Adverse Effects Of Environmental Exposures Research Articles

Toxic effects and mechanisms of nanoplastics on embryonic brain development using brain organoids model

Nanoplastics can be easily absorbed into the human body through inhalation, ingestion, and skin contact due to their physicochemical property. Despite the numerous studies postulating the potential adverse effects of environmental exposure to nanoplastics on neurodevelopment, the effects of nanoplastics and their regulatory mechanisms have not been specifically elucidated. We focused on the toxic effects of nanoplastics on brain developmental processes by investigating their interactions with brain organoids. Our findings indicated that nanoplastics exposure caused cellular dysfunction and structural disorders. Nanoplastics adversely affected critical cells in brain organoids, resulting in the reduction of neural precursor cells and neuronal cells. The expression of neural cadherin was also inhibited, which might lead to impaired axonal extension and formation of synaptic connections. In addition, transcriptome sequencing was performed to study the effects of different concentrations of nanoplastics on the signaling pathway. The qRT-PCR analysis confirmed that nanoplastics exposure resulted in decreased expression of several genes related to the Wnt signaling pathway, suggesting that nanoplastics may adversely affect embryonic brain growth through the suppression of the expression of these genes. Our research findings shed light on the deleterious effects of nanoplastics on embryonic brain development and have significant implications for the field of environmental toxicology.

Impact of air pollution on cardiovascular aging

The world population is aging rapidly, and by some estimates, the number of people older than 60 will double in the next 30 years. With the increase in life expectancy, adverse effects of environmental exposures start playing a more prominent role in human health. Air pollution is now widely considered the most detrimental of all environmental risk factors, with some studies estimating that almost 20% of all deaths globally could be attributed to poor air quality. Cardiovascular diseases are the leading cause of death worldwide and will continue to account for the most significant percentage of non-communicable disease burden. Cardiovascular aging with defined pathomechanisms is a major trigger of cardiovascular disease in old age. Effects of environmental risk factors on cardiovascular aging should be considered in order to increase the health span and reduce the burden of cardiovascular disease in older populations. In this review, we explore the effects of air pollution on cardiovascular aging, from the molecular mechanisms to cardiovascular manifestations of aging and, finally, the age-related cardiovascular outcomes. We also explore the distinction between the effects of air pollution on healthy aging and disease progression. Future efforts should focus on extending the health span rather than the lifespan.

Comparing perspectives on research needs from stakeholders vs. researchers in an exposome project

Abstract Background Exposome research looks into how combined exposures affect human health. The EU-funded Equal-Life project focuses on physical and social exposures in a child’s environment and its effects on children’s mental health and cognitive development in the life course. Perspectives and priorities on what to study in particular might differ between practitioners and researchers. Therefore, collaboration with external stakeholders from various fields is encouraged to integrate practical experience and link it to the researchers’ aims. Methods Two Delphi studies were conducted collecting and evaluating research questions to be studied in the project among a) the researchers within the project and b) among external stakeholders from various European countries. The exercise was to evaluate the research questions for group a) based on relevance and testability and for b) e.g. regarding practitioners’ work and options for policies. Involved stakeholders work in health care, and urban planning, among others. Prioritised questions are collated. Findings Within the researchers’ group, top-rated questions were mainly mechanism-directed in terms of how and to what extent certain factors affect children’s mental health and cognitive development, cumulative effects in different settings, among others. Stakeholders most value research questions on practical issues, e.g. effects of early experiences of discrimination, critical windows in children’s lives that are most sensitive regarding the impact of exposures on mental health and cognitive development, or impact of exposures in early stages of life. Discussion In comparing approaches of stakeholders and researchers, stakeholders’ input from the practical field can shape the approach of the research process. The second benefit is to derive implications for creating effective interventions and policies to prevent adverse effects of environmental exposures and to foster positive health in children and later on in life. Key messages • Bi-directional exchange between researchers and external stakeholders can make gaps visible. • Engaging stakeholders into a research process can help sharpening the aim and outcome of a project.

Toxicoepigenetics and Environmental Health: Challenges and Opportunities.

