Environmental Chemical Exposures Research Articles

Developmental exposure to a real-life environmental chemical mixture alters testicular transcription factor expression in neonatal and pre-pubertal rams, with morphological changes persisting into adulthood

Environmental chemical (EC) exposure may be impacting male reproductive health. The translationally relevant biosolids treated pasture (BTP) sheep model was used to investigate gestational low-level EC mixture exposure on the testes of F1 male offspring. Adult rams from ewes exposed to BTP 1 month before and throughout pregnancy had more seminiferous tubules with degeneration and depletion of elongating spermatids, indicating possible “recovery” from previously reported testicular dysgenesis syndrome-like phenotype in neonatal and pre-pubertal BTP lambs. Expression of transcription factors CREB1 (neonatal) and BCL11A and FOXP2 (pre-pubertal) were significantly higher in the BTP exposed testes, with no changes seen in adults. Increased CREB1, which is crucial for testes development and regulation of steroidogenic enzymes, could be an adaptive response to gestational EC exposure to facilitate the phenotypic recovery. Overall, this demonstrates that testicular effects from gestational exposure to low-level mixtures of ECs can last into adulthood, potentially impacting fertility and fecundity.

Tracking end-of-life stage of chemicals: A scalable data-centric and chemical-centric approach

Chemical flow analysis (CFA) can be used for collecting life-cycle inventory (LCI), estimating environmental releases, and identifying potential exposure scenarios for chemicals of concern at the end-of-life (EoL) stage. Nonetheless, the demand for comprehensive data and the epistemic uncertainties about the pathway taken by the chemical flows make CFA, LCI, and exposure assessment time-consuming and challenging tasks. Due to the continuous growth of computer power and the appearance of more robust algorithms, data-driven modelling represents an attractive tool for streamlining these tasks. However, a data ingestion pipeline is required for the deployment of serving data-driven models in the real world. Hence, this work moves forward by contributing a chemical-centric and data-centric approach to extract, transform, and load comprehensive data for CFA at the EoL, integrating cross-year and country data and its provenance as part of the data lifecycle. The framework is scalable and adaptable to production-level machine learning operations. The framework can supply data at an annual rate, making it possible to deal with changes in the statistical distributions of model predictors like transferred amount and target variables (e.g., EoL activity identification) to avoid potential data-driven model performance decay over time. For instance, it can detect that recycling transfers of 643 chemicals over the reporting years (1988 to 2020) are 29.87%, 17.79%, and 20.56% for Canada, Australia, and the U.S. Finally, the developed approach enables research advancements on data-driven modelling to easily connect with other data sources for economic information on industry sectors, the economic value of chemicals, and the environmental regulatory implications that may affect the occurrence of an EoL transfer class or activity like recycling of a chemical over years and countries. Finally, stakeholders gain more context about environmental regulation stringency and economic affairs that could affect environmental decision-making and EoL chemical exposure predictions.

The contribution of the exposome to the burden of cardiovascular disease.

Large epidemiological and health impact assessment studies at the global scale, such as the Global Burden of Disease project, indicate that chronic non-communicable diseases, such as atherosclerosis and diabetes mellitus, caused almost two-thirds of the annual global deaths in 2020. By 2030, 77% of all deaths are expected to be caused by non-communicable diseases. Although this increase is mainly due to the ageing of the general population in Western societies, other reasons include the increasing effects of soil, water, air and noise pollution on health, together with the effects of other environmental risk factors such as climate change, unhealthy city designs (including lack of green spaces), unhealthy lifestyle habits and psychosocial stress. The exposome concept was established in 2005 as a new strategy to study the effect of the environment on health. The exposome describes the harmful biochemical and metabolic changes that occur in our body owing to the totality of different environmental exposures throughout the life course, which ultimately lead to adverse health effects and premature deaths. In this Review, we describe the exposome concept with a focus on environmental physical and chemical exposures and their effects on the burden of cardiovascular disease. We discuss selected exposome studies and highlight the relevance of the exposome concept for future health research as well as preventive medicine. Wealso discuss the challenges and limitations of exposome studies.

