Endocrine disrupters

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1 Endocrine disrupters in mothers and their newborn The Um-MuKi - Bratislava-Vienna study I: Organic and organometallic compounds

2 Preview: the study Um-MuKi study design selected compounds results conclusions 2

Um-MuKi: A project within the European Transnational Co-operation 2007-2013 Slovak-Austrian cross-border cooperation programm

3 Um-MuKi: A project within the European Transnational Co-operation Slovak-Austrian cross-border cooperation programm supported by the European Regional Development Fund. Supporting European Unions strategies, goals and action plans Partners: 3

4 Supporting European Unions strategies, goals and action plans: SCALE: EU -Environment and Health Strategy Science - Children-Awareness Legal Instruments Evaluation Environment and Health Action Plan Human Biomonitoring: Instrument to assess total exposure: body burden.to provide scientifically grounded information needed to help to reduce the adverse health impacts of certain environmental factors 4

Um-MuKi: Environment- mothers and their children Focusing on the vulnerable group of mothers and their newborn Exposure assessment of endocrine disrupting chemicals Analyses in mothers and newborns

5 Um-MuKi: Environment- mothers and their children Focusing on the vulnerable group of mothers and their newborn Exposure assessment of endocrine disrupting chemicals Analyses in mothers and newborns venous blood and cord blood Assessing individual vulnerability (genes) 200 mother-child pairs (100 SK AT) heavy metals, gene poymorphisms 40 mother-child pairs (20 SK 20 AT): Me-Hg, PFAS and BPA

6 Cities: Bratislava - Vienna 50 km airline distance Iron curtain for ~50 years residents: density (res./km 2 ) : size: 5-1 6

7 Cities: Bratislava - Vienna Bratislava Wien 5 km 2012 Google - Map data 2012 GeoBasis-DE/BKG ( 2009), Google, Tele Atlas

8 About the study ethical commission (AT +SK) written consent healthy women aged giving birth to a healthy baby 8

9 Comprehensive Questionnaire beverages food focus on fish home environment life stile environment 9

10 work place health personal hygiene food beverages living conditions, environment smoking pregnancy birth 10

disease consumption of fish in heavily polluted area Serious cases of brain defects in

11 Selected Chemicals: methyl mercury Toxic organic species of mercury Origin: biomethylation of mercury in aquatic system bioaccumulation First known: Minamata disease consumption of fish in heavily polluted area Serious cases of brain defects in children Specific vulnerability of the unborn child Prenatal exposure leads to postnatal deficits 11

12 Selected Chemicals: PFAS: uses group of PERFLUORALKYLATED SUBSTANCES: more than 800 Perfluoroalkyl moiety C n F 2n+1 + functional group e.g.: Perfluorooctanoic acid (PFOA) Perfluorooctane sulphonate (PFOS) Polymers like PTFE (Teflon) Widely used: industrial and consumer applications stain and water resistant coatings: fabrics and carpets Coatings for paper products Fire fighting foams Surfactants, polishes, insecticide formulations 12

13 Selected Chemicals: PFAS: toxicity Worldwide distribution: environmental compartments, wildlife animals, human blood No degradation > very persistent; long half-life in humans PFOS: pesistent, bioaccumulative, toxic PFOA and PFOS are classified (CLP) as: Carc. 2: suspected of causing cancer Repr. 1B: may damage the unborn c. STOT RE 1: organ damage RE STOT RE 2: may cause organ dam. Acute Tox. 4: harmful if inhaled Acute Tox. 4: harmful if swallowed Lact (PFOS): may cause harm to breastfed children Aquatic chronic 2 (toxic to aquatic life with longlasting effects 13

Selected Chemicals: Bisphenol A: use manufactured in

(PC), polyvinyl chloride (PVC) and epoxy resins, Food

equipment, dental inlays, digital media, household

adhesives, can and powder coatings, floorings or

14 Selected Chemicals: Bisphenol A: use manufactured in very high quantities Use: production of polycarbonate (PC), polyvinyl chloride (PVC) and epoxy resins, Food storage, drinking bottles, But also: medical equipment, dental inlays, digital media, household appliances, microwave dishes, Epoxy resins: used in adhesives, can and powder coatings, floorings or industrial protective coating, and a multitude of other products 14

