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Requirements for a European Requirements for a European Human Biomonitoring Human Biomonitoring programmeprogramme

for priority assessment of for priority assessment of environmental chemicalsenvironmental chemicals

Matti JantunenMatti Jantunen, , TerttuTerttu VartiainenVartiainen, , HannuHannu KivirantaKiviranta

KTLKTL--Environmental Health, Kuopio, FINLANDEnvironmental Health, Kuopio, FINLAND

European Conference on Human BiomonitoringParis, November 4th – 5th, 2008

If you need to know something to make the right decision,and if you can measure what you need to know,

consider measuring it!

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Pros and cons of HBMPros and cons of HBM

Pros:Pros:HBM integrates theimpacts of - all exposure media,- all pathways and

routes of entry,- all geographic

locations and microenvironments,

- all activities and consumer products

Cons:Cons:• HBM is not applicable for all

chemicals of interest• HBM reflects exposures

differently for different chemicals

• Biological guideline values (BGV) are available for only a limited set of chemicals

• Relationships of HBM to exposure and to health are poorly known for most chemicals

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German Environmental SurveysGerman Environmental Surveys

RepresentativeRepresentativepopulation study withpopulation study with5000 subjects in each5000 subjects in each- GerES I 1985/6- GerES II 1990/1

incl. children 6-14 y former GDR 1991/2

- GerES III 1998- GerES IV 2003-6

1800 children, 3-14 y

HBM:HBM:– As, Pb, Cd, Hg, Ni– Creatinine, cotinine, nicotine, cortisol,

adrenalin, noradrenalin– PCBs, DDE, HCB, HCH, PAHs,

chlorophenols, pyrethroid metabolites, esters of phosphoric acid

– Fungi specific IgEAlso:Also:

– Noise, hearing and stress– Domestic environment

• House dust• Drinking water• Chemical & biological pollutants in

indoor air– Interviews

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CDC National Reports on Human CDC National Reports on Human Exposure to Environmental ChemicalsExposure to Environmental Chemicals

Nationally representativeNationally representativepopulation studypopulation study2000 2000 -- 9000 subjects 9000 subjects (1(1--)6 y and older )6 y and older - 1st Report, 2001

27 chemicals- 2nd Report, 2003

116 chemicals- 3rd Report, 2005

148 chemicals- 4th Report, 2008 (?)

ca. 200 chemicals

HBM:HBM:– 13 metals incl. Pb, Cd, Hg, U– Cotinine– 23 metabolites for PAHs incl. BaP– 52 PCDDs, PCDFs and PCBs– 12 phthalates– 6 phytoestrogens– 20 organochloride pesticides– 6 metabolites for organophosphate

pesticides– 7 herbicides– 5 pyrethroids– 3 other pesticides– 2 carbamate insecticides

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Feasibility Study for EHES:Feasibility Study for EHES:European Health Examination Survey European Health Examination Survey

Tolonen et al. KTL:n julkaisuja B 22/2008

ProposalProposal for nationally representativefor nationally representativepopulation health studies in Europepopulation health studies in Europe- 8..12 countries � all EU - 4000 - 10000 subjects in each country- - 25 - 64 y (…and older)MinimumMinimum- Physiological: Height, weight, waist circ.

diastolic and systolic blood pressure, - Blood: Total and HDL cholesterol, fasting

glucose- Questionnaire: SES, smoking, health; CV

disease, hypertension, hyperlipidemia, diabetesGeneralGeneral- Common protocols- Comparability across countries and time- EU funded coordination & QA/QC - Centralised database - National sampling nationally funded- Encouraged use for public health and research

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What should a European What should a European HBM HBM ProgrammeProgramme give us give us -- 1 1

Technical:Technical:- Body burdens (BB) of

environmental chemicals- Time trends

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Dioxin Dioxin BBsBBs (& exposures) of breastfeeding (& exposures) of breastfeeding mothers in Finland are declining rapidly mothers in Finland are declining rapidly

From 19871987

to

19931993--66

Cumulative distributions of TEQ BBs of Finnish women in 1993-6 (lower) vs 1987 (higher)

0

20

40

60

80

100

1,E-07 1,E-06gTEQ/individual

cum

ula

tive

freq

uen

cy (%

)

Kiviranta H. et al. 2005 Chemosphere 60(7):854-869Valentini M. 2007 MSc Thesis Univ Degli Studi di Milano

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What should a European What should a European HBM HBM ProgrammeProgramme give us give us -- 1 1

