Sex and Gender Differences on the Impact of Metabolism-Disrupting Chemicals on Obesity: A Systematic Review.

Obesity represents an important public health concern, being one of the leading causes of death worldwide. It is a multifactorial disease with many underlying intertwined causes, including genetic, environmental and behavioral factors. Notably, metabolism-disrupting chemicals (MDCs) can alter the set point control of metabolism, affecting the development and function of the adipose tissue.

Urinary Bisphenol A and Bis(2-Ethylhexyl) Phthalate Metabolite Concentrations in Children with Obesity: A Case-Control Study.

Introduction: Obesity is a worldwide public health problem. Experimental animal and in vitro studies suggest that the exposure to BPA and phthalates are associated to a higher risk of obesity.

Objective: The objective of the study was to determine urinary excretion of bisphenol A and phthalates in obese and normal weight children.

Special Issue "Molecular Mechanisms of Bisphenol A Toxicity and Effects of Environmental Levels on Health".

Bisphenol A (BPA) is a plasticizer that is widely used in the manufacturing of polycarbonate plastics (PC) and epoxy resins for use in a broad range of consumer products, including materials in contact with food and beverages, as well as medical devices, toys and dental sealants [...

Exposure to Endocrine Disruptors (Di(2-Ethylhexyl)phthalate (DEHP) and Bisphenol A (BPA)) in Women from Different Residing Areas in Italy: Data from the LIFE PERSUADED Project.

Phthalates and bisphenol A (BPA) are plasticizers used in many industrial products that can act as endocrine disruptors and lead to metabolic diseases. During the LIFE PERSUADED project, we measured the urinary concentrations of BPA and Di(2-ethylhexyl)phthalate (DEHP) metabolites in 900 Italian women representative of the Italian female adult population (living in the north, centre, and south of Italy in both rural and urban areas). The whole cohort was exposed to DEHP and BPA with measurable levels above limit of detection in more than 99% and 95% of the samples, respectively.

BDE-47, -99, -209 and Their Ternary Mixture Disrupt Glucose and Lipid Metabolism of Hepg2 Cells at Dietary Relevant Concentrations: Mechanistic Insight through Integrated Transcriptomics and Proteomics Analysis.

Polybrominated diphenyl ethers (PBDEs) are persistent organic chemicals implied as flame retardants. Humans are mainly exposed to BDE-47, -99, and -209 congeners by diet. PBDEs are metabolic disruptors with the liver as the main target organ.

Reactive Oxygen Species in the Adverse Outcome Pathway Framework: Toward Creation of Harmonized Consensus Key Events.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed as a result of natural cellular processes, intracellular signaling, or as adverse responses associated with diseases or exposure to oxidizing chemical and non-chemical stressors. The action of ROS and RNS, collectively referred to as reactive oxygen and nitrogen species (RONS), has recently become highly relevant in a number of adverse outcome pathways (AOPs) that capture, organize, evaluate and portray causal relationships pertinent to adversity or disease progression. RONS can potentially act as a key event (KE) in the cascade of responses leading to an adverse outcome (AO) within such AOPs, but are also known to modulate responses of events along the AOP continuum without being an AOP event itself.

In Vitro Assessment and Toxicological Prioritization of Pesticide Mixtures at Concentrations Derived from Real Exposure in Occupational Scenarios.

Humans are daily exposed to multiple residues of pesticides with agricultural workers representing a subpopulation at higher risk. In this context, the cumulative risk assessment of pesticide mixtures is an urgent issue. The present study evaluated, as a case study, the toxicological profiles of thirteen pesticide mixtures used for grapevine protection, including ten active compounds (sulfur, potassium phosphonate, metrafenone, zoxamide, cyflufenamid, quinoxyfen, mancozeb, folpet, penconazole and dimethomorph), at concentrations used on field.

Italian Children Exposure to Bisphenol A: Biomonitoring Data from the LIFE PERSUADED Project.

A human biomonitoring (HBM) study on bisphenol A (BPA) in Italian children and adolescents was performed within the LIFE PERSUADED project, considering the residing areas, sex and age. The median urinary BPA level was 7.02 µg/L, with children living in the South of Italy or in urban areas having higher levels than those residing in the North or in rural areas.

Lifestyle Habits and Exposure to BPA and Phthalates in Women of Childbearing Age from Northern Italy: A Pilot Study.

Endocrine-disrupting chemicals (EDCs) are compounds that interfere with aspects of hormonal signaling. Considerable attention has been paid to their biological effects especially in women of childbearing age or during pregnancy as EDCs have been reported to cross the placenta becoming concentrated in the fetus' circulation. Lifestyle habits, daily consumption of packaged foods and use of healthcare/cosmetic products are associated with increased EDCs levels.

Toxicological Assessment of Oral Co-Exposure to Bisphenol A (BPA) and Bis(2-ethylhexyl) Phthalate (DEHP) in Juvenile Rats at Environmentally Relevant Dose Levels: Evaluation of the Synergic, Additive or Antagonistic Effects.

Background: The general population (including children) is exposed to chemical mixtures. Plasticizers such as Bisphenol A (BPA) and Phthalates (mainly Bis(2-ethylhexyl) phthalate-DEHP) are widespread contaminants classified as endocrine disrupters which share some toxicological profiles and coexist in food and environment.

Methods: To identify hazards of DEHP and BPA mixtures, the juvenile toxicity test-where rodents are in peripubertal phase of development, resembling childhood-was selected using exposure data from biomonitoring study in children.

Metabolic, reproductive and thyroid effects of bis(2-ethylhexyl) phthalate (DEHP) orally administered to male and female juvenile rats at dose levels derived from children biomonitoring study.

