Unconventional oil and gas extraction as a novel source of endocrine disrupting chemicals to water and the potential for adverse human and animal health outcomes

The proper and unimpeded function of hormones is essential for normal development, maturation, and prevention of chronic diseases. Endocrine disrupting chemicals (EDCs) are exogenous chemicals that have been found to disrupt a number of receptor systems with adverse outcomes associated at environmentally relevant exposure levels. This body of work discusses a novel source of exposure to EDCs: unconventional oil and natural gas extraction operations utilizing hydraulic fracturing. Twenty-four hydraulic fracturing chemicals were tested for agonist and antagonist activities for five nuclear receptors, with the majority exhibiting antagonist receptor activities. Elevated estrogen and androgen receptor activities were measured in surface and ground water from drilling-dense sites with known spills, suggesting a route of potential human exposure. Lastly, increased body weights, organ weights, and decreased sperm counts were exhibited by male C57BL/6J mice exposed prenatally to a mixture of these chemicals in drinking water. In total, this work highlights a novel route of exposure to EDCs and suggests a potential threat to human and animal health in areas where these operations occur

Endocrine-Mediated Mechanisms of Metabolic Disruption and New Approaches to Examine the Public Health Threat

Obesity and metabolic disorders are of great societal concern and generate substantial human health care costs globally. Interventions have resulted in only minimal impacts on disrupting this worsening health trend, increasing attention on putative environmental contributors. Exposure to numerous environmental contaminants have, over decades, been demonstrated to result in increased metabolic dysfunction and/or weight gain in cell and animal models, and in some cases, even in humans. There are numerous mechanisms through which environmental contaminants may contribute to metabolic dysfunction, though certain mechanisms, such as activation of the peroxisome proliferator activated receptor gamma or the retinoid x receptor, have received considerably more attention than less-studied mechanisms such as antagonism of the thyroid receptor, androgen receptor, or mitochondrial toxicity. As such, research on putative metabolic disruptors is growing rapidly, as is our understanding of molecular mechanisms underlying these effects. Concurrent with these advances, new research has evaluated current models of adipogenesis, and new models have been proposed. Only in the last several years have studies really begun to address complex mixtures of contaminants and how these mixtures may disrupt metabolic health in environmentally relevant exposure scenarios. Several studies have begun to assess environmental mixtures from various environments and study the mechanisms underlying their putative metabolic dysfunction; these studies hold real promise in highlighting crucial mechanisms driving observed organismal effects. In addition, high-throughput toxicity databases (ToxCast, etc.) may provide future benefits in prioritizing chemicals for in vivo testing, particularly once the causative molecular mechanisms promoting dysfunction are better understood and expert critiques are used to hone the databases. In this review, we will review the available literature linking metabolic disruption to endocrine-mediated molecular mechanisms, discuss the novel application of environmental mixtures and implications for in vivo metabolic health, and discuss the putative utility of applying high-throughput toxicity databases to answering complex organismal health outcome questions

Systematic evidence on migrating and extractable food contact chemicals: Most chemicals detected in food contact materials are not listed for use

Food packaging is important for today’s globalized food system, but food contact materials (FCMs) can also be a source of hazardous chemicals migrating into foodstuffs. Assessing the impacts of FCMs on human health requires a comprehensive identification of the chemicals they contain, the food contact chemicals (FCCs). We systematically compiled the “database on migrating and extractable food contact chemicals” (FCCmigex) using information from 1210 studies. We found that to date 2881 FCCs have been detected, in a total of six FCM groups (Plastics, Paper & Board, Metal, Multi-materials, Glass & Ceramic, and Other FCMs). 65% of these detected FCCs were previously not known to be used in FCMs. Conversely, of the more than 12’000 FCCs known to be used, only 1013 are included in the FCCmigex database. Plastic is the most studied FCM with 1975 FCCs detected. Our findings expand the universe of known FCCs to 14,153 chemicals. This knowledge contributes to developing non-hazardous FCMs that lead to safer food and support a circular economy

Preconceptional, Gestational, and Lactational Exposure to an Unconventional Oil and Gas Chemical Mixture Alters Energy Expenditure in Adult Female Mice

Previous studies conducted in our laboratory have found altered adult health outcomes in animals with prenatal exposure to environmentally relevant levels of unconventional oil and gas (UOG) chemicals with endocrine-disrupting activity. This study aimed to examine potential metabolic health outcomes following a preconception, prenatal and postnatal exposure to a mixture of 23 UOG chemicals. Prior to mating and from gestation day 1 to postnatal day 21, C57BL/6J mice were developmentally exposed to a laboratory-created mixture of 23 UOG chemicals in maternal drinking water. Body composition, spontaneous activity, energy expenditure, and glucose tolerance were evaluated in 7-month-old female offspring. Neither body weight nor body composition differed in 7-month female mice. However, females exposed to 1.5 and 150 μg/kg/day UOG mix had lower total and resting energy expenditure within the dark cycle. In the light cycle, the 1,500 μg//kg/day group had lower total energy expenditure and the 1.5 μg/kg/day group had lower resting energy expenditure. Females exposed to the 150 μg/kg/day group had lower spontaneous activity in the dark cycle, and females exposed to the 1,500 μg/kg/day group had lower activity in the light cycle. This study reports for the first time that developmental exposure to a mixture of 23 UOG chemicals alters energy expenditure and spontaneous activity in adult female mice

Parma consensus statement on metabolic disruptors

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16–18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as “metabolic disruptors”, in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome

Murine in vitro cellular models to better understand adipogenesis and its potential applications

Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology

Endocrine-disrupting chemicals: economic, regulatory, and policy implications

International audienceEndocrine-disrupting chemicals (EDCs) substantially cost society as a result of increases in disease and disability but—unlike other toxicant classes such as carcinogens—have yet to be codified into regulations as a hazard category. This Series paper examines economic, regulatory, and policy approaches to limit human EDC exposures and describes potential improvements. In the EU, general principles for EDCs call for minimisation of human exposure, identification as substances of very high concern, and ban on use in pesticides. In the USA, screening and testing programmes are focused on oestrogenic EDCs exclusively, and regulation is strictly risk-based. Minimisation of human exposure is unlikely without a clear overarching definition for EDCs and relevant pre-marketing test requirements. We call for a multifaceted international programme (eg, modelled on the International Agency for Research in Cancer) to address the effects of EDCs on human health—an approach that would proactively identify hazards for subsequent regulation