EU Research on Environment and Health - Results from projects funded by the Fifth Framework Programme docx

EU Research on
Environment and Health -
Results from projects funded by
the Fifth Framework Programme
KI-NA-22816-EN-S
EU Research on Environment and Health - Results from projects funded by the Fifth Framework Programme
PROJECTS REPORT
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Over ninety multidisciplinary pan-European research projects dealing with environment
and health issues were funded by the European Commission’s Research Directorate-
General in the Fifth Framework Programme of Research (1998-2002). The results of
these projects have now become available and are presented in this catalogue. The
projects presented addressed a multitude of issues ranging from health impacts of
exposure to electromagnetic elds to air pollution. The results should be useful to many
stakeholders including the scientic community and policy makers.
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EU Research on
Environment and Health -
Results from projects funded by
the Fifth Framework Programme
ACKNOWLEDMENTS
The project related data was compiled for the most part by Dr Tuomo Karjalainen, European Commission,
Research Directorate-General, Directorate I (Environment), Unit Climate Change and Environmental Risks
(Head of Unit: Ms Elisabeth Lipiatou), with the skillful assistance of Ms Kerstin Johansson.
Valuable contributions from the Directorate E (Biotechnologies, Agriculture, Food), Unit Food-Health-Wellbeing
(Head of Unit: Antonio Di Giulio) are acknowledged, especially assistance from Drs Ana Nieto-Nuez and
Ebba Barany.
Activities and contributions of former Scientific Officers in this field (including Mr Callum Searle, Dr Kirsi Haavisto,
Ms Minna Wilkki) should not be forgotten.
The data in the project sheets was provided and validated for the most part by project coordinators and they
bear responsibility for their scientific content and accuracy.
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5
Foreword
It is pretty much accepted in our society that
environmental factors such as noise or air pollution
can have an adverse impact on human health and
well-being. Opinion polls show that the majority
of the European public has increasing concerns
about the influence of these factors on their health
and their children’s health in particular. The links
between environmental factors and disease trends
are now being discovered through numerous
scientific research projects. Amongst the links now
highlighted are:
Cancer rates, including children’s cancer, are
increasing by around 1% a year. This increase
is believed to be linked, at least partially, to a
number of environmental pollutants;
Fertility rates are declining at a worrying rate in

some EU countries, and environmental pollution
is also partly suspected;
Neurodevelopmental disorders are on the
increase in our children (including conditions
such as autism) and environmental exposures
could play a role here;
Allergies and asthma are increasing by 5% a year
across the continent, and air pollutants could be
partly to blame;

In addition, new and emerging technologies and
societal challenges, such as widespread use of mobile
phones and the consequences of climate change,
could bring new long-term health consequences
that must be risk assessed and managed.
The European Union has been at the forefront of
research on the environment and health for many
years. Through successive European Research
Framework Programmes and national science
programmes, we have greatly increased our
understanding of the complex links between
environmental risk factors and their effects on the
health of citizens, various vulnerable sections of
society and the population as a whole.
This accumulated scientific knowledge has helped
shape national and EU policy initiatives designed to
protect our environment and promote human health
throughout the continent. A good example of this is
the European Environment and Health Action Plan
adopted in 2004.

This publication brings together the final results of
all European-funded research projects in the field of
environment and health from the Fifth Framework
Programme of Research (FP5). Sponsored by the
European Commission’s Directorate-General for
Research, the projects covered a multitude of
issues in this complex area. I sincerely hope this
comprehensive overview will allow you to find some
answers to the many questions raised by the general
public, scientific community and policy-makers on
the links between environment and human health.
Janez Potocnik
Commissioner for
Science and Research
7
Table of contents
Introduction 8
Air pollution-r
elated health impacts 14
Chemicals and health impacts 20
Electr
omagnetic fields and health impacts 28
Noise-r
elated health impacts 32
UV light and ionising radiation-r
elated health impacts 34
Multiple str
essors and factors and health impacts 36
W

aterborne stressor-related health impacts 38
Climate change-r
elated health impacts 40
Nanoparticle-r
elated health impacts 42
The project summaries 44
Contacts and links for further information
230
Introduction
The most common diseases and medical conditions
that affect European citizens today result from a
combination of risk factors, which are both genetic
and environmental. Some of these risks are well
established, whilst others are emerging as a result
of societal change.
How specific health and medical issues affect
individuals varies with time, geography, even the
weather. An individual’s vulnerability is determined
by genetic factors, age, their diet and health status.
Assessing and managing the various established
and emerging risks to human health, inherent
in a modern, constantly evolving society, is an
immensely complex task. But it is a vital task that
can improve the quality of life of all citizens and
protect public health.
The need for research
Over the past few decades the role of environmental
factors has been highlighted in the health debate,
for example the role of environmental tobacco
smoke on increased lung cancer in non-smokers

and the possible implication of some chemicals
in the observed rise in testicular cancer in some
European countries. The focus was initially on
workplace exposures, but as many of these
industrial risks have been recognised, understood,
and effectively regulated, the focus has shifted to
more widespread risks. In particular, most recently,
the role of environmental factors in the health of
the young, even pre-natal, child has become a
growing concern.
Environmental pollutants such as tobacco smoke,
asbestos, pesticides, traffic fumes, and heavy
metals have all been linked to diseases like cancer,
cardiovascular disease and abnormal pre- or post-
natal development. In addition, excessive exposure
to sunlight has been linked to cancer, while unhealthy
nutrition can lead to heart disease. Besides these
effects, the noise of modern living can have serious
health effects, including sleep disturbance and
cardiovascular effects. Allergies and asthma are
on the increase and the cost of their treatment is a
significant strain on national medical budgets.
New challenges are joining the old. Climate change
will effect our environment which in turn will
present new health issues; new technologies such
as wireless communications and nanotechnology
could provide new potential for
risk that must be assessed.
The importance of environment-
related disease and the need to

