HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
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Schoeters Greet
Results of the first Europe-wide HBM study
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Outline
• The COPHES-DEMOCOPHES approach
• Calculation of “European exposure values”
• Comparison mothers and children
• Comparison across countries
• Factors which determine exposure – Personal factors
– Life style factors
– Environmental factors
• Comparison with health based guidance values
• Conclusions
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HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Feasibility to perform HBM in a coherent and harmonised approach throughout Europe by means of commonly developed protocols, strategies and scientific tools
ensuring reliable and comparable data.’
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Nov 2009 - Nov 2012
Dec 2010 - Nov 2012
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
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COPHES partners: 24 EU Member States and Switserland, Norway, Croatia
17 Active
DEMOCOPHES countries: BE, CY, DE, DK, PL, Ro, SI, ES, HU, SE, UK, PT, Cz, SK, LU, IE, CH
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Study population
• 120 children (6-11 yrs) and their mothers ( < 45 years) per country except for Cyprus and Luxembourg (60 mother-child pairs)
• Convenience samples from a rural and urban area selected from lower and upper end of urbanisation category, not industrial hot spots
– Selection via population register – Sampling via schools
• Provide hair and urine samples
• Stratification by age and gender
• Information on lifestyle, dietary habits, covariates through personalised interviews (paper or computerised questionnaires)
• 4 month recruitment period between October 2011 and January 2012
lead by Umweltbundesambt ,Germany (M. Kolossa –Gehring, K. Becker, G. Schwedler, U.. 5 Fiddicke, M. Seiwert)
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
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Chemicals
• Mercury:
Fish, amalgam fillings
Neurodevelopmental toxicant
• Cadmium: batteries, contaminated soils
Nephrotoxicant, reproduction & development
• Phthalates: DEHP, DEP, BiBP, MnBP, MBzP
plastics, PVC, food packaging, cosmetics Endocrine disruptors
• Tobacco smoke
Cancer
• Bisphenol A : tinned cans
Estrogen activity
hair
urine
urine
urine urine
H-Hg
U-Cd U-MEHP 5OH-MEHP 5oxo-MEHP U-MEP
U-BiBP U-MnBP U-MBzP U-cotinine
U-BPA
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
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• Centrally organised ICI / EQUAS rounds
• Web-based training
• BPA and TCS: no centrally organised QC/QA
Chemical analysis
lead by Univ of Dusseldorf (J. Angerer, H. Koch, B. Schindler) &
Instituto de Salud Carlos III, Spain (A. Castano , M. Esteban)
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Data management and statistical analysis
• European exposure values:
– Geometric means (95% confidence interval) - 90th percentile (95% CI) – Weighed: all countries contribute equally (except LU, CY)
– Adjusted for a priori defined confounders: age, gender, creatinine, smoking
• Comparison of countries:
– Weighed ANOVA
– Adjusted for confounders
• Exposure determinants
– Multiple mixed regression models: takes into account „clustering‟
Lead by VITO: G. Schoeters, E. Den Hond, E. Govarts 8
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Subject characteristics
Children (n=1844) Mothers (n=1844) Age, years (median, P25-P75) 8 (7-10) 39 (35-42)
Girls / boys 50.5% / 49.5% -
Frequent fish consumption 24% 26%
Smoking habits 0% smokers 15.3% daily smokers
5.7% occasional smokers 21.7% former smokers
% Environmental Tobacco Smoke
Home: 17%
Elsewhere: 42%
