Environmental Exposure Levels Research Articles

Household Water Lead and Hematologic Toxic Effects in Chronic Kidney Disease.

The consequences of low levels of environmental lead exposure, as found commonly in US household water, have not been established. To examine whether commonly encountered levels of lead in household water are associated with hematologic toxicity among individuals with advanced kidney disease, a group known to have disproportionate susceptibility to environmental toxicants. Cross-sectional analysis of household water lead concentrations and hematologic outcomes was performed among patients beginning dialysis at a Fresenius Medical Care outpatient facility between January 1, 2017, and December 20, 2021. Data analysis was performed from April 1 to August 15, 2023. Concentrations of lead in household water were examined in categorical proportions of the Environmental Protection Agency's allowable threshold (15 μg/L) and continuously. Hematologic toxic effects were defined by monthly erythropoiesis-stimulating agent (ESA) dosing during the first 90 days of incident kidney failure care and examined as 3 primary outcomes: a proportion receiving maximum or higher dosing, continuously, and by a resistance index that normalized to body weight and hemoglobin concentrations. Secondarily, hemoglobin concentrations for patients with data prior to kidney failure onset were examined, overall and among those with concurrent iron deficiency, thought to increase gastrointestinal absorption of ingested lead. Among 6404 patients with incident kidney failure (male, 4182 [65%]; mean [SD] age, 57 [14] years) followed up for the first 90 days of dialysis therapy, 12% (n = 742) had measurable lead in household drinking water. A higher category of household lead contamination was associated with 15% (odds ratio [OR], 1.15 [95% CI, 1.04-1.27]) higher risk of maximum monthly ESA dosing, 4.5 (95% CI, 0.8-8.2) μg higher monthly ESA dose, and a 0.48% (95% CI, 0.002%-0.96%) higher monthly resistance index. Among patients with pre-kidney failure hemoglobin measures (n = 2648), a higher household lead categorization was associated with a 0.12 (95% CI, -0.23 to -0.002) g/dL lower hemoglobin concentration, particularly among those with concurrent iron deficiency (multiplicative interaction, P = .07), among whom hemoglobin concentrations were 0.25 (95% CI, -0.47 to -0.04) g/dL lower. The findings of this study suggest that levels of lead found commonly in US drinking water may be associated with lead poisoning among susceptible individuals.

Exploring the correlation between environmental pesticide exposure and antioxidant level in recently diagnosed cancer patients

Aim: Within biological systems thiol and ascorbic acid are important antioxidant that play roles in the antioxidant defense systems. In this study, we investigated the correlation between environmental pesticide exposure and antioxidant level in recently diagnosed cancer patients. Methodology: Blood samples were collected from 87 participants (48 male and 39 female) including control, gallbladder, blood, and oral cancer patients. Serum total thiol content and antioxidant ascorbic acid levels were measured by biochemical method. We also examined whether there is any correlation between the plasma thiol content and ascorbic acid content in cancer prevention. Results: Analysis indicated that most of the cancer patients belonged to middle age and were mostly non-vegetarian. In the present study, it was found that the total thiol content of cancer pateints was high, while the ascorbic acid content was low in cancer patients as compared to control indicating the role of oxidative stress in cancer development. Interpretation: The present study suggests that pesticide exposure may increase the total thiol content and negatively impact ascorbic acid content in cancer patients. Key words: Antioxidant, Blood cancer, Epidemiology, Gallbladder cancer, Oral cancer, Pesticide

How Mobility and Temporal Contexts May Affect Environmental Exposure Measurements: Using Outdoor Artificial Light at Night (ALAN) and Urban Green Space as Examples

Temporal contexts are essential for the derivation of causally relevant environmental exposure in environmental and public health studies. We argue that the proper temporal contexts need further emphasis in the mobility-oriented research paradigm and articulate this issue using a study in Hong Kong. We use people’s exposure to outdoor artificial light at night (ALAN) and green space as two essential examples. We recruited 208 participants from two representative communities in Hong Kong and derived their mobility-oriented environmental exposures from high-resolution remote sensing data and Google Street View imagery. We employed one-standard-deviational ellipses to quantitatively represent participants’ activity spaces, and we further used participants’ seven-day Global Positioning System trajectories to derive their spatiotemporally weighted exposures to green space and outdoor ALAN in different temporal contexts. Multiple t tests were used to examine the disparities in activity spaces and measured exposures in different temporal contexts, and these exposure measurements were then used to predict people’s health outcomes. We found that people’s activity spaces are significantly different in size between day and night, for both weekdays and weekends, and in both geographic contexts. We further observed that improper temporal contexts could lead to significantly different environmental exposure levels and causally irrelevant modeling results.