The rapidly growing field of toxicoepigenetics seeks to understand how toxicant exposures interact with the epigenome to influence disease risk. Toxicoepigenetics is a promising field of environmental health research, as integrating epigenetics into the field of toxicology will enable a more thorough evaluation of toxicant-induced disease mechanisms as well as the elucidation of the role of the epigenome as a biomarker of exposure and disease and possible mediator of exposure effects. Likewise, toxicoepigenetics will enhance our knowledge of how environmental exposures, lifestyle factors, and diet interact to influence health. Ultimately, an understanding of how the environment impacts the epigenome to cause disease may inform risk assessment, permit noninvasive biomonitoring, and provide potential opportunities for therapeutic intervention. However, the translation of research from this exciting field into benefits for human and animal health presents several challenges and opportunities. Here, we describe four significant areas in which we see opportunity to transform the field and improve human health by reducing the disease burden caused by environmental exposures. These include (1) research into the mechanistic role for epigenetic change in environment-induced disease, (2) understanding key factors influencing vulnerability to the adverse effects of environmental exposures, (3) identifying appropriate biomarkers of environmental exposures and their associated diseases, and (4) determining whether the adverse effects of environment on the epigenome and human health are reversible through pharmacologic, dietary, or behavioral interventions. We then highlight several initiatives currently underway to address these challenges.

Prenatal Diet as a Modifier of Environmental Risk Factors for Autism and Related Neurodevelopmental Outcomes.

Environmental chemicals and toxins have been associated with increased risk of impaired neurodevelopment and specific conditions like autism spectrum disorder (ASD). Prenatal diet is an individually modifiable factor that may alter associations with such environmental factors. The purpose of this review is to summarize studies examining prenatal dietary factors as potential modifiers of the relationship between environmental exposures and ASD or related neurodevelopmental outcomes. Twelve studies were identified; five examined ASD diagnosis or ASD-related traits as the outcome (age at assessment range: 2-5years) while the remainder addressed associations with neurodevelopmental scores (age at assessment range: 6months to 6years). Most studies focused on folic acid, prenatal vitamins, or omega-3 fatty acids as potentially beneficial effect modifiers. Environmental risk factors examined included air pollutants, endocrine disrupting chemicals, pesticides, and heavy metals. Most studies took place in North America. In 10/12 studies, the prenatal dietary factor under study was identified as a significant modifier, generally attenuating the association between the environmental exposure and ASD or neurodevelopment. Prenatal diet may be a promising target to mitigate adverse effects of environmental exposures on neurodevelopmental outcomes. Further research focused on joint effects is needed that encompasses a broader variety of dietary factors, guided by our understanding of mechanisms linking environmental exposures with neurodevelopment. Future studies should also aim to include diverse populations, utilize advanced methods to optimize detection of novel joint effects, incorporate consideration of timing, and consider both synergistic and antagonistic potential of diet.

Digital Healthcare for Airway Diseases from Personal Environmental Exposure.

Digital technologies have emerged in various dimensions of human life, ranging from education to professional services to well-being. In particular, health products and services have expanded by the use and development of artificial intelligence, mobile health applications, and wearable electronic devices. Such advancements have enabled accurate and updated tracking and modeling of health conditions. For instance, digital health technologies are capable of measuring environmental pollution and predicting its adverse health effects. Several health conditions, including chronic airway diseases such as asthma and chronic obstructive pulmonary disease, can be exacerbated by pollution. These diseases impose substantial health burdens with high morbidity and mortality. Recently, efforts have been made to develop digital technologies to alleviate such conditions. Moreover, the COVID-19 pandemic has facilitated the application of telemedicine and telemonitoring for patients with chronic airway diseases. This article reviews current trends and studies in digital technology utilization for investigating and managing environmental exposure and chronic airway diseases. First, we discussed the recent progression of digital technologies in general environmental healthcare. Then, we summarized the capacity of digital technologies in predicting exacerbation and self-management of airway diseases. Concluding these reviews, we provided suggestions to improve digital health technologies’ abilities to reduce the adverse effects of environmental exposure in chronic airway diseases, based on personal exposure-response modeling.

Maternal exposure to metals and persistent pollutants and cord blood immune system biomarkers.