Home: 11%
Elsewhere: 56%
Educational level (family) Primary: 9.0%; Secondary: 32.9%; Tertiary: 58.1%
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HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
European exposure values:
Average exposure: geometric mean and 95%CI P90 and 95%CI
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HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Average EU exposure values: GM (95% CI)
Children Mothers
Mercury in hair µg/g 0.145 (0.139 – 0.151) 0.225 (0.216 – 0.234) U-Cotinine µg/L 0.797 (0.759 – 0.837) 2.751 (2.406 – 3.145) U-Cadmium µg/L 0.071 (0.069 – 0.074) 0.219 (0.211 – 0.228) U-DEHP metabolites µg/L 47.6 (46.0-49.3) 29.2 (28.1-30.3) U-MnBP µg/L 34.8 (33.5-36.2) 23.9 (23.0-24.9) U-MBzP µg/L 7.1 (6.8-7.5) 4.5 (4.3-4.7) U-MEP µg/L 34.4 (32.8-36.0) 48.2 (45.6-51.0) U-MiBP µg/L 45.4 (43.6-47.3) 30.1 (28.9-31.4) U-Bisphenol A µg/L 1.97 (1.81 – 2.15) 1.78 (1.62 – 1.94)
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Children Mothers
Mercury in hair µg/g 0.145 (0.139 – 0.151) 0.225 (0.216 – 0.234) U-Cotinine µg/L 0.797 (0.759 – 0.837) 2.751 (2.406 – 3.145) U-Cadmium µg/L 0.071 (0.069 – 0.074) 0.219 (0.211 – 0.228) U-DEHP metabolites µg/L 47.6 (46.0-49.3) 29.2 (28.1-30.3) U-MnBP µg/L 34.8 (33.5-36.2) 23.9 (23.0-24.9) U-MBzP µg/L 7.1 (6.8-7.5) 4.5 (4.3-4.7) U-MEP µg/L 34.4 (32.8-36.0) 48.2 (45.6-51.0) U-MiBP µg/L 45.4 (43.6-47.3) 30.1 (28.9-31.4) U-Bisphenol A µg/L 1.97 (1.81 – 2.15) 1.78 (1.62 – 1.94)
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
High correlation between mothers and children
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0 20 40 60 80 100
0 20 40 60
sum DEHP metabolites in urine (µg/L) , children
sum DEHP metabolites in urine (µg/L), mothers
DEHP metabolites in urine - correlation between children and mothers
0 20 40 60 80 100
0 20 40 60
MnBP in urine (µg/L), children
MnBP in urine (µg/L), mothers MnBP in urine - correlation between
children and mothers
0 5 10 15 20 25
0 5 10 15
MBzP in urine (µg/L), children
MBzP in urine (µg/L), mothers MBzP in urine - correlation between
children and mothers
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Biomarker values show a large variability in the population
Children Mothers
Biomarker Unit P90 P90/P10 P90 P90/P10
Mercury in hair µg/g 0.8 (0.7-0.9) 27 1.2 (1.1- 1.3) 25 U-Cotinine µg/L 4.9 (3.9-6.2) 26 1182 (974-1433) 4884 U-Cadmium µg/L 0.22 (0.21-0.23) 6 0.62 (0.58-0.66) 6 U-DEHP metab. µg/L 137 (126-150) 8 91 (84-100) 10 U-MnBP µg/L 95 (87- 104) 8 66 (61-72) 8 U-MBzP µg/L 28 (25-31) 12 17.7 (16.1-19.5) 13 U-MEP µg/L 159 (138-183) 18 252 (221-287) 26,4 U-MiBP µg/L 131 (117-147) 8 88 (81-96) 8 U-Bisphenol A µg/L 7.4 (6.2-8.7) 12 6.6 (5.6-7.7) 15
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HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
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Spain Portugal East –European
countries
Countries differ in their exposure profiles
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Mercury in hair: comparison within Europe
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0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Hungary
Romania Germany Slovak Republic Poland United Kingdom Switzerland Czech Republic Ireland ALL Sweden Slovenia Belgium Luxembourg Denmark Cyprus Portugal Spain
Mercury in hair (µg/g), adjusted for age
Mercury in hair - mothers
p<0.001 p<0.001
p<0.001 p<0.001
p<0.001 p<0.001 p<0.001
p=0.09 p<0.001
p=0.06 p<0.001
p<0.001 p<0.001
p<0.001
p<0.001 p<0.001
p<0.001
* NHANES 1999-2000; 16-49 yr. women; N=1736:
GM (95% CI) = 0.20 (0.16-0.24) µg Hg/g hair
* Health-based guideline (JECFA): 2.5 µg Hg/ g hair
0 20 40 60 80 100
Hungary Germany Poland Switzerland Romania Slovak Republic Ireland Czech Republic Slovenia Luxembourg Sweden United Kingdom Belgium Denmark Cyprus Spain Portugal
