Environmental Chemical Exposures Research Articles

OP31.07: Papillary bladder carcinoma of low‐malignant potential during pregnancy: 2D and 3D ultrasonography

Bladder neoplasm detected during pregnancy is a rare condition. The cardinal symptoms dysuria and hematuria are often mistakenly attributed to the pregnancy complications. Ninety percent of cases in women under 40 fortunately belong to superficial papillary urothelial neoplasm of low malignant potential (PUNLMP), known even as transitional cell cancer (TCC). Cigarette smoking, frequent urinary tract infections and environmental chemical carcinogens exposure are the most important risk factors for bladder carcinoma. A healthy 28-year-old pregnant primigravida woman, non-smoker, presented in gestational week 30+3 with intermittent painless macrohematuria, interpreted as vaginal bleeding. She underwent gynecological examinations twice without detection of any signs of bleeding. At the third examination an irregular papillary bladder neoplasm was suspected on 2D ultrasound. 3D image of the neoplasm was rendered using HDlive and the volume was measured. Colour and spectral Doppler shown a moderate vascularity with high peak systolic velocity (PSV=28cm/sec) inside of the neoplasm. Cystoscopy confirmed a suspicious neoplasm. Urine cytology was negative. In gestational week 34+0 an emergency Caesarean section was performed due to failure of induction of labour. Three days later a transurethral resection of neoplasm (TUR-B) was performed, uneventfully. Histology shown non-invasive papillary urothelial cancer (stage pTaG1). No adjuvant therapy was needed. Follow-up with cystoscopy, 4 and 10 months after treatment, were negative. Despite the rarity of bladder carcinoma during pregnancy an examination of urinary bladder should always be performed in case of atypical genital bleeding. Different diagnostic imaging as 2D and 3D ultrasound, followed by cystoscopy are sufficient and comfortable diagnostic modalities for bladder neoplasm during pregnancy. Transurethral resection of non-invasive bladder carcinoma can be performed safely either during pregnancy or after delivery.

In vitro models to study effects of the Endocrine Distrupting Chemicals (EDCs) in human placenta

To examine whether parents' concerns about environmental chemical exposures were associated with urinary phthalate and phenol concentrations in their school-age children.In a prospective cohort of 218 mother-child pairs from Cincinnati, Ohio (2010-2014), we measured 11 phthalate metabolites and 5 phenols in urine samples when children were age 8 years and used questionnaire data from caregivers. We estimated the covariate-adjusted percent difference in phthalates and phenols among children of parents who expressed concern about environmental chemical exposures compared with children whose parents did not.Concentrations of 4 phthalates, bisphenol S, and bisphenol A were lower among children whose parents expressed concern about environmental chemicals (n = 122) compared with those who did not (n = 96). Di-2-ethylhexyl phthalate metabolites, bisphenol S, and bisphenol A concentrations were 23% (95% CI −38, −5), 37% (95% CI −49, −21), and 13% (95% CI −26, 3) lower, respectively, among children whose parents expressed concern compared with those whose parents did not. Triclosan concentrations were 35% greater (95% CI −2, 87) among children whose parents expressed concern compared with children whose parents did not.Parental concern about environmental chemicals was associated with lower childhood urine concentrations of several phthalates and phenols; unexpectedly, parental concern was associated with greater triclosan concentrations. These results suggest that parental concern may be an important factor in mitigating children's phthalate and phenol exposures.

The environmental injustice of beauty: framing chemical exposures from beauty products as a health disparities concern

