Environmental Exposure Scenarios Research Articles

Apex carnivores coping with metal(loid) pollution and oxidative stress: Biological and environmental drivers of variation in kidney of European brown bear

Induction of oxidative stress and the associated lipid peroxidation is a prevalent mechanism through which certain metal(loid)s exert nephrotoxic effects in mammals. Research on the toxic impacts of metal(loid)s in free-ranging large mammals at high trophic positions is exceedingly rare, yet crucial for understanding environmental exposure scenarios relevant to both human and animal risk assessment. Renal cortex tissues (N = 457) of free-ranging brown bears (Ursus arctos) from the Dinara-Pindos population sampled in Croatia were analysed herein for toxic metal(loid)s and the underlying biological and environmental drivers of variation, with their time trend monitored during the 2009–2022 period. In 28 individuals from the 2021–2022 period, we additionally investigated associations between metal(loid)s and oxidative stress and damage biomarkers in renal cortex cells. The principal generalized linear models used to approximate variations in biomarkers of oxidative stress and damage included non-essential As, Cd, Pb, Tl and U, and essential Co, Cu, Fe and Zn. Age class and season of sampling had no impact on biomarker levels, except for lipid peroxidation, LP (April ↑). Age, sex (females ↑), body condition index (↓) and season of sampling significantly influenced metal(loid)s levels. Non-specific mammalian thresholds were crossed for Cd and Pb toxicity in 1–16% and 2% of population, respectively. Renal levels of metal(loid)s did not exhibit a clear trend over the 13-year period. The levels found in this study were higher than in sympatric carnivorous and herbivorous species, but in line with findings in ursids worldwide. Potential adverse health effects from environmental exposure in brown bears may arise from disruption of oxidative balance, as evidence clearly indicated associated changes in catalase activity (↑), glutathione content (↑), LP (↓), reactive oxygen species (↓), total antioxidant capacity (↑) in the renal cortex due to the presence of the most toxicologically relevant Cd and Pb.

Developing a consistent model for predicting equilibration in polymeric passive samplers across various HOC classes in sediment pore water.

The use of polymeric passive samplers (often polydimethylsiloxane, PDMS, or low-density polyethylene, LDPE) to indicate water concentrations of hydrophobic organic compounds under environmental conditions generally requires two key parameters, a compound-specific polymer-water equilibrium partition coefficient (), and the degree of equilibration achieved in a given environmental exposure scenario. Herein, we have developed model to extrapolate equilibration of performance reference compounds between polymer and pore water across different compound classes that is also dependent upon accurate estimates of . We have also developed quantitative structure-activity relationship (QSAR) models, to estimate for PAHs, PCBs, DDx, and dioxin/furans for the two most common polymeric samplers, PDMS and LDPE. The QSAR models developed in this study provide high accuracy consistent estimates for across the different HOC families. The root mean square error of the QSAR for was 0.226 log units based upon measured values for 159 compounds and 0.184 log units for based upon measured values for 131 compounds.

Assessment of biochemical biomarkers and environmental stress indicators in some freshwater fish

The mechanism by which an organism can adapt to subtle environmental changes is predicated on modifications to biochemical processes within the cellular metabolism in response to such changes. Changes in these processes have the potential to induce alterations in cellular structures and tissue organization, as well as establish a causal link between fluctuations in these parameters and stressors exposure. This investigation's main goal and innovation is to evaluate the environmental stress indicators in the aquatic ecosystem of Lake Qarun. Pesticide residues in freshwater fish should be the primary focus of evaluation of environmental stressor concentrations, since they serve as bioindicators at different times and places on a spatiotemporal scale. A thorough analysis of suggestive biochemical biomarker reactions should also be conducted. The effects of environmental stressors, specifically pesticide contamination in Qarun Lake, have been observed and investigated in relation to two fish species: Solea aejabtiaca and Oreochronis niloticus. The results of a hazard assessment conducted at six sampling sites using spatio-temporal data revealed elevated mean values for the pesticides, persistent organic pollutants (POPs), organochlorines, organophosphates, and pyrethroids that were detected. A multi biomarker approach facilitates a more comprehensive understanding of stress responses induced by exposure to pollutants. As a result, the activities of the biochemical biomarkers CYP-450, GST, GSH, and LDH in the blood and liver of fish samples were found to be notably elevated. The suitability of the identified variables for biomonitoring of aquatic pollution was validated, and the data unveiled variations in sensitivity among species, implying that Nile tilapia could potentially function as a bioindicator with high sensitivity. The findings were correlated with the concentrations of detrimental organochlorines, organophosphorus, and pyrethroids in the muscles and gills. The data indicates that pollutants linked to agricultural wastes, runoff, and municipal effluent may be discharged into the lake ecosystem. Consequently, to safeguard the environment, it is essential to enforce and implement policies, acts, and regulations that already exist. Assessing the effects of additional environmental stressors on aquatic ecosystems is another way in which biomarker screening with an integrative approach improves our comprehension of how toxicants impact various levels of biological organization and is particularly useful in realistic environmental exposure scenarios.