% children eating fish several times/week
Sea fish consumption
P 9 0
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Mercury in hair: effect of fish consumption
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0.206 0.135 0.311 0.218
0.00 0.20 0.40 0.60 0.80 1.00
> 1/months n=246
≤ 1/months n=1561
> 1/months n=298
≤ 1/months n=1515
Mercury in hair (µg/g)
Mercury in hair -
relation with fresh water fish consumption
CHILDREN MOTHERS
p<0.001 p<0.001
0.566 0.111 0.780 0.182
0.00 0.20 0.40 0.60 0.80 1.00
> 1/week n=283
≤ 1/week n=1549
> 1/week n=294
≤ 1/week n=1541
Mercury in hair (µg/g)
Mercury in hair -
relation with sea fish consumption
CHILDREN MOTHERS
p<0.001 p<0.001
Levels increase
Children: age, consumption of sea fish, shell fish, sea food products, fresh water fish, educational level of the family
Mothers: age, consumption of sea fish, shell fish, fresh water fish, educational level of the family
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Determinants of exposure to mercury in children:
multiple regression model
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Parameters Strata Estimate (95%CI) for
change (multiplicative factor)
p- value
overal l p- value Number of observations in model: n=1798
Gender
boys 0.96 (0.89 – 1.05) 0.37 0.37
girls 1.00 -
Age 5-8 years 1.08 (1.00 – 1.17) 0.06 0.06
9-11 years 1.00 -
Consumption of sea fish Several times per week 1.46 (1.26 – 1.69) <0.001 <0.001
Once per week or less 1.00
Consumption of shellfish Several times per week 1.56 (1.35 – 1.79) <0.001 <0.001
Once per week or less 1.00
Consumption of fresh water fish
Several times per week 1.23 (1.08 – 1.39) <0.001 <0.001
Once per week or less 1.00
Educational level of the familiy
primary 0.81 (0.69 – 0.96) 0.01 <0.001
secondary 0.81 (0.74 – 0.90) <0.001
tertiary 1.00 -
Area of residence Urban 1.35 (1.23 – 1.47) <0.001 <0.001
Rural 1.00
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Not all Europeans are equal
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0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Sweden Luxembourg Denmark Spain ALL Belgium Slovenia
BPA in urine (µg/L), adjusted for creatinine, age and gender
Bisphenol A in urine - children
Overall p-value:
p=0.04
p=0.008
p=0.56
p=0.72
p=0.78
p=0.17
p=0.02
0 10 20 30 40 50 60 70 80 90 100
Cyprus Luxembourg Switzerland Belgium United Kingdom Germany Denmark Slovenia Portugal Sweden ALL Hungary Ireland Czech Republic Spain Romania
Poland Slovac Republic
sum DEHP metabolites in urine (µg/L), adj. for creatinine, age, gender
sum DEHP metabolites in urine - children
p<0.001 p<0.001
p<0.001 p<0.001
p<0.001 p<0.001
p=0.001 p=0.54 p=0.21
p=0.004 p=0.009
p<0.001 p=0.96
p<0.001 p<0.001 p<0.001
p<0.001
0 5 10 15 20 25 30
Cyprus Romania United Kingdom
Switzerland Luxembourg Ireland Germany Hungary ALL Slovac Republic
Denmark Slovenia Portugal Belgium Czech Republic Poland Spain Sweden
MBzP in urine (µg/L), adjusted for creatinine, age and gender
MBzP in urine - children
p<0.001 p<0.001
p<0.001 p<0.001
p=0.002 p=0.004
p=0.10
p=0.55 p=0.71
p=0.55 p=0.41 p=0.04 p=0.61
p=0.01
p<0.001 p=0.03
p<0.001
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Environmental factors Trend p<0,05
Biomarker / matrix Studypopulation
Ice cream consumption U-DEHP metabolites children
U-MnBP mothers
U-MBzP mothers and children
Gum consumption U-DEHP metabolites children
U-MEP mothers
PVC in floors/ walls U-MnBP children
U-MBzP/MiBP mothers and children
Renovation of house U-MiBP mothers
Use of personal care products
MEP mothers and children
U-MiBP children
Consumption of canned food
U-BPA mothers
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Environmental factors Trend p<0,05
Biomarker / matrix Studypopulation