The effects of polyester microfibres on the development and seed yield of white mustard (Sinapis alba L.)

Microplastics are found in agricultural soils worldwide; however, little is known about the impacts of this ubiquitous pollutant on the growth and development of crops. Microfibres are one of the dominant microplastic types found in agricultural soils. Sources of microfibres in the agricultural environment are multiple, including soil amendment applications, wastewater irrigation and atmospheric deposition, with agricultural soils subsequently acting as an accumulating sink for plastics. A key consideration in an agricultural setting is yield; the seed yield is critical, as this is the part with economic value. This study investigates the influence of polyester microfibres, a prevalent type of microplastic in agricultural soils, on the growth and seed yield of Sinapis alba (white mustard). Polyester microfibres were added to soil samples at concentrations of 0.1% and 1% w/w, simulating environmental exposure levels. The study evaluated flower production, seed yield, pod-to-seed ratio, and chlorophyll fluorescence as indicators of plant health and reproductive success. Results revealed significant changes in chlorophyll fluorescence values (Fv/Fm), reduced flower production control (74 ± 37 flowers in the control, 31 ± 27 in the 0.1 treatment and 44 ± 31 in the 1 % treatment), and changes in pod-to-seed ratio (3.5 ± 0.65 seeds per pod in the control, 2.76 ± 0.5 seeds per pod in the 0.1% treatment and 2.83 ± 0.81 seeds per pod in the 1% treatment) in response to polyester microfibre exposure. Polyester microfibres were demonstrated to act as a stressor to S. alba, changing the chlorophyll fluorescence values, reducing the flower number, and in turn, reducing the pod-to-seed ratio. This study provides evidence that microfibres could reduce seed yield but that further research is required to elucidate the mechanisms by which these changes are occurring.

Fate and effects of a new generation fluorosurfactant (cC6O4) in freshwater mesocosms

Per- and polyfluorinated alkyl substances (PFAS) have raised international concerns due to their widespread use, environmental persistence and potential bioaccumulative and ecotoxicological effects. Therefore, the chemical industry has been dedicated to develop new generation fluorosurfactants which are aimed to replace the most concerning PFAS. Here we investigated the fate and effects of cyclic C6O4 (cC6O4), a compound used as alternative to long-chain perfluorocarboxylic acids, in freshwater mesocosms located in the Mediterranean region (Spain) over a period of 90 days. cC6O4 was applied as ammonium salt once at the following nominal concentrations: 0 µg/L (control), 1 µg/L, 20 µg/L, 400 µg/L, and 8,000 µg/L. The study shows that cC6O4 is relatively persistent in water (dissipation: 34–37 % after 90 days), has very low sorption capacity to sediments (sediment-water partition coefficient: 0.18–0.32 L/kg) and very limited bioconcentration (BCF: 0.09–0.94), bioaccumulation (BAF: 0.09–4.06) and biomagnification (BMF: 0.05–0.28) potential. cC6O4 did not result in significant adverse effects on aquatic populations and communities of phytoplankton and zooplankton at the tested concentrations. As for the macroinvertebrate community, the ephemeropteran Cloeon sp. showed a population decline at the highest test concentration on day 60 onwards, and a significant effect on the macroinvertebrate community was identified on the last sampling day at the same exposure level. Therefore, the calculated NOEC for cC6O4 in freshwater mesocosms exposed over a period of 90 days was 400 µg/L, which corresponded to a time weighted average concentration of 611 µg/L, given the water evaporation in the test systems. This concentration is about an order of magnitude higher than the highest exposure concentration monitored in freshwater ecosystems. Therefore, it can be concluded that cC6O4 poses insignificant ecological risks for freshwater plankton and macroinvertebrate communities given the current environmental exposure levels.

