Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study.

Background: Phthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear.

Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies.

Background: Exposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated.

Objective: To investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies.

Methods: In 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry.

Early heart and skeletal muscle mitochondrial response to a moderate hypobaric hypoxia environment.

In eukaryotic cells, aerobic energy is produced by mitochondria through oxygen uptake. However, little is known about the early mitochondrial responses to moderate hypobaric hypoxia (MHH) in highly metabolic active tissues. Here, we describe the mitochondrial responses to acute MHH in the heart and skeletal muscle.

Brain-derived neurotrophic factor (BDNF): an effect biomarker of neurodevelopment in human biomonitoring programs.

The present narrative review summarizes recent findings focusing on the role of brain-derived neurotrophic factor (BDNF) as a biomarker of effect for neurodevelopmental alterations during adolescence, based on health effects of exposure to environmental chemical pollutants. To this end, information was gathered from the PubMed database and the results obtained in the European project Human Biomonitoring for Europe (HBM4EU), in which BDNF was measured at two levels of biological organization: total BDNF protein (serum) and gene DNA methylation (whole blood) levels. The obtained information is organized as follows.

PFAS and Phthalate/DINCH Exposure in Association with Age at Menarche in Teenagers of the HBM4EU Aligned Studies.

Early puberty has been found to be associated with adverse health outcomes such as metabolic and cardiovascular diseases and hormone-dependent cancers. The decrease in age at menarche observed during the past decades has been linked to an increased exposure to endocrine-disrupting compounds (EDCs). Evidence for the association between PFAS and phthalate exposure and menarche onset, however, is inconsistent.

Association of exposure to perfluoroalkyl substances (PFAS) and phthalates with thyroid hormones in adolescents from HBM4EU aligned studies.

Background: Perfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in various types of consumer products. There is epidemiological and experimental evidence that PFAS and phthalates may alter thyroid hormone levels; however, studies in children and adolescents are limited.

Aim: To investigate the association of exposure to PFAS and phthalate with serum levels of thyroid hormones in European adolescents.

Xeno-estrogenic activity of real-life mixtures of perfluoroalkylated substances in human placenta homogenates.

Humans are simultaneously exposed to complex chemical mixtures, and its combined effect can affect human health. As part of the HBM4EU project, the actual mixture of perfluoroalkylated substances (PFAS) in 25 human placenta samples was extracted by chromatographic methods and assessed for xeno-estrogenic activity using two in-vitro bioassays: the estrogen receptor transactivity and the E-Screen assay. Most of the PFAS extracts displayed xeno-estrogenic activity, in one or both assays.

Rapid extraction and analysis of oxidative stress and DNA damage biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine: Application to a study with pregnant women.

Oxidative stress is an important toxicity and genotoxicity mechanism of many chronic adverse health outcomes. This study developed a sensitive extraction method for urine matrix (based on lyophilization, without the need for pre-cleaning by solid phase extraction), coupled to LC-MS/MS analysis of the biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG). The methodology was validated in urine samples from a cohort of Spanish pregnant women collected during the first, second and third trimester of pregnancy, and urine samples collected within 24 h after delivery (n = 85).

Human risk associated with exposure to mixtures of antiandrogenic chemicals evaluated using in vitro hazard and human biomonitoring data.

Background: Scientific evidence for underestimated toxicity from unintentional exposure to chemical mixtures is mounting. Yet, harmonized approaches on how to assess the actual risk of mixtures is lacking. As part of the European Joint programme 'Human Biomonitoring for Europe' we explored a novel methodology for mixture risk assessment of chemicals affecting male reproductive function.

Development and validation of brain-derived neurotrophic factor measurement in human urine samples as a non-invasive effect biomarker.

Background: Brain-derived neurotrophic factor (BDNF), a neurotrophic growth factor mainly expressed in the brain, has been proposed as a potential effect biomarker; that is, as a measurable biomarker whose values could be associated with several diseases, including neurological impairments. The European Human Biomonitoring Initiative (HBM4EU) has also recognized effect biomarkers as a useful tool for establishing link between exposure to environmental pollutants and human health. Despite the well-establish protocol for measuring serum BDNF, there is a need to validate its assessment in urine, a non-invasive sample that can be easily repeated over time.

Kisspeptin as potential biomarker of environmental chemical mixture effect on reproductive hormone profile: A pilot study in adolescent males.

Background: Kisspeptin has been proposed as an effect biomarker to understand the mechanisms by which some environmental chemicals adversely affect the human reproductive system.

Objective: To ascertain whether kisspeptin serum protein and DNA methylation levels are associated with exposure to several environmental chemicals (individually and as a mixture) and serum reproductive hormone levels in adolescent males.