The obstetrics-gynecology community has issued a call to action to prevent toxic environmental chemical exposures and their threats to healthy human reproduction. Recent committee opinions recognize that vulnerable and underserved women may be impacted disproportionately by environmental chemical exposures and recommend that reproductive health professionals champion policies that secure environmental justice. Beauty product use is an understudied source of environmental chemical exposures. Beauty products can include reproductive and developmental toxicants such as phthalates and heavy metals; however, disclosure requirements are limited and inconsistent. Compared with white women, women of color have higher levels of beauty product-related environmental chemicals in their bodies, independent of socioeconomic status. Even small exposures to toxic chemicals during critical periods of development (such as pregnancy) can trigger adverse health consequences (such as impacts on fertility and pregnancy, neurodevelopment, and cancer). In this commentary, we seek to highlight the connections between environmental justice and beauty product-related chemical exposures. We describe racial/ethnic differences in beauty product use (such as skin lighteners, hair straighteners, and feminine hygiene products) and the potential chemical exposures and health risks that are associated with these products. We also discuss how targeted advertising can take advantage of mainstream beauty norms to influence the use of these products. Reproductive health professionals can use this information to advance environmental justice by being prepared to counsel patients who have questions about toxic environmental exposures from beauty care products and other sources. Researchers and healthcare providers can also promote health-protective policies such as improved ingredient testing and disclosure for the beauty product industry. Future clinical and public health research should consider beauty product use as a factor that may shape health inequities in women's reproductive health across the life course.

Reducing chemical exposures at home: opportunities for action

Indoor environments can influence human environmental chemical exposures and, ultimately, public health. Furniture, electronics, personal care and cleaning products, floor coverings and other consumer products contain chemicals that can end...

Prenatal environmental chemical exposures and longitudinal patterns of child neurobehavior

BackgroundPrenatal chemical exposures may adversely affect neurodevelopment, but few studies have examined the persistence of these associations. We examined whether associations between prenatal bisphenol A (BPA) or polybrominated diphenyl ether (PBDE) exposures persist or resolve as children age. MethodsWe followed 346 mother-child pairs (enrolled 2003–2006) from Cincinnati, OH from pregnancy until children were 8 years old. We measured BPA in urine collected at 16 and 26 weeks gestation and PBDE-47 in serum collected at 16 weeks gestation. We administered repeated measures of children’s behavior, mental/psychomotor development, and IQ from ages 1–8 years. We determined if associations of BPA or PBDE-47 with child neurobehavior persisted or resolved as children aged using linear mixed models and estimated neurobehavioral measure reproducibility using intraclass correlation coefficients (ICCs). ResultsHigher BPA in girls and higher PBDE-47 in both boys and girls were associated with more externalizing behaviors; these associations persisted from ages 2–8 years (exposure×age interaction p-values≥0.36). Higher PBDE-47 concentrations were associated with decreases in MDI from ages 1–3 years (PBDE–47x age interaction p-value=0.03) and persistently lower IQ at ages 5 and 8 years (PBDE–47×age interaction p-value=0.56). Mental/psychomotor abilities had fair reproducibility from ages 1–3 years (ICCs∼0.4), cognitive abilities from ages 5 to 8 years had excellent reproducibility (ICCs=0.7-0.8), and parent-reported behaviors from ages 2–8 years had poor to good reproducibility (ICCs=0.38–0.59). ConclusionsPrenatal BPA and PBDE-47 concentrations were persistently associated with more externalizing behaviors. PBDE-47 concentrations were inversely associated with cognitive abilities that strengthened over time.

Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

BackgroundAdverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear.ObjectivesTo conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes.MethodsWe used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES).ResultsWe identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46–9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53–2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification.ConclusionsWe found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

A new method to study the change of miRNA-mRNA interactions due to environmental exposures.

MotivationIntegrative approaches characterizing the interactions among different types of biological molecules have been demonstrated to be useful for revealing informative biological mechanisms. One such example is the interaction between microRNA (miRNA) and messenger RNA (mRNA), whose deregulation may be sensitive to environmental insult leading to altered phenotypes. The goal of this work is to develop an effective data integration method to characterize deregulation between miRNA and mRNA due to environmental toxicant exposures. We will use data from an animal experiment designed to investigate the effect of low-dose environmental chemical exposure on normal mammary gland development in rats to motivate and evaluate the proposed method.ResultsWe propose a new network approach—integrative Joint Random Forest (iJRF), which characterizes the regulatory system between miRNAs and mRNAs using a network model. iJRF is designed to work under the high-dimension low-sample-size regime, and can borrow information across different treatment conditions to achieve more accurate network inference. It also effectively takes into account prior information of miRNA–mRNA regulatory relationships from existing databases. When iJRF is applied to the data from the environmental chemical exposure study, we detected a few important miRNAs that regulated a large number of mRNAs in the control group but not in the exposed groups, suggesting the disruption of miRNA activity due to chemical exposure. Effects of chemical exposure on two affected miRNAs were further validated using breast cancer human cell lines.Availability and implementationR package iJRF is available at CRAN.Supplementary information Supplementary data are available at Bioinformatics online.

Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats

Environmental chemicals exposure is one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans. The discovery of early and sensitive microRNA (miRNA) biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. To study this, we performed next generation sequencing of the livers of Sprague-Dawley rats treated with TAA at three doses (4.5, 15 and 45 mg/kg) and four time points (3-, 7-, 14- and 28-days). Overall, 330 unique differentially expressed miRNAs (DEMs) were identified in the entire TAA-treatment course. Of these, 129 DEMs were found significantly enriched for the “liver cancer” annotation. These results were further complemented by pathway analysis (Molecular Mechanisms of Cancer, p53-, TGF-β-, MAPK- and Wnt-signaling). Two miRNAs (rno-miR-34a-5p and rno-miR-455-3p) out of 48 overlapping DEMs were identified to be early and sensitive biomarkers for TAA-induced hepatocarcinogenicity. We have shown significant regulatory associations between DEMs and TAA-induced liver carcinogenesis at an earlier stage than histopathological features. Most importantly, miR-34a-5p is the most suitable early and sensitive biomarker for TAA-induced hepatocarcinogenesis due to its consistent elevation during the entire treatment course.

The Hokkaido Birth Cohort Study on Environment and Children\u2019s Health: cohort profile\u2014updated 2017

The Hokkaido Study on Environment and Children’s Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.

Chemical Risk Assessment: Traditional vs Public Health Perspectives.

Preventing adverse health effects of environmental chemical exposure is fundamental to protecting individual and public health. When done efficiently and properly, chemical risk assessment enables risk management actions that minimize the incidence and effects of environmentally induced diseases related to chemical exposure. However, traditional chemical risk assessment is faced with multiple challenges with respect to predicting and preventing disease in human populations, and epidemiological studies increasingly report observations of adverse health effects at exposure levels predicted from animal studies to be safe for humans. This discordance reinforces concerns about the adequacy of contemporary risk assessment practices for protecting public health. It is becoming clear that to protect public health more effectively, future risk assessments will need to use the full range of available data, draw on innovative methods to integrate diverse data streams, and consider health endpoints that also reflect the range of subtle effects and morbidities observed in human populations. Considering these factors, there is a need to reframe chemical risk assessment to be more clearly aligned with the public health goal of minimizing environmental exposures associated with disease.

Parental Concern about Environmental Chemical Exposures and Children's Urinary Concentrations of Phthalates and Phenols

To examine whether parents' concerns about environmental chemical exposures were associated with urinary phthalate and phenol concentrations in their school-age children. In a prospective cohort of 218 mother-child pairs from Cincinnati, Ohio (2010-2014), we measured 11 phthalate metabolites and 5 phenols in urine samples when children were age 8 years and used questionnaire data from caregivers. We estimated the covariate-adjusted percent difference in phthalates and phenols among children of parents who expressed concern about environmental chemical exposures compared with children whose parents did not. Concentrations of 4 phthalates, bisphenol S, and bisphenol A were lower among children whose parents expressed concern about environmental chemicals (n = 122) compared with those who did not (n = 96). Di-2-ethylhexyl phthalate metabolites, bisphenol S, and bisphenol A concentrations were 23% (95% CI -38, -5), 37% (95% CI -49, -21), and 13% (95% CI -26, 3) lower, respectively, among children whose parents expressed concern compared with those whose parents did not. Triclosan concentrations were 35% greater (95% CI -2, 87) among children whose parents expressed concern compared with children whose parents did not. Parental concern about environmental chemicals was associated with lower childhood urine concentrations of several phthalates and phenols; unexpectedly, parental concern was associated with greater triclosan concentrations. These results suggest that parental concern may be an important factor in mitigating children's phthalate and phenol exposures.

Environmental perfluorooctane sulfonate exposure drives T cell activation in bottlenose dolphins.