Effects of metformin on wild fathead minnows (Pimephales promelas) using in-lake mesocosms in a boreal lake ecosystem

Due to its widespread use for the treatment of Type-2 diabetes, metformin is routinely detected in surface waters globally. Laboratory studies have shown that environmentally relevant concentrations of metformin can adversely affect the health of adult fish, with effects observed more frequently in males. However, the potential risk to wild fish populations has yet to be fully elucidated and remains a topic of debate. To explore whether environmentally relevant metformin exposure poses a risk to wild fish populations, the present study exposed wild fathead minnows (Pimephales promelas) to 5 or 50 μg/L metformin via 2 m diameter in-lake mesocosms deployed in a natural boreal lake in Northern Ontario at the International Institute for Sustainable Development - Experimental Lakes Area (IISD-ELA). Environmental monitoring was performed at regular intervals for 8-weeks, with fish length, weight (body, liver and gonad), condition factor, gonadosomatic index, liver-somatic index, body composition (water and biomolecules) and hematocrit levels evaluated at test termination. Metabolic endpoints were also evaluated using liver, brain and muscle tissue, and gonads were evaluated histologically. Results indicate that current environmental exposure scenarios may be sufficient to adversely impact the health of wild fish populations. Adult male fish exposed to metformin had significantly reduced whole body weight and condition factor and several male fish from the high-dose metformin had oocytes in their testes. Metformin-exposed fish had altered moisture and lipid (decrease) content in their tissues. Further, brain (increase) and liver (decrease) glycogen were altered in fish exposed to high-dose metformin. To our knowledge, this study constitutes the first effort to understand metformin's effects on a wild small-bodied fish population under environmentally relevant field exposure conditions.

Development and application of an interactive generic physiologically based pharmacokinetic (igPBPK) model for adult beef cattle and lactating dairy cows to estimate tissue distribution and edible tissue and milk withdrawal intervals for per- and polyfluoroalkyl substances (PFAS)

Humans can be exposed to per- and polyfluoroalkyl substances (PFAS) through dietary intake from milk and edible tissues from food animals. This study developed a physiologically based pharmacokinetic (PBPK) model to predict tissue and milk residues and estimate withdrawal intervals (WDIs) for multiple PFAS including PFOA, PFOS and PFHxS in beef cattle and lactating dairy cows. Results showed that model predictions were mostly within a two-fold factor of experimental data for plasma, tissues, and milk with an estimated coefficient of determination (R2) of >0.95. The predicted muscle WDIs for beef cattle were <1 day for PFOA, 449 days for PFOS, and 69 days for PFHxS, while the predicted milk WDIs in dairy cows were <1 day for PFOA, 1345 days for PFOS, and zero day for PFHxS following a high environmental exposure scenario (e.g., 49.3, 193, and 161 ng/kg/day for PFOA, PFOS, and PFHxS, respectively, for beef cattle for 2 years). The model was converted to a web-based interactive generic PBPK (igPBPK) platform to provide a user-friendly dashboard for predictions of tissue and milk WDIs for PFAS in cattle. This model serves as a foundation for extrapolation to other PFAS compounds to improve safety assessment of cattle-derived food products.