Bis(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in several items, non-covalently bound to plastics and easily released, since metabolites were found in human matrices. DEHP is an endocrine disrupter and children are particularly vulnerable and susceptible to DEHP effects due to higher exposure levels and developmental stage. A juvenile toxicity study was performed to identify DEHP hazard and mode of action in Sprague-Dawley rats of both sexes during peri-pubertal period - corresponding to childhood phase - from weaning, post-natal day (PND) 23, to full sexual maturity (PND60); the dose levels of 0, 9, 21 and 48 mg/kg bw/day were derived from LIFE PERSUADED biomonitoring study in children.

Integrated Approach to Evaluate the Association between Exposure to Pesticides and Idiopathic Premature Thelarche in Girls: The PEACH Project.

Several pesticides are recognized as endocrine-disrupting chemicals (EDCs) since they can interfere with the dysregulation of sexual, thyroid and neuro-endocrine hormones. Children are particularly vulnerable to the adverse effects of EDCs due to their developmental stage, peculiar lifestyle and dietary habits. In this context, the exposure to pesticides represents an important risk factor associated with early development.

Biomonitoring of Bis(2-ethylhexyl)phthalate (DEHP) in Italian children and adolescents: Data from LIFE PERSUADED project.

The Bis(2-ethylhexyl)phthalate (DEHP), a widespread plasticizer, is considered an endocrine disrupting chemical with main toxicological effects on reproductive and metabolic systems. Human biomonitoring (HBM) studies are promoted to evaluate the background exposure levels. In the frame of LIFE PERSUADED project, the HBM study measured DEHP main metabolites (mono-(2-ethylhexyl) phthalate, MEHP; 2-ethyl-5-hydroxy-hexylphthalate, MEHHP; 2-ethyl-5-oxo-hexylphthalate, MEOHP) in Italian children and adolescent (4-14 years old) according to geographical macro-areas and areas, age and sex.

Juvenile Toxicity Rodent Model to Study Toxicological Effects of Bisphenol A (BPA) at Dose Levels Derived From Italian Children Biomonitoring Study.

Bisphenol A (BPA) is a plasticizer with endocrine disrupting properties particularly relevant for children health. Recently BPA has been associated with metabolic dysfunctions but no data are yet available in specific, long-term studies. This study aimed to evaluate BPA modes of action and hazards during animal juvenile life-stage, corresponding to childhood.

The LIFE PERSUADED project approach on phthalates and bisphenol A biomonitoring in Italian mother-child pairs linking exposure and juvenile diseases.

Phthalates and bisphenol A (BPA), plasticizers used in several products of daily life, are considered as endocrine disrupters, therefore children exposure is particularly relevant. The LIFE PERSUADED project aims to define the following: (a) the evaluation of internal levels of DEHP's metabolites and BPA in Italian children and their mothers, (b) the association of the exposure with puberty development and obesity diseases, and (c) the effects of exposure in juvenile in vivo model. The cross-sectional study has involved 2160 mother-child pairs, including males and females, children and adolescents, from urban and rural areas of North, Center, and South Italy.

[A network of LIFE projects to promote the transfer and exchange of knowledge on environment and health].

Eleven projects within the LIFE programme (through which the Directorate-General for Environment of the European Commission provides funding for projects aim at protecting environment and nature) addressing environmental-health-related issues have been involved in a collaborative network called KTE LIFE EnvHealth Network. The shared issues tackled by that projects are knowledge transfer and exchange (KTE). The objective of the LIFE programme is to support the implementation of the environmental legislation in the European Union, to provide new tools and knowledge that will help to better protect both the territory and the communities.

Biomonitoring of chemicals in biota of two wetland protected areas exposed to different levels of environmental impact: results of the "PREVIENI" project.

The PREVIENI project (funded by the Ministry of Environment) investigated the exposure to endocrine disrupters in samples of human population and environmental biota in Italy. The environmental biomonitoring considered two Italian WWF Oasis, with the aim to compare the presence and effects of endocrine disruptors in organisms from two protected natural areas, respectively, upstream and downstream a chemical emission site. Chemical analysis of pollutants' tissue levels was made on tissues from earthworm, barbell, trout, and coot, selected as bioindicator organisms.

Relative toxicological ranking of eight polybrominated diphenyl ether congeners using cytotoxicity, chemical properties and exposure data.

Polybrominated diphenyl ethers are widely used flame retardants which persist and diffuse in the environment thus entering the food chain. Eight congeners, most relevant for human exposure (BDE-28, 47, 99, 100, 153, 154, 183 and 209), were analyzed in vitro and in silico to derive a relative toxicological ranking. Cytotoxicity was assessed on human liver (HepG2) and colon (DLD-1) cell lines, by three assays (MTS, ATP and DNA content) in a range of realistic concentration (1pM - 10 nM).

The relevance of the food production chain with regard to the population exposure to chemical substances and its role in contaminated sites.

Food may be contaminated with many chemical substances at any level along the production chain. Chemicals that may be found in food items can simultaneously be present in other matrices, as air, water, soil and dust; therefore, human exposure to chemicals via food has to be summed to the exposure through all the other possible routes. The role played by the food production chain with regard to the population exposure to chemicals assumes amplified proportions when considering contaminated sites.

Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features.

Internal levels of selected endocrine disruptors (EDs) (i.e., perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di-2-ethylhexyl-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and bisphenol A (BPA)) were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas.

Exposure to endocrine disrupters and nuclear receptor gene expression in infertile and fertile women from different Italian areas.

Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERa, ERb, AR, AhR, PPARg, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.