Radiation Dose Does Not Affect the Predictive Value of Thyroid Biopsy for Diagnosing Papillary Thyroid Cancer in a Belarusian Cohort Exposed to Chernobyl Fallout

Introduction: The Chernobyl nuclear accident exposed residents of contaminated territories to substantial quantities of radioiodines and was followed by an increase in thyroid cancer, primarily papillary thyroid cancer (PTC), among exposed children and adolescents. Although thyroid biopsy is an essential component of screening programs following accidental exposure to radioiodines, it is unknown whether the predictive value of biopsy is affected by different levels of environmental exposure. Methods: A cohort of 11,732 Belarusians aged ≤18 years at the time of the Chernobyl accident with individual thyroid radiation dose estimates was screened at least once 11–22 years later. Paired cytologic conclusions and histopathologic diagnoses were possible for 258 thyroid nodules from 238 cohort members. Cytologic conclusions were divided into five reporting categories, with all follicular lesion aspirates combined into a single indeterminate category. Standard performance indicators, risk of malignancy (ROM), and odds ratios for a correct cytologic conclusion were calculated, both overall and according to quintile of thyroid radiation dose. Results: The arithmetic mean thyroid dose estimate for the study group was 1.73 Gy (range: 0.00–23.64 Gy). The final histopathologic diagnosis was cancer for 136 of 258 biopsies (52.7%; 135 papillary and 1 follicular). The overall ROM was 96.7% for cytologies definite for PTC, 83.7% for suspicious for PTC, 33.0% for indeterminate, 8.1% for benign, and 31.0% for non-diagnostic. The ROM showed little change according to level of radiation exposure. Overall, there was no association between thyroid radiation dose and the odds ratio for a correct cytologic conclusion (p = 0.24). When analyzed according to dose quintile, the odds ratio for a correct conclusion increased two-fold at 0.10–0.29 Gy compared to a dose of 0.00–0.09 Gy and decreased at doses of 0.3–24 Gy (p value for linear trend = 0.99). Conclusions: At radiation doses received by a cohort of young Belarusians exposed to radioiodines by the Chernobyl accident, the predictive value of thyroid biopsy for diagnosing PTC was not significantly affected by level of radiation exposure.

Relationship of single and co-exposure of per-and polyfluoroalkyl substances and their alternatives with uric acid: A community-based study in China

Numerous studies have suggested per-and polyfluoroalkyl substances (PFASs) are related to uric acid levels, but evidence related to PFAS alternatives is limited. Moreover, the effect of the combined exposure to PFASs and their alternatives on uric acid has not been reported. Hence, we conducted a cross-sectional study involving 1312 adults in Guangzhou, China. Generalized linear regression model was adopted to explore the effect of single PFAS exposure on serum uric acid levels. Further, multi-pollutant models such as Bayesian kernel machine regression, weighted quantile sum, and quantile G-computation were employed to investigate the combined association of PFASs and alternatives with serum uric acid levels. We performed molecular docking to understand the potential interaction of PFAS with Organic Anion Transporters (OATs), involved in the secretion of uric acid. Per log serum 6:2 Cl-PFESA and PFOA increases were accompanied with an increase of serum uric acid with statistical significance (for 6:2 Cl-PFESA: beta: 0.19 ng/mL, 95% CI 0.11–0.26 and for PFOA: beta: 0.43 ng/mL, 95% CI 0.34–0.52). The associations were strongest among overweight and elderly. Multi-pollutant models also revealed a positive association. These positive associations may be PFASs can competitively combine with OAT1 and OAT3, leading to the increase of serum uric acid.

Protein S-palmitoylation enhances profibrotic signaling in response to cadmium

Cadmium (Cd) is a naturally occurring, toxic environmental metal found in foods. Humans do not have an efficient mechanism for Cd elimination; thus, Cd burden in humans increases with age. Cell and mouse studies show that Cd burden from low environmental levels of exposure impacts lung cell metabolism, proliferation signaling and cell growth as part of disease-promoting profibrotic responses in the lungs. Prior integrative analysis of metabolomics and transcriptomics identified the zDHHC11 transcript as a central functional hub in response to Cd dose. zDHHC11 encodes a protein S-palmitoyltransferase, but no evidence is available for effects of Cd on protein S-palmitoylation. In the present research, we studied palmitoylation changes in response to Cd and found increased protein S-palmitoylation in human lung fibroblasts that was inhibited by 2-bromopalmitate (2-BP), an irreversible palmitoyltransferase inhibitor. Mass spectrometry-based proteomics showed palmitoylation of proteins involved in divalent metal transport and in fibrotic signaling. Mechanistic studies showed that 2-BP inhibited palmitoylation of divalent metal ion transporter ZIP14 and also inhibited cellular Cd uptake. Transcription analyses showed that Cd stimulated transforming growth factor (TGF)-β1 and β3 expression within 8 h and lung fibrotic markers α-smooth muscle actin, matrix metalloproteinase-2, and collagen 1α1 gene expression and that these effects were blocked by 2-BP. Because 2-BP also blocked palmitoylation of proteins controlled by TGFβ1, these results show that palmitoylation impacts Cd-dependent fibrotic signaling both by enhancing cellular Cd accumulation and by supporting post-translational processing of TGFβ1-dependent proteins.

