endocrine disruption
health risk of
endocrine disruption
HUCPA
meeting
26.
April 2013
Dr. Zoltan L. Marcsek, Ph.D., C.Sc.
Department of Chemical Safety Research,
National Institute of Chemical Safety, Hungary
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IPCS
2002 |
UNEP/WHO
2012 |
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Pesticide Impacts on
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EC DG Environment:
January 2013. State
of the art assessment of endocrine
disrupters Andreas Kortenkamp, Brunel
University Michael Faust, F+B Env
Consulting Olwenn Martin, Rebecca
McKinlay, Richard Evans, Frances Orton, Erika Rosivatz Brunel
University |
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human and wildlife health
depends on the ability to
reproduce and develop
normally
this is not possible without a healthy
endocrine system
neuro-endocrine system: controls most
processes
neuronal signaling
hormonal signaling
responsive tissues
hormones - signal
molecules
polypeptides - non-polypeptides
chemical sigals
the endocrine system in human
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non-polypeptide hormones
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endocrine disruptors
definition (UNEP/WHO)
“An endocrine disrupter
is an exogenous substance or mixture
that alters
function(s) of the endocrine system and
consequently causes
adverse health effects
in an intact organism, or its
progeny, or (sub)populations.”
not all EAS are EDs
“A possible endocrine
disrupter is a chemical that is
able to alter the functioning of the endocrine
system
but for which information
about
possible adverse consequences
of that alteration
in an intact organism is
uncertain”.(OECD)
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normal endocrine function: - Your favourite chocolate bar increases blood level of glucose - Increase in glucose causes insulin to be released - Insulin causes tissues to take up glucose (this is NOT
“homeostasis”) Thus, a chocolate bar is not an ED |
an ED is an exogenous chemical, or mixture of chemicals, that interferes with: - The ability of glucose to cause insulin release - The ability of insulin to interact with its receptor - The ability of insulin-receptor interaction to cause glucose uptake
and/or utilization |
example: an ED is an exogenous chemical, or mixture of chemicals, that:
- Interferes with thyroid
hormone action during brain development and reduces the intellectual potential
of the individual and population
- Interferes
with fat development, predisposing the individual and population to obesity and
diabetes
evidence for endocrine disruption in humans
– endocrine disruptors and:
– adrenal disorders
– bone disorders
– thyroid related diseases and disorders
– neurodevelopment
– immune function,
– hormone related cancers diseases and disorders
and wildlife
– sex ratios (T Vartiainen, L Kartovaara,J Tuomisto:
Environmental Chemicals and Changes in Sex Ratio: Analysis Over 250 Years in
Finland. Environmental Health Perspectives, Vol 107,813, 1999)
testicular cancer increases
in "the Nordic Countries"
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• Incidence increases
– the most frequent malignancy in young males
• in the past 30 yrs
3-4-times (+) increase in Scandinavia
high fish consumption countries - Atlantic coast, Baltic
& North sea
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contamined
seawater?
• no association with smoking
• recognized environmental factors
• association: decreased
andogenic effect in fetal age
• association: DDE/DDT, several
PCB, PBDE, organo-chloro pesticides
• no information: antiandrogenic EDs (pl. phalates,
azol-fungicides, etc)
• no information: mixture effects, combined effects
• no experimental model
ED exposition - time frame -
"window"
critical windows of ED
exposure
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most sensitive: from conception till puberty (testicular differentiation)
dyslexia, dysgraphia, learning skills
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irreversibility !
low dose effects
and thresholds
• Problems with
reproducibility over-emphasised in the past
• Estimating low dose
effects – new perspectives (NRC 2008 “Silver Book”)
– Very large
epidemiological studies – thresholds not observed
– Absence of
thresholds at the population level
• Pre-existing
(endogenous) exposures – no thresholds – relevance to estrogens
methods
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OECD Conceptual Framework (for identification of EDs) is used as starting point
It comprises in vitro and in vivo test methods that are (or soon will be) validated in 5 Levels
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DNA "expression
profiling" in fish - DNA chip
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needs many data (historical data) and validation
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Which are the Endocrine Disrupting Chemicals?
Property/Behaviour based grouping
● Persistent & Bioaccumulativechemicals
– POP (Stockholm Convention)
– Other P and B chemicals (Lipophilic and Proteinophilic)
● Semi-persistent chemicals
– Chemicals with high persistency but without bioaccumulation potential
● Pseudo-persistent chemicals
– Chemicals for which continous exposure may occur, leading to stady state
levels in exposed organisms
● Metals and metalloids
Multiple Routes of EDC Exposure
• ED exposure occurs via:
• ingestion of food, dust, and water
•inhalation of gases and particles
in the air
•dermal uptake
• Pregnant
females can transfer
EDs to the developing fetus through the placenta and to offspring in mother’s milk,
which may affect development of her offspring and also their
offspring over several generations (i.e., transgenerational effects).
• Multiple routes of exposure to a variety of EDs means that humans
and wildlife are exposed to multiple EDs at the same time.
• Animal studies show exposures to mixtures of EDs produce additive effects, which can occur even when the
chemicals do not produce effects individually.
more than 800 chemicals with ED properties
the majority of
all chemicals in use are not tested
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Thank you!