scholarly journals Chemical mixtures and neurobehavior: a review of epidemiologic findings and future directions

2020 ◽  
Vol 35 (3) ◽  
pp. 245-256
Author(s):  
Ann M. Vuong ◽  
Kimberly Yolton ◽  
Joseph M. Braun ◽  
Bruce P. Lanphear ◽  
Aimin Chen

AbstractBackgroundEpidemiological studies have historically focused on single toxicants, or toxic chemicals, and neurodevelopment, even though the interactions of chemicals and nutrients may result in additive, synergistic, antagonistic, or potentiating effects on neurological endpoints. Investigating the impact of environmentally-relevant chemical mixtures, including heavy metals and endocrine disrupting chemicals (EDCs), is more reflective of human exposures and may result in more refined environmental policies to protect the public.ObjectiveIn this review, we provide a summary of epidemiological studies that have analyzed chemical mixtures of heavy metals and EDCs and neurobehavior utilizing multi-chemical models, including frequentist and Bayesian methods.ContentStudies investigating chemicals and neurobehavior have the opportunity to not only examine the impact of chemical mixtures, but they can also identify chemicals from a mixture that may play a key role in neurotoxicity, investigate interactive effects, estimate non-linear dose response, and identify potential windows of susceptibility. The examination of neurobehavioral domains is particularly challenging given that traits emerge and change over time and subclinical nuances of neurobehavior are often unrecognized. To date, only a handful of epidemiological studies examining neurodevelopment have utilized multi-pollutant models in the investigation of heavy metals and EDCs. However, these studies were successful in identifying contaminants of importance from the exposure mixtures.Summary and OutlookInvestigators are encouraged to broaden their focus to include more environmentally relevant mixtures of chemicals using advanced statistical approaches, particularly to aid in identifying potential mechanisms underlying associations.

2020 ◽  
Vol 11 ◽  
Author(s):  
Margarita Aguilera ◽  
Yolanda Gálvez-Ontiveros ◽  
Ana Rivas

Endogenous steroid hormones and Endocrine Disrupting Chemicals (EDC) interact with gut microbiota through different pathways. We suggest the use of the term “endobolome” when referring to the group of gut microbiota genes and pathways involved in the metabolism of steroid hormones and EDC. States of dysbiosis and reduced diversity of the gut microbiota may impact and modify the endobolome resulting at long-term in the development of certain pathophysiological conditions. The endobolome might play a central role in the gut microbiota as seen by the amount of potentially endobolome-mediated diseases and thereby it can be considered an useful diagnostic tool and therapeutic target for future functional research strategies that envisage the use of next generation of probiotics. In addition, we propose that EDC and other xenobiotics that alter the gut microbial composition and its metabolic capacities should be categorized into a subgroup termed “microbiota disrupting chemicals” (MDC). This will help to distinguish the role of contaminants from other microbiota natural modifiers such as those contained or released from diet, environment, physical activity and stress. These MDC might have the ability to promote specific changes in the microbiota that can ultimately result in common intestinal and chronic or long-term systemic diseases in the host. The risk of developing certain disorders associated with gut microbiota changes should be established by determining both the effects of the MDC on gut microbiota and the impact of microbiota changes on chemicals metabolism and host susceptibility. In any case, further animal controlled experiments, clinical trials and large epidemiological studies are required in order to establish the concatenated impact of the MDC-microbiota-host health axis.


Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 137 ◽  
Author(s):  
Eleonora Rotondo ◽  
Francesco Chiarelli

The purpose of this article is to review the evidence linking background exposure to endocrine-disrupting chemicals (EDCs) with insulin resistance in children. Although evidence in children is scarce since very few prospective studies exist even in adults, evidence that EDCs might be involved in the development of insulin resistance and related diseases such as obesity and diabetes is accumulating. We reviewed the literature on both cross-sectional and prospective studies in humans and experimental studies. Epidemiological studies show a statistical link between exposure to pesticides, polychlorinated bisphenyls, bisphenol A, phthalates, aromatic polycyclic hydrocarbides, or dioxins and insulin resistance.


2010 ◽  
Vol 75 (4) ◽  
pp. 471-492 ◽  
Author(s):  
Yan Cheng ◽  
Hui-ming Chen ◽  
Wen-lian Yu ◽  
Yuan Cui ◽  
Li-li Zhou ◽  
...  

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have become emerging persistent organic pollutants (POPs), but their health effects on humans remain controversial because of contradictory experimental and epidemiological studies. In this study, we used three-dimensional quantitative structure–activity relationship (3D-QSAR) method by applying Surflex-dock to study and compare the binding modes between PFOS, PFOA and eight other endocrine disrupting chemicals, and human estrogen receptor (hERα), human androgen receptor (hAR) and human thyroid receptor (hTRβ). Molecular docking and hydrogen bond studies indicated that PFOS and PFOA had high affinity potency toward hERα, hAR and hTRβ due to low free binding energies, while the highest value was obtained toward hTRβ. This means that PFOS and PFOA might have more disrupting effects on thyroid than on estrogen and androgen receptors. Hydrogen bonding interactions revealed that Met313 in hTRβ might act as the critical amino acid residue in the binding of ligand–receptor complex, which would provide an explanation for the interaction mechanisms. Our results provide an important reference and direction for the interaction mode and mechanism study between PFOS/PFOA and human endocrine systems.


2019 ◽  
Vol 10 (4) ◽  
pp. 447-458 ◽  
Author(s):  
Jaclyn M. Goodrich ◽  
Mary E. Ingle ◽  
Steven E. Domino ◽  
Marjorie C. Treadwell ◽  
Dana C. Dolinoy ◽  
...  