Exploring the pathology of liver, kidney, muscle, and stomach of fledgling seabirds associated with plastic ingestion

There remain significant gaps in knowledge about ‘sub-lethal’ impacts of plastic ingestion, particularly chronic impacts on cells, tissues, or organs. Few studies have applied traditional animal health tools, such as histopathology, to assess physiological damage to wildlife, with fewer still providing information on the dosage or exposure to plastics needed to elicit negative effects. Our study seeks to investigate a common hypothesis in plastic pollution research; that an increasing plastics burden will have an impact on an animal’s health, examining two wild species with high levels of environmental exposure to plastic through their diet. Here we assess the histopathology of the muscle, upper digestive tract, liver and kidney of two seabird species that are known to be commonly exposed to plastic, comparing exposed and non-exposed individuals. Fledgling seabirds showed histopathological evidence of cumulative pressures such as starvation, disease, and endoparasite burden. However, we observed no evidence of chronic harm that could be explicitly linked to the plastics. We found one case of haemorrhage, reaffirming that large/sharp plastic foreign bodies may cause acute physical damage. Given the numerous interacting pressures on the health of fledging seabirds, including exposure to plastic, this study highlights the need to scrutinise plastic-animal interactions and research though a One Health lens.

Perturbation of IP3R-dependent endoplasmic reticulum calcium homeostasis by PPARδ-activated metabolic stress leads to mouse spermatocyte apoptosis: A direct mechanism for perfluorooctane sulfonic acid-induced spermatogenic disorders

Perfluorooctane sulfonic acid (PFOS) as an archetypal representative of per- and polyfluoroalkyl substances (PFAS) is ubiquitously distributed in the environment and extensively detected in human bodies. Although accumulating evidence is suggestive of the deleterious effects of PFOS on male reproduction, the direct toxicity of PFOS towards spermatogenic cells and the relevant mechanisms remain poorly understood. The aims of the present study were to explore the direct effects and underlying molecular mechanisms of PFOS on spermatogenesis. Through integrating animal study, transcriptome profiling, in silico toxicological approaches, and in vitro validation study, we identified the molecular initiating event and key events contributing to PFOS-induced spermatogenic impairments. The mouse experiments revealed that spermatocytes were involved in PFOS-induced spermatogenic disorders and the activation of peroxisome proliferator-activated receptor delta (PPARδ) was linked to spermatocyte loss in PFOS-administrated mice. GC-2spd(ts) cells were treated with an increased gradient of PFOS, which was relevant to environmental and occupational exposure levels of PFOS in populations. Following 72-h treatment, cells was harvested for RNA sequencing. The transcriptome profiling and benchmark dose (BMD) modeling identified endoplasmic reticulum (ER) stress as the key event for PFOS-mediated spermatocyte apoptosis and determined the point-of-departure (PoD) for perturbations of ER stress signaling. Based on the calculated PoD value, further bioinformatics analyses combined with in vitro and in vivo validations showed that PFOS caused metabolic stress by activating PPARδ in mouse spermatocytes, which was responsible for Beclin 1-involved inositol 1,4,5-trisphosphate receptor (IP3R) sensitization. The disruption of IP3R-mediated ER calcium homeostasis triggered ER calcium depletion, leading to ER stress and apoptosis in mouse spermatocytes exposed to PFOS. This study systematically investigated the direct impacts of PFOS on spermatogenesis and unveiled the relevant molecular mechanism of PFOS-induced spermatogenic disorders, providing novel insights and potential preventive/therapeutic targets for PFAS-associated male reproductive toxicity.