Emotional experience in uncomfortable indoor environments: A combined examination of personal factors

Emotional experience is a critical element in human perception and interaction with the social environment. These experiences, while partially determined by internal human processes, are also influenced by physical environmental factors. This study aimed to investigate the impact of unfavorable environmental conditions on emotional experiences, considering personal factors. To achieve this, we recruited 52 subjects and conducted experiments using a climate chamber capable of simulating various environmental exposure scenarios. The subjects assessed their emotional experiences in real-time using a joystick annotator while viewing 30 emotion-evoking video stimuli, each clip lasting 10 s. This process was conducted under seven different environmental conditions within the chamber, including varying temperature and lighting conditions. The study aimed to answer two key research questions: (i) does the indoor environment significantly interfere with the self-perceived emotional experience of individuals exposed to it? and (ii) can personal factors modulate the emotional experience of individuals exposed to an indoor environment? This study found that an uncomfortable thermal environment tends to increase the intensity of human emotional experience, and individuals who are low in neuroticism and extraversion but high in satisfaction with the environment are more likely to have a misperception of emotional experience. Also, an uncomfortable lighting environment not only increased the intensity of human emotional experience but also changed the emotional aspects, and those with low agreeableness and conscientiousness tended to misunderstand emotional experiences.

Importance of Dietary Uptake for in Situ Bioaccumulation of Systemic Fungicides Using Gammarus pulex as a Model Organism.

Bioaccumulation of organic contaminants from contaminated food sources might pose an underestimated risk toward shredding invertebrates. This assumption is substantiated by monitoring studies observing discrepancies of predicted tissue concentrations determined from laboratory-based experiments compared with measured concentrations of systemic pesticides in gammarids. To elucidate the role of dietary uptake in bioaccumulation, gammarids were exposed to leaf material from trees treated with a systemic fungicide mixture (azoxystrobin, cyprodinil, fluopyram, and tebuconazole), simulating leaves entering surface waters in autumn. Leaf concentrations, spatial distribution, and leaching behavior of fungicides were characterized using liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) and matrix-assisted laser desorption ionization-mass spectrometric imaging. The contribution of leached fungicides and fungicides taken up from feeding was assessed by assembling caged (no access) and uncaged (access to leaves) gammarids. The fungicide dynamics in the test system were analyzed using LC-HRMS/MS and toxicokinetic modeling. In addition, a summer scenario was simulated where water was the initial source of contamination and leaves contaminated by sorption. The uptake, translocation, and biotransformation of systemic fungicides by trees were compound-dependent. Internal fungicide concentrations of gammarids with access to leaves were much higher than in caged gammarids of the autumn scenario, but the difference was minimal in the summer scenario. In food choice and dissectioning experiments gammarids did not avoid contaminated leaves and efficiently assimilated contaminants from leaves, indicating the relevance of this exposure pathway in the field. The present study demonstrates the potential impact of dietary uptake on in situ bioaccumulation for shredders in autumn, outside the main application period. The toxicokinetic parameters obtained facilitate modeling of environmental exposure scenarios. The uncovered significance of dietary uptake for detritivores warrants further consideration from scientific as well as regulatory perspectives. Environ Toxicol Chem 2023;00:1-14. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Radiological risk assessment to marine biota from exposure to NORM from a decommissioned offshore oil and gas pipeline

Scale residues can accumulate on the interior surfaces of subsea petroleum pipes and may incorporate naturally occurring radioactive materials (NORM). The persistent nature of ‘NORM scale’ may result in a radiological dose to the organisms living on or near intact pipelines. Following a scenario of in-situ decommissioning of a subsea pipeline, marine organisms occupying the exteriors or interiors of petroleum structures may have close contact with the scale or other NORM-associated contaminated substances and suffer subsequent radiological effects. This case study used radiological dose modelling software, including the ERICA Tool (v2.0), MicroShield® Pro and mathematical equations, to estimate the likely radiological doses and risks of effects from NORM-contaminated scale to marine biota from a decommissioned offshore oil and gas pipeline. Using activity concentrations of NORM (226Ra, 210Po, 210Pb, 228Ra, 228Th) from a subsea pipeline from Australia, environmental realistic exposure scenarios including radiological exposures from both an intact pipe (external only; accounting for radiation shielding by a cylindrical carbon steel pipe) and a decommissioned pipeline with corrosive breakthrough (resulting in both internal and external radiological exposure) were simulated to estimate doses to model marine organisms. Predicted dose rates for both the external only exposure (ranging from 26 μGy/h to 33 μGy/h) and a corroded pipeline (ranging from 300 μGy/h to 16,000 μGy/h) exceeded screening levels for radiological doses to environmental receptors. The study highlighted the importance of using scale-specific solubility data (i.e., Kd) values for individual NORM radionuclides for ERICA assessments. This study provides an approach for conducting marine organism dose assessments for NORM-contaminated subsea pipelines and highlights scientific gaps required to undertake risk assessments necessary to inform infrastructure decommissioning planning.