reduce uncertainty regarding the
health effects of environmental
factors are clear. The health
and quality of life of European
citizens would significantly
benefit from reducing exposure
to key pollutants.
8
Environment and health research:
long-lasting EU effort
European Research Framework Programmes (FPs)
have been implemented since 1984, but a specific
reference to concerns on the “personal environment”
first appeared in the third European Commission
Medical and Health Research Programme (MHR3) in
1982 to 1986. The subsequent MHR4 programme
(1987 – 1991) included “environment and lifestyle-
related health problems” in its priorities as well
as examining the effects of passive smoking and
exposure to industrial chemicals.
The Biomedicine and Health Research programmes
BIOMED1 (1990 – 1994) and BIOMED2 (1994
– 1998) both covered environmental issues under
the theme “risk factors, especially in the context
of occupational medicine” and “diseases of major
socio-economic impact”. In parallel, human health
issues were the subject of a number of projects
in the first and second “Specific Research and
Technological Development Programmes in the
field of Environment” ENV1 (1990 – 1994) and

ENV2 (1994 – 1998).
Environment and Health
issues in FP5
The Fifth European Community Research
Framework Programme (FP5) built on the results of
these previous initiatives through a number of more
integrated thematic programmes. Environment and
health issues were mainly addressed within the
Quality of Life and Management of Living Resources
theme under Key Action 4 (KA4): Environment and
Health. With a budget of €160 million over the
period 1998 – 2002, KA4 initiated more than 90
trans-national research projects the results from
which are presented together in this brochure for
the first time. Projects were also funded by two
key actions within the Energy, Environment and
Sustainable Development programme.
The general objective of environment and health
research in FP5 was to study the health effects of air
pollution, noise, dust and fibres, heavy metals and
other toxic chemicals, UV light and electromagnetic
radiation, and to find ways to minimise any health
risks. Special attention was paid to pollution in the
workplace and to the effects on children and other
vulnerable groups.
The scientific and technological objectives were:
Research into diseases and allergies related to, or
influenced by, the environment, their prevention
and their treatment;
The development of new methods of risk

assessment, and of processes to reduce the
causes and environmental factors which are
harmful to health.
Results of FP5 research - highlights
The research undertaken in FP5 consisted of nine
priorities:
Air pollution-related health impacts

Chemicals and health impacts
Electromagnetic fields and health impacts
Noise-related health impacts

UV light and ionising radiation-related health
impacts

Multiple stressors and factors and their health
impacts
Waterborne stressors and their health impacts
Climate change-related health impacts
Nanoparticles and health impacts
The first two priorities were the main focus of
environment and health research for FP5, accounting
for some 61 projects and 73% of the budget.
Highlights of results for all priorities:

The adverse respiratory health effects of fine
particles, nitrogen oxides and in particular
smoking was repeatedly demonstrated. The use of
biomarkers to give early indication of either potential
to develop disease or evidence of exposure showed

the utility of this emerging science for a variety of
environmental stressors. Effects were also observed
on
other organs such as the cardiovascular system.
9
These results have effectively fed into the EU policy
process on air pollution.

Endocrine-related reproductive effects were
widely studied showing correlations between
exposure to a range of chemicals and adverse
effects in a variety of animal models ranging
from invertebrates to various mammals. Human
studies showed, among others, that reproductive
health is deteriorating in several regions in Europe
as evidenced by declining sperm counts and
other parameters, but causes behind this change
remain unclear. In addition, developmental and/or
neurobehavioural effects of some chemicals were
observed in animals as well as in exposed human
populations. Studies on chemical pollution,
including how they are absorbed by the skin,
yielded new tools that will be of use in REACH
and workplace risk assessment.

Fears about the adverse health effect of mobile
phone use and other electromagnetic sources were
not supported by research findings, although certain
genotoxic effects were seen in vitro, and the results
of some large-scale studies are still awaited.

Clear evidence of links between transport noise,
classroom performance and health indicators
were made. The additive effect of noise with
other environmental stressors was also clearly
demonstrated. Noise can also have adverse
effects on the cardiovascular system.
Genetic mechanisms for skin cancer development
were determined and biomarkers for early
diagnosis of UV damage identified.

A major result of FP5 research was the development of
integrated environment and health risk assessment,
which was pioneered and shown to be effective.
This approach paved the way for further more
extensive activity funded under the Sixth Framework
Programme of Research (FP6 – 2002-2006)
.
New technologies and methodologies were
developed to help ensure the safety of bathing
and drinking water across Europe.
Initial work on the effects of global warming on
diseases patterns and the potential effects of
nanoparticles on human health was undertaken.
This work is continuing in FP6.
In general, the knowledge gained from projects
funded under FP5 helped to provide a scientific
basis for assessing environmental risks, a main
driver for developing knowledge-based policies
to protect public health.
This research input is critical to good policy

formulation across a wide range of areas including:

The European Environment and Health Action Plan
Sustainable Development Strategy
Thematic Strategy on Air Pollution
Thematic Strategy on Urban Environment
Community Strategy for Endocrine Disrupters
GEOSS – Global Earth Observation System of
Systems
REACH – Registration, Evaluation and
Authorisation of Chemicals
Programme of Community Action in the Field of
Public Health
EU Noise Policy
Full details of the research undertaken, its context,
short project summaries and links to individual
project sheets for all nine priorities can be found in
individual chapters in this brochure.
Continuing and future research
Following FP5, FP6 saw an increase in annual
funding for Environment and Health projects from
around €40 million a year to around €50 million
for the period 2002 - 2006. The relevant funded
projects were spread over four of the FP6 priorities:
Food Quality and Safety
1
(main area); Sustainable
Development, Global Change and Ecosystems
2
;

