616-006-02:661(082) 286625280 KAZALO UVODNIK RAZISKOVANJE VPLIVA OKOLJA NA ZBOLEVANJE ZA RAKOM IN OCENJEVANJE TVEGANJA RAKOTVORNO DELOVANJE KEMIKALIJ IZ OKOLJA HORMONSKI MOTILCI ZDRAVA TLA – ZDRAVI LJUDJE KEMIKALIJE V PITNI VODI RAKOTVORNE KEMIKALIJE V HRANI KLIMATSKE SPREMEMBE IN ZDRAVJE DRUGI VIRI IZPOSTAVLJENOSTI KEMIKALIJAM IZ OKOLJA: NADZOR IN OMEJEVANJE TVEGANJ ZA ZDRAVJE KOMUNIKACIJA O OKOLJSKIH TVEGANJIH SEZNAM IN NASLOVI AVTORJEV XXIV. seminar “In memoriam dr. 5 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 Njegov namen je bil zmanjšati zbolevnost in umrljivost za rakom v Sloveniji ter gmotno pomagati pri opremljanju Onkološkega inštituta. Ministrstvo za cije in status društva, ki deluje v javnem interesu. Zveza slovenskih društev z a bo j p r o ti r a ku s i z r eg i j s ki mi d r u š t v i p r i z ad ev a p o s t a ti p r e poznaven Evropskega kodeksa proti raku. Vsako od postavk Kodeksa snjujemo z dodatnimi informacijami in razlagami, ki jih podajamo v pisnih park Gardaland. Druge naše naloge so zagovorništvo, zbiranje sredstev za akcije, s katerimi regijskih društev za boj proti raku, sodelovanje z drugimi sorodnimi društvi in organizacijami doma, v Evropi in v svetu. z regijskimi društvi, si društva v svojem okolju prizadevajo za skupne cilje še z lokalnimi akcijami. vsi zdravstveni delavci na primarni ravni zdravstvenega varstva in zaposleni stvene vzgoje, ki naj to znanje predajajo ljudem, za katere skrbijo. Letos 6 je namenjen pregledu morebitnih zdravstvenih posledic, med njimi tudi seminar namenjamo pregledu znanstvenih dognanj o povezanosti med predsednica Zveze slovenskih društev za boj proti raku 7 RAZISKOVANJE VPLIVA OKOLJA NA ZBOLEVANJE ZA RAKOM IN OCENJEVANJE TVEGANJA Vesna Zadnik Povzetek UVOD 8 zlasti bolezni dihalnih poti, alergije in rak [1]. Med rake, ki lahko nastanejo tudi kot posledica izpostavljenosti kemikalijam v delovnem ali bivalnem bušnice (npr. mezoteliom zaradi delovanja azbesta), bezgavk, jeter, ledvic, levkemije ter, manj pa še nekatere druge vrste rakov [2]. ohlapna [2]. strokovnih krogih, predvsem pa v raznih skupinah s civilnimi iniciativami, pa 9 International Agency for Research on Cancer 10 Arzen in njegove anorganske spojine zrak Benzen zraku izpostavljenost 11 OCENJEVANJE TVEGANJA Identifikacija nevarnosti 12 stavljenost škodovala njihovemu zdravju. V ocenjevanju tveganja n e ugotavljamo morebitne rakotvornosti snovi po postopkih, opisanih v prej- okolja (Environmental Protection Agency Agency for Toxic Substances and Disease Registry kakšen je odnos med odmerkom in pojavljanjem bolezni pri ljudeh. Pri ne- 13 Zaradi predpostavke o majhnih dozah, ki na zdravje nimajo vpliva, se tak Ocenjevanje izpostavljenosti To je postopek, pri katerem ocenjujemo dejansko izpostavljenost ljudi v nadomestne mere izpostavljenosti, ki dejansko izpostavljenost odrazijo bolj oceno izpostavljenosti direktne metode uporabijo le izjemoma, saj smo 14 15 Povzeto po [13] 16 17 strah. Nedostopnost ustreznih informacij ali pa neprimerno oziroma LITERATURA 18 10. EPA. Human health risk assessment. Pridobljeno 25. 8. 2016 s spletne strani https://www. epa.gov/risk/human-health-risk-assessment. 19 RAKOTVORNO DELOVANJE KEMIKALIJ IZ OKOLJA POVZETEK. UVOD za nastanek raka: 20 MEHANIZMI DELOVANJA RAKOTVORNIH KEMIKALIJ 21 22 Absorpcija Majhni, nizkomolekularni DNK-adukti najpogosteje nastanejo po alkilaciji kovalentne vezave funkcionalne alkilne skupine na molekulo DNK. N a splošno je alkilacija dušika nukleinske baze manj mutagena od alkilacije skupino spadajo N-nitrozo spojine in nitrozamini, ki nastajajo tudi endogeno, 23 Reactive Oxygen Species CpG islands 24 RAKOTVORNO DELOVANJE KADMIJA 25 Slika 3. Mehanizem karcinogenega delovanja kadmija prek indukcije poškodb DNK, inhibicije 26 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. 27 HORMONSKI MOTILCI POVZETEK in utero UVOD endocrine disruptor i n 28 endocrine active substance 29 adverse effect mode of action key event mechanism of action 30 tudi druge vrste signaliziranja, ki poteka prek receptorjev [9], kar dodatno zapleta interpretacijo vplivov KPHM in HAS. KPHM HAS vezavo na hormonske receptorje lahko delujejo kot agonisti ali antagonisti. Poleg tega lahko vplivajo na: kompleksov; nevro-endokrino signalizacijo in uravnavanje endokrinih funkcij [3, 9]. Pri ljudeh in drugih organizmih so raziskovalci v raznih predelih sveta razvoja in delovanja imunskega sistema ter porast hormonsko odvisnih razmahnilo intenzivno raziskovanje z namenom, da se pojasnijo vzroki in 31 KONTROVERZNOSTI IN NEGOTOVOSTI 32 in vivo 33 34 35 Pomanjkljivosti testnih metod in utero 36 in utero LITERATURA 37 38 31. Tinwell H, Colombel S, Blanck O, Bars R. The screening of everyday life chemicals in validated assays targeting the pituitary-gonadal axis. Regul Toxicol Pharmacol 2013; 66: 184–96. 