Uranium: an overview of physicochemical properties, exposure assessment methodologies, and health effects of environmental and occupational exposure.

Uranium is chemo- and radiotoxic element which can cause multifactorial health hazards. Natural and anthropogenic uranium contamination raises concerns about potential public health problems. Natural contamination plays a significant role with regard to uranium exposure in the general population, whereas anthropogenic contamination leads to occupational uranium exposure, particularly in nuclear industry workers. In this review, we present a state-of-the-art status concerning uranium-induced health risks with a focus on epidemiological findings of uranium processing and enrichment plant workers. We provide a general overview of physicochemical properties of uranium and analytical methods for measuring or monitoring uranium, describe environmental and occupational exposure scenarios, and discuss the challenges for objectively investigating risks from uranium exposure.

MESOCOSM: A mesocosm database management system for environmental nanosafety

Engineered nanomaterials (ENMs) are intentionally designed and produced by humans to revolutionize the manufacturing sector, such as electronic goods, paints, tires, clothes, cosmetic products, and biomedicine. With the spread of these ENMs in our daily lives, scientific research have generated a huge amount of data related to their potential impacts on human and environment health. To date, these data are gathered in databases mainly focused on the (eco)toxicity and occupational exposure to ENMs. These databases are therefore not suitable to build well-informed environmental exposure scenarios covering the life cycle of ENMs. In this paper, we report the construction of one of the first centralized mesocosm database management system for environmental nanosafety (called MESOCOSM) containing experimental data collected from mesocosm experiments suited for understanding and quantifying both the environmental hazard and exposure. The database, which is publicly available through https://aliayadi.github.io/MESOCOSM-database/, contains 5200 entities covering tens of unique experiments investigating Ag, CeO2, CuO, TiO2-based ENMs as well as nano-enabled products. These entities are divided into different groups i.e. physicochemical properties of ENMS, environmental, exposure and hazard endpoints, and other general information about the mesocosm testing, resulting in more than forty parameters in the database. The MESOCOSM database is equipped with a powerful application, consisting of a graphical user interface (GUI), allowing users to manage and search data using complex queries without relying on programmers. MESOCOSM aims to predict and explain ENMs behavior and fate in different ecosystems as well as their potential impacts on the environment at different stages of the nanoproducts lifecycle. MESOCOSM is expected to benefit the nanosafety community by providing a continuous source of critical information and additional characterization factors for predicting ENMs interactions with the environment and their risks.

Evaluation of dietary dose administration as an alternative to oral gavage in the rodent uterotrophic and Hershberger assays

The rodent uterotrophic and Hershberger assays evaluate potential estrogenic and (anti)-androgenic effects, respectively. Both US EPA and OECD guidelines specify that test substance is administered daily either by subcutaneous injection or oral gavage. However, dietary administration is a relevant exposure route for agrochemical regulatory toxicology studies due to potential human intake via crop residues. In this study, equivalent doses of positive control chemicals administered via dietary and gavage routes of administration were compared in the uterotrophic (17α-ethinyl estradiol) and Hershberger (flutamide, linuron, dichloro-2,2-bis(4-chlorophenyl) ethane; 4,4′-DDE) assays in ovariectomized and castrated rats, respectively. For all positive control chemicals tested, statistically significant changes in organ weights and decreases in food consumption were observed by both routes of test substance administration. Decreased body weight gain observed for dietary linuron and 4,4′-DDE indicated that the maximum tolerated dose was exceeded. Hershberger dietary administration resulted in a similar blood exposure (AUC24) for each positive control chemical when compared to gavage. Overall, the correlation in organ weight changes for both the uterotrophic and Hershberger assays suggest that dietary administration is an acceptable route of exposure with similar sensitivity to oral gavage dosing for evaluation of the endocrine potential of a test substance and represents a more appropriate route of test substance administration for most environmental exposure scenarios.