Premature ovarian insufficiency associated with environmental chemical exposure among Korean women: a study based on the Korean National Environmental Health Survey (2009–2012)

Premature ovarian insufficiency associated with environmental chemical exposure among Korean women: a study based on the Korean National Environmental Health Survey (2009–2012)

The Role of Environmental Chemicals in the Etiology of Learning Difficulties: A Novel Theoretical Framework.

Children from economically disadvantaged communities have a disproportionate risk of exposure to chemicals, social stress, and learning difficulties. Although animal models and epidemiologic studies link exposures and neurodevelopment, little focus has been paid to academic outcomes in environmental health studies. Similarly, in the educational literature, environmental chemical exposures are overlooked as potential etiologic factors in learning difficulties. We propose a theoretical framework for the etiology of learning difficulties that focuses on these understudied exogenous factors. We discuss findings from animal models and longitudinal, prospective birth cohort studies that support this theoretical framework. Studies reviewed point to the effects of prenatal exposure to polycyclic aromatic hydrocarbons on reading comprehension and math skills via effects on inhibitory control processes. Long term, this work will help close the achievement gap in the United States by identifying behavioral and neural pathways from prenatal exposures to learning difficulties in children from economically disadvantaged families.

Deciphering Gut Microbiome Responses upon Microplastic Exposure via Integrating Metagenomics and Activity-Based Metabolomics.

Perturbations of the gut microbiome are often intertwined with the onset and development of diverse metabolic diseases. It has been suggested that gut microbiome perturbation could be a potential mechanism through which environmental chemical exposure induces or exacerbates human diseases. Microplastic pollution, an emerging environmental issue, has received ever increasing attention in recent years. However, interactions between microplastic exposure and the gut microbiota remain elusive. This study aimed to decipher the responses of the gut microbiome upon microplastic polystyrene (MP) exposure by integrating 16S rRNA high-throughput sequencing with metabolomic profiling techniques using a C57BL/6 mouse model. The results indicated that MP exposure significantly perturbed aspects of the gut microbiota, including its composition, diversity, and functional pathways that are involved in xenobiotic metabolism. A distinct metabolite profile was observed in mice with MP exposure, which probably resulted from changes in gut bacterial composition. Specifically, untargeted metabolomics revealed that levels of metabolites associated with cholesterol metabolism, primary and secondary bile acid biosynthesis, and taurine and hypotaurine metabolism were changed significantly. Targeted approaches indicated significant perturbation with respect to the levels of short-chain fatty acids derived from the gut microbiota. This study can provide evidence for the missing link in understanding the mechanisms behind the toxic effects of microplastics.

Neonatal Exposure to Valproate Induces Long-Term Alterations in Steroid Hormone Levels in the Brain Cortex of Prepubertal Rats

Valproic acid (VPA) is a known drug for treating epilepsy and mood disorders; however, it is not recommended for pregnant women because of its possible teratogenicity. VPA affects neurotransmission and gene expression through epigenetic mechanisms by acting as a histone deacetylase inhibitor and has been used to establish animal models of autism spectrum disorder (ASD). However, studies on the long-term effects of early exposure to VPA on glucocorticoid and neurosteroid synthesis in the brain are lacking. Therefore, this study aimed to investigate the long-term changes in metabolic alterations and gene expression regulation according to sex, using metabolic steroid profiling data from cerebral cortex samples of rats four weeks after VPA exposure (400 mg/kg). In neonatal VPA-exposed models, estradiol levels decreased, and cytochrome P450 19A1 gene (Cyp19a1) expression was reduced in the prepubertal male cortex. Progesterone and allopregnanolone levels decreased, and 3β-hydroxysteroid dehydrogenase 1 gene (Hsd3b1) expression was also downregulated in the prepubertal female cortex. Furthermore, cortisol levels increased, and mRNA expression of the nuclear receptor subfamily 3 group C member 1 gene (Nr3c1) was downregulated in the cortices of both sexes. Unlike the neonatal VPA-exposed models, although a decrease in progestin and estradiol levels was observed in females and males, respectively, no differences were observed in cortisol levels in the cortex tissues of 8-week-old adult rats administered VPA for four weeks. These results indicate that early environmental chemical exposure induces long-term neurosteroid metabolic effects in the brain, with differences according to sex.