32. Besbelli N, Zastenskaya I (editors). Identification of risks from exposure to endocrine- disrupting chemicals at the country level. Geneva: World health organization, 2014. 33. Fuglestad AJ, Boys CJ, Chang PN, Miller BS, Eckerle JK, Deling L, et al. Overweight and obesity among children and adolescents with fetal alcohol spectrum disorders. Alcohol Clin Exp Res 2014; 38 (9): 2502–8. 34. Jensen TK, Gottschau M, Madsen JO, Andersson AM, Lassen TH, Skakkebaek NE, et al. Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men. BMJ Open 2014; 4 (9): e005462. 35. Mazej D, Snoj Tratnik J, Šlejkovec Z, Jagodic M, Fajon V, Pavlin M, et al. Esencialni in neesencialni elementi pri slovenski populaciji: rezultati humanega biomonitoringa. In: Pridobljeno 11. 5. 2015 s spletne strani http://www.tox.si/attachments/article/189/ merged _document.pdf. 36. Wikoff D, Thompson C, Perry C, White M, Borghoff S, Fitzgerald L, et al. Development of toxicity values and exposure estimates for tetrabromobispehnol A: application in a margin of exposure assessment. J Appl Toxicol 2015; 35 (11): 1292–308. 37. WHO (World health organization). Human biomonitoring: facts and figures. Copenhagen: WHO Regional Office for Europe, 2015. Pridobljeno 10. 3. 2016 s spletne strani http:// www.euro.who.int/_data/assets/pdf_file/0020/276311/Human-biomonitoring-facts- figures-en.pdf. example from Slovenia. Arh Hig Rada Toksikol 2016; 67: 93–8. 39. Zadnik V, Krajc M. Epidemiologic trends of hormone-related cancers in Slovenia. Arh Hig Rada Toksikol 2016; 67 (2): 83–92. 40. Slob W. Thresholds in toxicology and risk assessment. Int J Toxicol 1999; 18: 259–68. 41. Rhomberg LR, Goodman JE, Haber LT, Dourson M, Andersen ME, Klaunig JE et al. Linear low-dose extrapolation for noncancer health effects is the exception, not the rule. Crit Rev Toxicol 2011; 41: 1–19. 42. Zoeller RT, Brown TR, Doan LL, Gore AC, Skakkebaek NE, Soto AM, et al. Endocrine- disrupting chemicals and public health protection: A statement of principles from The Endocrine Society. Endocrinol 2012; 153 (9): 4097–110. 43. Munn S, Goumenou M. Thresholds for endocrine disrupters and related uncertainties report of the endocrine disrupters. Expert advisory group, 2013. Ispra, Italy; European Commission. Joint research centre. Institute for health and consumer protection. Pridobljeno 10. 12. 2013 s spletne strani: https://ec.europa.eu/jrc/sites/default/files/lb- na-26-068-en-n.pdf. 44. NTP (National Toxicology Program). National toxicology program’s report of the endo- crine disruptors low dose peer review. Research Triangle Park, North Carolina; National institute of environmental health sciences, 2001. 45. Rhomberg LR, Goodman JE. Low-dose effects and nonmonotonic dose–responses of endocrine disrupting chemicals: Has the case been made? Regulat Toxicol Pharmacol 2012; 64: 130–3. 39 46. Connolly RB, Lutz WK. Nonmonotonic dose-response relationships: Mechanistic basis, kinetic modeling, and implications for risk assessment. Toxicol Sci 2004; 77: 151–7. 47. Calabrese EJ. Hormesis and medicine. Br J Clin Pharmacol 2008; 66: 594–617. risk assessment of pesticide residues in food. Toxicol Lett 2008; 180: 137–50. consumer protection directorate general 2011. Pridobljeno 25. 2. 2013 s spletne strani ingforendocrinedisrupters.htm. isation of endocrine disrupting substances. Report of the endocrine disrupters expert 40 Povzetek 3 41 številni, tudi geografsko pogojeni dejavniki, kot tudi vrsta goriva za ogre- vanje stanovanja in kuhanje [6]. Namen prispevka je na podlagi pregleda dokumentov Svetovne zdravstvene organizacije (SZO) in Mednarodne agencije za raziskovanje raka (IARC) njem in notranjem zraku na zdravje. ZUNANJI ZRAK V zunanjem zraku se v epidemioloških raziskavah najpogosteje raziskuje vpliv trdnih delcev z aerodinamskim premerom do 10 μm (PM10), dušiko- vega dioksida (NO2), ozona (O3 dioksida (SO2 stalnih merilnih mestih [9]. V Sloveniji in Evropski uniji se v manjšem obsegu 6H6) in benzo(a)pirena [9, 10]. Pri razvrstitvi snovi v okolju je IARC v skupino 1, kar pomeni rakotvorno snov val [11]. Med najpogosteje raziskovanimi in spremljanimi posameznimi Trdne delci z aerodinamskim premerom do 10 μm (PM10) je IARC razvrstil pojavljanjem raka na mehurju [11]. Hamra in sodelavci [12] so v metaanalizi 3 . Izpusti delcev PM10 so predvsem rezultat razširjenega ogrevanja gospo- dinjstev z biomaso v zastarelih kurilnih napravah, hkrati pa pozimi zunanji zunanjem zraku pripomorejo tudi neugodne vremenske razmere v slabo prevetrenih dolinah in kotlinah celinskega dela Slovenije. Zaradi slabe izpostavljenih ljudeh [13]. 