Environmental exposure and sensitization patterns in a Swiss alpine pediatric cohort

BackgroundThe level of environmental exposure throughout life may contribute to the prevalence of allergic sensitization and allergic disease. The alpine climate has been considered a healthy climate with little allergen exposure and pollution. We conducted a cross-sectional study to investigate local environmental exposure and concomitant prevalence of allergic sensitization among local school children born and raised in an alpine environment. MethodsClinical and demographic data were collected with a questionnaire. Allergen content was assessed in residential settled dust samples, lifetime exposure to pollen and air pollution was calculated using data from national pollen and air pollution monitoring stations, and the allergic sensitization profile was determined with component resolved diagnostics (ISAC®). Univariate and multivariate regression models were used to estimate the relation between exposure and sensitization. ResultsIn a cohort of children born and raised in an alpine environment, sensitization to aeroallergens is quite common (38%), especially to grass (33%) and cat (16%). House dust mite allergen was detected in up to 38% of residential dust samples, but sensitization to HDM was low (2.5%). Pollutant levels were low, but an increasing trend was observed in the amount of ozone and PM10. Living close to a busy road was associated with increased odds OR (95% CI) for being sensitized to any allergen 2.7 (1.0–7.2), to outdoor allergens 2.8 (1.1–7.1) and being sensitized plus reporting symptoms of rhinoconjunctivitis 4.4 (1.3–14.8) and asthma 5.5 (1.4–21). Indoor living conditions, including the presence of visible mold, increased the odds of being sensitized to indoor allergens (1.9 (1.1–3.2) and being sensitized plus reporting symptoms of rhinoconjunctivitis 1.9 (1.0–3.6) and asthma 2.1 (1.0–4.1). ConclusionIn a healthy alpine environment, pollution might still be an important factor contributing to allergic sensitization.

Durability of unstabilized rammed earth in temperate climates: A long term study

This paper describes a 16-year study on the weathering behavior of unstabilized rammed earth constructed in the temperate climate of the Northeastern United States with an average annual precipitation of 1,174 mm. A freestanding experimental rammed earth wall utilizing natural clay binders was constructed on the campus of the Massachusetts Institute of Technology in 2005 to evaluate its durability over time. The research documents the erosion of the 450 mm thick wall and identifies the environmental factors responsible for the observed deterioration. While erosion levels are highly dependent on localized environmental factors, results show that regions of the test wall with high levels of environmental exposure have an erosion rate of 3.5 mm/year, regions with medium exposure have an erosion rate of 1.5 mm/year, and regions with low exposure have an erosion rate of 0.5 mm/year. The estimated lifespan of the freestanding unstabilized rammed earth wall with minimal protection from natural climatic conditions in a temperate climate is between 37 and 75 years before repairs are required to preserve structural integrity. This lifespan is comparable to the typical service life of structures in North America built with more carbon-intensive materials such as concrete. The results presented, which are specific to the minimally protected test wall, can be considered conservative. Historic structures provide ample evidence that when adequately protected, unstabilized rammed earth can last nearly indefinitely, suggesting that this low impact material could be used to replace more carbon intensive construction materials with significant environmental benefits.

A Comprehensive Analysis of the Influence of Temperature and Humidity on Dry Eye Disease.

To investigate the effects of humidity and temperature on dry eye disease (DED). A retrospective clinic-based study was conducted on DED patients undergoing dry eye treatment. Patients were followed up at least twice, and symptoms and signs were evaluated using the Symptoms Assessment Questionnaire in Dry Eye (SANDE) score, tear secretion, tear film break-up time (TBUT), ocular staining score, and tear osmolarity. Mean humidity and temperature values for one week before ocular examinations were used as the environmental exposure level. The relationship between humidity and temperature, with DED clinical parameters was analyzed in single and multi-environmental factor models. The study included 33 patients with a mean age of 53.9±12.2 years. The low-humidity group showed significantly higher SANDE scores and tear osmolarity (P=0.023/0.008), and the low-temperature group had higher SANDE scores, ocular staining scores, and tear osmolarity (P=0.004/0.036/<0.001). In the linear mixed model, single factor analysis showed that an increase in humidity resulted in decreased SANDE scores (P=0.043), and an increase in temperature led to a decrease in SANDE score, ocular staining score, and tear osmolarity (P=0.007/0.007/0.012). In the multi-factor analysis, changes in humidity had no significant effect on dry eye parameters, but an increase in temperature was significantly correlated with decreased SANDE score, ocular staining score, and tear osmolarity (P=0.026/0.024/0.002). Lower temperature led to aggravated symptoms and signs of DED and the effect of temperature on DED was more pronounced than humidity. Tear osmolarity was the most sensitive clinical parameter to be affected by climate factors in DED patients.

