Children in Their Environments: Vulnerable, Valuable & at Risk

EEA, WHO Europe & the Collegium Ramazzini workshop June 22nd, 2004

Biomonitoring, towards more integrated approaches

Dr. Ludwine CasteleynChair TWG Biomonitoring of Children

Ministry of the Flemish CommunityAMINAL

TWG Biomonitoring for ChildrenBloemen Louis, Brits Ethel, Boogaard Peter, Canna Michaelidou Stella, Fréry Nadine, Fucic Aleksandra, Harrison Paul, Jakubowski Marek, Lehners Maryse, Lorente Christine, Ramet José, Seifert Bernd, Schoeters Greet, Steenhout Anne, Ten Tusscher Gavin W., Wattiez Catherine, van Wijnen Joop Co Chairs: Sala Carlo, Knudsen Lisbeth E., Chair: Casteleyn LudwineAssisted by: Joas Reinhard, Bauer Sonja Commission: Van Tongelen Birgit.

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Human Biomonitoring = measuring in humans (effect) of exposure

air

water soil

food

consumables

“Monitoring activities in children, using biomarkers, that focus on environmental exposures, diseases and/or disorders and genetic susceptibility, and their potential relationships”.

Newborns: 1600 Adolescents: 1600 (14-15y)

Adults: 1600 (50-65y)

Markers of exposure

Cord blood: cadmium, lead Cord blood serum: marker PCBs, pesticides, dioxine-activity

Blood: cadmium, lead Serum: marker PCBs, pesticides Urine: 1-OH pyrene, tt-muconic acid

Serum: marker PCBs, pesticides, dioxine-activity Urine: 1-OH pyrene, tt-muconic acid, cadmium

Markers of effect

Biometry, TSH (heel prick), Apgar score, time to pregnancy Questionnaire: asthma & allergy Follow- up of part of children

Blood: comet test Serum: hormone balance Biometry, sexual development, hearingtest, Questionnaire: asthma & allergy

Blood: comet test, HPRT Serum: tumour markers Urine: 8-OH dG Questionnaire: asthma & allergy

Confounders Questionnaire: general+ food Biochemical analyses: cholesterol, iron status cord blood

Questionnaire: general + food Biochemical analyses: cholesterol, iron status blood, urinary creatinine

Questionnaire: general + food Biochemical analyses: cholesterol, iron status blood, urinary creatinine

Biomarkers

http://www.milieu-en-gezondheid.be 2001-2006

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Flemish Health and Environment Study Pilot study (1999)

Test feasibility, assess relevance (small scale study) “whether residence in areas with different pollution

pressure has a significant impact on internal exposure to pollutants and resulted in adverse biological effects”

2 industrial suburbs of Antwerp: Wilrijk: 2 waste incinerators Hoboken: large non-ferrous smelter- known lead pollution

1 rural municipality: Peer (“control area” - measured environmental pollution low)

http://www.wvc.vlaanderen.be/gezondmilieu/Koppen et al, 2001 Toxicology Letters, 123, 59-67Koppen et al, 2002, Chemosphere, 48, 811-852Nawrot et al, 2002, Env Health Perspectives, 110, 583-589 Staessen et al, 2001, Lancet, 357,1660-1669

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0

0.25

0.5

0.75

1

Peer Wilrijk Hoboken

µg

/L

adolescentswomen

* *

Pilot studyCadmium blood

7

0

0.05

0.1

Peer

Wilr

ijk

Hoboken

µg

/g c

reat

inin

e

adolescents

women

*

*

Pilot study1-OH pyreen urine

0.15

8

Pilot study Marker PCBs serum

0

100

200

300

400

500

Peer Wilrijk Hoboken Nederland(gem. 29j)('90-'92)

Zweden(gem. 42j)('86-'91)

ng

/g v

et

adolescents

women

*

*

9

Pilot studyDioxine-like substances

0

5

10

15

20

25

30

35

40

45

50

Peer Wilrijk Hoboken Belgian women

gem.32 j ('96-’98)

pg

TE

Q/ g

vet

adolescentswomen

**

10

Pilot study: Women: HPRT mutant-frequency

0

1

2

3

4

5

6

7

8

9

10

Peer Wilrijk Hoboken

nu

mb

er/m

illio

n c

ells

normal range

*

Van Larebeke et al, Biomarkers, vol. 9, no 1, 2004, 71-84

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Pilot study Men: Sperm + testosterone