Lower level of education of family
Mercury in hair mothers and children
U-cotinine children and non- smoking mothers
U-cadmium mothers
U-DEHP metabolites mother
U-MnBP children
U-MiBP mothers
U-MEP children
U-BPA children
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Cotinine in urine: ETS exposure
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7,027 1,595 0,574 2,117 0,648
0 1 2 3 4 5 6 7 8 9
ETS daily n=175
ETS less than
daily n=128
ETS never n=1513
ETS n=158
no ETS n=1259
Cotinine in urine (µg/g creatinine)
Cotinine in urine - relation with ETS at home
CHILDREN MOTHERS
p<0.001 p<0.001
non-smoking mothers
1,163 0,588 0,847 0,624
0,0 0,5 1,0 1,5 2,0
ETS n=768
no ETS n=1048
ETS n=811
no ETS n=611
Cotinine in urine (µg/g creatinine)
Cotinine in urine - relation with ETS elsewhere
CHILDREN MOTHERS
p=0.11 p<0.001
non-smoking mothers only
Levels increase
Children: urinary creatinine, age,ETS at home, ETS elsewhere, ETS last 24 hrs, educational level of the family
Non smoking mothers: ETS at home,ETS during last 24hrs, educational level of the family
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Cotinine in urine: distribution within EU
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0.0 0.5 1.0 1.5 2.0 2.5 3.0
Sweden Germany Luxembourg Switzerland Slovenia Belgium Denmark United Kingdom Ireland ALL Cyprus Slovac Republic Portugal Spain Poland Czech Republic Hungary Roemenia
Cotinine in urine (µg/L), adjusted for creatinine, age and gender
Cotinine in urine - results in children
p<0.001 p<0.001
p<0.001 p<0.001
p<0.001 p=0.01
p=0.04
p=0.71 p=0.049
p=0.002 p=0.001
p<0.001 p=0.21
p<0.001 p<0.001 p<0.001
p<0.001
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Exposure to second hand smoke and legislation
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
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Environmental determinants of exposure
Mercury and fish consumption
Cotinine and exposure to tobacco smoke Cadmium and tobacco smoke
Pthtalates and personal care products, use of PVC in floors/walls, ice cream, gum
Bisphenol A and consumption of canned foods
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Exposure vs. health-based guidance values
• German HBM commission: HBM I & HBM II values
• Biomonitoring Equivalents (BE)
= concentration of a chemical, consistent with existing health- based guidance values e.g. TDI
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<HBM I no adverse health effects expected
>HBM I & <HBM II adverse health effects can not be excluded with sufficient certainty
>HBM II adverse health effects expected
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Mercury in hair: health-based guidance values
2.3 µg/g hair JECFA/WHO 5 µg/g hair HBMI
Total N HBM I
>5 µg Hg/g hair
Provisional threshold value JECFA/WHO:
>2.3 µg Hg/g hair
Children 1836 5 (0.3%) 25 (1.4%)
Mothers 1839 6 (0.3%) 62 (3.4%)
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Conclusions
• Biomarker values showed a large variability in the population and between the countries
• Exposure of the general population in EU is well below the current health based guidance values, very few participants had values which were higher that the health based guidance values.
• The biomarker levels in children were highly correlated with the levels in their mother, especially for mercury and cotinine, which may indicate a common environmental factor that influences the biomarker level.
• The information reported by the participants on their environment and life style allowed to identify factors that influence the biomarker levels and hence indicate a leverage for intervention
27 Environmental research , 141, August 2015
Environ Health Perspect. 2015 Mar;123(3):255-63. doi: 10.1289/ehp.1408616.