42 3 2 in SO 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 3 3 x 3 3 in 3 43 3 44 stopnjo izobrazbe, status zaposlitve in socialnoekonomski status ter NOTRANJI ZRAK H H8 ), 3) 4 Benzen 45 pod stavbo, manj pa gradbeni material, voda in plin za ogrevanje. Radon se nahaja v zaprtih prostorih, v katere prodira skozi slabo izolirana tla in Trikloroetilen in tetrakloroetilen sta verjetno rakotvorni snovi za ljudi trikloretilenu in pojavom rakavih bolezni pri ljudeh. Trikloretilen nastaja pri prehaja v notranji zrak z aerosoli, ki nastanejo med prhanjem in pomivanjem posode z vodo, v katero prehaja tetrakloroetilen iz cevi iz umetnih mas. Naftalen z zunanjim zrakom zaradi nenadzorovanih izpustov industrije in izpušnih plinov motornih vozil, sicer pa je v notranjem zraku predvsem posledica formaldehid na povezanost med izpostavljenostjo formaldehidu v notranjem zraku in in vitro dehida pri izpostavljenih delavcih. Izpostavljenost formaldehidu na delovnem mestu pomembno prispeva k pojavu raka nosne sluznice, lahko pa tudi na organih, ki ne prihajajo v neposredni stik s formaldehidom, ni rakavih 46 sprememb, saj je formaldehid tako reaktiven, da se hitro lokalno presnavlja ni prispe- ter kadil [21]. 47 LITERATURA 1. Yassi A, Kjellstroem T, de Kok T, Guidotti TL. Basic environmental health. New York: Oxford University Press, 2001: 180–208. 2. Mednarodna agencija za raziskovanje raka (IARC). Air pollution and cancer. 2013. Pri- dobljeno 8. 8. 2016 s spletne strani https://www.iarc.fr/en/publications/books/sp 161/Air PollutionandCancer161.pdf. 3. Svetovna zdravstvena organizacija (SZO). WHO expert consultation: Available evidence for the future update of the WHO global air quality guidelines (AQGs). Meeting report Bonn, Germany 29 September–1 October 2015. 4. Svetovna zdravstvena organizacija (SZO). 7 million premature deaths annually linked to air pollution. 2014. Pridobljeno 12. 8. 2016 s spletne strani http://www.who.int/media centre/news/releases/2014/air-pollution/en/. 5. Künzli N, Perez L, Rapp R. Air quality and health. Lausanne: European respiratory society, 2010. 6. Svetovna zdravstvena organizacija (SZO). Air quality guidelines. Global update 2005. Kopenhagen: Urad Svetovne zdravstvene organizacije za Evropo, 2006. 7. Künzli N, Kaiser R, Medina S, Studnicka M, Chanel O, Filliger P, et al. Public-health impact of outdoor and traffic-related air pollution: a european assessment. Lancet 2000; 356 (9232): 795–801. defining the effects of outdoor air pollution on children’s health at the population level – a systematic review. IJSER 2015; 9 (1): 35–49. 9. Agencija Republike Slovenije za okolje (ARSO). Kakovost zraka v Sloveniji v letu 2014. Ljubljana: Agencija Republike Slovenije za okolje, 2015. 10. Evropska agencija za okolje (EAO). Environment and human health. Luksemburg: 11. Mednarodna agencija za raziskovanje raka (IARC). Outdoor air pollution a leading en- vironmental cause of cancer deaths. Press release No 221. 2013. Pridobljeno 1. 3. 2016 s spletne strani http://www.iarc.fr/en/media-centre/iarcnews/pdf/pr221_E.pdf. 12. Hamra GB, Guha N, Cohen A, Laden F, Raaschou-Nielsen O, Samet JM, et al. Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis. Environ Health Perspect 2014; 122(9): 906–11. 13. Mednarodna agencija za raziskovanje raka (IARC). Diesel and gasoline engine exhausts and some nitroarenes. Lyon: IARC, 2013. 14. Mednarodna agencija za raziskovanje raka (IARC). List of classifications. Volumes 1–116. Pridobljeno 28. 7. 2016 s spletne strani http://monographs.iarc.fr/ENG/Classification/ latest_classif.php. 15. Yang WS, Zhao H, Wang X, Deng Q, Fan WY, Wang L. An evidence-based assessment for the association between long-term exposure to outdoor air pollution and the risk of lung cancer. Eur J Cancer Prev 2016; 25 (3): 163–72. 16. Mednarodna agencija za raziskovanje raka (IARC). Overall evaluations of carcinogenicity: An updating of IARC monographs. Volumes 1 to 42. IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans, 1987; Suppl 7. 