The Superfund Research Program Analytics Portal: linking environmental chemical exposure to biological phenotypes

The OSU/PNNL Superfund Research Program (SRP) represents a longstanding collaboration to quantify Polycyclic Aromatic Hydrocarbons (PAHs) at various superfund sites in the Pacific Northwest and assess their potential impact on human health. To link the chemical measurements to biological activity, we describe the use of the zebrafish as a high-throughput developmental toxicity model that provides quantitative measurements of the exposure to chemicals. Toward this end, we have linked over 150 PAHs found at Superfund sites to the effect of these same chemicals in zebrafish, creating a rich dataset that links environmental exposure to biological response. To quantify this response, we have implemented a dose-response modelling pipeline to calculate benchmark dose parameters which enable potency comparison across over 500 chemicals and 12 of the phenotypes measured in zebrafish. We provide a rich dataset for download and analysis as well as a web portal that provides public access to this dataset via an interactive web site designed to support exploration and re-use of these data by the scientific community at http://srp.pnnl.gov.

Associations Between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

ABSTRACT Preterm birth is a leading cause of neonatal mortality. Preterm birth is a public health burden, particularly in the United States, where approximately 10% of deliveries are preterm. Although the underlying cause of most preterm births is unknown, environmental chemical exposures (such as phthalates) possibly contribute. Phthalates are common in consumer products, and exposure can occur through diet, personal care products, and even household dust. Consequently, exposure is ubiquitous for pregnant individuals. Prenatal phthalate exposure has been associated with adverse neurodevelopment in children and disordered development of the male reproductive tract. This study reviewed 16 prospective studies conducted within the United States to pool individual-level data to examine prenatal urinary biomarkers of phthalate exposure and preterm birth. In addition, potential influence of exposure to overall phthalate mixture was assessed to determine the potential impact of reduced exposure on preterm birth. Results of the study indicated that of 6045 pregnant women, 539 (9%) delivered preterm. Overall, of the entire included cohort, 802 individuals were Black (13.3%), 2576 were White (42.6%), 2323 were Latina (38.4%), and 328 had other race identity (including Native Hawaiian, Alaskan Native, or American Indian). Characteristics of participants were similar between those who delivered preterm versus term. Some 96% of urine samples displayed detectable concentrations of urinary phthalate metabolites. As demonstrated by regression analyses, higher concentrations of most phthalate metabolites bore an association of slightly higher odds (12%–16% higher) for preterm birth. In addition, the study estimated that reducing the mixture of phthalate metabolite concentrations by 10%, 30%, or 50%, respectively, could prevent 1.8, 5.9, and 11.1 preterm births per 1000 live births. The study found a relationship between higher maternal pregnancy concentrations of urinary phthalate metabolites and preterm birth. The findings of this study identify a potential benefit of phthalate exposure reduction among pregnant individuals via either regulations or behavioral interventions. Because phthalate exposure can occur through many environments and sources, the US Consumer Product Safety Commission has attempted to pinpoint major sources of phthalate exposure and has determined that the predominate exposures appear to occur through food and medications, although uncertainty in the primary source of exposure remains. Phthalate exposure also widely varies in the United States based on several factors such as whether a person is at a disadvantaged socioeconomic status, is pregnant, or is of a marginalized race or ethnicity. Targeted interventions, such as altering personal care products, is made challenging as consumers are not readily able to access accurate ingredients lists. In the United States, for example, fragrance ingredient lists are not required to list phthalates when they are included in the product. Diet interventions intending to reduce phthalate exposure have had mixed results. Although federally mandated restrictions have limited the use of phthalates in products for children, few such restrictions exist for products intended for pregnant individuals. As 28 phthalates are currently allowed as food additives or in food contact materials, they are difficult to avoid. Mitigation of population-level health effects from phthalates through regulatory means would be most effective when considering phthalates not as individual chemicals, but rather as a class. This study found that higher concentrations of several urinary phthalate metabolites in pregnancy were associated with preterm birth, a consistent finding across 16 prospective US studies. Such findings emphasize the importance of the development of policy measures and public health around phthalate exposure reduction, especially among pregnant individuals.