AbstractExposures to endocrine disrupting chemicals and metals are near ubiquitous worldwide, and their potential impact on children is a major public health concern. This pilot study was designed to characterize exposures to phthalates, phenols and metals among pregnant women in the first trimester, and to examine associations with fetal biometrics and birth weight. A total of 41 chemicals and elements were analyzed in urine from 56 mothers with full-term newborns from the Michigan Mother–Infant Pairs study. Bivariate analyses identified predictors of exposure biomarkers. Associations between birth weight, Fentonz-scores and second trimester fetal biometrics with toxicants were examined via multivariable linear regression. An average of 30 toxicants were detected in maternal urine. Fast food consumption was associated with several phthalate metabolites, phenols and metals, and canned food consumption with bisphenol F (P<0.05). Mono (3-carboxypropyl) phthalate was significantly associated with higher birth weight and Fentonz-score while the opposite was observed for bisphenol S. Estimated femur length from ultrasonography was significantly inversely associated with arsenic, barium and lead. While limited by sample size, this study is one of the first to evaluate birth outcomes with respect to emerging endocrine disrupting chemicals and to examine associations between toxicants and fetal biometrics. Exposure assessment was provided by the National Institute of Environmental Health Sciences’ Children’s Health Exposure Analysis Resource (NIEHS CHEAR), a resource available to children’s studies with the goal of combining data across cohorts in an effort to characterize the impact of toxicants on child health from birth and beyond.


2020 ◽  
Vol 21 (23) ◽  
pp. 9139
Author(s):  
Louisane Eve ◽  
Béatrice Fervers ◽  
Muriel Le Romancer ◽  
Nelly Etienne-Selloum

Breast cancer (BC) is the second most common cancer and the fifth deadliest in the world. Exposure to endocrine disrupting pollutants has been suggested to contribute to the increase in disease incidence. Indeed, a growing number of researchershave investigated the effects of widely used environmental chemicals with endocrine disrupting properties on BC development in experimental (in vitro and animal models) and epidemiological studies. The complex effects of endocrine disrupting chemicals (EDCs) on hormonal pathways, involving carcinogenic effects and an increase in mammary gland susceptibility to carcinogenesis—together with the specific characteristics of the mammary gland evolving over the course of life and the multifactorial etiology of BC—make the evaluation of these compounds a complex issue. Among the many EDCs suspected of increasing the risk of BC, strong evidence has only been provided for few EDCs including diethylstilbestrol, dichlorodiphenyltrichloroethane, dioxins and bisphenol A. However, given the ubiquitous nature and massive use of EDCs, it is essential to continue to assess their long-term health effects, particularly on carcinogenesis, to eradicate the worst of them and to sensitize the population to minimize their use.


2019 ◽  
Vol 102 (2) ◽  
pp. 276-291 ◽  
Author(s):  
William Nelson ◽  
Ding-Yuan Liu ◽  
Yin Yang ◽  
Zhao-Hui Zhong ◽  
Ying-Xiong Wang ◽  
...  

Abstract Anti-androgenic endocrine-disrupting chemicals (EDCs) can cross the placenta to modify early offspring sexual dimorphic markers. These changes are linked to anogenital distance (AGD), which is an androgen-sensitive anthropometric parameter used as a biomarker of perineal growth and caudal migration of the genital tubercle. This review aimed to summarize strength of evidence for associations of in utero exposure to EDCs with AGD and to identify gaps and limitations in the literature so as to inform future research. We performed an electronic search of English literature in September 2019 in medical literature analysis and retrieval system online (MEDLINE), Web of Science and Toxline. We included epidemiological studies that examined in utero exposure to persistent and nonpersistent EDCs and considered AGD in offspring as an outcome. Our review contained 16 investigations examining exposure to persistent EDCs (nine studies) and nonpersistent EDCs (seven studies). Some individual studies reported an inverse association between exposure to bisphenol A (BPA), dioxins, perfluoroalkyl substances, and organochlorides and AGD in both male and female offspring. Meta-analysis of three studies found a small reduction of AGD in female offspring exposed to BPA. The number of studies per chemical is small, and number of subjects examined is limited; so, replication of these results is needed. To achieve more specificity and better replication of results, future studies should establish the association of nonpersistent EDCs using multiple urine samples, evaluate the cumulative impact of exposure to a mixture of anti-androgenic chemicals, and offer adequate consideration of more maternal- and children-related confounding factors.


Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 13 ◽  
Author(s):  
Julie M. Hall ◽  
Callie W. Greco

Much of the early work on Nuclear Hormone Receptors (NHRs) focused on their essential roles as mediators of sex steroid hormone signaling in reproductive development and function, and thyroid hormone-dependent formation of the central nervous system. However, as NHRs display tissue-specific distributions and activities, it is not surprising that they are involved and vital in numerous aspects of human development and essential for homeostasis of all organ systems. Much attention has recently been focused on the role of NHRs in energy balance, metabolism, and lipid homeostasis. Dysregulation of NHR function has been implicated in numerous pathologies including cancers, metabolic obesity and syndrome, Type II diabetes mellitus, cardiovascular disease, hyperlipidemia, male and female infertility and other reproductive disorders. This review will discuss the dysregulation of NHR function by environmental endocrine disrupting chemicals (EDCs), and the associated pathological consequences of exposure in numerous tissues and organ systems, as revealed by experimental, clinical, and epidemiological studies.


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