Eurocat humane biomonitoring
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Human biomonitoring: prenatal exposure and early effects on the newborn

Human biomonitoring: prenatal exposure and early effects on the newborn
By Greet Schoeters

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Eurocat humane biomonitoring Presentation Transcript

  • 1. Human biomonitoring: prenatal environmentalexposure to chemicals and effects on thenewborn30/06/2011Greet SchoetersUnit Environment and Health Risk- VITOUniversity of Antwerp
  • 2. Outline» Are current levels of environmental pollution associated with adverse health effects on the newborns? » Some examples» Biomonitoring contributes to the weight of evidence » Prospective birth cohorts 30/06/2011 2 © 2011, VITO NV
  • 3. Between 1953 and 1965 there were Methyl mercuryover a hundred adult men andwomen developing symptoms of poisoning in Japancentral nervous system disorders such Congenital Minamata Syndromeas ataxia, alterations in gait, tremors,altered sight and sensation. In 1955 inthe Minamata Bay area of Kyushu,Japan, there was a large influx ofcases of severe neurological disordersin newborn children. There werecases of cerebral palsy, some childrenwere diplegic and others weretetraplegic. They were all mentallyhandicapped. Some villages had 6-12% of their newborns affected.Together, these disorders are nowknown as Congenital MinamataSyndrome. In 1959, it was found thatmethylmercury was being dumpedinto the bay by a plant of the ChissoCorporation. 30/06/2011 3 © 2011, VITO NV
  • 4. Reproductive Effects Of Lead • lead crosses the placenta • miscarriages • premature birth • Stillbirth • low infant birth weight • retarded mental development 30/06/2011 4 © 2011, VITO NV
  • 5. Health outcomes in prenatally – exposed children to dioxins and PCBsDioxins: Seweso accident (1976)PCBs: Yusho (Japan 1968) and Yucheng (Taiwan1978)US (Michigan, North Carolina, Lake Oswego)- fish eatersSweden, Finland, The Netherlands, Fetal PCB syndrome : altered dentition, altered skull calcification Intrauterine growth retardation Cognitive and Behavioral Impairment Increased incidence of middle ear infectionsDevelopmental Alterations Occurring at “High End” of Background population 30/06/2011 5 © 2011, VITO NV
  • 6. Organic Pollutants with hormone disrupting propertiesEndocrine disrupting Class Model compoundactivityThyroid hormone Brominated flame retardants PBDE-47, 99PXR/CAR induction HBCDAnti-androgenicAhR binding Dioxin-like compounds TCDDCYP1A inductionAnti-estrogenicPXR/CAR induction, Non dioxinlike PCBs PCB 153Thyroid hormoneEstrogenic Organochlorine pesticides HCB, DDTanti-androgenic p,p’DDEPeroxisome proliferator- Perfluorinated compounds PFOA, PFOSactivated receptor (PPAR)inductionPPAR induction Phthalates metabolites 30/06/2011 6 © 2011, VITO NV
  • 7. Comparison of potency of environmental chemicals versus endogene hormones Witters H. et al., Reproductive Toxicology 30 (2010), 60-72 30/06/2011 7 © 2011, VITO NV
  • 8. Exposure to environmental chemicals» Transported, through air, water and migratory species, across international boundaries and deposited far from their place of release» Resist degradation» Bioaccumulate in terrestrial and aquatic ecosystems,» Transfer through the food chain» Inhalation of polluted air» Ingestion of soil» Ingestion of drinking water» Consumer products – electronics, flame retardants, solvents, pesticides» Personal care products 30/06/2011 8 © 2011, VITO NV