Technical:Technical:- Body burdens (BB) of

environmental chemicals- Time trends - Areal distributions

(geographic, urban/industrial/ rural/traffic, proximity to sources)

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Proximity to the source did not increase Proximity to the source did not increase HpCDFHpCDF and OCDF body burdens and OCDF body burdens

Kiviranta H. et al. 2005 Chemosphere 60(7):854-869Valentini M. 2007 MSc Thesis Univ Degli Studi di Milano

Cumulative distributions of HpCDF BBs from Kuusankoski of women in Kymijoki basin vs. rest of Finland

0

20

40

60

80

100

1,E-11 1,E-10 1,E-09 1,E-08 1,E-07

HpCDF (gTEQ/individual)

cum

ulat

ive

freq

uenc

y (%

)

45 % of women in Kymijoki basin and

25 % of all women in Finland do not eat fish

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What should a European What should a European HBM HBM ProgrammeProgramme give us give us -- 1 1

Technical:Technical:- Body burdens (BB) of

environmental chemicals- Time trends- Areal distributions

(geographic, urban/industrial/ rural/traffic, proximity to sources)

- Population distributions (age, gender, SES, ethnicity, etc.)

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Accumulation of PCDD/Fs in Finnish men over age Accumulation of PCDD/Fs in Finnish men over age

Male PCDD/F body burdens in Finland

y = 2E-08x - 3E-07R2 = 0,35

1,E-08

1,E-07

1,E-06

1,E-0510 20 30 40 50 60 70 80 90

age (y)

WH

O:T

EQ

(g/in

divi

dual

)

Kiviranta H. et al. 2005 Chemosphere 60(7): 854-869Valentini M. 2007 MSc Thesis Univ Degli Studi di Milano

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What should a European What should a European HBM HBM ProgrammeProgramme give us give us -- 1 1

Technical:Technical:- Body burdens (BB) of

environmental chemicals- Time trends- Areal distributions

(geographic, urban/industrial/ rural/traffic, proximity to sources)

- Population distributions (age, gender, SES, ethnicity, etc.)

- Links (occupation, housing, diet, consumer products, etc.)

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Professional fishermenProfessional fishermen’’s dioxin exposures are an order s dioxin exposures are an order of magnitude higher than the otherof magnitude higher than the other’’ss

Cumulative distributions of TEQ (PCDDs+PCDFs) in the fishermen (blue) and all men (brown)

0

20

40

60

80

100

1,E-07 1,E-06 1,E-05 gTEQ/individual

cum

ulat

ive

freq

uen

cy (%

)

Kiviranta H. et al. 2005 Chemosphere 60(7):854-869

Valentini M. 2007 MSc Thesis UnivDegli Studi di Milano

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What should a European What should a European HBM HBM ProgrammeProgramme give us give us -- 1 1

Technical:Technical:- Body burdens (BB) of

environmental chemicals- Time trends- Areal distributions

(geographic, urban/industrial/ rural/traffic, proximity to sources)

- Population distributions (age, gender, SES, ethnicity, etc.)

- Links (occupation, housing, diet, consumer products, etc.)

Policy:Policy:- Early warnings for emerging

risks - Identification of vulnerable

groups- Guidance for policy targeting

and development- Assessments for policy

effectiveness, accountability

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What could a European What could a European HBM HBM ProgrammeProgramme give us give us -- 2 2

•• Maps and graphicsMaps and graphics digestible for the public and decision makers

• Data for attribution of the attribution of the exposuresexposures to

– sources – products– locations – activities – target groups

using factor analysis techniques, e.g., PCA and PMF

• Data to model past exposures model past exposures using, e.g., regression modelling techniques

Triad of chemical risks:Triad of chemical risks:I: Low concernI: Low concern

- decreasing BBs, - no hot spots, - no vulnerable groups, - BBs small fractions on NOAEL

- Keep in the HBM programmeIII:III: High concernHigh concern

- BBs increase in time, - BBs high relative to BGVs for

- certain region(s), hot spots - population group(s), - users of certain product(s),

- Investigate, act, target researchII: Intermediate concernII: Intermediate concern

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BackBackBack

Linking Linking BBsBBs of known toxins to health may surprise of known toxins to health may surprise

Total and disease specific mortality of Baltic fishermen and fishermen’s spouses in Finland