17. Boffetta P. Epidemiology of environmental and occupational cancer. Oncogene 2004; 23 (38): 6392–403. 18. Hashim D, Boffetta P. Occupational and environmental exposures and cancers in de- veloping countries. Ann Glob Health 2014; 80 (5): 393–411. 48 19. Raaschou-Nielsen O, Beelen R, Wang M, Hoek G, Andersen ZJ, Hoffmann B, et al. Particulate matter air pollution components and risk for lung cancer. Environ Int 2016; 87: 66–73. 20. Svetovna zdravstvena organizacija (SZO). Reducing global health risks through miti- gation of short-lived climate pollutants. Scoping report for policy-makers. Švica: Sve- tovna zdravstvena organizacija, 2015. 21. Svetovna zdravstvena organizacija (SZO). WHO guidelines for indoor air quality: selected pollutants. Kopenhagen: Urad Svetovne zdravstvene organizacije za Evropo, 2010. 22. Darby S, Hill D, Auvinen A, Barros-Dios JM, Baysson H, Bochicchio F, et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies. BMJ 2004; 330 (7485): 223. 23. Kreuzer M, McLaughlin J. Radon. In: WHO guidelines for indoor air quality: selected pollutants. Danska, 2010: 347–69. 24. US Environmental protection agency (EPA). A citizen’s guide to radon. The guide to protecting yourself and your family from radon. Indoor rnvironments division, 2012. 25. Gray A, Read S, McGale P, Darby S. Lung cancer deaths from indoor radon and the cost effectiveness and potential of policies to reduce them. BMJ 2009; 338: a3110. nika 2010; 55 (4): 579–82. gartens in different geological and climate regions of Slovenia. J Radioanal Nucl Chem 1998; 238 (1–2): 61–6. 28. Zhu HC, Charlet JM, Tondeur F. Geological controls to the indoor radon distribution in southern Belgium. Sci Total Environ1998; 220: 195–214. 29. Gallelli G, Panattoa D, Lai P, Orlando P, Risso D. Relevance of main factors affecting radon concentration in multi-storey buildings in Liguria (Northern Italy). J Environ Radio- act 1998; 39: 117–28. building materials in Serbia. Physics, Chemistry Technol 2006; 4: 11–20. 31. Leban M. Vpliv okolja in bivalnih navad na raven radona v domovih. Diplomsko delo. Nova Gorica: Univerza v Novi Gorici, Fakulteta za znanosti o okolju, 2013. 32. Huang L, Mo J, Sundell J, Fan Z, Zhang Y. Health risk assessment of inhalation ex- posure to formaldehyde and benzene in newly remodeled buildings, Beijing. PloS One 2013; 8 (11). 49 ZDRAVA TLA – ZDRAVI LJUDJE Marko Zupan ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 50 ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 51 KEMIKALIJE V PITNI VODI Ivanka Gale Povzetek. Zahteve, ki jih mora izpolnjevati pitna voda z namenom varovanja zdravja ljudi Escherichia coli pitni vodi. UVOD Council Directive 52 PRAVNA UREDITEV KEMIKALIJ V PITNI VODI monitoring 53 54 International Agency for Research on Cancer pesticidi 55 1 2 Cr 1 Nitrat 4 5 0 5 Nitrit 4 0 , 5 0 5 0,10 9 1 11 dibromoklorometan 56 3) 2 nematocidi, organski akaricidi, organski algicidi, organski rodenticidi, organski pripravki, ki DOSTOPNOST DO PITNE VODE IN NJENA KAKOVOST – MONITORING PITNE VODE Dostopnost do pitne vode v Sloveniji V Sloveniji je v letu 2014 91 % prebivalcev dobivalo pitno vodo na oskrbo- 844 leta 2014 in 977 leta 2004. Razlike so opazne tudi med posameznimi Kakovost pitne vode v Sloveniji 57 58 Water Safety Plan Disability-Adjusted Life Years 59 Primer ocene tveganja zradi atrazina in njegovih kloro-s-triazinskih presnovkov – desetilatrazina, desizopropilatrazina, diaminoklorotri- azina [1, 2] letnih širokolistnih in travnatih plevelov v kmetijstvu (na poljih s koruzo, no-observed-ad- verse-effect level lowest-observed- adverse-effect level 60 The Joint FAO/WHO Meeting on Pesticide Residues Acceptable Daily Intake 61 Guideline value Pesti- cides database European Food Safety Authority 62 63 LITERATURA 1. Pitna voda. Pridobljeno 10. 8. 2016 s spletne strani: http://www.nijz.si/sl/podrocja-dela/ moje-okolje/pitna-voda. 2. Guidelines for drinking-water quality. 4th ed. World Health Organization 2011: 319–320. Pridobljeno 10. 8. 2016 s spletne strani: http://apps.who.int/iris/bitstream/10665/44584/ 1/9789241548151_eng.pdf 3. Pravilnik o pitni vodi. Ur l RS 19/04, 35/04, 26/06, 92/06, 25/09 in 74/15. Pridobljeno 10. 8. 2016 s spletne strani: http://www.pisrs.si/Pis.web/pregledPredpisa?id=PRAV3713 4. Council Directive 98/83/EC on the quality of water intended for human consumption. Pridobljeno 10. 8. 