Do environmentally relevant concentrations of fluoxetine and citalopram impair stress-related behavior in zebrafish (Danio rerio) embryos?

Selective serotonin reuptake inhibitors (SSRIs) have been shown to interfere with various physiological functions of aquatic organisms, yet the neuroactive potential of low concentrations of SSRIs in the aquatic environment is unclear. The current study investigated the effects of fluoxetine and citalopram on the visual motor response (VMR) of 107 h old zebrafish (Danio rerio) embryos. Results document a reduction in stress-related swimming activity of zebrafish embryos at environmentally relevant concentration levels, with fluoxetine being more effective than citalopram. Further experiments were designed to elucidate (1) if the lower neuroactive potential of citalopram is due to differences in uptake kinetics, (2) if the metabolite of fluoxetine, norfluoxetine, contributes to the neuroactive potential of fluoxetine, (3) and how SSRIs and their metabolites interact in equimolar mixtures.At the stage of 120 h, zebrafish embryos accumulate citalopram at significantly lower rates (up to 127 times) than fluoxetine. Moreover, it was demonstrated that norfluoxetine reduces the embryonic VMR similarly to fluoxetine resulting in additive effects of these substances on stress-related behavior in zebrafish embryos. In contrast, the interaction of fluoxetine, norfluoxetine and citalopram varied with test concentrations of the equimolar mixtures. Findings provide evidence that environmentally relevant concentrations of fluoxetine reduce stress-related behavior of zebrafish embryos, while these effects may be enhanced by the interaction of multiple SSRIs and their metabolites in environmental exposure scenarios.

Life stage-dependent toxicities of 1-ethyl-3-methylimidazolium bromide on Caenorhabditis elegans

Ionic liquids (ILs) are considered as extracting solvents in soil remediation. However, they can be pollutants themselves, and their own toxicities are of concerns. Notably, organisms were exposed to pollutants at random life stages in actual environmental exposure scenario, which is different from the set-up of one uniform life stage in usual experiment designs. The influence of life stages on ILs toxicities will provide essential information on their actual environmental risks. In the present study, effects of 1-ethyl-3-methylimidazolium bromide ([C2mim]Br) were measured on C. elegans with egg exposure and adult exposure. In egg exposure, [C2mim]Br increased the lifespan, stimulated initial reproduction and inhibited the total reproduction. Biochemical indices including oxidative stress, antioxidant responses and oxidative damage were further measured to explore the toxicity mechanisms. Results showed that [C2mim]Br significantly stimulated O2−· as the oxidative stress and superoxide dismutase (SOD) as the antioxidant defense. In adult exposure, [C2mim]Br inhibited initial reproduction, total reproduction and lifespan. Biochemical results showed that [C2mim]Br significantly stimulated H2O2 and oxidized glutathione (GSSG). The overall findings demonstrated that [C2mim]Br caused life stage-dependent toxicities on C. elegans. Future studies are still needed for the detailed mechanisms.

Multigenerational Exposures of Daphnia Magna to Pristine and Aged Silver Nanoparticles: Epigenetic Changes and Phenotypical Ageing Related Effects.