10
1. />2. />Life Sciences, Genomics and
Biotechnology for Health
3
, and
Scientific Support to Policy
4
.
The first priority had a specific
‘Environmental Health Risks’
area, from which small and
large-scale research projects
and networks have been funded
related to many environment and
health issues such as cancer or
allergies/asthma. A large majority
of these projects are ongoing.
The Sustainable Development,
Global Change and Ecosystems
priority devoted a large effort on
the improvement of integrated
environment and health risk
assessment as well health impact
assessment including valuation
and cost/ benefit analyses were
also funded in the Scientific
Support priority. Genomics and
Biotechnology for Health sponsored epidemiological
and toxicological studies as well as projects related
to alternatives to animal testing. Finally, the so-called

‘Priority 8’ (Scientific Support to Policy) has funded
a number of research projects with direct relevance
to policy making.
One of the main drivers for research in FP6 was the
European Commission’s Environment and Health
Action Plan, adopted in 2004
5
. The plan aims to
improve our understanding of the links between
environmental factors and health. It was partially
inspired by a need to more fully engage policy
with new research results coming out of FP5 and
its precursors. Implementation of the Action Plan’s
goals was started with FP6 via the funding of several
large projects referred to above.
FP6 also saw the introduction of integrated
environment and health risk assessment
methodologies. This move
towards integrated risk
assessment reflected lessons
learnt in FP5 about the
complexity and interaction
between risks. It also offers a
better way to link environment
and health data in a manner that
supports policy-making. This is
also a systematic approach,
incorporating the identification
of pollution sources, exposures
(including the use of human

biomonitoring pioneered
in FP5), making links with
health effects, and economic
valuation. The development
of economic valuation models
and tools for assessing the
impact of policies is a vital link
for effective regulation.
Although funding for environment and health issues
was higher in FP6, there were fewer projects,
though this was compensated by their size. In FP6,
an increased emphasis was put on integrated risk
assessment, as described above, and multiple
stressor effects. Less funding was given to
environmental stressors such as noise, air pollution
and electromagnetic fields in FP6 as the results from
ongoing projects in FP5 were awaited in order to
direct further research. In addition, projects covering
risk/ benefit and cost/ benefit gained in importance
as did those relating to climate change – an area
that had first been investigated during FP5.
We are now entering FP7, which was launched at the
beginning of 2007. This seven-year programme sees
a significant boost in overall funding and environment
and health is identified as one of three activities under
the theme “Environment (including Climate Change)”
of the Cooperation Programme
6
.
11

3. />4. />5. />6. />Three priorities have been identified for environmental
and health activity:
Health effects of exposure to emerging
environmental stressors
Climate change and health
Novel approaches to environment and health risk
assessment
Other FP7 themes – in particular “Health” and
“Food, Agriculture, Fisheries and Biotechnology”
– will complement environment and health activities
and there may be opportunities for joint calls.
FP5 was an important precursor in the field of
environment and health, delivering new knowledge,
pointing the way for further research and setting the
basis for policy-making. However, a lot of information
on how environmental factors interact with human
health is still required. In many ways the more
answers we find, the more questions we generate!
The integrated approach, focusing on multiple
stressors, pathways and effects, will be particularly
valuable in yielding definitive insights on the extent
to which environmental factors impact our health at
both the individual and societal levels.
Environment and health
issues: joint effort at EU
and global levels
Reflecting the complexity
of issues involved, the
actors involved at the
Community and global level

are numerous. As regards
FP5 and FP6, within the
Research Directorate-
General, two directorates
were chiefly involved with
sponsoring environment and health-related
r
esearch activities: Directorate E (Biotechnologies,
Agriculture, Food) and Directorate I (Environment).
In FP7 Directorate I is taking the lead, with the
Health and Food Directorates playing a lesser
role. DG Information Society and Media will also
fund research in this area, for example concerning
personal exposure monitoring.
Other European actors that play significant roles
in environment and health issues are DG Joint
Research Centre
7
, the European Environmental
Agency (EEA)
8
and the European Food Standards
Agency (EFSA)
9
. EEA and EFSA have been
important end-users of research funded by the
Framework Programmes.
The main policy-making Directorate-Generals that
benefit from the research input are Environment
10

,
Health and Consumer Protection
11
and Enterprise
12
.
European research also interacts with other national
and international endeavours. In particular, the
European Commission works actively with bodies such
as the World Health Organisation (WHO) on initiatives
like the Children’s Health and Environment Action
Plan for Europe (CEHAPE)
13
and the Organisation for
Economic Co-operation and Development (OECD)
Task Force on Endocrine Disrupters.
12
7. />8. />9. />10. />11. />12. />13. />Air pollution-related
health impacts
European context
Although for most parts of Europe dense industrial
“smog” is no longer a common feature of our
larger cities due to various clean air regulations, air
pollution, though less visible, is still a major health
hazard. In particular the significant recent increases
in traffic volumes has brought with it new risks.
Air pollution includes dust, smoke and gases
in the air that we breathe. Such pollution can
have natural sources like volcanic eruptions or