Fishermen (6410) Fishermen’s wives (4260) Mortality compared to total

male and female population SMR 95 % CI SMR 95 % CI

All causes 0.78 0.73 – 0.82 0.84 0.68 – 0.94

Circulatory diseases 0.75 0.68 – 0.82 0.81 0.68 – 0.94

Malignant neoplasms 0.90 0.80 – 1.01 0.97 0.80 – 1.15

Diabetes 0.43 0.14 – 0.99 0.83 0.27 – 1.94

Respiratory diseases 0.58 0.44 – 0.75 0.32 0.14 – 0.62

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Requirements for the European HBM Requirements for the European HBM programmeprogramme

-- Representative population Representative population samplesample – ca. 10 000 per year –all Europe and subpopulations of interest

-- Continuous samplingContinuous sampling and analysis programme

-- Blood & urine samplesBlood & urine samples from each individual

-- Broad range of analysesBroad range of analyses of the known toxic but also harmless compounds

-- PBPK or simpler modelsPBPK or simpler models to estimate BBs and doses from the measured HBM data

Steering committeeSteering committee representing representing EC EC and and MSsMSs

Independent Independent programmeprogrammemanagementmanagement and and QA/QCQA/QC

• Centralised protocols, sample analysis and GIS database

• Inter-linguistically validated exposure questionnaires to collect

• environment characteristics – natural and man made – for the sampled individuals

National population sampling and National population sampling and HBM sample collectionHBM sample collection

MaximumMaximum data accessibilitydata accessibility for the public, media, industry, public authorities and scientists

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This would be expensive!This would be expensive!Who should, who would pay? Who should, who would pay?

- EHBM programme would cost in the order of 10-20 M�/yr- … only a fraction of the costs of the current environmental monitoring

programmes in Europe- Yet, the European HBM Programme data would much more directly

serve chemical risk identification, assessment and prevention- If I am asked, EU should pay for the centralised programme

development, management, sample analysis and database operationsand the Member States should pay for the national sampling

-- The EHBM Programme benefits for Europe would exceed its costs The EHBM Programme benefits for Europe would exceed its costs by far via by far via

-- early identification of public health risks , and early identification of public health risks , and -- effective allocation of resources effective allocation of resources

for the development, implementation and accountability for the development, implementation and accountability assessment of chemical risk policiesassessment of chemical risk policies

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EHBM EHBM –– EHES? EHES?

Close collaboration between EHBM and EHES wouldClose collaboration between EHBM and EHES would- create a huge, diverse and not easily managed programme with many

countries, interests, parties and – obviously – conflicts,- save cost and resources for both programmes, - improve the quality of, reduce the time and resource requirements for

and enable otherwise unfeasible EH assessments, and - create unforeseen environmental health research, risk assessment,

risk management and policy assessment opportunities.

- For the European level HBM programme blood/urine samples from only 2..5 % of the EHES sample would be necessary

- For national HBM interests – regional, urban/rural/industrial-hot-spots, ethnic subpopulations, etc. – a larger proportion of the domestic EHES population sample could be chosen.

The moment for coordinating EHBM The moment for coordinating EHBM –– EHES is now!EHES is now!

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I I I appreciateappreciateappreciate youryouryour invitationinvitationinvitation & & & attentionattentionattention

QUESTIONS?QUESTIONS?QUESTIONS?

So, when you need to know something to make the right decision,and when you really can measure what you need to know,By all means, do measure it!

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Privacy issues!? Privacy issues!? AggregatedAggregated, unidentifiable individual or , unidentifiable individual or identifiable individualidentifiable individual data?data?

-- That is the problem!That is the problem!

- Identification of and attribution of exposures to sources is based on advanced statistical techniques – PCA and PMF

- These techniques require individual level data but not identificationof the individuals

- Consequently, with individual data on the BBs of chemicals, personal environments, activities and behaviour, we can attribute exposures to sources in the homes, workplaces, transport, consumer products and personal activities

- … but we do not need spatial resolution, and can, therefore, protect each individual’s identity

- EHBM programme’s spatial coverage is – anyway – too low to identify and assess the impacts of local sources.

If only aggregated data can be used, we have the data If only aggregated data can be used, we have the data but are not allowed to analyse it!but are not allowed to analyse it!

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Contribution from one industrial source of Contribution from one industrial source of HpCDFHpCDF and and OCDF can be seen in the elevated OCDF can be seen in the elevated HpCDFHpCDF/PCDD+PCDF /PCDD+PCDF

ratio in the human ratio in the human BBsBBs

0

10

20

30

40

50

60

70

80

90

100

1,E-04 1,E-03 1,E-02 1,E-01

HpCDF/WHO TEQ ratio

Cum

ulat

ive

freq

uen

cy (%

)

Valentini M. 2007 MSc Thesis Univ Degli Studi di Milano