Social and environmental stressors and cardiometabolic risk

Abstract Background Cardiometabolic health is influenced by many social and environmental factors, as demonstrated by the ubiquitous health inequalities. Exposures to social and environmental stressors produce individual biological and behavioural responses and thus may lead to impaired health both directly and indirectly. This study investigated several social and environmental stressors and describe the paths of their effect on cardiometabolic health. Methods We analysed a cross-sectional population sample of 2154 Czech subjects (aged 25-64 years, 55% women). The composite score (range 0-5) of metabolic disorders was calculated using 5 biomarkers: waist circumference, blood pressure, fasting blood glucose, HDL-cholesterol, and triglycerides. The higher score represents the higher cardiometabolic risk (CMR). The effects of social stressors (education, income), environmental stressors (air pollution, greenspace, noise) and behavioural factors (unhealthy diet, smoking, alcohol intake, sedentary behaviours) on CMR were assessed using a structural pathway model. Results We observed a significant direct effect of higher education on CMR (β=-0.101; 95% CI [-0.146, -0.056], as well as an indirect effect mediated via an unhealthy diet (β=-0.013; 95% CI [-0.022, -0.006]), smoking (β=-0.015; 95% CI [-0.028, -0.003]), and sedentary behaviours (β = 0.013; 95% CI [0.007, 0.022]). We also observed a significant indirect effect of higher income via sedentary behaviours (β = 0.012; 95% CI [0.006, 0.019]). The only environmental stressor significantly predicting CMR was noise (β = 0.054; 95% CI [0.006, 0.019]), which was also mediating the effect of higher education (β=-0.003; 95% CI [-0.008, -0.001]). Conclusions The effect of social stressors on the development of CMR had a higher magnitude than the effect of the assessed environmental factors. Social stressors lead to an individual's unhealthy behaviour and predispose individuals to higher levels of environmental stressors exposures. Key messages • Social stressors exhibited a greater magnitude of effect on cardiometabolic risk compared to environmental stressors. • Social stressors lead to unhealthy behaviours and predispose individuals to higher environmental stressors exposure.

Worker studies suggest unique liver carcinogenicity potential of polyvinyl chloride microplastics.

Plastic debris pervades our environment. Some breaks down into microplastics (MPs) that can enter and distribute in living organisms causing effects in multiple target organs. MPs have been demonstrated to harm animals through environmental exposure. Laboratory animal studies are still insufficient to evaluate human impact. And while MPs have been found in human tissues, the health effects at environmental exposure levels are unclear. We reviewed and summarized existing evidence on health effects from occupational exposure to MPs. Additionally, the diverse effects documented for workers were organized by MP type and associated co-contaminants. Evidence of the unique effects of polyvinyl chloride (PVC) on liver was then highlighted. We conducted two stepwise online literature reviews of publications focused on the health risks associated with occupational MP exposures. This information was supplemented with findings from animal studies. Our analysis focused on 34 published studies on occupational health effects from MP exposure with half involving exposure to PVC and the other half a variety of other MPs to compare. Liver effects following PVC exposure were reported for workers. While PVC exposurecausesliver toxicity and increases the risk of liver cancers, including angiosarcomas and hepatocellular carcinomas, the carcinogenic effects of work-related exposure to other MPs, such as polystyrene and polyethylene, are not well understood. The data supporting liver toxicity are strongest for PVC exposure. Overall, the evidence of liver toxicity from occupational exposure to MPs other than PVC is lacking. The PVC worker data summarized here can be useful in assisting clinicians evaluating exposure histories from PVC exposure and designing future cell, animal, and population exposure-effect research studies.