traditional agricultural practices, but the main
day-to-day contributors are from traffic and
industry. In addition to outdoor pollution, there is
also indoor pollution, with a long list of potential
contributors. These include: ambient air pollution,
dust, inefficient combustion of fuel for cooking and
heating, household chemical products, fabrics and
coverings, and, in particular, tobacco smoke.
Air pollution can be harmful to all the vital organs
of the human body. It can penetrate the lungs and
transfer into the blood system moving around the
body through the blood vessels to the heart and into
the immune system. This means that air pollution
does not only aggravate respiratory problems and can
cause asthma and other allergic responses, but can
also be involved in cardiovascular health problems.
The net result is that in cities across Europe, air
pollution may be causing tens of thousands of
premature deaths from respiratory and cardiovascular
diseases annually. Indoor and outdoor air pollution are
the environmental factors with the greatest impact
on general health in Europe and are responsible for
the largest burden of environment-related disease.
Recent estimates indicate that 20 million Europeans
suffer from respiratory problems every day
14
.
Particulate matter and especially small particles
with diameter less than 2.5 micrometres (μm) – also
known as PM2.5 – are associated with increased

mortality, especially from cardiovascular and
cardiopulmonary diseases.
Asthma is increasing all over Europe, although the
rate of increase has considerable variation across the
continent. The cost to European society of asthma is
estimated at €3 billion per year
15
. The annual increase of
childhood asthma/allergy cases in Europe is estimated
at 5%; thus by 2050 one out of two European children
will be likely to suffer from allergic disease.
FP5 projects – Revealing the link between
air pollution and health
Among the environment and health projects funded
by FP5, the 20 projects listed here are related directly
Air Pollution-Related Environmental Stressors
Common outdoor and indoor pollutants include:

Gases such as ozone, carbon monoxide, nitrogen oxides, sulphur dioxide;

Particulate matter, mineral ash, smoke, and engine exhaust fumes; and

Tobacco smoke, dust containing various allergens, substances emanating from building materials
and consumer products.
14
14. “Environment and Health”, EEA Report No. 10/2005 />15 “Environment and Health”, EEA Report No. 10/2005 />to various aspects of air pollution.
Their aim was to reveal casual
links between pollutants and
health effects and provide tools
for measuring real life exposures

and effects. The projects
favoured the development
of protective measures and
have fed into the process of
regulating pollutant emissions.
European Commission funding
for these projects represented
around 17% of the total budget
allocated to environment and
health in FP5.
Research results
The FP5 projects undertaken in this area can be
classified into four groups:
Air pollution and respiratory health – 11 projects
Air pollution and carcinogenic or genotoxic
effects – 4 projects
Air pollution and cardiovascular effects –
3 projects
Air pollution and networking, risk assessment
– 2 projects
The findings of research on respiratory health
highlighted correlations between asthma and
allergies and cooking with gas, smoking and some
domestic cleaning sprays. In particular ensuring
adequate ventilation for domestic gas cookers
to reduce ambient nitrogen oxides could have a
significant impact on indoor air quality.
The invasive nature and damage caused by small
particles (PM10, PM2.5 etc.) in the lungs and other
areas of the body were extensively investigated.

Although particle samples vary widely across
Europe, correlations between inflammatory lung
responses and particle pollution were observed and
also related to genotoxicity. Some particles were
found to have high poly aromatic hydrocarbon and/
or arsenic content.
All the projects accumulated further evidence
that reinforces the need to regulate to reduce the
concentration of these particles being produced by
human activities – in particular those emanating from
diesel transport. Smoking and the use of solid fuel
for residential heating were also significant sources.
The emerging science of biomarkers was shown
to be very useful as a method for the early
diagnosis and assessment of respiratory disease.
New methods were developed to rapidly identify
potential exposure to occupational allergens. New
accurate calibration methods for lung diagnostic
equipment will also help medical intervention and
clinical support in this area.
The potential for carcinogenic activity of polycyclic
aromatic hydrocarbons was demonstrated including
DNA damage and inhibition of repair processes;
similar DNA damage was also observed for smokers.
Detrimental genotoxic effects of environmental
pollution were also shown in children with
chromosomal aberrations most affected by chemical
pollution whilst other genetic effects were influenced
by environmental tobacco smoke and smoking
during pregnancy. Adverse genetic and carcinogenic

effects of traffic pollution were found, in particular for
ex-smokers (up to 10 years after quitting the habit),
and further evidence for the undesirable health
effects of environmental tobacco smoke.
15
Further evidence to assist regulation of vehicle fuel
was found when investigating cardiovascular effects.
There was some contradictory evidence on the
effects of particles effects, however high sulphur fuels
– now effectively regulated out of the transport market
– were shown as a primary trigger for DNA damage.
The significant impact of fine airborne particles and
ozone leading to increasing premature death gave
further evidence for regulation and preventative
measures, while new markers for and understanding
of mercury exposure will help public protection.
Further work
Health-related air pollution research in FP6 is focused
in three ongoing projects ENVIE
16
(a coordination
action on indoor air quality and health effects),
PRONET
17
(Policy reductions option network that
will exchange useful practices at a regional level
on indoor air quality and road traffic hazards), and
CAIR4HEALTH support action (Clean Air for Health
– research needs for sustainable development
policies).

Air pollution also features as an aspect of the large
integrated risk assessment project INTARESE
18

(integrated assessment of health risks of
environmental stressors in Europe) and a variety of
other such projects.
For FP7, research on air pollution-related activities
may be funded under the Health (cohort studies),
Information and Communication Technologies
(personalised exposure measurement devices) and
Energy and Transport themes. However, the main
focus of activity concerning health impacts of air
pollution will be the Environment (including climate
change) theme
19
.
FP5 projects list
Brief details of each project in this area are given
below. For more details please see the individual
project summary sheets.
Air Pollution and Respiratory Health
AIRALLERG – Effects of Outdoor and Indoor
Air Pollution on the Development of Allergic
Disease in Childr
en.
Variations in levels of indoor nitrogen dioxide (NO
2
)
and nitrous acid (HONO) were correlated with use

of gas for cooking and smoking; other correlations
included floor type with levels of floor dust amounts
and biocontaminants.
[Page 44]
BIOAIR – Longitudinal Assessment of Clinical
Course and Biomarkers in Severe Chronic
Airway Disease.
This in-depth study has provided new insights on
the mechanisms involved and interventions possible
for patients suffering these widespread debilitating
diseases.
[Page 46]
ECHRS II – European Prospective Study on
Envir
onment, Allergy and the Lung.
A large survey found asthma symptoms are more
common in those exposed to gas cooking and
domestic cleaning sprays.
[Page 48]
HELIOS – Biomarkers for the Non-invasive
Assessment of Acute and Chronic Effects of Air
Pollutants on the Respiratory Epithelium.