Endocrine Disrupting Chemicals Influence Hub Genes Associated with Aggressive Prostate Cancer

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men in the world. Its prevention has been limited because of an incomplete understanding of how environmental exposures to chemicals contribute to the molecular pathogenesis of aggressive PCa. Environmental exposures to endocrine-disrupting chemicals (EDCs) may mimic hormones involved in PCa development. This research aims to identify EDCs associated with PCa hub genes and/or transcription factors (TF) of these hub genes in addition to their protein-protein interaction (PPI) network. We are expanding upon the scope of our previous work, using six PCa microarray datasets, namely, GSE46602, GSE38241, GSE69223, GSE32571, GSE55945, and GSE26126, from the NCBI/GEO, to select differentially expressed genes based on |log2FC| (fold change) ≥ 1 and an adjusted p-value < 0.05. An integrated bioinformatics analysis was used for enrichment analysis (using DAVID.6.8, GO, KEGG, STRING, MCODE, CytoHubba, and GeneMANIA). Next, we validated the association of these PCa hub genes in RNA-seq PCa cases and controls from TCGA. The influence of environmental chemical exposures, including EDCs, was extrapolated using the chemical toxicogenomic database (CTD). A total of 369 overlapping DEGs were identified associated with biological processes, such as cancer pathways, cell division, response to estradiol, peptide hormone processing, and the p53 signaling pathway. Enrichment analysis revealed five up-regulated (NCAPG, MKI67, TPX2, CCNA2, CCNB1) and seven down-regulated (CDK1, CCNB2, AURKA, UBE2C, BUB1B, CENPF, RRM2) hub gene expressions. Expression levels of these hub genes were significant in PCa tissues with high Gleason scores ≥ 7. These identified hub genes influenced disease-free survival and overall survival of patients 60-80 years of age. The CTD studies showed 17 recognized EDCs that affect TFs (NFY, CETS1P54, OLF1, SRF, COMP1) that are known to bind to our PCa hub genes, namely, NCAPG, MKI67, CCNA2, CDK1, UBE2C, and CENPF. These validated differentially expressed hub genes can be potentially developed as molecular biomarkers with a systems perspective for risk assessment of a wide-ranging list of EDCs that may play overlapping and important role(s) in the prognosis of aggressive PCa.

Adult exposure of atrazine alone or in combination with carbohydrate diet hastens the onset/progression of type 2 diabetes in Drosophila

AimThe combined impact of traditional and non-traditional risk factors of type 2 diabetes (T2D) on the development and progression of insulin resistance and associated complications is poorly understood. Therefore, we assessed the effect of moderately rich sugar diet coupled with environmental chemical exposure on the development and progression of T2D using Drosophila as a model organism. Main methodsWe reared newly eclosed Drosophila males on a diet containing atrazine (20 μg/ml; non-traditional risk factor) and/or moderately high sucrose (0.5 M/1 M; to mimic binge eating, Traditional risk factor) for 20–30 days. Subsequently, we assessed diabetic parameters, oxidative stress parameters and also the abundance of advanced glycation end products (AGEs) along with their receptor (RAGE) in these flies. For diabetic cardiomyopathy, we examined the pericardin (tissue fibrosis marker) level in Drosophila heart. Key findingsFlies reared on 20 μg/ml atrazine alone showed T2D hallmarks at 30 days. In contrast, flies reared on 0.5 M sucrose+ 20 μg/ml atrazine showed insulin resistance characterized by hyperglycemia and increased Drosophila insulin-like peptides along with reduced insulin signaling at 20 days, similar to those reared on high sucrose diet. In addition, both groups had high levels of oxidative stress and showed starvation response (converting triglycerides into fatty acids). Alarmingly, flies fed with sucrose+atrazine for 20 and 30 days had elevated pericardin in heart tissues, indicating early onset of diabetic complications such as cardiomyopathy. SignificanceLifestyle-chemical exposure synergistically impairs glucose metabolism, affects organisms' redox state and leads to the early onset of T2D and associated complications like cardiomyopathy.

