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