Perfluoroalkyl acids (PFAAs) are highly stable compounds that have been associated with immunotoxicity in epidemiologic studies and experimental rodent models. Lengthy half-lives and resistance to environmental degradation result in bioaccumulation of PFAAs in humans and wildlife. Perfluorooctane sulfonate (PFOS), the most prevalent PFAA detected within the environment, is found at high levels in occupationally exposed humans. We have monitored the environmental exposure of dolphins in the Charleston, SC region for over 10 years and levels of PFAAs, and PFOS in particular, were significantly elevated. As dolphins may serve as large mammal sentinels to identify the impact of environmental chemical exposure on human disease, we sought to assess the effect of environmental PFAAs on the cellular immune system in highly exposed dolphins. Herein, we utilized a novel flow cytometry-based assay to examine T cell-specific responses to environmental PFAA exposure ex vivo and to exogenous PFOS exposure in vitro. Baseline PFOS concentrations were associated with significantly increased CD4+ and CD8+ T cell proliferation from a heterogeneous resident dolphin population. Further analysis demonstrated that in vitro exposure to environmentally relevant levels of PFOS promoted proinflammatory cytokine production and proliferation in a dose-dependent manner. Collectively, these findings indicate that PFOS is capable of inducing proinflammatory interferon-gamma, but not immunoregulatory interleukin-4 production in T cells, which may establish a state of chronic immune activation known to be associated with susceptibility to disease. These findings suggest that PFOS directly dysregulates the dolphin cellular immune system and has implications for health hazards. Copyright © 2017 John Wiley & Sons, Ltd.

The mouse mammary gland as a sentinel organ: distinguishing \u2018control\u2019 populations with diverse environmental histories

BackgroundThere are numerous examples of laboratory animals that were inadvertently exposed to endocrine disrupting chemicals (EDCs) during the process of conducting experiments. Controlling contaminations in the laboratory is challenging, especially when their source is unknown. Unfortunately, EDC contaminations can interfere with the interpretation of data during toxicological evaluations. We propose that the male CD-1 mouse mammary gland is a sensitive bioassay to evaluate the inadvertent contamination of animal colonies.MethodsWe evaluated mammary glands collected from two CD-1 mouse populations with distinct environmental histories. Population 1 was born and raised in a commercial laboratory with unknown EDC exposures; Population 2 was the second generation raised in an animal facility with limited exposures to xenoestrogens from caging, feed, etc. Mammary glands were collected from all animals and evaluated using morphometric techniques to quantify morphological characteristics of the mammary gland.ResultsPopulation 1 (with suspected history of environmental chemical exposure) and Population 2 (with known limited history of xenoestrogen exposure) were morphologically distinguishable in adult males, prepubertal females, and pubertal females. Mammary glands from males raised in the commercial animal facility were significantly more developed, with larger ductal trees and more branching points. The appearance of these mammary glands was consistent with prior reports of male mice exposed to low doses of bisphenol A (BPA) during early development. In females, the two populations were morphologically distinct at both prepuberty and puberty, with the most striking differences observed in the number, size, and density of terminal end buds, e.g. highly proliferative structures found in the developing mammary gland.ConclusionsCollectively, these results suggest that the mouse mammary gland has the potential to be used as a sentinel organ to evaluate and distinguish animal colonies raised in different environmental conditions including potential EDC exposures. Our findings could help researchers that wish to perform a posteriori evaluations to determine whether inadvertent contamination with xenoestrogens (and potentially other EDCs) has occurred in their animal colonies, especially after new materials (feed, caging, water bottles) have been introduced. Finally, our results challenge the relatively common practice of using historical controls in toxicological experiments.

Environmental chemicals and preterm birth: Biological mechanisms and the state of the science.

Preterm birth is a significant worldwide health problem of uncertain origins. The extant body of literature examining environmental contaminant exposures in relation to preterm birth is extensive but results remain ambiguous for most organic pollutants, metals and metalloids, and air pollutants. In the present review we examine recent epidemiologic studies investigating these associations, and identify recent advances and the state of the science. Additionally, we highlight biological mechanisms of action in the pathway between chemical exposures and preterm birth, including inflammation, oxidative stress, and endocrine disruption, that deserve more attention in this context. Important advances have been made in the study of the environment and preterm birth, particularly in regard to exposure assessment methods, exploration of effect modification by co-morbidities and exposures, and in identification of windows of vulnerability during gestation. There is strong evidence for an association between maternal exposure to some persistent pesticides, lead, and fine particulate matter, but data on other contaminants is sparse and only suggestive trends can be noted with the current data. Beyond replicating current findings, further work must be done to improve understanding of mechanisms underlying the associations observed between environmental chemical exposures and preterm birth. By examining windows of vulnerability, disaggregating preterm birth by phenotypes, and measuring biomarkers of mechanistic pathways in these epidemiologic studies we can improve our ability to detect associations with exposure, provide additional evidence for causality in an observational setting, and identify opportunities for intervention.

Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells.

Emerging evidence from epidemiological studies suggests a link between environmental chemical exposure and progression of aggressive breast cancer subtypes. Of all clinically distinct types of breast cancers, the most lethal phenotypic variant is inflammatory breast cancer (IBC). Overexpression of epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER) negativity is common in IBC tumor cells, which instead of a solid mass present as rapidly proliferating diffuse tumor cell clusters. Our previous studies have demonstrated a role of an adaptive response of increased antioxidants in acquired resistance to EGFR-targeting drugs in IBC. Environmental chemicals are known to induce oxidative stress resulting in perturbations in signal transduction pathways. It is therefore of interest to identify chemicals that can potentiate EGFR mitogenic effects in IBC. Herein, we assessed in ER-negative IBC cells a subset of chemicals from the EPA ToxCast set for their effect on EGFR activation and in multiple cancer phenotypic assays. We demonstrated that endocrine-disrupting chemicals such as bisphenol A (BPA) and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane can increase EGFR/ERK signaling. BPA also caused a corresponding increase in expression of SOD1 and anti-apoptotic Bcl-2, key markers of antioxidant and anti-apoptotic processes. BPA potentiated clonogenic growth and tumor spheroid formation in vitro, reflecting IBC-specific pathological characteristics. Furthermore, we identified that BPA was able to attenuate the inhibitory effect of an EGFR targeted drug in a longer-term anchorage-independent growth assay. These findings provide a potential mechanistic basis for environmental chemicals such as BPA in potentiating a hyperproliferative and death-resistant phenotype in cancer cells by activating mitogenic pathways to which the tumor cells are addicted for survival.

Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic β-Cell Function.

Bisphenol A (BPA) and phthalates are common environmental contaminants that have been proposed to influence incidence and development of types 1 and 2 diabetes. Thus, effects of BPA and three phthalate metabolites (monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and mono-(2-ethylhexyl) phthalate (MEHP)) were studied in the pancreatic β-cell line INS-1E, after 2–72 h of exposure to 5–500 μM. Three endpoints relevant to accelerated development of types 1 or 2 diabetes were investigated: β-cell viability, glucose-induced insulin secretion, and β-cell susceptibility to cytokine-induced cell death. BPA and the phthalate metabolites reduced cellular viability after 72 h of exposure, with BPA as the most potent chemical. Moreover, BPA, MEHP, and MnBP increased insulin secretion after 2 h of simultaneous exposure to chemicals and glucose, with potency BPA > MEHP > MnBP. Longer chemical exposures (24–72 h) showed no consistent effects on glucose-induced insulin secretion, and none of the environmental chemicals affected susceptibility to cytokine-induced cell death. Overall, BPA was more potent than the investigated phthalate metabolites in affecting insulin secretion and viability in the INS-1E pancreatic β-cells. In contrast to recent literature, concentrations with relevance to human exposures (1–500 nM) did not affect the investigated endpoints, suggesting that this experimental model displayed relatively low sensitivity to environmental chemical exposure.

Timing of Maternal Exposure and Foetal Sex Determine the Effects of Low-level Chemical Mixture Exposure on the Foetal Neuroendocrine System in Sheep.