Generation of the Chemical and Social Stressors Integration Technique (CASS-IT) to identify areas of holistic public health concern: An application to North Carolina

Due to structural racism and income inequality, exposure to environmental chemicals is tightly linked to socioeconomic factors. In addition, exposure to psychosocial stressors, such as racial discrimination, as well as having limited resources, can increase susceptibility to environmentally induced disease. Yet, studies are often conducted separately in fields of social science and environmental science, reducing the potential for holistic risk estimates. To tackle this gap, we developed the Chemical and Social Stressors Integration Technique (CASS-IT) to integrate environmental chemical and social stressor datasets. The CASS-IT provides a framework to identify distinct geographic areas based on combinations of environmental chemical exposure, social vulnerability, and access to resources. It incorporates two data dimension reduction tools: k-means clustering and latent profile analysis. Here, the CASS-IT was applied to North Carolina (NC) as a case study. Environmental chemical data included toxic metals – arsenic, manganese, and lead – in private drinking well water. Social stressor data were captured by the CDC's social vulnerability index's four domains: socioeconomic status, household composition and disability, minority status and language, and housing type and transportation. Data on resources were derived from Federal Emergency Management Agency (FEMA's) Resilience and Analysis Planning Tool, which generated measures of health resources, social resources, and information resources. The results highlighted 31 NC counties where exposure to both toxic metals and social stressors are elevated, and health resources are minimal; these are counties in which environmental justice is of utmost concern. A census-tract level analysis was also conducted to demonstrate the utility of CASS-IT at different geographical scales. The tract-level analysis highlighted specific tracts within counties of concern that are particularly high priority. In future research, the CASS-IT can be used to analyze United States-wide environmental datasets providing guidance for targeted public health interventions and reducing environmental disparities.

Childhood exposures to environmental chemicals and neurodevelopmental outcomes in congenital heart disease.

Children with congenital heart defects have an increased risk of neurodevelopmental disability. The impact of environmental chemical exposures during daily life on neurodevelopmental outcomes in toddlers with congenital heart defects is unknown. This prospective study investigated the impacts of early childhood exposure to mixtures of environmental chemicals on neurodevelopmental outcomes after cardiac surgery. Outcomes were assessed at 18 months of age using The Bayley Scales of Infant and Toddler Development-III. Urinary concentrations of exposure biomarkers of pesticides, phenols, parabens, and phthalates, and blood levels of lead, mercury, and nicotine were measured at the same time point. Bayesian profile regression and weighted quantile sum regression were utilized to assess associations between mixtures of biomarkers and neurodevelopmental scores. One-hundred and forty infants were enrolled, and 110 (79%) returned at 18 months of age. Six biomarker exposure clusters were identified from the Bayesian profile regression analysis; and the pattern was driven by 15 of the 30 biomarkers, most notably 13 phthalate biomarkers. Children in the highest exposure cluster had significantly lower adjusted language scores by -9.41 points (95%CI: -17.2, -1.7) and adjusted motor scores by -4.9 points (-9.5, -0.4) compared to the lowest exposure. Weighted quantile sum regression modeling for the overall exposure-response relationship showed a significantly lower adjusted motor score (β = -2.8 points [2.5th and 97.5th percentile: -6.0, -0.6]). The weighted quantile sum regression index weights for several phthalates, one paraben, and one phenol suggest their relevance for poorer neurodevelopmental outcomes. Like other children, infants with congenital heart defects are exposed to complex mixtures of environmental chemicals in daily life. Higher exposure biomarker concentrations were associated with significantly worse performance for language and motor skills in this population.

Undertreatment with Osimertinib in patient with multiple chemical sensitivity. A case report.

Multiple chemical sensitivity (MCS), is a syndrome characterised by increased sensitivity to the exposure of environmental chemicals (1). There are considerable difficulties in reaching a good estimate of the prevalence of disease and the main pathogenetic hypotheses take into account both the organic and psychiatric/psychological factors. Treatment with epidermal growth factor tyrosine kinase receptor inhibitors (tkis), like Osimertinib, results in improved progression-free survival (PFS) compared to chemotherapy, in Non-small-cell lung carcinoma (NSCLC) with epidermal growth factor receptor (EGFR) mutation (2). We describe the case of a 74 year old woman with history of MCS and fibromyalgia in treatment with Osimertinib for EGFR-mutated NSCLC. Patient initially refused any form of active therapy for lung cancer, but thanks to teamwork and the important support of the psychologist, the patient decided to start treatment with Osimertinib at a reduced dose, not 80 mg but 40 mg. Subsequently, after few days , of his own free will and without informing the staff physicians, the patient changed the treatment schedule by taking one quarter of the dose of the medicine every other day, justifying this choice in therapeutic modification because of her fear and intolerance to any type of medicine and/ or chemical substance, being influenced by MCS. Despite the changes in the treatment plan, a PET scan performed after two months showed a sigificative lung response and the stability of bone metastases. Discussion. Our case describes a significative response with Osimertinib despite the change in dosage and schedule in a patient with MCS. Our experience deserves to be considered in the light of its particularity and uniqueness as it shows an excellent response to treatment with Osimertinib despite the change made to the dosage and schedule, in a patient presenting in her medical history this rare pathological condition: MCS syndrome.

