Project structure

The current framework of human epidemiology and toxicological risk assessment is ill-equipped to deal with the issue of cumulative exposures to endocrine disrupting chemicals (EDC) and their possible impact on reproductive health. All too often, attempts are made to study associations between single chemicals and human reproductive disorders. However, European citizens are exposed to multiple chemicals with hormonal activity.

CONTAMED aims to improve this situation by adopting a more holistic approach. Instead of focusing on single chemicals, an attempt will be made to exploit established in vitro assays responsive to entire classes of EDC (e.g. anti-androgens) to derive biomarkers for cumulative internal EDC exposure. These measures will be used to test whether there are associations between cumulative EDC exposures and male reproductive disorders. Chemical and metabolomic analyses for specific known EDCs will complement this approach.

Tissue specimens and body fluids from existing European mother-child cohorts will be analysed to develop biomarkers of total effective internal exposures to EDC. Cohorts with subjects already diagnosed for congenital malformations by medical specialists will be used.

	Leads derived from human studies need to be validated under controlled experimental conditions and CONTAMED will approach this by conducting mixture studies at environmentally relevant exposures using an extended developmental toxicity model in the rat and in vitro EDC screens. However, the outcomes of laboratory studies are not always easy to link with results from human studies, partly because external exposures (ill-defined in humans, controlled in the lab) cannot be compared directly. To overcome this difficulty, CONTAMED will relate the levels of chemicals found in human tissues with those that give rise to quantifiable effects in laboratory animals after controlled exposures to EDC mixtures. These comparisons will rely not only on chemical analyses, but also on biomarkers of total effective EDC load in the tissues and on metabolomic profiling of rat tissues to identify biomarkers in the pool of xenobiotic and endogenous metabolites that can be used as indicators of exposure to EDCs in rat and human studies.