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New EU criteria for endocrine disrupters

Background: The endocrine system is composed of about one hundred hormones that maintain the internal balance by coordinating organ functions and respond to environmental cues. It has therefore a high degree of adaptability and is particularly sensitive to environmental stimuli during foetal and early postnatal life. This is because the regulation of hormone action on target cells and interaction between hormonal pathways are largely being shaped during early development. This ability to prepare for the postnatal environment was previously an advantage, to survive and reproduce. This adaptability is now cause for concern since it can predispose for adult disease. We are presently exposed to novel substances, endocrine disruptors (EDs), which could adversely affect human health. The challenge is to identify ED targets and the shortand long-term consequences of the ED interference. Aim: To present an overview of mechanism and mode of action of selected endocrine disruptors at doses below the established no or lowest observed adverse effects levels (NOAEL/LOAEL); effects of early and exposure on disorder/disease development (fertility, cardiovascular disease, diabetes, cancers, obesity, behaviour). Methods: The selected EDs were BPA; phthalates (DEHP, BBP, DBP, DINP, DIDP); antioxidants (BHA, BHT); parabens (Me-, Et-, Pro-); dithiocarbamate pesticides (mancozeb, maneb, metiram, propineb, thiram, ziram) and phytoestrogen (genistein). PubMed searches were performed and manually curated to exclude studies that did not fill the criteria (non-endocrine effects, non-oral administration, non-mammalian species; ED-mixtures; hypothesis/review/opinion papers; only doses above NOAEL). Results: BPA, genistein and DEHP are the most studied of the selected EDs, with established mechanisms of action as oestrogen agonists (BPA and genistein) or as androgen antagonist (DEHP). New research show that many of the selected EDs can