Selected Chemicals: Bisphenol A: tox According to CLP regulation: BPA can cause serious eye damage (H318, R41 ), respiratory irritation (H335, R37), allergic skin reaction (H317,

15 Selected Chemicals: Bisphenol A: tox According to CLP regulation: BPA can cause serious eye damage (H318, R41 ), respiratory irritation (H335, R37), allergic skin reaction (H317, R43) and is hazardous to aquatic organisms (R52). The substance may also have harmful effects on the human reproduction system (H361f, R62). BPA is an endocrine disrupting substance. 15

Analytical Methods and Results MeHg: HPLC-CV-ICP-MS PFAS: LC-MS/MS BPA: LC-MS/MS In te

7 Da ID: PF4C_1 from Sample 22 (10 ng/ml PFOS in ACN / H2O ) of 20120118_A11451_Luna.

0e4 7.0e4 6.0e4 5.0e4 4.0e4 3.0e4 11.80 2.0e4 1.0e4 Max. 2.3e4 cps. 0.

16 Analytical Methods and Results MeHg: HPLC-CV-ICP-MS PFAS: LC-MS/MS BPA: LC-MS/MS In te n s ity, c p s XIC of -MRM (51 pairs): 213.1/168.7 Da ID: PF4C_1 from Sample 22 (10 ng/ml PFOS in ACN / H2O ) of _A11451_Luna.wiff (Turbo Spra e5 1.8e5 1.7e5 1.6e5 1.5e5 1.4e5 1.3e5 1.2e5 1.1e5 1.0e5 9.0e4 8.0e4 7.0e4 6.0e4 5.0e4 4.0e4 3.0e e4 1.0e4 Max. 2.3e4 cps Time, min All substances were present in mothers and children Regional compound specific differences observed 16

17 MeHg: mothers children Vienna mothers children Bratislava 17

18 MeHg concentrations: fish consumption Bratislava Vienna fish consumption g/week 18

concentration (µg/l) PFAS Regional differences: mothers 18 16 14

19 concentration (µg/l) PFAS Regional differences: mothers Vienna Bratislava PFOA PFNA PFDA PFUA PFHxS PFOS

20 concentration [µg/l] PFAS Regional differences: children Vienna Bratislava PFOA PF9C PF10C PF11C PF6S PFOS

21 Median concentration (ng/ml) Median concentration (ng/ml) Comparison with other studies: concentrations of PFOS and PFOA PFOA and PFOS in maternal blood PFOA and PFOS in cord blood PFOA PFOS

22 Results: Bisphenol A ng/g Detection frequency mothers Bratislava n=20 children Bratislava n=20 mothers Vienna n=20 children Vienna n=20 55% 50% 35% 10% range n.n 3.3 n.n-3.8 n.n

23 Comparison with other studies: BPA in maternal blood samples Germany This study 23

24 µg/l Conclusions: PFAS % Perzentile PFOS+PFOA-Reference Values PFOS PFOA mothers babys Bratislava mothers babys Wien 24

25 Conclusions: PFAS Reference values: (95% percentile) German commission for human biomonitoring PFOS: 10 µg/l: women and children All values below: Highest group: mothers from Vienna: 3.73µg/l PFOA: 10 µg/l: men/women/children Values in Slovakian mothers (95% percentile): 16,4 µg/l All other groups below (Austrian mothers: 5,73 µg/l) 25

26 Conclusions: PFAS Systemic effects: serum lipids, uric acid, hormone system Evidences for thyroid disruption: PFOA-exposed community: T4 levels and T3 uptake (Knox et al 2011) general US population: PFAS > thyroid diseases (Melzer et al 2010) Pregnant females: PFAS > foetal thyroid hormone levels (Kim et al 2011) Thyroid gland: metabolism, energy homeostasis, brain development 26

