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

Abstract

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.

Aryl-hydrocarbon receptor binding and the incidence of type 2 diabetes: the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

“…Following this reasoning, the presence of POPs such as dioxins, not present during the evolution of these cellular mechanisms, may produce a pathological disruption of metabolism involving both insulin resistance and beta cell decline, apparently partially mediated by the AhR and at least partially the result of mitochondrial dysfunction. Our data, together with others [ 5 , 11 , 30 ], who have used the same cell-based assays here employed provide epidemiologic evidence produced in free-living populations which validates previous basic science and clinical research on the role of mitochondrial dysfunction in the pathophysiology of diabetes [ 5 , 7 , 25 , 26 , 29 , 30 ], especially in the presence of greater AhR activation, thus strengthening the contention that POPs cause diabetes and providing a causal pathway for their action.…”

“…As recently suggested, to establish a firm link between POPs and diabetes, the scientific community must respond to three questions [26]: 1. Can we predict the net effect of endocrine disrupting chemical mixtures in the real world?…”

Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates

“…The late onset of the resulting clinical disorders (often many years later, or even trans-generational), the complex interactions and the nonlinear dose-response all hinder the recognition of a causal relation and the establishment of tolerable threshold levels or protection [11,[13][14][15]. While in vitro evidence focuses on one or a handful of EDCs with a similar activity profile, in everyday life a varied combination of EDCs can act simultaneously and may also involve modulated or antagonistic interactions, making it impossible to predict the net biological effect of the mixture [15,16].…”

Removal of Pharmaceutical Contaminants in Wastewater Using Nanomaterials: A Comprehensive Review

“…Particularly, the inhibition of proliferation of human embryonic cells by a complex cocktail of antibiotics and the development of antibiotic resistance genes, which are transferable among bacterial generations have been witnessed [8][9][10]. Pharmaceutical contaminants have also been suspected to be associated with altered reproductive systems in males, altered immunity and neurodevelopment delays in children [11]. They seem to affect human health directly as their presence has been detected in our food chain including vegetables, fruits and drinking water [12,13].…”