2016 s spletne strani: http://eurlex.europa.eu/LexUriServ/LexUriServ. do?uri=OJ:L:1998:330:0032:0054:EN:PDF okolju in zdravju (EUR/55934/5.1 Rev 2.), Parma, 10–12 Marec 2010. 6. Nacionalni laboratorij za zdravje, okolje in hrano (NLZOH). Zbirka podatkov o sistemih za oskrbo s pitno vodo in o skladnosti pitne vode 2014. Maribor: NLZOH, 2015. Monitoring pitne vode. Pridobljeno 10. 8. 2016 s spletne strani: http://www.nijz.si/sites/ www.nijz.si/files/uploaded/publikacije/letopisi/2014/3.7.1_pitne_vode_2014.pdf. 8. ARSO – Kazalci okolja (http://www.arso.gov.si/). Dostop do varne pitne vode. Pridobljeno 10. 8. 2016 s spletne strani: http://kazalci.arso.gov.si/?data=indicator&ind_id=707. 9. ARSO – Kazalci okolja (http://www.arso.gov.si/). Kakovost pitne vode. Pridobljeno 10. 8. 2016 s spletne strani: http://kazalci.arso.gov.si/?data=indicator&ind_id=709. 10. International Agency for Research on Cancer. Pridobljeno10. 08. 2016 s spletne strani: http://monographs.iarc.fr/ENG/Classification/ClassificationsAlphaOrder.pdf. 11. Commission Directive (EU) 2015/1787 of 6 October 2015 amending Annexes II and III to Council Directive 98/83/EC on the quality of water intended for human consumption. Pridobljeno 10. 01. 2016 s spletne strani: http://eur-lex.europa.eu/legal-content/EN/TXT/ PDF/?uri=CELEX:32015L1787&from=EN (http://eur-lex.europa.eu/legal-content/EN/ TXT/ ?uri=OJ%3AJOL_2015_260_R_0003). 12. Water safety plan manual. Step-by-step risk management for drinking-water suppliers. World Health Organization 2009. Pridobljeno 10. 04. 2015 s spletne strani: http://www. who.int/water_sanitation_health/publication_9789241562638/en/ in http://apps.who.int/ iris/bitstream/10665/75141/1/9789241562638_eng.pdf. 13. EU – Pesticides database. Pridobljeno 10. 8. 2016 s spletne strani: http://ec.europa.eu/ food/plant/pesticides/eu-pesticides-database/public/?event=homepage&language=EN. 14. Guidance on default values to be used in the absence of measured data 2012: Guidance on selected default values to be used by the EFSA Scientific committee, Scientific panels and Units in the absence of actual measured data. EFSA J 2012; 10 (3): 2579: 32 pp. 64 RAKOTVORNE KEMIKALIJE V HRANI Urška Blaznik, Mojca Fuart Gatnik Povzetek UVOD Take 65 nastajajo v procesih priprave hrane. Tako je bilo na primer šele v letu 2002 ne kemikalije in njihove mešanice in njihov pomen pri nastanku raka so še katere obstaja sum, do so rakotvorne, še posebej zahtevno. Za uspešno obvladovanje rakotvornih kemikalij je nujna postavitev prioritet, je v nadaljevanju predstavljena ocena vrednosti mejne izpostavljenosti Disability Adjusted Life Years izpostavljenimi primeri. S spoznavanjem nastajanja raka se je spreminjal tudi pristop k obravnavi nek in razvoj tumorjev; delujejo kot spodbujevalci rasti tumorjev, hormonski penost in vnetje Starejša primera prepoznanih rakotvornih kemikalij v hrani sta dovoljena 66 organ/testna vrsta [mg/kg telesne mase] E 954 najvišje anizol E 320 najvišje konzervansi 2 3 najvišje seznam številna mesta mikotoksinov 67 Saharin (E 954) Scientific Committee for Food, European Food Safety Authority Acceptable Daily Intake, Butilirani hidroksianizol (BHA, E 320) 68 izdelkov iz Velike Britanije (t.i. breakfast sausages). Barvilo se v telesu presnovi do anilina, za katerega je dokazana rakotvornost, poleg tega ni Nitriti/nitrati (E 249–E 252) Clostridium botulinum 69 Arome, primer furfurala in arom dima Threshold of Toxicological Concern in vitro 70 jemo kot dioksinom podobni PCB dioksinom nepodobni PCB 71 Mikotoksini – ohratoksin A 72 as low as reasonable achievable Cancer Risk meje izpostavljenosti Margin Of Exposure 73 organ B1, M1 suho sadje in mejne sadja in mejne in mejne vode mejne Mikotoksini – aflatoksini 74 Akrilamid 75 Etilkarbamat Joint FAO/WHO Expert Committee on Food Additives in vitro in in vivo 76 izpostavljenosti ter spremljanje vsebnosti v hrani in okolju je pomembna Kovine – primer arzena v anorganski obliki 77 Pesticidi – primer glifosata Glifosat in vitro in in vivo 78 loškimi raziskavami. Ko so karcinogeni prepoznani in je znan njihov meha- nizem delovanja, so na vrsti ukrepi, ki naj bi obvladali njihovo pojavljanje v temeljijo na oceni tveganja, ki izhaja iz podatkov, ki so trenutno na voljo. Ti Kljub temu da so kemijski dejavniki v hrani pogosto predstavljeni in zaznani velikokrat prevladajo nad tveganji. LITERATURA 1. Uredba (ES) št. 178/2002 Evropskega parlamenta in sveta, z dne 28. januarja 2002, o za varnost hrane in postopkih, ki zadevajo varnost hrane. Pridobljeno 16. 