No evidence of chronic toxic effects on lung function
that correlated with differences in air quality across
Europe was found. In particular no effect due to
ozone. However, trichloramine above a certain
threshold has major effect on children’s lungs.
[Page 50]
HEPMEAP –

Health Effects of Particles from
Motor Engine Exhaust and Ambient Air
Pollution.

Particulate matter collected in this project varied
widely across Europe but coarse and fine particles
appear to have similar toxic effects when compared
on an equal mass basis.
[Page 52]
16
16 />17 www.proneteuropa.eu
18 www.intarese.org
19 />MOCALEX – Measurement of Occupational
Allergen Exposure.
Methodologies were developed to analyse for a
variety of allergens: nasal sampling of employees
was shown as a feasible approach for short-term
measurements and a lateral flow immunoassay was
developed as a rapid test method for occupational
allergen exposur
e. [Page 54]
PAMCHAR – Chemical and Biological
Characterisation of Ambient Air Coarse, Fine
and Ultrafine Particles for Human Health Risk
Assessment in Eur
ope.
High PM10-2.5 concentration in samples correlated
with strong inflammatory lung responses; increased
health risks were suggested in communities with
heavy use of solid fuel for residential heating.

[Page 56]
PATY – Pollution and the Young: Combined
Analyses of Cross-sectional Studies of
Respiratory Health of Children and Air Pollution.
Uncertainties remain about the impacts of air
pollution on the young. By bringing together a large
number of comparable data, which have already
been collected, this study offers a cost-effective
route to improved assessments of the effects of the
long term impacts of air pollution using data from
12 countries and a combined study size of over
60
000 children. [Page 58]
PAWG –
Programmable Air Wave Generator with
Controlled Temperature, Pressure, Humidity and
Air W
ave Frequencies for Calibration.
This project has developed new methods and tools
for accurate calibration of lung diagnostic and other
medical equipment. This is important for efficient
and ef
fective diagnosis and treatment. [Page 60]
RAIAP – Respiratory Allergy and Inflammation
due to Ambient Particles – A Europe-wide
Assessment.
Chemical characterisation of fine and coarse
samples showed distinct differences across
Europe and allergy and inflammation responses
were measured – the inflammation response was

gr
eatest for coarse samples. [Page 62]
RUPIOH – Relationship between Ultrafine and
Fine Particulate Matter in Indoor and Outdoor
Air and Respiratory Health.

It was found that using a central urban sampling point
allowed a good estimate for temporal distribution
across a metropolitan area; little difference in particle
concentration between central and suburban outdoor
sites was found, but there was little correlation
between outdoor and indoor air concentrations.

[Page 64]
17
Air Pollution and Genotoxic or
Carcinogenic Effects
AMBIPATH – Mechanism-based Approaches to
Improved Cancer Risk Assessment of Ambient
Air Polycyclic Aromatic Hydrocarbons (PAHs).
The mutagenic potency of PAHs was found to parallel
their carcinogenic potency and mixture studies show
evidence of additive effects - in some cases at doses
close to those of envir
onmental relevance. [Page 66]
CHILDRENGENONETWORK – European
Network on Children’s Susceptibility and
Exposure to Environmental Genotoxicants.
Age and exposure-related increases in a number of
cytogenetic endpoints in children with increase in

environmental pollutants (chemicals and tobacco
smoke) wer
e found. [Page 68]
EXPAH – Effects of PAHs in Environmental Pollution
on Exogenous and Endogenous DNA Damage.
DNA adducts were found to be more abundant in
exposed population (compared to control group)
and exposure to PAHs significantly influenced the
DNA repair process in the subjects’ lymphocytes.
[Page 70]
GEN-AIR – Molecular Changes and Genetic
Susceptibility in Relation to Air Pollution and
Environmental Tobacco Smoke: a Case-Control
Study in Non-smokers Nested in the Epic
Investigation.

High exposure to traffic pollution increased potential
for lung cancer in ex-smokers with no observable
effect on people who had never smoked; in
addition, DNA adducts seem to be associated with
subsequent risk of lung cancer
. [Page 72]
Air Pollution and Cardiovascular Effects
AIRGENE – Air Pollution and Inflammatory
Response in Myocardial Infraction Survivors:
Gene-environment-interactions in High-risk
Group.
No association was found between ambient
air pollution and risk indicators for heart attack,
suggesting that medication, such as statins, may

be acting protectively and susceptibility was heavily
r
elated to personal characteristics. [Page 74]
HEAPSS – Health Effects of Air Pollution on
Susceptible Subpopulations: Ultrafine Particles
and Myocardial Infarction.
This study did see a relation
between air pollution and heart
attacks although results with
mortality were less consistent:
total particle number and carbon
monoxide concentration were
the most strongly related with the
health ef
fects studied. [Page 76]
MAAPHRI – Multidisciplinary
Approaches to Airborne Pollutants
Health-Related Issues.
High sulphur fuels were shown to
be the main toxic component to
trigger DNA damage and systemic
inflammation. A new danger with
increased NO
2
emissions was
identified that can trigger acute
car
diorespiratory impacts. [Page 78]
18
Air Pollution and Networking,

Risk Assessment
AIRNET – A Thematic Network on Air Pollution
and Health.
Impact assessment revealed that ozone and fine
air particle pollution could result in several tens to
hundreds of thousands of premature deaths each
year acr
oss Europe. [Page 80]
EMECAP – European Mercury Emission from
Chlor
-alkali Plants.
This study has increased our knowledge of
environmental exposure to mercury, identified markers
for early biological effects and developed innovative
analytical devices for large area monitoring.