Engineered nanoparticles (NPs) undergo physical, chemical, and biological transformation after environmental release, resulting in different properties of the "aged" versus "pristine" forms. While many studies have investigated the ecotoxicological effects of silver (Ag) NPs, the majority focus on "pristine" Ag NPs in simple exposure media, rather than investigating realistic environmental exposure scenarios with transformed NPs. Here, the effects of "pristine" and "aged" Ag NPs are systematically evaluated with different surface coatings on Daphnia magna over four generations, comparing continuous exposure versus parental only exposure to assess recovery potential for three generations. Biological endpoints including survival, growth and reproduction and genetic effects associated with Ag NP exposure are investigated. Parental exposure to "pristine" Ag NPs has an inhibitory effect on reproduction, inducing expression of antioxidant stress related genes and reducing survival. Pristine Ag NPs also induce morphological changes including tail losses and lipid accumulation associated with aging phenotypes in the heart, abdomen, and abdominal claw. These effects are epigenetic remaining two generations post-maternal exposure (F2 and F3). Exposure to identical Ag NPs (same concentrations) aged for 6 months in environmentally realistic water containing natural organic matter shows considerably reduced toxicological effects in continuously exposed generations and to the recovery generations.

Chemical and Colloidal Dynamics of MnO2 Nanosheets in Biological Media Relevant for Nanosafety Assessment.

Many layered crystal phases can be exfoliated or assembled into ultrathin 2D nanosheets with novel properties not achievable by particulate or fibrous nanoforms. Among these 2D materials are manganese dioxide (MnO2 ) nanosheets, which have applications in batteries, catalysts, and biomedical probes. A novel feature of MnO2 is its sensitivity to chemical reduction leading to dissolution and Mn2+ release. Biodissolution is critical for nanosafety assessment of 2D materials, but the timing and location of MnO2 biodissolution in environmental or occupational exposure scenarios are poorly understood. This work investigates the chemical and colloidal dynamics of MnO2 nanosheets in biological media for environmental and human health risk assessment. MnO2 nanosheets are insoluble in most aqueous phases, but react with strong and weak reducing agents in biological fluid environments. In vitro, reductive dissolution can be slow enough in cell culture media for MnO2 internalization by cells in the form of intact nanosheets, which localize in vacuoles, react to deplete intracellular glutathione, and induce cytotoxicity that is likely mediated by intracellular Mn2+ release. The results are used to classify MnO2 nanosheets within a new hazard screening framework for 2D materials, and the implications of MnO2 transformations for nanotoxicity testing and nanosafety assessment are discussed.

Impact of temperature on the toxicity of Kraft 36 EC® (a.s. abamectin) and Score 250 EC® (a.s. difenoconazole) to soil organisms under realistic environmental exposure scenarios

Pesticides can affect all receiving compartments, especially soils, and their fate and effects may be enhanced by temperature, increasing their risk to ecological functions of soils. In Brazil, the most widely used pesticides are the insecticide Kraft 36EC® (a.s. abamectin) and the fungicide Score 250EC® (a.s. difenoconazole), which are commonly used in strawberry, often simultaneously as a mixture. The aim of this study was to evaluate the toxicity of realistic environmental applications, single and in mixtures, for both pesticides to the springtail Folsomia candida and the plant species Allium cepa (onion) and Lycopersicum esculentum (tomato). Mesocosms filled with Brazilian natural soil (lattosolo) were dosed with water (control), Kraft (10.8g a.s/ha), Score (20g.a.s/ha) and Kraft+Score (10.8+20g a.s./ha). The applications were repeated every 7 days, during 18 days of experiment, and simulating rainfall twice a week. Collembola reproduction tests were conducted with soils from the first (day 1) and last day (day 18) of experiment for each treatment. Plant toxicity tests were carried out in the experimental units. The experiments were run at 23°C and 33°C. Kraft, alone and in the binary mixture, showed high toxicity to the springtails in soils from both days 1 and 18, especially at 23°C where it caused 100% mortality. Score however, was not toxic to the springtails. Plant growth was reduced by Score, but responses varied depending on temperature. This study indicates a high environmental risk of the insecticide Kraft, particularly at lower temperatures (23°C), and an influence of temperature on pesticide fate and effects.