8. 2016 s 2. Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnquist M. Analysis of acrylamide, a eu/food/fs/sc/oldcomm7/out26_en.pdf. 79 13. Walker R. Nitrates, nitrites and N-nitroso compounds: a review of the occurence in food and diet, and toxicological implications. Food Add Contam 1990; 7: 717–68. 14. Grosse Y, Baan R, Straif K, Secretan B, El Ghissassi F, Cogliano V. WHO International agency for research on cancer. Monograph working group. Carcinogenicity of nitrate, nitrite and cyanobacterial peptide toxins. Lancet Oncol 2006; 7: 628–9. 15. Scientific opinion of the Panel on contaminants in the food chain. Nitrate in vegetables. EFSA J 2008; 689: 1–79. 16. Barlow S. Threshold of toxicological concern: A tool for assessing substances of unknown toxicity present at low levels in the diet. ILSI Europe Concise Monograph Series 2005; ILSI Europe, Brussels. 17. Commission decision 1999/217/EC as regards the register of flavouring substances used in or on foodstufs. C 2002/113/EC. OJ L49: 1–160. 18. Extracts from first report on chemically defined flavouring substances. Annex 6 to the minutes of the 98th meeting of the Scientific Committee on Food, 1995. 19. Opinion of the Scientific panel on food additives, flavourings, processing aids and materials in contact with food on a request from the Commission related to furfural and furfural diethylacetal. EFSA J 2004, 67: 1–27. 20. European commision. Food safety. Food improvement agents. Pridobljeno 16. 8. 2016 s spletne strani: http://ec.europa.eu/food/safety/food_improvement_agents/flavourings/eu _lists_flavourings/index_en.htm. 21. Carcinogenicity of consumption of red and processed meat. Lancet 2015; 16:1599– 1600. Pridobljeno 16. 8. 2016 s spletne strani: http://www.thelancet.com/pdfs/journals/ lanonc/PIIS1470-2045%2815%2900444-1.pdf 22. Hernández ÁR, Boada LD, Mendoza Z, Ruiz-Suárez N, Valerón PF, Camacho M, et al. Consumption of organic meat does not diminish the carcinogenic potential associated with the intake of persistent organic pollutants (POPs). Environ Sci Pollut Res Int 2015; 19. ribah in školjkah = Hazard assessment of chemical contaminants that may be present in fish and bivalve molluscs. Enboz, 2016; 6: 16–28. Pridobljeno 16. 8. 2016 s spletne strani: http://www.nijz.si/sites/www.nijz.si/files/uploaded/enboz_junij_2016_0.pdf. 24. World health organization. Dioxins and their effects on human health. Pridobljeno 16. 8. 2016 spletne strani: http://www.who.int/mediacentre/factsheets/fs225/en/. 25. Shin ES, Kim J, Choi SD, Kang YW, Chang YS. Estimated dietary intake and risk assessment of polychlorinated dibenzo-p-dioxins and dibenzofuran s a n d d i o x i n - l i k e polychlorinated biphenyls from fish consumption in the Korean general population. Chemosphere 2016; 146: 419–25. cereals and cereal products in Slovenia – Official control of foods in the years 2008– 2012. Food Control 2015; 50: 157–65. 27. Commission regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs. OJ 2006, L 364, 5–24. 28. Opinion of the Scientific Panel on Contaminants in the Food Chain on a request from the Commission related to Ochratoxin A in food. The EFSA Journal 2006; 365: 1–56. 29. Pratt I, Barlow S, Kleiner J, Larsen JC. The influence of thresholds on the risk asses- sment of carcinogens in food. Mutat Res. 2009; 678(2): 113–7. 30. Guidelines for Carcinogen Risk Assessment. EPA/630/P-03/001, F. March 2005. Prido- bljeno 16. 8. 2016 s spletne strani https://www.epa.gov/sites/production/files/2013-09/ documents/cancer_guidelines_final_3-25-05.pdf. 80 31. Opinion of the Scientific Committee on a request from EFSA related to a harmonised approach for risk assessment of substances which are both genotoxic and carcinogenic. EFSA J 2005; 282: 1–31. 32. Principles and methods for the risk assessment of chemicals in food. Chapter 7: Risk Characterisation. World Health Organization 2009. 33. Opinion of the Scientific panel on contaminants in the food chain on a request from the Commission related to the potential increase of consumer health risk by a possible in- crease of the existing maximum levels for aflatoxins in almonds, hazelnuts and pistachios and derived products. EFSA J 2007; 446: 1 – 127. 34. Ministrstvo za kmetijstvo, gozdarstvo in prehrano. Uprava za varno hrano, veterinarstvo 2015. Pridobljeno 16. 8. 2016 s spletne strani http://www.uvhvvr.gov.si/si/delovna_pod rocja/zivila/onesnazevala_v_zivilih/. 