[Page 82]
19
Chemicals
and health impacts
Friends or foe?
HPC - Halogenated Phenolic Compound
PAH - Polycyclic Aromatic Hydrocarbon
PCB - Polychlorinated Biphenyl
POP - Persistent Organic Pollutant
NO
2
- Nitrogen dioxide
European context
Chemicals are ubiquitous. Everything in our

world is made of chemicals including all living
organisms, our food and the air we breathe.
Our environment and ourselves are essentially
a complex, interacting mixture of chemical
molecules. In addition to natural environmental
chemicals, human activity and ingenuity has
added new synthetic molecules.
This technological advance has done much to
enhance European quality of life over the last
century, but has resulted in the release of many
potentially toxic substances into the environment,
some of which contaminate the air and soil, and
find their way into ground and coastal waters.
Chemicals enter our environment through many
human activities. Mining sites can release heavy
metals, acids and organic compounds. Combustion
plants, waste incinerators, heating systems and the
internal combustion engine emit acid gases, ozone
precursors and persistent organic pollutants such
as dioxins and furans. Mercury and volatile organic
compounds can evaporate from old industrial sites.
Industries and households discharge chemicals
– including synthetic hormones derived from the
wide-scale use of the birth control pill – into sewers
and thus into rivers. Farmers use synthetic fertilisers
and pesticides over large areas. In and outside our
buildings, at home, work or play, our materials,
furnishings and fibres are all coated with paint,
flame retardants and fungicides.
Once chemicals are in

the environment they can
move around by a variety of
mechanisms. Some react with
light or other chemicals, some
are degraded, but others persist
for many years. Following
ingestion by living organisms
some chemicals can become
‘bio-accumulated’ and become
more concentrated as they move
up the food chain. Unexpectedly
high (and toxic) concentrations
20
can be achieved in predator species and humans.
Other mechanisms have caused concentration of
persistent chemicals in unpredicted regions such
as the Arctic and Antarctic.
More than 10 million individual chemicals have been
identified, of which some 100 000 are registered in
the European Union and about 30 000 of these are
used regularly in industrial processes. Some are
known to be harmful to humans, wildlife and/ or the
environment, but for others toxicity and ecotoxicity
data are not readily available.
FP5 projects –
Towards a better understanding
Understanding the effects of chemical contaminants
on human health was a major priority for FP5 and a
significant minority of all projects in the Environment
and Health area were tasked to investigate this area.

Some focused explicitly on the chemicals and many
more examined their effects and interactions.
The projects focused on a number of issues:
Hazard and risk characterisation of various
groups of chemicals including heavy metals,
endocrine disrupters (please see box on
Endocrine Disrupters), dioxins, PCBs, styrene,
and asbestos;
Epidemiological approaches to exposure
assessment including the use of biomarkers,
birth cohorts etc.;
Development of new methods and tests for
analysis of toxicity;
Exploring the role of genetic susceptibility in
disease development;

Investigation of mechanisms of disease development
in various organs in ‘real life’ exposure situations,
i.e., low doses and multiple exposures.
European Commission funding for these projects
represented over 50% of the total budget
allocated to environment and health in FP5. In
fact, around 20% of the budget was allocated
to investigation of projects focused on endocrine
disruption alone.
Research results
The FP5 projects undertaken in this area have been
classified into four groups:
Chemicals with Reproductive and Developmental
Effects – 15 projects

Chemicals and Genotoxic and Carcinogenic
Effects – 8 projects
Chemicals with Multiple Effects – 3 projects
Chemicals: Risk Assessment, Testing and Models
– 15 projects
Endocrine-related reproductive effects were widely
studied showing correlations especially between
exposure to a variety of chemicals and reproductive
parameters in a variety of animal models and also
in human studies. In particular, a significant new
hypothesis called testicular dysgenesis syndrome
was developed that provides an explanation for
a plausible link between environmental factors
including endocrine disrupting chemicals and the
21
What are Endocrine Disrupters?
Endocrine disrupters are chemicals that interfere
with the functions of the endocrine (or hormo-
nal) system of organisms. Chemicals that exhibit
endocrine disrupting activity can be natural or
synthetic hormones or other natural or synthetic
chemical compounds. Potential endocrine dis-
rupters include the synthetic chemicals: polychlo-
robiphenyls, dioxins, persistent pesticides and
some chemicals used in the plastics and deter-
gents industry.
Potential health effects of endocrine disrupters
include breast, prostate and testicular cancer,
urogentital malformations and reduced male fer-
tility. Exposure in children may affect thyroid and

immune systems and alter physical and mental
development. Endocrine disrupters can have a
significant effect on the health of humans and
other organisms, so represent a major, medical,
environmental and social concern.
observed medical outcomes such as reduced
semen quality or testicular cancer.
Neurobehavioural effects of some chemicals were
observed. In particular, elevated polychlorinated
biphenyl (PCB) serum concentration was correlated
with poor sensomotor function in children. In
contrast other studies, found no ill effects and/
or unacceptable exposures for brominated
halogenated phenolic compounds and pesticides.
Some potential androgenic/ anti- androgenic
chemicals were shown to have clear effects in animal
models including invertebrates but acceptable daily
dietary intake levels for humans were not found to
be exceeded in Europe.
The carcinogenic risk of arsenic was investigated,
mechanisms for its effect on DNA proposed and a
lower limit for impact due to oral exposure determined.
New biomarkers for cancer were established
including early identification of high risk individuals.
Potential health risks from wood dust were assessed
and molecular mechanisms proposed. Asbestos-
substitute materials were evaluated and while all
samples could induce markers for lung inflammation
two showed potential genotoxic effects.
Chemicals that interfere with cell division were

