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Contenuto archiviato il 2024-05-14

Assessment of human risk for adverse effects of endocrine active environmental organohalogen contaminants.

Obiettivo

The objective of this project is to provide a scientific basis for assessment of risks for adverse health effects, with special emphasis on developmental effects in human infants, following environmental exposure to endocrine active organichalogenated substances. The efforts will be concentrated on hydroxylated PCB and related phenolic organohalogens with a high fetal accumulation potential.

We will develop a two-tired method for identification of potential endocrine disruptors in human samples. The
method will involve bioassays, for analysis of endocrine activity, and sophisticated chemical analysis, for
structural identification of "unknown" compounds that elicit endocrine activity in the bioassays.
We will synthesise and chemically characterise "unknown" OHS with structural resemblance to thyroid and/or
sex hormones that will be indicated by the bioassays as potential endocrine disruptors. These synthesised
compounds will be used as standards for analytical purposes and as model compounds in the bioassays, X-ray
crystallography and toxicological studies.
We will provide detailed information on structural requirements for endocrine disrupting effects; structure activity relationships. This will be achieved by organohalogen-binding competition studies using hormone
binding proteins (transthyretin (TTR), nuclear thyroxine (T3) receptor and oestrogenic receptor (ER) in
combination with X-ray crystallography studies for structural refinement of the OHS - protein interactions. In
addition, the functionality of the "putative" endocrine disruptors will be measured in thyroid- and estragen-linked
reporter gene expression systems.
We will study the toxicological impact of identified endocrine disrupting OHS, such as 4-hydroxy-2,3,5,3',4'-
pentachlorobiphenyl and its parent compound PCB 105. The effects of perinatal exposure to these compounds
on hormone metabolism, neurodevelopment, reproduction and immunological functions will be studied in rat
offspring. In addition, toxicokinetic studies will be performed on these compounds. The in vivo toxicological
data obtained will serve as a base for risk assessment and extrapolation from animal to man.
We will measure in humans the presence of endocrine active OHS and their metabolites in maternal and cord
blood plasma from high and low exposure groups and in adult males with high or with no consumption of
contaminated Baltic fish in conjunction with analyses on hormonal levels. The blood analyses will be correlated
to epidemiological and clinical data on growth, physical landmarks, neurobehavioural, reproduction and
immunological parameters in human infants and to some extent in adults.
We will assess human perinatal risk for endocrine-related adverse effects of background exposure to OHS and
to provide a scientific basis for the assessment of risk for adverse developmental and health effects in human
infants, after perinatal exposure to back ground levels of endocrine disrupting contaminants, focusing mainly
on phenolic organohalogens.

Campo scientifico (EuroSciVoc)

CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: Il Vocabolario Scientifico Europeo.

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Coordinatore

STOCKHOLM UNIVERSITET
Contributo UE
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Indirizzo
Svante Arrhenius vaeg, 12
106 91 STOCKHOLM
Svezia

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Partecipanti (4)

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