Evidence of the Possible Harm of Endocrine-Disrupting Chemicals in Humans: Ongoing Debates and Key Issues.

Evidence has emerged that endocrine-disrupting chemicals (EDCs) can produce adverse effects, even at low doses that are assumed safe. However, systemic reviews and meta-analyses focusing on human studies, especially of EDCs with short half-lives, have demonstrated inconsistent results. Epidemiological studies have insuperable methodological limitations, including the unpredictable net effects of mixtures, non-monotonic dose-response relationships, the non-existence of unexposed groups, and the low reliability of exposure assessment. Thus, despite increases in EDC-linked diseases, traditional epidemiological studies based on individual measurements of EDCs in bio-specimens may fail to provide consistent results. The exposome has been suggested as a promising approach to address the uncertainties surrounding human studies, but it is never free from these methodological issues. Although exposure to EDCs during critical developmental periods is a major concern, continuous exposure to EDCs during non-critical periods is also harmful. Indeed, the evolutionary aspects of epigenetic programming triggered by EDCs during development should be considered because it is a key mechanism for developmental plasticity. Presently, living without EDCs is impossible due to their omnipresence. Importantly, there are lifestyles which can increase the excretion of EDCs or mitigate their harmful effects through the activation of mitohormesis or xenohormesis. Effectiveness of lifestyle interventions should be evaluated as practical ways against EDCs in the real world.