We have shown that continuous maternal exposure to the complex mixture of environmental chemicals (ECs) found in human biosolids (sewage sludge), disrupts mRNA expression of genes crucial for development and long‐term regulation of hypothalamic‐pituitary gonadal (HPG) function in sheep. The present study investigated whether exposure to ECs only during preconceptional period or only during pregnancy perturbed key regulatory genes within the hypothalamus and pituitary gland and whether these effects were different from chronic (life‐long) exposure to biosolid ECs. The findings demonstrate that the timing and duration of maternal EC exposure influences the subsequent effects on the foetal neuroendocrine system in a sex‐specific manner. Maternal exposure prior to conception, or during pregnancy only, altered the expression of key foetal neuroendocrine regulatory systems such as gonadotrophin‐releasing hormone and kisspeptin to a greater extent than when maternal exposure was ‘life‐long’. Furthermore, hypothalamic gene expression was affected to a greater extent in males than in females and, following EC exposure, male foetuses expressed more ‘female‐like’ mRNA levels for some key neuroendocrine genes. This is the first study to show that ‘real‐life’ maternal exposure to low levels of a complex cocktail of chemicals prior to conception can subsequently affect the developing foetal neuroendocrine system. These findings demonstrate that the developing neuroendocrine system is sensitive to EC mixtures in a sex‐dimorphic manner likely to predispose to reproductive dysfunction in later life.

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV⩽3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.

Review of developmental origins of health and disease publications in environmental epidemiology

The Developmental Origins of Health and Disease (DOHaD) scientific field investigates the influence of early life environmental stressors on later life health outcomes. Environmental chemical exposures are a particular focus area within this field. Although the DOHaD hypothesis originated in the 1990s, the data evaluating this hypothesis in environmental epidemiology has not been comprehensively summarized. We conducted a scoping literature review to describe the human evidence for the DOHaD hypothesis and to identify, 1) where there may be reasonable data to draw conclusions, and 2) areas warranting further research. Using PubMed and Web of Science we identified 425 publications through 2014 that met our criteria for evaluating the DOHaD hypothesis in environmental epidemiology. These publications covered 60 different chemicals. The majority of publications focused on neurological/cognitive outcomes, followed by cancer, and respiratory outcomes. We note areas ready for more detailed review, those requiring more data and ideas for future directions.

Les relations entre le bisphénol A et les troubles du spectre autistique se précisent : la sérotonine est-elle le lien manquant ?

The etiology of autism spectrum disorders (ASD) is believed to be multifactorial and to involve genetic and environmental components. Environmental chemical exposures are increasingly understood to be important in causing neurotoxicity in fetuses and newborns. Recent data from the Centers for Disease Control and Prevention in the United States suggest a substantial increase in ASD prevalence, only partly explicable by factors such as diagnostic substitution. Bisphenol A (BPA) is an ubiquitous xenoestrogen widely employed in a variety of consumer products including plastic and metal food and beverage containers, dental sealants and fillings, medical equipment and thermal receipts. Therefore, most people are exposed almost continuously to BPA in industrialized countries. Sources of BPA exposure are predominantly diet, but also through inhalation or dermal absorption. BPA can be measured in many human fluids and tissues including saliva, serum, urine, amniotic fluid, follicular fluid, placental tissue and breast milk. There is concern that BPA exposure may influence human brain development and may contribute to the increasing prevalence of neurodevelopmental and behavioural problems. Epigenetic mechanisms are suggested by a mouse study that demonstrated that BPA exposure during gestation had long lasting, transgenerational effects on social recognition. Previous epidemiological studies suggested a relationship between maternal BPA exposure and ASD. A recent study of 46 children with ASD and 52 controls found for the first time a direct association between children with ASD and BPA exposure and demonstrated that BPA is not metabolized well in children with ASD. The metabolomic analyses showed a correlation between ASD and essential amino acid metabolism pathways. Essential amino acids are precursors of neurotransmitters, for example tryptophan for serotonin. Fetal and prenatal BPA exposure was suggested to perturb the serotonergic system in rat and mice models. On the other hand, hyperserotonemia was reported in approximately one-third of autistic patients and also in relatives. Moreover, neuroimaging studies revealed two fundamentally different types of serotonin synthesis abnormality in children with autism compared to age-matched nonautistic children, a difference in whole-brain capacity and focal abnormalities. Finally, decreased serotonin transporter and serotonin receptor binding have been reported in both children and adults with autism. So, the link between BPA and autism could be a defect of the normal in utero or perinatal serotonergic system development. In France, BPA was banned in baby bottles in 2010 and in any food or beverage packaging since January 2015. Therefore, there is an urgent need to find safe alternatives in the use of BPA in the manufacture of industrial products.