Methods: Three phenols (bisphenol A [BPA], methyl-paraben [MPB], and benzophenone-3 [BP3]); two toxic metals (arsenic and cadmium); and four metabolites of non-persistent pesticides, including insecticides (2-isopropyl-6-methyl-4-pyrimidinol [IMPy], malathion diacid [MDA], and dimethylcyclopropane carboxylic acid [DCCA]) and fungicides (ethylene thiourea [ETU]) were measured in first-morning urine samples of 133 adolescent males aged 15-17 years from the INMA-Granada cohort.

BDNF as a potential mediator between childhood BPA exposure and behavioral function in adolescent boys from the INMA-Granada cohort.

Background: Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF).

Objective: To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain).

Exploring the relationship between metal exposure, BDNF, and behavior in adolescent males.

Background: Brain-derived neurotrophic factor (BDNF) plays an important role in brain development by regulating multiple pathways within the central nervous system. In the Human Biomonitoring for Europe Project (HBM4EU), this neurotrophin is being implemented as a novel effect biomarker to evaluate the potential threats of environmental chemicals on neurodevelopment.

Objectives: To explore the relationships among exposure to environmental metals, BDNF biomarkers at two levels of biological complexity, and behavioral function in adolescent males.

Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas.

Humans are simultaneously exposed to complex mixtures of chemicals with limited knowledge on potential health effects, therefore improved tools for assessing these mixtures are needed. As part of the Human Biomonitoring for Europe (HBM4EU) Project, we aimed to examine the combined biological activity of chemical mixtures extracted from human placentas using one in vivo and four in vitro bioassays, also known as biomarkers of combined effect. Relevant endocrine activities (proliferative and/or reporter gene assays) and four endpoints were tested: the estrogen receptor (ER), androgen receptor (AR), and aryl hydrocarbon receptor (AhR) activities, as well as thyroid hormone (TH) signaling.

Receptor-based in vitro activities to assess human exposure to chemical mixtures and related health impacts.

Humans are exposed to a large number of chemicals from sources such as the environment, food, and consumer products. There is growing concern that human exposure to chemical mixtures, especially during critical periods of development, increases the risk of adverse health effects in newborns or later in life. Historically, the one-chemical-at-a-time approach has been applied both for exposure assessment and hazard characterisation, leading to insufficient knowledge about human health effects caused by exposure to mixtures of chemicals that have the same target.

Bisphenol A and its analogues: A comprehensive review to identify and prioritize effect biomarkers for human biomonitoring.

Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g.

Influence of a Multidisciplinary Program of Diet, Exercise, and Mindfulness on the Quality of Life of Stage IIA-IIB Breast Cancer Survivors.

Integrative oncology has proven to be a useful approach to control cancer symptoms and improve the quality of life (QoL) and overall health of patients, delivering integrated patient care at both physical and emotional levels. The objective of this randomized trial was to evaluate the effects of a triple intervention program on the QoL and lifestyle of women with breast cancer. Seventy-five survivors of stage IIA-IIB breast cancer were randomized into 2 groups.

Bisphenols and Oxidative Stress Biomarkers-Associations Found in Human Studies, Evaluation of Methods Used, and Strengths and Weaknesses of the Biomarkers.

Bisphenols, particularly bisphenol A (4,4'-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008‒2019) related to six health endpoints and evaluated their suitability as effect biomarkers. database searches identified 27 relevant articles that were used for data extraction.

Bisphenol A and cognitive function in school-age boys: Is BPA predominantly related to behavior?

Background: Bisphenol A (BPA) has been associated with impairments in children's behavior, but few studies have investigated its relationship with cognitive function.

Objective: To investigate the association of urinary BPA concentrations with cognitive domains and intelligence quotient (IQ) in Spanish boys.

Methods: BPA levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS-MS) in one spot urine sample from 269 boys of the INMA-Granada cohort, in their follow-up at 9-11 years of age.

A strategy to validate a selection of human effect biomarkers using adverse outcome pathways: Proof of concept for phthalates and reproductive effects.

Human biomonitoring measures the concentrations of environmental chemicals or their metabolites in body fluids or tissues. Complementing exposure biomarkers with mechanistically based effect biomarkers may further elucidate causal pathways between chemical exposure and adverse health outcomes. We combined information on effect biomarkers previously implemented in human observational studies with mechanisms of action reported in experimental studies and with information from published Adverse Outcome Pathways (AOPs), focusing on adverse reproductive effects of phthalate exposure.

Bisphenol A and adiposity measures in peripubertal boys from the INMA-Granada cohort.

Introduction: Childhood obesity is one of the most serious public health challenges of our times. Although an important body of experimental evidence highlights the obesogenic potential of endocrine disruptors such as bisphenol A (BPA), the epidemiological evidence remains inconclusive and limited.

Objective: To assess associations between urinary BPA concentrations and several adiposity measures in peripubertal boys from the Environment and Childhood (INMA) cohort in Granada, Spain.