The biocide triclosan as a potential developmental disruptor in Mytilus early larvae

The broadly utilized biocide triclosan (TCS) is continuously discharged in water compartments worldwide, where it is detected at concentrations of ng-µg/L. Given its lipophilicity and bioaccumulation, TCS is considered potentially harmful to human and environmental health and also as a potential endocrine disruptor (ED) in different species. In aquatic organisms, TCS can induce a variety of effects: however, little information is available on its possible impact on invertebrate development. Early larval stages of the marine bivalve Mytilus galloprovincialis have been shown to be sensitive to environmental concentrations of a number of emerging contaminants, including EDs. In this work, the effects of TCS were first evaluated in the 48 h larval assay in a wide concentration range (0.001–1,000 μg/L). TCS significantly affected normal development of D-veligers (LOEC = 0.1 μg/L; EC50 = 236.1 μg/L). At selected concentrations, the mechanism of action of TCS was investigated. TCS modulated transcription of different genes involved in shell mineralization, endocrine signaling, ceramide metabolism, and biotransformation, depending on larval stage (24 and 48 h post-fertilization-hpf) and concentration (1 and 10 μg/L). At 48 hpf and 10 μg/L TCS, calcein staining revealed alterations in CaCO3 deposition, and polarized light microscopy showed the absence of shell birefringence due to the mineralized phase. Observations by scanning electron microscopy highlighted a variety of defects in shell formation from concentrations as low as 0.1 μg/L. The results indicate that TCS, at environmental exposure levels, can act as a developmental disruptor in early mussel larvae mainly by interfering with the processes of biomineralization.

Cardiac Toxicity Induced by Long-Term Environmental Levels of MC-LR Exposure in Mice.

Cyanobacterial blooms are considered a serious global environmental problem. Recent studies provided evidence for a positive association between exposure to microcystin-LR (MC-LR) and cardiotoxicity, posing a threat to human cardiovascular health. However, there are few studies on the cardiotoxic effects and mechanisms of long-term low-dose MC-LR exposure. Therefore, this study explored the long-term toxic effects and toxic mechanisms of MC-LR on the heart and provided evidence for the induction of cardiovascular disease by MC-LR. C57BL/6 mice were exposed to 0, 1, 30, 60, 90, and 120 μg/L MC-LR via drinking water for 9 months and subsequently necropsied to examine the hearts for microstructural changes using H&E and Masson staining. The results demonstrated fibrotic changes, and qPCR and Western blots showed a significant up-regulation of the markers of myocardial fibrosis, including TGF-β1, α-SMA, COL1, and MMP9. Through the screening of signaling pathways, it was found the expression of PI3K/AKT/mTOR signaling pathway proteins was up-regulated. These data first suggested MC-LR may induce myocardial fibrosis by activating the PI3K/AKT/mTOR signaling pathway. This study explored the toxicity of microcystins to the heart and preliminarily explored the toxic mechanisms of long-term toxicity for the first time, providing a theoretical reference for preventing cardiovascular diseases caused by MC-LR.

Comparative toxicity assessment of glyphosate and two commercial formulations in the planarian Dugesia japonica.

Introduction: Glyphosate is a widely used, non-selective herbicide. Glyphosate and glyphosate-based herbicides (GBHs) are considered safe for non-target organisms and environmentally benign at currently allowed environmental exposure levels. However, their increased use in recent years has triggered questions about possible adverse outcomes due to low dose chronic exposure in animals and humans. While the toxicity of GBHs has primarily been attributed to glyphosate, other largely unstudied components of GBHs may be inherently toxic or could act synergistically with glyphosate. Thus, comparative studies of glyphosate and GBHs are needed to parse out their respective toxicity. Methods: We performed such a comparative screen using pure glyphosate and two popular GBHs at the same glyphosate acid equivalent concentrations in the freshwater planarian Dugesia japonica. This planarian has been shown to be a useful model for both ecotoxicology and neurotoxicity/developmental neurotoxicity studies. Effects on morphology and various behavioral readouts were obtained using an automated screening platform, with assessments on day 7 and day 12 of exposure. Adult and regenerating planarians were screened to allow for detection of developmentally selective effects. Results: Both GBHs were more toxic than pure glyphosate. While pure glyphosate induced lethality at 1mM and no other effects, both GBHs induced lethality at 316μM and sublethal behavioral effects starting at 31.6μM in adult planarians. These data suggest that glyphosate alone is not responsible for the observed toxicity of the GBHs. Because these two GBHs also include other active ingredients, namely diquat dibromide and pelargonic acid, respectively, we tested whether these compounds were responsible for the observed effects. Screening of the equivalent concentrations of pure diquat dibromide and pure pelargonic acid revealed that the toxicity of either GBH could not be explained by the active ingredients alone. Discussion: Because all compounds induced toxicity at concentrations above allowed exposure levels, our data indicates that glyphosate/GBH exposure is not an ecotoxicological concern for D. japonica planarians. Developmentally selective effects were not observed for all compounds. Together, these data demonstrate the usefulness of high throughput screening in D. japonica planarians for assessing various types of toxicity, especially for comparative studies of several chemicals across different developmental stages.