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Conclusion: EU wide human biomonitoring at the cross cutting of environment, life style and health:
a new joint venture for a healthier Europe
• Man made chemicals are prevalent in the general population but we need comparable data ( cfr US NHANES) than can be linked to
environment and life style in the EU
• EU wide human biomonitoring : evaluates policy measures and sets new priorities , to protect all citizens alike
• Solid human biomonitoring data are needed to quantify linkage to
health outcomes
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Thanks
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• Protocol development : L. Casteleyn (KUL, Be)
• Recruitment and sampling: M. Kolossa –Gehring ( UBA, De)
• Sample processing and QA: J. Angerer (RUB, De), A. Castano ( ISCIII, Es)
• Data analysis and interpretation: G. Schoeters, E. Den Hond (VITO, Be)
• Communication: O. Sepai ( PHE, UK)
• Training; L. Bloemen (EHSI, Nl) , M. Horvat (JSI, Sv)
• HBM and related research: L.E. Knudsen (UCPH, Dk)
• HBM and policy: A. Joas (BIPRO, De)
• Coordination: R. Joas (BIPRO, DE)
COPHES was funded by the European Commission (FP7 grant agreement 244237) DEMOCOPHES was funded by LIFE+ ( grant agreement LIFE09ENV/BE/000410) Coordinated by P. Biot & D. Aerts (FPS, Be)
HUMAN BIOMONITORING FOR EUROPE a harmonised approach HUMAN BIOMONITORING FOR EUROPE a harmonised approach
United Kingdom:
Health Protection Agency (HPA)
Ireland:
Health Service Executive
(HSE) The Netherlands:
Environmental Health Sciences International (EHSI)
The Netherlands:
National Institute of Public Health and the Environment (RIVM)
Spain:
Instituto de Salud Carlos III (ISCIII)
Italy:
Istituto Superiore di Sanità (ISS)
Germany:
BiPRO GmbH
Coordinator COPHES
Belgium:
FPS Health, Food chain safety and environment Katholieke universiteit Leuven
Coordinator DEMOCOPHES
Denmark:
University of Copenhagen (UCHP)
Estonia:
National Institute for Health Development (NIHD)
Belgium:
Flemish Institute for technological Research (VITO)
Belgium:
Joint Research Centre (JRC)
Belgium:
CEFIC Belgium:
Health and Environment Alliance (HEAL)
Switzerland:
Federal Office of Public Health Germany:
Umweltbundesamt (UBA)
Germany:
Deutsche Gesetzliche Unfallversicherung (DGUV)
Austria:
Umweltbundesamt GmbH Czech Republic:
National Institute of Public Health (NIPH) Hungary:
National Institute of Environmental Health (NIEH)
France:
Institut de Veille Sanitaire
(InVS) Croatia:
Institute for Medical Research and Occupational Health (IMROH)
Lithuania:
Nvytautas Magnus University (VDU)
Luxembourg:
Centre de Recherche Public – Gabriel Lippmann (CRP-GL)
Finland:
National Institute for Health and Welfare (THL)
Sweden:
Karolinska Institutet (KI-IMM) Norway:
National Institute of Public Health Norway (NIPH-NO)
Poland:
Nofer Institute of Occupational Medicine (NIOM)
Romania:
Environmental Health Center (EHC)
Slovenia:
Jozef Stefan Institute (JSI)
Slovakia:
Public Health Authority of the Slovak Republic (UVZ SR)
Greece:
National Hellenic Research Foundation (NHRF)
Cyprus:
Ministry of Health - State General Laboratory (SGL)
HUMAN BIOMONITORING FOR EUROPE a harmonised approach
Austria
Umweltbundesamt GmbH Belgium
VITO
Switzerland Federal Office of Public
Health Cyprus
SGL Larnaca Hospital Czech Republic
NIPH
Germany UBA
Hungary NIEH
Denmark UCHP
United Kingdom HPA Estonia
NIHD
Spain ISCIII Finland
THL France
InVS
Greece NHRF Croatia IMROH
Ireland HSE Italy ISS Lithuania
VDU Luxembourg
CRP-GL
Laboratoire National de Santé the Netherlands
EHSI RIVM Norway NIPH-NO
Poland NIOM Portugal AIDFL / IMP
Romania EHC
Slovenia JSI Slovakia
UVZ SR
Sweden KI-IMM JRC
CEFIC HEAL FPS & KUL Coordinator DEMOCOPHES
DGUV BiPRO Coordinator COPHES
Luxembourg:
Laboratoire Nationale de Santé (THL)
Cyprus:
Larnaca Hospital Portugal:
Institute of Preventive Medicine, Lisbon Faculty of Medicine (AIDFM / IMP)