360

380

400

420

440

460

480

Peer Wilrijk Hoboken

ng

/dL

te

sto

ste

ron

e

0

2

4

6

8

10

12

14

16

18

20

% n

orm

al

testosterone blood

morphology sperm

NORMAAL

OK

*

*

Pilot studyAdolescents: sexual maturation

Nog niet volledig ontwikkelde genitaliën (jongens) of borsten (meisjes) op 17-18j leeftijd

0

20

40

60

Peer Wilrijk Hoboken

% v

an d

e ad

ole

scen

ten

*

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Pilot study: conclusions

geographical differences & individual differences

adolescents and adults: geographical differences not following same trends

despite low measured environmental pollution ‘Peer’ not always reference area

findings suggest that current environmental standards are insufficient to avoid measurable biological effects

...

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Flemish biomonitoring program for surveillance of environmental health

Flemish Institute for Technological Research (VITO), Belgium

Greet Schoeters et al

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Goals

Analyse time trends : efficacity of environmental measures for public health

Analyse spatial trends : healthy and unhealthy areas

Detect yet unknown environmental threaths: early warning system for unknown pollution sources / pollutants

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Legal framework

(B.S. 03-02-2004) Preventiedecreet Art 51 § 1

The Flemish government:

1. can set up a network for surveillance of exposure (measured in humans) and/or effects of exposure to physical and chemical factors in the population, with the intention to take measures to protect public health.

2.takes at least measures for the development and execution of a program for biomonitoring.

3. can - in execution of &1 - set up a fund (…). For this purpose a mandatory financial contribution can be imposed on industries or citizens that are responsible for the presence of physical or chemical factors harmful to health.

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total number of questionnaires received: 97 reported budget with 47 questionnaires: about

57 million euro about 480 000 children are covered (basis 90

questionnaires) 42 covered heavy metals, 25 projects examined asthma or allergies 19 projects covered dioxin/PCB exposure, 4 covered endocrine disrupters

… generally not carried out using the same methodological approach.

Human biomonitoring studies related to children in European countries

difficult to compare the data generated

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A substantial amount of biomarker data is collected

addressing simultaneously markers of exposure, effect and susceptibility and also additional data on environmental factors and health

addressing both children and their parents (particularly their mothers, therefore integrating prenatal and postnatal exposure)

Integrating:

various routes of exposurevarious sources of past and recent exposure

Biomonitoring = Integration

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2 types of biomarker activities

SURVEY projects: activities that aim at periodical measurements in order to produce information on the prevalence of exposure to environmental agents and the related public health impact with a view to developing and evaluating policies that protect health

RESEARCH projects: activities that aim at improvement of knowledge on causal links between environmental factors and health by hypothesis generation and testing

• to generate representative data on the concentration distribution of environmental pollutants in media like air, water, soil, dust, food, and in human specimens, such as blood or urine;

• to establish reference values based on these distributions;  

• to document and interpret spatial and temporal differences in population exposure;       

• to provide policy makers with information if and what measures should be taken.        

Objectives of the German Environmental Surveys (GerES)

• to get insight into the contribution of different compartments (air, water, food) to the body burden;       

B. Seifert, K. Becker, C. Schulz, C. KrauseFederal Environmental Agency, Germany

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Recruitment of study population

Biological samples such as blood and urine are difficult to obtainespecially in children

less invasive sampling techniques /financial incentives

Biomarkers

validation of biomarkers is incomplete

Logisticsbiomonitoring is a time consuming effort sufficient staff is not always available high investment of medical staff is needed continued funding of long term studies is problematic

Problems and deficits

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Communication

to the participants/public: what and how to communicate when the links with health risks, especially at the individual level, are not well defined

to the authorities: reporting to the relevant authorities is often lacking

good communication is crucial and an active involvement of professionals in the field is needed