Impact of phenanthrene co-administration on the toxicokinetics of benzo[a]pyrene in humans. UPLC-accelerator mass spectrometry following oral microdosing

Current risk assessments for environmental carcinogens rely on animal studies utilizing doses orders of magnitude higher than actual human exposures. Epidemiological studies of people with high exposures (e.g., occupational) are of value, but rely on uncertain exposure data. In addition, exposures are typically not to a single chemical but to mixtures, such as polycyclic aromatic hydrocarbons (PAHs). The extremely high sensitivity of accelerator mass spectrometry (AMS) allows for dosing humans with known carcinogens with de minimus risk. In this study UPLC-AMS was used to assess the toxicokinetics of [14C]-benzo[a]pyrene ([14C]-BaP) when dosed alone or in a binary mixture with phenanthrene (Phe). Plasma was collected for 48 h following a dose of [14C]-BaP (50 ng, 5.4 nCi) or the same dose of [14C]-BaP plus Phe (1250 ng). Following the binary mixture, Cmax of [14C]-BaP significantly decreased (4.4-fold) whereas the volume of distribution (Vd) increased (2-fold). Further, the toxicokinetics of twelve [14C]-BaP metabolites provided evidence of little change in the metabolite profile of [14C]-BaP and the pattern was overall reduction consistent with reduced absorption (decrease in Cmax). Although Phe was shown to be a competitive inhibitor of the major hepatic cytochrome P-450 (CYP) responsible for metabolism of [14C]-BaP, CYP1A2, the high inhibition constant (Ki) and lack of any increase in unmetabolized [14C]-BaP in plasma makes this mechanism unlikely to be responsible. Rather, co-administration of Phe reduces the absorption of [14C]-BaP through a mechanism yet to be determined. This is the first study to provide evidence that, at actual environmental levels of exposure, the toxicokinetics of [14C]-BaP in humans is markedly altered by the presence of a second PAH, Phe, a common component of environmental PAH mixtures.

Multiple responses of Mytilus galloprovincialis to plastic microfibers

Plastic microfibers (MF) represent the major source of MF found in the environment, the majority made of polyester (PES). Marine bivalves, suspension feeders widespread in coastal areas subjected to higher anthropogenic input, can accumulate MF from the water column in their tissues. This raised some concern about their possible impact on bivalve health and potential transfer along the food chain. In this work, the effects of PES-MF on the mussel Mytilus galloprovincialis were investigated, utilizing MF obtained by cryo-milling of a fleece cover. Fiber characterization indicated the polymer composition as polyethylene terephthalate (PET); the size distribution was in a length range resembling that of MF released from textile washing, and including those that can be ingested by mussels. MF were first screened for short-term in vitro immune responses in mussel hemocytes. The effects of in vivo exposure (96 h, 10 and 100 μg/L, corresponding to about 150 and 1500 MF/mussel/L, respectively), were then evaluated. Data are presented on hemolymph immune biomarkers (Reactive Oxygen Species and nitric oxide production, lysozyme activity), and on antioxidant biomarkers (catalase and glutathione S-transferase) and histopathology in gills and digestive gland. Tissue MF accumulation was also evaluated.MF exposure stimulated extracellular immune responses both in vitro and in vivo, indicating induction of immune/inflammatory processes. In both tissues, stimulation of antioxidant enzyme activities, suggesting oxidative stress conditions, and histopathological changes were observed, with stronger effects often observed at lower concentration. Although mussel retained a very small fraction of MF, their accumulation was higher in the digestive gland than in gills, and in both tissues of mussels exposed to the lowest concentration. Selective accumulation of shorter MF was also observed, particularly in gills. Overall, the results demonstrate that at environmental exposure levels, PET-MF have a significant impact on mussel physiology, affecting multiple processes in different tissues.