDY PHWRGRORãNHJD SULVWRSD NYDOLWHWH SRGDWNRY NRQVL VWHQWQRVWL VSHFLILþQRVWL LQ SRQRYOMLYRVWL UH]XOWDWRY ELRORãNH YHUMHWQRVWL WHU RYUHGQRWHQMDSRGDWNRYYOXþLSRVWDYOMHQHKLSRWH]H.3+0RVWDMDMRSRPHPEQD UD]LVNRYDOQD MDYQR]GUDYVWYHQD LQ UHJXODWRUQD SULRULWHWD 3ULþDNXMHPR GD