BackgroundThe fetal time period is a critical window of immune system development and resulting heightened susceptibility to the adverse effects of environmental exposures. Epidemiologists and toxicologists have hypothesized that persistent organic pollutants, pesticides and metals have immunotoxic properties. Immunotoxic effects may manifest as an altered immune system profile at birth. Immunoglobulin E, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) may be implicated in the etiology of childhood allergy and are detectable at birth. The objective of this study was to examine the potential relationship between maternal concentrations of metals, persistent organic pollutants, and pesticides and elevated umbilical cord blood concentrations of IgE, TSLP, and IL-33 in a Canadian birth cohort.MethodsThis study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2,001 pregnant women. Of these women, 1258 had a singleton, term birth and cord blood sample. Logistic regression was used to determine associations between log-transformed continuous variables and immune system biomarkers.ResultsInverse relationships were observed between lead, DDE, PCB-118, and a summary index of organophosphorous metabolites and jointly elevated concentrations of IL-33 and TSLP. None of the environmental contaminants were associated with increased odds of a high cord blood immune system biomarker concentration.ConclusionsIn this primarily urban Canadian population of pregnant women and their newborns, maternal blood or urine concentrations of persistent organic pollutants, pesticides, and metals were not associated with immunotoxic effects that manifest as increased odds of elevated concentrations of IgE, TSLP or IL-33.

Prenatal exposure to phthalates, bisphenol A and perfluoroalkyl substances and cord blood levels of IgE, TSLP and IL-33

The fetal time period is a critical window of immune system development and resulting heightened susceptibility to the adverse effects of environmental exposures. Epidemiologists and toxicologists have hypothesized that phthalates, bisphenol A (BPA) and perfluoroalkyl substance have immunotoxic properties. Immunotoxic effects of chemicals may manifest in an altered immune system profile at birth. Immunoglobulin E, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) are integral in the etiology of childhood allergy and detectable at birth. The objective of this study was to determine the association between maternal levels of phthalates, bisphenol A (BPA), and perfluoroalkyl substances and elevated umbilical cord blood levels of IgE, TSLP, and IL-33. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Of these women, 1258 had a singleton, term birth and cord blood sample. A Bayesian hierarchical model was employed to determine associations between log-transformed continuous variables and immune system biomarkers while adjusting for potential confounding from correlated environmental contaminants. Inverse, nonlinear associations were observed between maternal urinary MCPP levels and elevated levels of both IL-33/TSLP and IgE and between maternal urinary BPA levels and elevated levels of IL-33/TSLP. In this primarily urban Canadian population of pregnant women and their newborns, maternal urinary and plasma concentrations of phthalate metabolites, BPA, and perfluoroalkyl substances were not associated with immunotoxic effects that manifest as increased odds of elevated levels of IgE, TSLP or IL-33.

Overview of Emerging Contaminants and Associated Human Health Effects.

In recent decades, because of significant progress in the analysis and detection of trace pollutants, emerging contaminants have been discovered and quantified in living beings and diverse environmental substances; however, the adverse effects of environmental exposure on the general population are largely unknown. This review summarizes the conclusions of the comprehensive epidemic literature and representative case reports relevant to emerging contaminants and the human body to address concerns about potential harmful health effects in the general population. The most prevalent emerging contaminants include perfluorinated compounds, water disinfection byproducts, gasoline additives, manufactured nanomaterials, human and veterinary pharmaceuticals, and UV-filters. Rare but statistically meaningful connections have been reported for a number of contaminants and cancer and reproductive risks. Because of contradictions in the outcomes of some investigations and the limited number of articles, no significant conclusions regarding the relationship between adverse effects on humans and extents of exposure can be drawn at this time. Here, we report that the current evidence is not conclusive and comprehensive and suggest prospective cohort studies in the future to evaluate the associations between human health outcomes and emerging environmental contaminants.

Translational toxicology: a developmental focus for integrated research strategies.