Problems and deficits

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Ethical issues need special attention since sensitive

information may be derived from biomonitoring and the child is not able to consent. Issues of confidentiality and data protection should have special attention as well as opportunities of opting out later when mature (18 years of age)

see report of meeting in Copenhagen 5-7th Dec www.pubhealth.ku.dk/cgn

Ethics

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A more harmonised biomonitoring approach

Comparability would contribute to the EU Strategy for E & H by:

Providing data on distribution of exposure and related health impact across Europe

• definition of reference values• detection of spatial differences in exposure

(populations/regions at risk) • detection of temporal differences in exposure

Providing policy makers with better information on control measures to be taken

• identification of priorities in exposure reduction strategies

• allowing follow up of the efficiency of reduction strategies,

• allowing a geographically differentiated E&H policy

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A more harmonised EU biomonitoring approach

Enable a more effective use of resources by shared development of tools and strategies

Enable more meaningful results of national surveys as the number of study subjects involved becomes larger

Allow for a more equal distribution of efforts

amongst European countries and a better respecting of the equal right of each European citizen on healthy environments.

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Action Plan

Approach: Step-by-Step Strategy

I Develop guidelines for a harmonised EU approach for biomonitoring

II Start an European wide pilot project

III Develop tools to translate results into a response system

http://www.brussels-conference.org/Download/baseline_report/BR_Biomonitoring_final.pdfhttp://europa.eu.int/comm/environment/health/pdf/040330biomonitoring.pdf

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I. DEVELOP GUIDELINES

Develop technical guidelines for common use with the aim of harmonising

The guidelines should address issues related to initiation, performance and follow up of biomonitoring activities:

• Design and protocol for surveys• Sampling strategy and analysis• Data treatment• Dissemination and information of results• Ethical rules and practices, social and legal aspects

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II. START EU WIDE PILOT PROJECT

“Learning by doing” tool

Test and validate common harmonised approaches for all steps

Facilitate the establishment of collaboration networks and the sharing of methodologies

Promote the idea of harmonisation in biomonitoring.

Identify possible problems linked with such harmonisation

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II. START EU WIDE PILOT PROJECT

In view of not complicating the study by major analytical problems it is proposed to select a pollutant:

for which there is already sufficient analytical

experience.

for which the exposure and health relevance is well known

Possible candidates: lead and mercury

in line with a WHO proposal to ensure regular biomonitoring of lead (amongst other hazardous chemicals) in at risk children.

lead and mercury

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III Translate results into a response system

Develop scenarios for translation of biomonitoring data into a response system. Such scenarios require integration of biological monitoring data with environmental

monitoring and health data the development of

reference values to which biomarker results from different areas or time periods can be compared

health based action levels that can help indicate when measures need to be taken in order to reduce body burden

for most exposure- and effect biomarkers

NO health based values exist

Child-specific

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In order to translate the results of biomonitoring into policy measures, effective communication is needed.

Effective communication needs participation and exchange between the different stakeholders (general public, study participants, general practitioners, regulators, scientists, public interest NGO’s, industry, others) and will promote public awareness.

A communication plan is an essential part of a biomonitoring programme and should be a part of the study design.

III: Translate results into a response system

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HOW ?

Establish specific working group(s)

Bringing together existing expertise and experiences From MS already carrying out surveillance programmes From occupational health field From research field

Aim: to develop harmonised technical procedures a protocol for carrying out a pilot project tools allowing for translation of biomarker results into

intervention strategies

In coordination with Commission and MS

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Integration of environment and health

Human biomonitoring is an excellent tool to better integrate the two fields, environment and health

One of its big advantages is that within the

chain it is much closer to health effects than environmental monitoring

Biomarker of susceptibility

Biomarkers of exposure

Internal dose

Biological effective dose

Biomarker of effect

Early response

Altered structure and funcion

Disorder Disease

Exposure Emission Ambient level

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to measure is to know …

the pitfalls lay in who’s to read and how?

for proper policy making:

interpretation - by experts - in combination with other data

- respons- prevention and precaution- communication