  • 9. Human biomonitoring: direct measurement in human tissues Environmental biomarkers monitoring of exposure Preconception Mothers / fathers Blood air Urine air Hair dust Pregnancy Mothers BloodConsumer Urineproducts Hair Neonate Birth water Cord blood Placenta soil meconium soil Urine Post natal Neonate 30/06/2011 © 2011, VITO NV exposure Breast milk9
  • 10. Swedish mothers milk data 30/06/2011 10 © 2011, VITO NV
  • 11. A toxic environment early in life?» Dozens of chemicals are detectable at measurable levels in humans and in many cases at higher levels in children –CDC surveys. » exposure of the parents before conception» Chemicals are transfered in the womb to the fetus via the placenta, the fetus is surrounded by a large number of chemicals.» Chemicals are transferred to the neonate via breast milk which concentrates lipophylic compounds such as dioxins, PCBs,… 30/06/2011 11 © 2011, VITO NV
  • 12. Fetuses, infants and children are especially vulnerable to toxic chemical exposure» Reduced ability to break down and excrete many chemicals compared to adults» Great vulnerability during windows of susceptibility in early development» More years of future life –i.e., many decades in which consequences of early exposures can become manifest 30/06/2011 12 © 2011, VITO NV
  • 13. Human biomonitoring: direct measurement in human tissuesEnvironmental biomarkers biomarkers adversemonitoring of exposure of effects health effects air air Birth weight dust Blood lead Hormone levels Growth Cotinine in urine DNA damageConsumer IQproducts behaviour MeHg in hair Gene expression … puberty water Epigenetic changes soil Asthma soil Cancer 30/06/2011 13 © 2011, VITO NV
  • 14. Flemish human biomonitoring campaignEnvironmental healthMonitoring for action…2002-2006-2011Commissioned, financed , steered by the Ministry of the Flemish Community (Dept ofScience, Public Health and Environment ) 30/06/2011 14 © 2011, VITO NV
  • 15. 1600 youngsters Oct 2003- July 2004 42 schools 18 mL blood, 50 mL urine 1200 newborns 1600 adultsSept 2002- Dec 2003 Sept 2004- June 200525 maternities + 2stem cell banks 43 municipalities30 mL cord blood 35 mL blood, 50 mL urine 30/06/2011 15 © 2011, VITO NV
  • 16. Birth cohorts in Flanders 30/06/2011 16 © 2011, VITO NV
  • 17. Asthma/allergy follow-up (N=150)Neurodevelopment follow-up (N=200) Exhaled breath: •condensate proteins •Gas phase VOC Questionnaire: growth, diet, pets, 8-oxodG urine Cord blood diseases, allergy symptoms, hygiene, indoor Pb, Cd, PCBs, Gut flora (faeces: 3wk, 6m, 12m) eNO Questionnaire: dioxin-like compounds SPT growth,diet, pets, TSH, fT3, fT4 diseases, allergy symptoms, hygiene, swimming, indoor 0 1 2 3 4 5 6……12m……..2y……………………3y….……4y…5y…6y…7y…8y Interpolated outdoor air conc. NO2, PM10 weight circumfe- rence, Cognitive and fat/fat free Questionnaire: behavioural tests behaviour child, mass child, IQ-test mother, (impedance), emotional status mother, Observation Home life-events arm/back Environment (HOME), fold… 30/06/2011 cortisol 17 © 2011, VITO NV
  • 18. ENvironmental health RIsks in European birth COhorts: Birth weight declined by 150g per 1µg/Lincrease in PCB 153 cord serum concentration OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life 30/06/2011 18 © 2011, VITO NV
  • 19. Conclusion» Birth weight declined by 150g per 1µg/L increase in PCB 153 cord serum concentration» No statistically significant effect for p,p’-DDE» The magnitude of effect is equivalent to that reported for cigarette smoking (~ 55–189 g reduction) (Dejmek et al. 2002). 30/06/2011 19 © 2011, VITO NV