studied and a battery of new tests to determine the
biological and health significance of such chemicals
developed – the same study found that current
levels of exposure to bisphenol A in Europe did not
represent a significant health threat. Encouraging
data showing reduced workplace exposure to
process dust in the rubber industry was also found.
Work on multiple effects of chemicals focused, among
others, on dioxin which highlighted developmental
effects (such as tooth development) as highly
sensitive while cancer effects were less sensitive
than previously believed. Work on multiple effects of
endocrine disrupters gave contradictory results with
some research demonstrating no morphological
effects, while others found effects, elaborated
mechanisms and proposed risk assessments for
non-reproductive organs in humans.
New methods such as bioassays and models such as
transgenic animals for risk assessment provide valuable
tools and can give new insights on mechanistic effects.
New methods for estimating the effects of endocrine
disrupting mixtures, biomarkers and other methods for
endocrine detection and characterisation, and effects of
endocrine active substances on bone development were
developed. Better prediction of pesticide concentrations
in the environment and their detection with biosensors
was demonstrated. Studies of how chemicals are
absorbed by the skin also yielded new tools that will be
of use in REACH and workplace risk assessment.
Other new predictive method development included

new “DNA chip” technology for immunotoxicity
testing, fragrance allergy testing that reduced
animal use and provided more information on
sensitisers, neurotoxic effects of volatile chemicals
and biomonitoring for occupational exposure to
styrene. The effect of toxic metals and insecticides
on the immune function, pregnancy and foetal
development was also studied.
Further work
Considerable resources continued to be invested in
research on chemicals and health during FP6 and will
continue during FP7. Focus is shifting in particular on
early exposures to multiple chemicals and their long-
term health impacts in vulnerable populations such as
children. New efficient methods for genotoxic analysis
and methods for risk assessment of chemicals – in
particular computational or in vitro methods – that
reduce, refine or replace the use of animal testing are
of particular interest both to gain new knowledge and
as supports to significant new chemicals regulation
(REACH) aimed at increasing public safety.
FP5 projects list
Brief details of each project in this area are given
on the next page. For more details please see the
individual project summary sheets.
22
Chemicals with Reproductive and
Developmental Effects
ANEMONE – Assessment of Neurobehavioural
Endpoints and Markers of Neurotoxicant

Exposures.
PCB concentration in children from the Faeroe islands
were on average 60% those of their mothers but
this increased with duration of breastfeeding. Their
performance in neurobehavioural tests decreased with
the extent of exposure to prenatal methyl mercury.

[Page 84]
BEEP – Biological Effects of Environmental
Pollution in Marine Coastal Ecosystems.
A range of biomarkers were developed to evaluate
pollutant effects on the reproductive health of mussels
and fish to give a standardised array of biomarkers
for use in international monitoring programmes.

[Page 86]
BIOCET – Bioaccumulation of Persistent
Organic Pollutants (POPs) in Small Cetaceans
in European Waters: Transport Pathways and
Impact on Reproduction.
POP levels in female common dolphins were linked to
diet, area and reproductive status; POP concentrations
were commonly recorded above levels where effects
on r
eproduction would be expected.
[Page 88]
COMPARE – Comparison of Exposure-Effect
Pathways to Improve the Assessment of
Human Health Risks of Complex Environmental
Mixtures of Organohalogens.

The study concluded that there is a sufficient
margin of safety for brominated HPCs (halogenated
phenolic compounds) and current exposure of
humans to such HPCs does not pose any risk for
adverse health ef
fects. [Page 90]
COMPRENDO – Comparative Research on
Endocrine Disrupters: Phylogenic Approach and
Common Principles focusing on Androgenic/
Anti-androgenic Compounds.
The level of contamination of food by pesticides,
organochlorine and organotin compounds was
found not to exceed Acceptable Daily Intake
levels; however, observations of the effects of
these chemicals on a variety of animal models
has resulted in some new Predicted No Effect
Concentrations for risk assessment.

[Page 92]
ENDISRUPT –
Identification of Critical Rat
Testicular Genes altered after Fetal Androgenic
Disruption by Flutamide: Use of DNA
Microarray.
This project showed that in utero exposure to
anti-androgenic chemicals induced long-term
programmed cell death in testicular germ cells. A
health risk associated with foetal exposure to such
endocrine disrupters was suggested.
[Page 94]

ENDOMET – Dysregulation of Endogenous
Steroid Metabolism Potentially alters Neuronal
and Reproductive System Development: Effects
of Environmental Plasticisers.
A number of plasticisers were demonstrated to have
a variety of effects on gene regulation, cell signalling
and reproduction. The project provided new in
vitro test protocols that can identify the endocrine
disrupting potential of chemicals.
[Page 96]
ENV REPROD HEALTH – Increasing Incidence
of Human Male Reproductive Health Disorders
in Relation to Environmental Effects on
23
Growth- and Sex Steroid Induced Alterations in
Programmed Development.
The project showed significant differences in
sperm quality between countries (Denmark and
Finland) with differences reflecting incidence of
testicular cancer and other genital malformations. A
significant new hypothesis was proposed: testicular
dysgenesis syndr
ome. [Page 98]
EUROPIT – Toxicological Evaluation of the
Immune Function of Pesticide Workers, a
Europe-wide Assessment.
No clinical effects of exposure to pesticides were
observed although some subtle immune alterations
wer
e noted. [Page 100]

EXPORED – Multi-organic Risk Assessment of
Selected Endocrine Disrupters.
Analysis showed that exposure to PBDE
(polybrominated diphenyl ethers) was associated
with increased risk of the male genital malformation
cryptorchidism. Associations with other individual
chemicals were not clear but a combined statistical
analysis of the eight most abundant persistent
pesticides showed levels in breast milk were
significantly higher for boys with cryptorchidism.
[Page 102]
FIRE – Risk Assessment of Brominated Flame
Retardants as Suspected Endocrine-Disrupters
for Human and Wildlife Health.