27 PFAS: risk PFOS: EFSA-2008 comparison of NOAEL* concentrations in animals (effects on thyroid hormones in monkeys) with human exposure NO RISK (MOS: ) But : persons with highest intakt could exceed TDI (60 ng/kg) Stockholm-convention on POPs: Persistant Organic Pollutants (2009): ---Further decrease expected NOAEL*: No observed adverse effect level 27

28 PFAS: risk PFOA: No correlation found so far ( drinking water?, carpets?).. Precursors: PFAS- alcohols in consumer products Comparison: animal study with this study: LOAEL-Werte: 0,3 mg/kg KG/day = 20 µg/ml Serum ~1000- fold lower values in this study EFSA: no risk but Uncertainties related to development PFOA-levels in Slovakia higher then reference values: Analyses of drinking water? LOAEL*: Lowest observed adverse effect level: *NHANES -USA 28

29 Maternal blood Correlation with drinking water? Bratislava Vienna Drinking Water : L Analyses of drinking water? 29

30 Bisphenol A: risk Reference values for urine available Comparison with mother child studies : concentrations low in this study But: free BPA detectable EFSA 2006, 2010: TDI - 0,05 mg/kg BW agreed No risk under current exposure conditions But: minority opinion Low dose effects on biochemical changes in brain, behaviour, immune- modulatory effects system, Enhanzed suszeptibility to breast tumours Due to short comings of study not reliable for TDI- derivation, Workshop on low dose effects with experts and MS: EFSA- opinion

31 Methyl mercury: risk Methyl mercury; highly toxic Higher concentrations in babys than mothers Specific vulnerability of developing brain No treshold effects for methyl mercury EFSA: The opinion looked at the contribution of different foods towards overall human exposure and the risks to vulnerable groups, in particular pregnant women and children. The Panel concluded that methylmercury toxicity has been demonstrated at low exposure levels, and therefore exposure to this compound should be minimised. However, it also noted that fish constitutes an important part of a balanced diet. Information note EU-COM: Methyl mercury in fish and fishery products (2004): vulnerable groups should avoid consumption of specific species 31

32 Exposure to endocrine disrupters Multitude of substances present in humans Multitude of endocrine disrupters present Danish EPA*: Assessment of exposure of pregnant women to multiple endocrine disrupters (phthalates, bisphenol A, pesticides, UV-.filters,.) highest exposed individuals and their babys at risk * DANISH EPA- DANISH ENVIRONMENT PROTECTION AGENCY (2012) Assessment of exposure of pregnant women to multiple endocrine disrupters. ISBN:

33 33 Schlumpf, M.,Kypke, K., Wittassek, M., Angerer J., Mascher J,Mascher D, Vökt C, Birchler M, Lichtensteiger W. (2010) Exposure patterns of UV filters, fragrances, parabens, phthalates, organochlor pesticides, PBDEs, and PCBs in human milk: Correlation of UV filters with use of cosmetics: Chemosphere Exposition towards mixtures EU-Commission: COM(2012)252 Current EU legislation does not provide for a comprehensive and integrated assessment of cumulative effects of different chemicals taking into account different routes of exposure. Several studies demonstrate need for action: e.g.: Schlumpf et al. 2010*: chemicals in mothers milk Kopenhagen Workshop on endocrine Disrupters

34 Conclusions Measurable body burden in mothers and children environment and lifestile related Measures Awareness Rising Protection of environment essential: especially persistant,bioaccumulative and toxic substances should be further restricted. 34

35 Thanks giving funding institutions technical secretary contributing mothers and babys Partners : colleges engaged in chemical analyses statistical evaluations publicity measures..

36 contact & information Maria Uhl Tel. Nr.: +43-(0) /

Per- and poly- fluoroalkyl substances (PFAS): information for clinicians

Per- and poly- fluoroalkyl substances (PFAS): information for clinicians Introduction The purpose of this information is to provide guidance to aid clinicians with patient consultations on perfluoroalkyl