  • 20. pollutants in the perinatal period of life ↕child’s healthA. Biometry ( lenghth , weight): at birth, 1-3yB. Thyroid hormone levels at birthC. Neurobehavioral & cognitive development 0-3y (led by Dr Viaene- OPZ)D. Respiratory health 0-3y ( led by Dr. Desager-UA) 30/06/2011 20 © 2011, VITO NV
  • 21. Negative relation between POPs and thyroid hormones measured in cord blood Multiple linear regression model /contaminant , 200 participants adjusted for plasma total lipids, gestational age, gender, alcohol consumption during pregnancy, and age of the mother. MAERVOET et al, , Environmental Health Perspectives (2007) ln fT3 (pmol/L) ln fT4 (pmol/L) ln TSH (mIU/L) β p n β p n β p nPolychlorinated biphenyls ∑ 5 PCBs (ng/ml) -0.198 0.01 195 -0.345 < 0.001 196 -0.055 0.50 196Organochlorinated pesticides HCB (ng/ml) -0.154 0.03 195 -0.287 < 0.001 196 -0.061 0.42 196 p,p´-DDE (ng/ml) -0.074 0.29 195 -0.146 0.04 196 -0.048 0.51 196Dioxin-like compounds Calux-TEQ (pg/ml) -0.154 0.04 138 -0.165 0.04 138 -0.018 0.83 138Heavy Metals Cadmium (ng/ml) -0.084 0.23 186 -0.041 0.58 187 -0.035 0.63 187 Lead (ng/ml) -0.100 0.15 186 0.064 0.37 187 0.041 0.57 187 30/06/2011 21 © 2011, VITO NV
  • 22. Free thyroxin vs concentration of sum marker PCB’s in cord bloodClinically irrelevant? (Kimbrough and Krouskas, 2001)Very subtible changes in T4/TSH homeostasis may affect development of human fetus(Boas et al., 2006; Zöller, 2001) 30/06/2011 22 © 2011, VITO NV
  • 23. Neurological behaviour follow-up Info on pregnancy Postnatal depression 0 1 12 24 36 months Cord blood(Pb, Cd, PCB’s, dioxins, Cognitive andTSH,FT3, FT4),nutrition, Behaviour child, Behavioural tests covariates emotional status mother, child, IQ-test mother, life-events Observation Home Environment, Cortisol monthly quesionnaire on food & development 3-monthly “ “ “ 30/06/2011 23 © 2011, VITO NV
  • 24. Prenatal exposures and health outcomes:methylmercury in maternal hairFish intake : Faroe island cohort Grandjean , Weihe 30/06/2011 24 © 2011, VITO NV
  • 25. Prenatal exposures: a wide range of effects with life long consequences» Wide range of health effects » Body energy levels » Growth and development » Immune effects » Internal balance of body systems, or homeostasis» Persistence of biological effects» Response to low dose matters  chemical analytical challenges?  large populations needed» Combination of doses  effective biomarkers of combined internal dose? 30/06/2011 25 © 2011, VITO NV
  • 26. Mechanisms of late effects?» hormone levels,» oxidative stress» epigenetic changes? mechanisticearly warning 30/06/2011 26 © 2011, VITO NV
  • 27. Control of Persistent Pollutants: Global POPsConvention (Stockholm Convention onPersistent Organic Pollutants)Covers the “dirty dozen” POPs chemicals and pesticides + 9 chemicals recently added» Such pollutants move around the globe; once they have entered the environment; you can’t just turn off the tap.» Chemicals included are: the pesticides aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, mirex, toxaphene, and hexachlorobenzene; the industrial chemicals PCB’s; dioxins and furans,» Recently added: alpha hexachlorocyclohexane; beta hexachlorocyclohexane; chlordecone; hexabromobiphenyl; hexabromodiphenyl ether and heptabromodiphenyl ether (commercial octabromodiphenyl ether); lindane; pentachlorobenzene; perfluorooctane sulfonic acid, its salts and perfluorooactane sulfonyl fluoride; tetrabromodiphenyl ether and pentabromodiphenyl ether (commercial pentabromodiphenyl ether). 30/06/2011 27 © 2011, VITO NV
  • 28. The tip of the iceberg? 30/06/2011 28 © 2011, VITO NV