BackgroundGiven that toxicology studies the potential adverse effects of environmental exposures on various forms of life and that clinical toxicology typically focuses on human health effects, what can and should the relatively new term of "translational toxicology" be taken to mean?DiscussionOur assertion is that the core concept of translational toxicology must incorporate existing principles of toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond simple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of exposures.The field of toxicology has now reached a point where advances in multiple areas of biomedical research and information technologies empower us to make fundamental transitions in directly impacting human health. Translational toxicology must encompass four action elements as follows:1) Assessing human exposures in critical windows across the lifespan2) Defining modes of action and relevance of data from animal models3) Use of mathematical models to develop plausible predictions as the basis for4) Protective and restorative human health interventions.The discussion focuses on the critical window of in-utero development.SummaryExposure assessment, basic toxicology and development of certain categories of mathematical models are not new areas of research; however overtly integrating these in order to conceive, assess and validate effective interventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is what we should do in translational toxicology so that we have a portfolio of interventional options to improve human health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics.

Longitudinal Cohort Studies on Child Health in South East Asia

Children are more vulnerable to adverse environmental exposures than adults and are often exposed to higher doses of toxicants. The consequences of exposure depend on the developmental stage during which the exposures occur. While many organ systems are mature at or soon after birth the respiratory, immune, and central nervous system have prolonged periods of postnatal maturation making them vulnerable to environmental exposures occurring after birth. While cross-sectional studies can provide information about associates between exposures and health outcomes, the optimal method for determining the adverse effects of environmental exposures is to follow a group of children from before or at birth, carefully measuring exposures and outcomes over time. Longitudinal cohort studies present a particular set of challenges that need to be overcome. Such studies are expensive to undertake and require dedicated personnel. Many studies are too small to identify links between exposures and less common outcomes. Here, the use of harmonized protocols can be beneficial in allowing data to be combined from a number of studies, thus increasing the power to detect small effects. This presentation will focus on a general approach to conducting longitudinal studies on respiratory health and neurodevelopment. Examples from existing cohorts and studies in the planning phase will be used.

Proteomic approaches to characterize protein modifications: new tools to study the effects of environmental exposures.

Proteomics is the study of proteomes, which are the collections of proteins expressed in cells. Whereas genomes are essentially invariant in different cells in an organism, proteomes vary from cell to cell, with time and as a function of environmental stimuli and stress. The integration of new mass spectrometry (MS) methods, data analysis algorithms, and information from databases of protein and gene sequences has enabled the characterization of proteomes. Many environmental agents directly or indirectly generate reactive electrophiles that covalently modify proteins. Although considerable evidence supports a key role for protein adducts in adverse effects of chemicals, limitations in analytical technology have slowed progress in this area. New applications of liquid chromatography-tandem mass spectrometry (LC-MS-MS) now offer the potential to identify protein targets of reactive electrophiles and to map adducts at the level of amino acid sequence. Use of the data-analysis tools Sequest and SALSA (Scoring Algorithm for Spectral Analysis) together with LC-MS-MS analyses of protein digests enables the identification of modified forms of proteins in a sample. These approaches can map adducts to specific amino acids in protein targets and are being adapted to searches for protein adducts in complex proteomes. These tools will facilitate the identification of new biomarkers of chemical exposure and studies of mechanisms by which protein modifications contribute to the adverse effects of environmental exposures.

Hsp70 expression and function during embryogenesis.

This review focuses on the expression and function of 70-kDa heat shock proteins (Hsp70s) during mammalian embryogenesis, though many features of embryogenesis and the developmental expression of Hsp70s are conserved between mammals and other vertebrates. A variety of Hsp70s are expressed from the point of zygotic gene activation in cleavage-stage embryos, through blastulation, implantation, gastrulation, neurulation, organogenesis, and on throughout fetal maturation. The regulation and patterns of hsp70 gene expression and the known and putative Hsp70 protein functions vary from constitutive and metabolic housekeeping to stress-inducible and embryo-protective roles. Understanding the genetic regulation and molecular function of Hsp70s has been pursued by developmental biologists interested in the control of gene expression in early embryos as well as reproductive toxicologists and teratologists interested in how Hsp70s protect embryos from the adverse effects of environmental exposures. These efforts have also been joined by those interested in the chaperone functions of Hsp70s, and this confluence of effort has yielded many advances in our understanding of Hsp70s during critical phases of embryonic development and cellular differentiation.

Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age

Objective: To study possible adverse effects of environmental exposure to polychlorinated biphenyls (PCB) and dioxins on cognitive functioning in young children. Methods: In a follow-up of the Dutch PCB/Dioxin study, cognitive abilities were assessed with the Kaufman Assessment Battery for Children in 42-month-old children (n = 395). In a subgroup (n = 193) verbal comprehension was assessed with the Reynell Language Developmental Scales. Prenatal PCB exposure was estimated from the sum of PCBs 118, 138, 153, and 180 (ΣPCB) in maternal plasma. Lactational exposure was assessed from breast milk PCB and dioxin concentrations, multiplied by the number of weeks of breast-feeding. Current PCB body burden was estimated from ΣPCB in 42-month-old plasma samples. Results: After adjustment was done for covariables, maternal ΣPCB was associated with lower scores on the overall cognitive and sequential and simultaneous processing scales of the Kaufman Assessment Battery for Children (all P < .05). The highest exposed group (ΣPCB ≥ 3 μg/L) scored 4 points lower on all 3 scales of the K-ABC when compared with the lowest exposed group (ΣPCB < 1.5 μg/L). Both lactational exposure and current exposure to PCBs and dioxins were not related to 42-month cognitive performance. Conclusions: In utero exposure to “background” PCB concentrations is associated with poorer cognitive functioning in preschool children. Children of mothers at the upper end of exposure are especially at risk. Therefore maternal PCB body burden should be reduced, and breast-feeding should not be discouraged. (J Pediatr 1999;134:33-41)

Effects on reserve capacity: Significance for exposure limits

The human body has a certain capacity to withstand potentially adverse effects of environmental exposures. Chemical exposures may result in a weakening of the body defenses, i.e. a decrease in reserve capacity, thus leading to increased susceptibility to other exposures. Thus, despite normal hematological findings in the initial examination of a group of lead-exposed workers, the lead exposure caused a decreased reserve capacity for blood formation; these effects became prominent only after phlebotomy where the lead-exposed workers showed a decreased rate of blood regeneration. Evidence from studies of cell attrition and age-related functional decreases of the nervous system and the kidneys suggest that a reserve capacity exists and that it may be vulnerable to chemical exposures. Reserve capacity may therefore be a notion of wide significance with regard to chemical exposures as part of multicausal disease etiologies.

Cancer Risk Assessment and Prevention: Where Do We Stand?

This paper reviews selected aspects of progress and setbacks in cancer risk assessment and prevention during the four decades since the founding in 1947 of the Institute of Environmental Medicine at the New York University Medical Center. The period has been marked by substantial gains in quantifying the risks posed by exposures to known human carcinogens such as tobacco and ionizing radiation. By contrast, the search for sensitive and specific laboratory screens for human carcinogens has met setbacks, and epidemiological data still are needed to monitor the adverse effects of environmental exposures. The determination of acceptable levels of exposure to potential human carcinogens remains a formidable task, one for which no scientific framework yet exists. Future challenges in cancer risk assessment include the validation and use of biological markers of exposure and effective monitoring of risk among exposed populations. Future challenges in cancer prevention include the elimination of tobacco consumption and the acquisition of knowledge needed to prevent nutritionally and hormonally related cancers such as cancers of the bowel, prostate, and breast.

Cancer risk assessment and prevention: where do we stand?

This paper reviews selected aspects of progress and setbacks in cancer risk assessment and prevention during the four decades since the founding in 1947 of the Institute of Environmental Medicine at the New York University Medical Center. The period has been marked by substantial gains in quantifying the risks posed by exposures to known human carcinogens such as tobacco and ionizing radiation. By contrast, the search for sensitive and specific laboratory screens for human carcinogens has met setbacks, and epidemiological data still are needed to monitor the adverse effects of environmental exposures. The determination of acceptable levels of exposure to potential human carcinogens remains a formidable task, one for which no scientific framework yet exists. Future challenges in cancer risk assessment include the validation and use of biological markers of exposure and effective monitoring of risk among exposed populations. Future challenges in cancer prevention include the elimination of tobacco consumption and the acquisition of knowledge needed to prevent nutritionally and hormonally related cancers such as cancers of the bowel, prostate, and breast.