Tetrabromobisphenol A (TBBPA) is known to act on
the thyroid gland accompanied by neurobehavioural
changes, this project demonstrated endocrine
disrupting activity in both human and fish subjects.
[Page 104]
GENDISRUPT – Genetic Markers and
Susceptibility to the Effects of Endocrine
Disruptors during Mammalian Testis
Development.
Extensive microarray analysis of the genetic effect
of selected endocrine disrupters on testicular cells
showed that mono ester phthalate (MEHP) produced
the highest deregulation. The findings support a
genetic basis for human male infertility and the
project developed an in vitro assay to identify and

quantify estrogenic activity of endocrine disrupters.

[Page 106]
INUENDO – Biopersistent organochlorines
in Diet and Human Fertility. Epidemiological
Studies of time in Pregnancy and Semen Quality
in Inuit and European Populations.
Concentration of polychlorinated biphenyls (PCBs)
in serum related to reduced fertility in Greenland
but not in Caucasian couples. High PCB exposure
associated with 50% increase in sperm with
damaged DNA in Caucasian males; however, no
correlations were seen between fertility and other
chemicals including POP markers.
[Page 108]
PBDE-NTOX – Developmental Neurotoxicity
of Polybrominated Diphenyl-ethers (PBDE):
Mechanisms and Effects.
The project demonstrated a link between
gestational or early postnatal exposure to PBDE
and interference with a number of neurobehavioural
experimental endpoints.
[Page 110]
PCBRISK – Evaluating Human Health Risk from
Low-dose and Long-term PCB Exposure.
A Slovakian child cohort showed significant
associations between PCB serum concentrations
and performance in sensomotor tests. Significant
effects also demonstrated on thyroid activity, tooth
development and hearing.

[Page 112]
24
Chemicals with Genotoxic and
Carcinogenic Effects
ASHRAM – Arsenic Risk Assessment and
Molecular Epidemiology.
Positive association was found between exposure
to arsenic and three types of cancer: basal cell
carcinoma of the skin is associated with lifetime
average arsenic concentration, bladder cancer with
cumulative arsenic dose, and kidney cancer with
peak arsenic daily dose.
[Page 114]
ASRISK – The Mechanistic Basis for providing a
Realistic Cancer Risk Assessment for Exposure
to Inorganic Arsenic within the European
Community.
Human studies showed that induction of micronuclei
in human white blood cells was the most sensitive
biological indicator for oral exposure to arsenic. The
project also shed light on the mechanism by which
arsenic disrupted DNA repair and other processes
such as r
eplication. [Page 116]
CANCERRISKBIOMARKERS – Cytogenetic
Biomarkers and Human Cancer Risk.
The frequency of chromosomal aberrations was
shown to be a potential biomarker for cancer, in
particular for stomach and colorectal cancers. The
project also suggested that frequency of micronuclei

may have value as a pr
edictor. [Page 118]
EXASRUB – Improved Exposure Assessment
for Prospective Cohort Studies and Exposure
Contr
ol in the Rubber Manufacturing Industry.
This comprehensive database shows a clear
downward time trend for inhalable and respirable
rubber process dust with average occupational
exposure in most European countries now below
exposur
e limits.
[Page 120]
FIBRETOX – Mechanisms of Toxicity of Asbestos-
Substitute Mineral Fibres: New Approaches to
Hazard and Risk Assessment.
All four fibres tested could induce changes in
early biomarkers for lung inflammation, but only
two (amosite, RW1) induced potential persistent
inflammation with associated increased DNA
damage.
[Page 122]
OXEXRISK – Oxidative Stress and Chronic
Diseases: Exocyclic DNA Adducts as Markers
for Disrupted Genomic Integrity and Risk.
The project provided further validation for the use
of etheno-adducts as promising biomarkers in
aetiology and cancer prevention research including
early identification of risk groups or individuals.
[Page 124]

PEPFAC – Protection of the European Population
from Aneugenic Chemicals.
Aneugenic agents affect cell division mechanisms and
can result in the loss or gain of whole chromosomes.
This project developed a range of methods to detect
and assess the effects of such chemicals and
showed that bisphenol A is not a significant health
risk at its curr
ent levels. [Page 126]
WOODRISK – Risk Assessment of Wood Dust:
Assessment of Exposure, Health Effects and
Biological Mechanisms.
Wood dust appears to induce pulmonary
inflammation processes, generate reactive
oxygen species and genotoxic effects. The
project also gave estimates of current workplace
exposur
e rates in Europe.
[Page 128]
Chemicals with Multiple Effects
ESTROGENS & DISEASE – The Impact
of Developmental Exposure to Weak
(Environmental) Estrogens on the Incidence of
Diseases in Target Organs later in Life.
Although no significant morphological effects of
oestrogen exposure in testis, ovary, prostate,
brain or mammary glands was found, the general
conclusion was that exposure to low dose oestrogen
before birth can cause subtle, long-term changes in
the expression of specific genes and proteins.

[Page 130]
25