Chemical Induced Rodent Model of Autism Spectrum Disorders

The term Autism spectrum disorder (ASD) refers to a neuro-developmental disorder that include repetitive behaviours, extremely constrained interests and deficits in social communication. In the last ten years, the numerous epidemiological papers discussing connection between autism and environmental chemical exposures has significantly increased. These findings are crucial because they focus on modifiable risk factors that may open up new possibilities for the primary prevention of the autism-related disability, which is now recognised to be more strongly related to environmental factors than was previously thought. A variety of environmental factors have been known as significant factors relevant to aetiology of ASD, such as lead and mercury (heavy metals), PCB(organic contaminant) and phthalates and BPA. The most accurate animal model of autism among all other models is valproic acid-induced autism, which can reproduce almost all of the molecular and cellular changes seen in humans with ASD. This review provide insight into various diagnostic available for autism, pathophysiology of autism and animal model of autism to develop a pharmacological therapeutic intervention for the treatment of disease.

Exposure forecasting - ExpoCast - for data-poor chemicals in commerce and the environment.

Estimates of exposure are critical to prioritize and assess chemicals based on risk posed to public health and the environment. The U.S. Environmental Protection Agency (EPA) is responsible for regulating thousands of chemicals in commerce and the environment for which exposure data are limited. Since 2009 the EPA's ExpoCast ("Exposure Forecasting") project has sought to develop the data, tools, and evaluation approaches required to generate rapid and scientifically defensible exposure predictions for the full universe of existing and proposed commercial chemicals. This review article aims to summarize issues in exposure science that have been addressed through initiatives affiliated with ExpoCast. ExpoCast research has generally focused on chemical exposure as a statistical systems problem intended to inform thousands of chemicals. The project exists as a companion to EPA's ToxCast ("Toxicity Forecasting") project which has used in vitro high-throughput screening technologies to characterize potential hazard posed by thousands of chemicals for which there are limited toxicity data. Rapid prediction of chemical exposures and in vitro-in vivo extrapolation (IVIVE) of ToxCast data allow for prioritization based upon risk of adverse outcomes due to environmental chemical exposure. ExpoCast has developed (1) integrated modeling approaches to reliably predict exposure and IVIVE dose, (2) highly efficient screening tools for chemical prioritization, (3) efficient and affordable tools for generating new exposure and dose data, and (4) easily accessible exposure databases. The development of new exposure models and databases along with the application of technologies like non-targeted analysis and machine learning have transformed exposure science for data-poor chemicals. By developing high-throughput tools for chemical exposure analytics and translating those tools into public health decisions ExpoCast research has served as a crucible for identifying and addressing exposure science knowledge gaps.

Environmental chemical risk factors of breast cancer in Nigeria I: Broad overview

Nigeria is currently experiencing a most disturbing level of incidence rate, morbidity and mortality from the ravages of female breast cancer, with its attendant burden of emotional, social and financial consequences. Tens of thousands of chemicals make their way into our everyday products and environment, with little regard for safety. The need to explore the impact of adverse environmental chemical exposures to breast health in Nigeria informed this study as there is need for public health approach to long term prevention. After exploring the robust scientific database on environmental chemical risk factors for female breast cancer, we found that many mammary toxicants are ubiquitous in our environment in Nigeria but have been taken for granted as inevitable in normal life exposures. This study identifies some of the potential environmental chemical risk factors of breast cancer in Nigeria. We describe the special exposure scenarios in Nigeria and prescribe some modest but practical ways to mitigate exposures. The factors that constitute risk to breast cancer could potentially be modified either through community education or government action and regulation. The subject is discussed in multiple Parts before releasing the manuscripts for publication to prevent criminalizing only a few chemicals if discussed and published to the exclusion of others. To our knowledge, this is the first ever comprehensive work on the subject in the African continent and is useful to typical developing countries as are found in sub-Saharan countries and elsewhere since findings and recommendations are usually generic in nature and mutually beneficial.