Environmental exposure scenario for reagents used in in-vitro diagnostics

In-vitro diagnostic assays involve various substances that may be released into the environment via a sewage treatment plant if the effluent from diagnostic instruments is discharged into the drains. Because the release of liquid waste into the public sewer system is regulated at national and/or local levels, a risk assessment per site should be performed to determine whether the release of the effluent from in-vitro diagnostic equipment is compliant with applicable regulations.To facilitate the assessment, we developed a screening tool to generate exposure scenarios for chemical substances used in in-vitro diagnostic assays. This screening tool helps in determining a) whether release of the effluent into the sewer system would be allowed from a regulatory point of view and b) whether such release would result in potential risks to surface water.The screening tool is based on conditions encountered at typical usage sites in Switzerland and Germany, with the option to adapt them to other local settings. In addition, measured analytical results of liquid waste together with typical operational parameters of diagnostic equipment were defined as default input parameters. The resulting concentrations in liquid waste and predicted environmental concentrations (PEC) are compared with regulatory limit values for release into the sewer system and predicted no-effect concentrations (PNEC) for surface water for risk estimation.The functioning of the presented screening tool is demonstrated by two assessments performed for fictitious but typical hospitals in Switzerland and Germany. It identified substances that cause potential concern for which a more advanced assessment is required.

DNA damage response in peripheral mouse blood leukocytes in vivo after variable, low-dose rate exposure.

Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1-1.2Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7days with total accumulated dose up to 2.7Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2Gy and ≥ 2Gy, highlighting the potential of γ-H2AX MFI as a biomarker fordosimetry in a protracted, environmental exposure scenario.

Comparison of DNA methylation profiles associated with spontaneous preterm birth in placenta and cord blood

BackgroundThe etiology and mechanism of spontaneous preterm birth (sPTB) are still unclear. Accumulating evidence has documented that various environmental exposure scenarios may cause maternal and fetal epigenetic changes, which initiates the focus on whether epigenetics can contribute to the occurrence of sPTB. Therefore, we conducted the current study to examine and compare the DNA methylation changes associated with sPTB in placenta and cord blood.MethodsThis hospital-based case-control study was carried out at three Women and Children’s hospitals in South China, where 32 spontaneous preterm births and 16 term births were recruited. Genome-wide DNA methylation profiles of the placenta and cord blood from these subjects were measured using the Illumina HumanMethylation EPIC BeadChip, and sPTB-associated differential methylated CpG sites were identified using limma regression model, after controlling for major maternal and infant confounders. Further Gene Ontology analysis was performed with PANTHER in order to assess different functional enrichment of the sPTB-associated genes in placenta and cord blood.ResultsAfter controlling for potential confounding factors, one differentially methylated position (DMP) in placenta and 31 DMPs in cord blood were found significantly associated with sPTB (Bonferroni corrected p < 0.05). The sPTB-associated CpG sites in placenta were mapped to genes that showed higher enrichment on biological processes including biological regulation, multicellular organismal process, and especially response to stimulus, while those in cord blood were mapped to genes that had higher enrichment on biological processes concerning cellular process, localization, and particularly metabolic process.ConclusionFindings of this study indicated that DNA methylation alteration in both placenta and cord blood are associated with sPTB, yet the DNA methylation modification patterns may appear differently in placenta and cord blood.

Effects of environmentally relevant metformin exposure on Japanese medaka (Oryzias latipes)

Metformin is one of the most prevalent pharmaceuticals in both surface and waste waters, yet little is known about the bioavailability and/or effects of developmental exposure on early life stage (ELS) fish. Here, we demonstrate that embryo-larval stages of medaka are capable of taking up metformin from the aquatic environment, provided exposure occurs prior to chorion hardening (∼6-hpf). Once transferred to clean water, ELS medaka are able to completely depurate metformin in <24-hours. Furthermore, ELS medaka exposed to a range of relevant concentrations of waterborne metformin (from 6 hpf through 28-days post hatch) had significantly reduced growth metrics, altered metabolomes, and changes in the expression of genes associated with cell growth. The range of concentrations investigated were 1.0, 3.2, 10, 32, and 100 μg·L−1. To examine effects of chronic, low level metformin exposure across the full medaka life-cycle, we exposed newly fertilized embryos to 3.2 μg L−1 waterborne metformin for 165-days. The weight and length of adult fish were examined, as were effects on the production of some steroid hormones, specifically a significant increase (control females: 0.161 ± 0.023 pg/mg; metformin treated females: 3.42 ± 0.543) in the production of 11-ketotestosterone was observed in adult female medaka. Collectively, these results suggest that current environmental exposure scenarios may be sufficient to cause effects on developing fish.