35. Biedermann M, Grob K. Model studies on acrylamide formation in potato, wheat flour and corn starch. Mitteilungen aus Lebensmitteluntersuchung und Hygiene 2003; 94: 406–22. 36. Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M. Analysis of acrylamide, car- cinogen formed in heated foodstuffs. J Agric Food Chem 2002; 50: 4998–5006. 37. Scientific opinion on acrylamide in food. EFSA J 2015;13 (6): 4104–425. 38. Ethyl carbamate and hydrocyanic acid in food and beverages. Scientific opinion of the Panel on Contaminants. EFSA J 2007; 551: 1–44. 2015. Pridobljeno 16. 8. 2016 s spletne strani http://www.nijz.si/sites/www.nijz.si/files /uploaded/enboz_pah_3.pdf. 40. Lee J-G, Kim S-Y, Moon J-S, Kim S-H, Kang D-H, Yoon H-J. Effect of grilling procedures on levels of polycyclic aromatic hydrocarbons in grilled meats. Food Chem 2016; 199: 632–8. 41. Culp SJ, Gaylor DW, Sheldon WG, Goldstein LS, Beland FA. A comparison of the tumours induced by coal tar and benzo[a]pyrene in a 2-year bioassay. Carcinogenesis 1998; 19: 117–24. 42. World health organization. International agency for research on cancer. Agents classified by the IARC monographs. Pridobljeno 16. 8 2016 s spletne strani https://monographs. 43. Scientific opinion of the Panel on contaminants in the food chain on a request from the Euro- pean commission on polycyclic aromatic hydrocarbons in food. EFSA J 2008; 724: 1–114. 44. World health organization. Arsenic. Pridobljeno 16. 8. 2016 s spletne strani http://www. who.int/mediacentre/factsheets/fs372/en/. 45. Scientific opinion on arsenic in food. EFSA J 2009; 7 (10): 1351–550. using chemoinformatics: Examples from the IARC Monographs on pesticides. Environ Health Persp 2016; advance publication. 47. Conclusion on the peer review of the pesticide risk assessment of the active substance glyphosate. EFSA J 2015; 13 (11): 4302–409. bljeno 16. 8. 2016 s spletne strani http://www.nijz.si/sl/ostanki-herbicida-glifosata-v- nemskem-pivu. 49. Portier JC, Armstrong BK, Baguley B, Baur X, Belyaev I, Belle R, et al. Differences in the carcinogenic evaluation of glyphosate between the International Agency for research on cancer (IARC) and the European food safety authority (EFSA). J Epidemiol Community Health doi:10.1136/jech-2015-207005. 81 KLIMATSKE SPREMEMBE IN ZDRAVJE Povzetek CO 2 UVOD 82 83 KAKŠNI BODO VPLIVI PODNEBNIH SPREMEMB V EVROPI? Tudi ko bi se izpusti toplogrednih plinov danes ustavili, se bodo podnebne spremembe nadaljevale še veliko desetletij zaradi preteklih izpustov in inercije podnebnega sistema [4]. Poleg segrevanja se bo spremenili tudi vode. Podnebne spremembe so prizadele evropska morja z zakisanjem in dvigovanjem temperatur morske vode. Tudi obale so ranljive, izpostavljene poreditvi, izpostavljeni pa so tudi širjenju invazivnih tujerodnih vrst. Vplivi na jugozahodni Evropi. Tudi gozdovi so prizadeti zaradi spremenjenih vzorcev pojavljanja in intenzivnosti viharjev, škodljivcev, bolezni, suš in gozdnih ekosistemskih storitev in do upadanja biotske raznovrstnosti. Sredozemska turizma. V srednji in vzhodni Evropi bodo podnebno prihodnost najbolj zaznamovale stoletja presega variabilnost temperature v obdobju, odkar imamo meritve meteoroloških spremenljivk, bodo podnebne razmere marsikje verjetno dosegle tudi stanja, ki si jih na osnovi poznavanja preteklosti ne moremo predstavljati. Scenariji prihodnjega podnebja za Slovenijo so dokaj negotovi, 84 85 lokalni ravni [6]. in pa na slabšanje kakovosti zraka (Tabela 1). V nadaljevanju preglejmo izbiro velikosti in razporeditve oken. Tudi zelenje in vodne površine v Kakovost zraka problem še poglobilo. 86 Dvig poletne temperature temperature UV-B poleti 87 Drugi ekstremni vremenski pojavi 88 podaljšala za 10–11 dni. Ocene so pokazale, da spremembe podnebja Prenašalci bolezni Posredni vplivi 89 90 KAKO NAJ SE ZDRAVSTVO ODZOVE NA PODNEBNE SPREMEMBE? Zdravstvo se mora vsekakor odzvati na podnebne spremembe. Po eni 91 lahko, da mora Slovenija nameniti veliko pozornost usposabljanju in krepitvi talne znanstvene pristope v tem primeru ni dovolj, saj je treba predvideti podnebje. Vsekakor je nujno tudi medsektorsko sodelovanje in izvajanje LITERATURA 92 93 DRUGI VIRI IZPOSTAVLJENOSTI KEMIKALIJAM IZ OKOLJA; NADZOR IN OMEJEVANJE TVEGANJ ZA ZDRAVJE Alojz Grabner Povzetek. Ko govorimo o izpostavljenosti ljudi kemikalijam oziroma kemijskim tveganjem iz okolja, moramo okolje definirati v širšem pomenu. Poleg zraka, vode in zemlje, ki so trije osnovni elementi izpostavljenosti, moramo