Urinary phthalate metabolite concentrations and hot flash outcomes: Longitudinal associations in the Midlife Women's Health Study

Midlife in women is an understudied time for environmental chemical exposures and menopausal outcomes. Recent cross-sectional research links phthalates with hot flashes, but little is known regarding such associations over time. Our objective was to estimate longitudinal associations between repeated measures of urinary phthalate metabolite concentrations and hot flash outcomes in midlife women. Using data from the Midlife Women's Health Study (MWHS), a prospective longitudinal study, we fit generalized linear mixed-effects models (GLMMs) and Cox proportional hazards regression models to repeated measures over a 4-year period. Recruitment occurred in Baltimore and surrounding counties, Maryland, USA between 2006 and 2015. Participants were premenopausal/perimenopausal women (n = 744) aged 45–54 years, who were not pregnant, not taking menopausal symptom medication or oral contraceptives, did not have hysterectomy/oophorectomy, and irrespective of hot flash experience. Baseline mean (SD) age was 48.4 (2.45), and 65% were premenopausal. Main outcome measures included adjusted odds ratios (ORs) for 4 self-reported hot flash outcomes (ever experienced, past 30 days experience, weekly/daily, and moderate/severe), and hazard ratios (HRs) for incident hot flashes. We observed mostly increased odds of certain hot flash outcomes with higher concentrations of metabolites of di (2-ethylhexyl) phthalate (DEHP), monoisobutyl phthalate (MiBP), and a molar summary measure of plasticizer phthalate metabolites (DEHP metabolites, mono-(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP)). Some associations between exposures and outcomes indicated decreased odds. In conclusion, phthalate metabolites were associated with certain hot flash outcomes in midlife women. Midlife may be a sensitive period for higher phthalate metabolite concentrations with respect to menopausal symptoms.

Determinants of gene expression in the human liver: Impact of aging and sex on xenobiotic metabolism

There is a need to characterize the potential susceptibility of older adults to toxicity from environmental chemical exposures. Liver xenobiotic metabolizing enzymes (XMEs) play important roles in detoxifying and eliminating xenobiotics. We examined global gene expression in the livers of young (21–45 years) and old (69+ years) men and women. Differentially expressed genes (DEG) were identified using two-way ANOVA (p ≤ 0.05). We identified 1437 and 1670 DEGs between young and old groups in men and women, respectively. Only a minor number of the total number of genes overlapped (146 genes). Aging increased or decreased pathways involved in inflammation and intermediary metabolism, respectively. Aging led to numerous changes in the expression of XME genes or genes known to control their expression (~90 genes). Out of 10 cytochrome P450s activities examined, there were increased activities of CYP1A2 and CYP2C9 enzymes in the old groups. We also identified sex-dependent genes that were more numerous in the young group (1065) than in the old group (202) and included changes in XMEs. These studies indicate that the livers from aging humans when compared to younger adults exhibit changes in XMEs that may lead to differences in the metabolism of xenobiotics.

Advances in Metal-organic Frameworks (MOFs) based Biosensors for Diagnosis: An Update.

Metal-organic frameworks (MOFs) have significant advantages over other candidate classes of chemo-sensory materials owing to their extraordinary structural tunability and characteristics. MOF-based biosensing is a simple and convenient method for identifying various species. Biomarkers are molecular or cellular processes that link environmental exposure to a health outcome. Biomarkers are important in understanding the links between environmental chemical exposure and the development of chronic diseases, as well as in identifying disease-prone subgroups. Until now, several species, including nanoparticles (NPs) and their nanocomposites, small molecules, and unique complex systems, have been used for the chemical sensing of biomarkers. Following the overview of the field, we discussed the various fabrication methods for MOFs development in this review. We provide a thorough overview of the previous five years of progress to broaden the scope of analytes for future research. Several enzymatic and non-enzymatic sensors are offered, together with a mandatory measuring method that includes detection range and dynamic range. In addition, we reviewed the comparison of enzymatic and non-enzymatic biosensors, inventive edges, and the difficulties that need to be solved. This work might open up new possibilities for material production, sensor development, medical diagnostics, and other sensing fields.