Results of the first Europe-wide HBM study · Results of the first Europe-wide HBM study . ......

HUMAN BIOMONITORING FOR EUROPE

a harmonised approach HUMAN BIOMONITORING FOR EUROPE

a harmonised approach

1

Schoeters Greet

Results of the first Europe-wide HBM study




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

2




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.’

3

Nov 2009

- Nov 2012

Dec 2010

- Nov 2012




4

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




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

5

lead by Umweltbundesambt ,Germany (M. Kolossa –Gehring, K. Becker, G. Schwedler, U..

Fiddicke, M. Seiwert)




6

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




7

• 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)




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‟

8 Lead by VITO: G. Schoeters, E. Den Hond, E. Govarts




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%

9




European exposure values:

Average exposure: geometric mean and 95%CI

P90 and 95%CI

10




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)

11

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)




High correlation between mothers and children

12

0

20

40

60

80

100

0 20 40 60

sum

DEH

P m

etab

olit

es in

uri

ne (µ

g/L)

, c

hild

ren

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

Mn

BP

in u

rin

e (µ

g/L)

, ch

ildre

n

MnBP in urine (µg/L), mothers

MnBP in urine - correlation between children and mothers

0

5

10

15

20

25

0 5 10 15

MB

zP in

uri

ne

(µg/

L), c

hild

ren

MBzP in urine (µg/L), mothers

MBzP in urine - correlation between children and mothers




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 13




14

Spain

Portugal East –European

countries

Countries differ in their exposure profiles




Mercury in hair: comparison within Europe

15

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0

Hungary RomaniaGermany

Slovak RepublicPoland

United KingdomSwitzerland

Czech RepublicIreland

ALLSweden

SloveniaBelgium

LuxembourgDenmark

CyprusPortugal

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




Mercury in hair: effect of fish consumption

16

0.206 0.135 0.311 0.2180.00

0.20

0.40

0.60

0.80

1.00

> 1/monthsn=246

≤ 1/monthsn=1561

> 1/monthsn=298

≤ 1/monthsn=1515

Me

rcu

ry i

n h

air

(µ

g/g

)

Mercury in hair -relation with fresh water fish consumption

CHILDREN MOTHERS

p<0.001 p<0.001

0.566 0.111 0.780 0.1820.00

0.20

0.40

0.60

0.80

1.00

> 1/weekn=283

≤ 1/weekn=1549

> 1/weekn=294

≤ 1/weekn=1541

Mer

cury

in h

air

(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




Determinants of exposure to mercury in children:

multiple regression model

17

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




Not all Europeans are equal

18

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




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




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




Cotinine in urine: ETS exposure

21

7,027 1,595 0,574 2,117 0,6480

1

2

3

4

5

6

7

8

9

ETS daily

n=175

ETS less than

dailyn=128

ETS never

n=1513

ETS

n=158

no ETS

n=1259

Co

tin

ine

in

uri

ne

(µ

g/g

cre

ati

nin

e)

Cotinine in urine - relation with ETS at home

CHILDREN MOTHERS

p<0.001p<0.001

non-smoking mothers

1,163 0,588 0,847 0,6240,0

0,5

1,0

1,5

2,0

ETS n=768

no ETSn=1048

ETSn=811

no ETS n=611

Co

tin

ine

in

uri

ne

(µ

g/g

cre

ati

nin

e)

Cotinine in urine - relation with ETS elsewhere

CHILDREN MOTHERS

p=0.11p<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




Cotinine in urine: distribution within EU

22

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




Exposure to second hand smoke and legislation




24

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




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

25

<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




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%)




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.




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




Thanks

29

• 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)




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)



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)

Results of the first Europe-wide HBM study · Results of the first Europe-wide HBM study . ......

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