kot del okolja v širšem pomenu pojmovati tudi manj zavestnim ravnanjem in obnašanjem, predvsem pa z uporabo številnih izdelkov, proizvodov UVOD ena najpomembnejših industrijskih panog in nosilcev gospodarstva Evropske prepoznamo kot »kemikalije« in s tem kot »potencialno nevarne« proiz- svinec v spojkah, zaviralci gorenja v avtomobilskih materialih (decaBDE (dekabromodifenileter), HBCD (heksabromociklododekan)), antibakterijski premazi v športnih tekstilnih izdelkih (srebro), 94 UPRAVLJANJE S TVEGANJI INDUSTRIJSKIH KEMIKALIJ – PRISTOP REACH REACH registration, evaluation, authorization and restriction of chemicals REACH registration evaluation authorization and 95 restriction of chemicals, slovensko registracija, evalvacija, avtorizacija in omejevanje kemikalij [2]. REACH vzpostavlja celovit in skupni evropski register vseh industrijsko relevantnih snovi, njihovih osnovnih kemijskih, fizikalnih, toksikoloških in vsako snov (v nekaterih primerih tudi za proizvode, ki to snov vsebujejo), ki agenciji predati t.i. registracijski dosje. Skrb za kakovost teh podatkov v sistemu REACH zahteva tudi izvedbo dodatnih raziskav. zaskrbljenost (Substances of Very High Concern, SVHC). Te snovi so lahko: persistent bioaccumu- lative toxic (very persistent very bioaccumulative druge snovi, za katere obstaja znanstveni dokaz o verjetnih resnih Te snovi se po sistemu REACH pa je po sistemu REACH uporabe, prometa ali proizvodnje. Omejitev je popolnoma neodvisna od zgoraj naštetih elementov REACH in se lahko uporabi za katero koli snov samo ali v zmeseh oz. izdelkih. 96 REACH je univerzalni sistem upravljanja s kemijskimi tveganji v EU, ki se POSEBNE SKUPINE KEMIKALIJ REACH ne 97 98 Nanotehnologija in nanomateriali postavljajo pred upravljavce tveganj s kemikalijami povsem nove izzive, saj znanstveni postopki, ki jih uporabljamo LITERATURA 99 KOMUNIKACIJA O OKOLJSKIH TVEGANJIH Darinka Pek Drapal ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 100 ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 101 SEZNAM IN NASLOVI AVTORJEV Dr. Urška Blaznik, univ. dipl. kem. Nacionalni inštitut za javno zdravje Trubarjeva 2, 1000 Ljubljana Telefon: (01) 520 57 72 in 031 393 718 E-naslov: urska.blaznik@nijz.si Telefon: (05) 923 28 61 E-naslov: metka.filipic@nib.si Dr. Mojca Fuart Gatnik, univ. dipl. biol. Nacionalni inštitut za javno zdravje Trubarjeva 2, 1000 Ljubljana Telefon: (01) 244 15 87 Ivanka Gale, dr. med. Nacionalni inštitut za varovanje zdravja Zaloška 29, 1000 Ljubljana Telefon: (01) 244 15 80 Nacionalni inštitut za javno zdravje Zaloška 29, 1000 Ljubljana Telefon: (01) 244 15 61 Telefon (01) 400 60 39 Zdravstvena pot 5, 1000 Ljubljana Zoisova cesta 12, 1000 Ljubljana E-naslov: anja.jutraz@fa.uni-lj.si Jamnikarjeva 101, 1000 Ljubljana Medicinska fakulteta, Univerza v Ljubljani Zaloška 4, 1000 Ljubljana Telefon: (01) 543 75 66 E-naslov: andreja.kukec@mf.uni-lj.si E-naslov: darinka.drapal@consensus.si Po abecedi priimkov 102 100 ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 103 100 ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 104 100 ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 105 100 ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 106 100 ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ ........................................................................................................................ 107 Mediline mešana trgovska družba, d.o.o. Perovo 30 | p.p. 5 | SI-1241 Kamnik | Slovenija T +386 (0)1 830 80 40 | F +386 (0)1 830 80 70 / 63 E info@mediline.si | I www.mediline.si 4titude, Advanced Instruments (Anoxomat, Mart Microbiology), Bimos – Interstuhl Büromöbel, Bio-Rad Medical Diagnostics, Biolin Scientific, Delta T, DiaSorin (Focus Diagnostics), EKF Diagnostic, Eppendorf, Eurofins GeneScan, Eurofins Genomics, Fluidigm, Hain Lifescience, Hoefer, Liofilchem, Medical Wire (MWE), Merck/Heipha/ Hycon, Miele, Molecular Devices (Genetix), Molzym, PathoNostics, Proteintech Group, Qiagen, R-Biopharm, Rosco Diagnostica, Sarstedt, Sifin, Tecan, Thermo Fisher Scientific (Revco, Samsung), Ultra Violet Products (UVP) laboratorijska oprema potrošni materiali reagenti EDINO LJUDJE, KI SE BORIJO Z RAKOM, SO VELIKO BOLJ TRDOŽIVI KOT NJIHOV RAK. Eli Lilly farmacevtska družba, d.o.o. KORAK NAPREJ pri zdravljenju onkoloških bolnikov. Datum priprave informacije: avgust 2016 MAT114/16 AstraZeneca UK Limited, Podružnica v Sloveniji, Verovškova 55, 1000 Ljubljana, t. 01/51 35 600.