Open AccessArticle
Differences in Reproductive Behavior between Spawning and Non-Spawning Zebrafish Pairs and the Effects of 17α-Ethinylestradiol (EE2)
Toxics 2016, 4(3), 22; doi:10.3390/toxics4030022 -
Abstract
Reproductive success manifested by spawning and fertilization, in most fish, depends partly on an appropriate courtship behavior by both sexes. The zebrafish reproductive behavior can be resolved in some of its constituent elements by a computerized vision system and described in unbiased [...] Read more.
Reproductive success manifested by spawning and fertilization, in most fish, depends partly on an appropriate courtship behavior by both sexes. The zebrafish reproductive behavior can be resolved in some of its constituent elements by a computerized vision system and described in unbiased quantitative terms. Pairs of adult male and female zebrafish were monitored with automatic video tracking at 16 Hz for 45 min in a tank with a spawning area in one corner. Subsequently, spawning, if any, was registered and the swimming behavior and mutual interactions of the two fish were quantified. Further, temporal and frequency distributions of average velocity and turning rate were produced. It is demonstrated that the courtship behavior in spawning pairs differs markedly from non-spawning pairs with differences in both male and female behavior. EE2 (17α-ethinylestradiol), a contraceptive hormone found in aquatic environments, has only a slight effect on these behavior differences between spawning and non-spawning pairs. Full article
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Open AccessArticle
Evaluation of Common Use Brominated Flame Retardant (BFR) Toxicity Using a Zebrafish Embryo Model
Toxics 2016, 4(3), 21; doi:10.3390/toxics4030021 -
Abstract
Brominated flame retardants (BFRs) are used to reduce the flammability of plastics, textiles, and electronics. BFRs vary in their chemical properties and structures, and it is expected that these differences alter their biological interactions and toxicity. Zebrafish were used as the model [...] Read more.
Brominated flame retardants (BFRs) are used to reduce the flammability of plastics, textiles, and electronics. BFRs vary in their chemical properties and structures, and it is expected that these differences alter their biological interactions and toxicity. Zebrafish were used as the model organism for assessing the toxicity of nine structurally-diverse BFRs. In addition to monitoring for overt toxicity, the rate of spontaneous movement, and acetylcholinesterase and glutathione-S-transferase (GST) activities were assessed following exposure. The toxicities of BFRs tested can be ranked by LC50 as tetrabromobisphenol A (TBBPA) < 4,4′-isopropylidenebis[2-(2,6-dibromophenoxyl)ethanol] (TBBPA-OHEE) < Pentabromochlorocyclohexane (PBCH) < 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) < hexabromocyclododecane (HBCD) < hexabromobenzene (HBB) < Tetrabromophthalic anhydride (PHT4). No adverse effect was observed in di(2-ethylhexyl) tetrabromophthalate (TBPH) or dibromoneopentyl glycol (DBNPG)-treated embryos. The rate of spontaneous movement was decreased in a concentration-dependent manner following exposure to four of the nine compounds. GST activity was elevated following treatment with PBCH, TBBPA, HBCD, and HBB. The results indicate that exposure to several BFRs may activate an antioxidant response and alter behavior during early development. Some of the BFRs, such as TBBPA and TBBPA-OHEE, induced adverse effects at concentrations lower than chemicals that are currently banned. These results suggest that zebrafish are sensitive to exposure to BFRs and can be used as a comparative screening model, as well as to determine alterations in behavior following exposure and probe mechanisms of action. Full article
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Open AccessArticle
Assessment of Toxicological Perturbations and Variants of Pancreatic Islet Development in the Zebrafish Model
Toxics 2016, 4(3), 20; doi:10.3390/toxics4030020 -
Abstract
The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue [...] Read more.
The pancreatic islets, largely comprised of insulin-producing beta cells, play a critical role in endocrine signaling and glucose homeostasis. Because they have low levels of antioxidant defenses and a high perfusion rate, the endocrine islets may be a highly susceptible target tissue of chemical exposures. However, this endpoint, as well as the integrity of the surrounding exocrine pancreas, is often overlooked in studies of developmental toxicology. Disruption of development by toxicants can alter cell fate and migration, resulting in structural alterations that are difficult to detect in mammalian embryo systems, but that are easily observed in the zebrafish embryo model (Danio rerio). Using endogenously expressed fluorescent protein markers for developing zebrafish beta cells and exocrine pancreas tissue, we documented differences in islet area and incidence rates of islet morphological variants in zebrafish embryos between 48 and 96 h post fertilization (hpf), raised under control conditions commonly used in embryotoxicity assays. We identified critical windows for chemical exposures during which increased incidences of endocrine pancreas abnormalities were observed following exposure to cyclopamine (2–12 hpf), Mono-2-ethylhexyl phthalate (MEHP) (3–48 hpf), and Perfluorooctanesulfonic acid (PFOS) (3–48 hpf). Both islet area and length of the exocrine pancreas were sensitive to oxidative stress from exposure to the oxidant tert-butyl hydroperoxide during a highly proliferative critical window (72 hpf). Finally, pancreatic dysmorphogenesis following developmental exposures is discussed with respect to human disease. Full article
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Open AccessReview
Zebrafish Get Connected: Investigating Neurotransmission Targets and Alterations in Chemical Toxicity
Toxics 2016, 4(3), 19; doi:10.3390/toxics4030019 -
Abstract
Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly [...] Read more.
Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed. Full article
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Open AccessReview
The Synapse as a Central Target for Neurodevelopmental Susceptibility to Pesticides
Toxics 2016, 4(3), 18; doi:10.3390/toxics4030018 -
Abstract
The developmental period of the nervous system is carefully orchestrated and highly vulnerable to alterations. One crucial factor of a properly-functioning nervous system is the synapse, as synaptic signaling is critical for the formation and maturation of neural circuits. Studies show that [...] Read more.
The developmental period of the nervous system is carefully orchestrated and highly vulnerable to alterations. One crucial factor of a properly-functioning nervous system is the synapse, as synaptic signaling is critical for the formation and maturation of neural circuits. Studies show that genetic and environmental impacts can affect diverse components of synaptic function. Importantly, synaptic dysfunction is known to be associated with neurologic and psychiatric disorders, as well as more subtle cognitive, psychomotor, and sensory defects. Given the importance of the synapse in numerous domains, we wanted to delineate the effects of pesticide exposure on synaptic function. In this review, we summarize current epidemiologic and molecular studies that demonstrate organochlorine, organophosphate, and pyrethroid pesticide exposures target the developing synapse. We postulate that the synapse plays a central role in synaptic vulnerability to pesticide exposure during neurodevelopment, and the synapse is a worthy candidate for investigating more subtle effects of chronic pesticide exposure in future studies. Full article
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Open AccessReview
Impact of Spent Mushroom Substrates on the Fate of Pesticides in Soil, and Their Use for Preventing and/or Controlling Soil and Water Contamination: A Review
Toxics 2016, 4(3), 17; doi:10.3390/toxics4030017 -
Abstract
Intensive crop production involves a high consumption of pesticides. This is a cause of major environmental concern because the presence of pesticides in water is becoming increasingly common. Physicochemical methods based on soil modification with organic residues have been developed to enhance [...] Read more.
Intensive crop production involves a high consumption of pesticides. This is a cause of major environmental concern because the presence of pesticides in water is becoming increasingly common. Physicochemical methods based on soil modification with organic residues have been developed to enhance the immobilization and/or degradation of pesticides in agricultural soils, which may control both the diffuse and the point pollution of soils and waters. This review summarizes the influence of spent mushroom substrate (SMS) on the environmental fate of pesticides when both are simultaneously applied in agriculture. The processes of adsorption, leaching and dissipation of these compounds in SMS-amended soils were evaluated at laboratory and field scale. Relationships were established between the experimental parameters obtained and the properties of the soils, the SMS, and the pesticides in order to determine the effect that the application of SMS in agricultural soils has on the environmental impact of pesticides. Accordingly, this review highlights the use of SMS as a strategy for the prevention and/or control of soil and water contamination by pesticides to strike a balance between agricultural development and the use of these compounds. Full article
Open AccessArticle
Groundwater Contamination by Uranium and Mercury at the Ridaura Aquifer (Girona, NE Spain)
Toxics 2016, 4(3), 16; doi:10.3390/toxics4030016 -
Abstract
Elevated concentrations of uranium and mercury have been detected in drinking water from public supply and agricultural wells in alluvial and granitic aquifers of the Ridaura basin located at Catalan Coastal Ranges (CCR). The samples showed high concentrations of U above the [...] Read more.
Elevated concentrations of uranium and mercury have been detected in drinking water from public supply and agricultural wells in alluvial and granitic aquifers of the Ridaura basin located at Catalan Coastal Ranges (CCR). The samples showed high concentrations of U above the U.S. standards and the World Health Organization regulations which set a maximum value of 30 µg/L. Further, high mercury concentrations above the European Drinking Water Standards (1 μg/L) were found. Spatial distribution of U in groundwater and geochemical evolution of groundwater suggest that U levels appear to be highest in granitic areas where groundwater has long residence times and a significant salinity. The presence of high U concentrations in alluvial groundwater samples could be associated with hydraulic connection through fractures between the alluvial system and deep granite system. According to this model, oxidizing groundwater moving through fractures in the leucocratic/biotitic granite containing anomalous U contents are the most likely to acquire high levels of U. The distribution of Hg showed concentrations above 1 μg/L in 10 alluvial samples, mainly located near the limit of alluvial aquifer with igneous rocks, which suggests a possible migration of Hg from granitic materials. Also, some samples showed Hg concentrations comprised between 0.9 and 1.5 μg/L, from wells located in agricultural areas. Full article
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Open AccessArticle
Air Quality and Hospital Outcomes in Emergency Medical Admissions with Respiratory Disease
Toxics 2016, 4(3), 15; doi:10.3390/toxics4030015 -
Abstract
Background: The impact of very low levels of air pollutants, particulate matter (PM10) and sulfur dioxide (SO2) concentrations, on human health is not well characterized. We examined the outcomes (30-day in-hospital mortality) of emergency hospitalizations of respiratory patients and the [...] Read more.
Background: The impact of very low levels of air pollutants, particulate matter (PM10) and sulfur dioxide (SO2) concentrations, on human health is not well characterized. We examined the outcomes (30-day in-hospital mortality) of emergency hospitalizations of respiratory patients and the level of local pollutants on the day of admission. Methods: All emergency admissions (82,421 episodes in 44,660 patients) were recorded over 13 years (2002–2014) and mortality assessed. The median interquartile ranges (IQR) age was 64.5 (43.9, 78.5) years with the proportion of males at 48.5%. Univariate and multivariate logistic regression was used to examine relationships between pollutant concentration (PM10 and SO2) and odds ratio (OR) for 30-day in hospital death, after adjustment for acuity. Results: Mortality related to each pollutant variable assessed (as quintiles of increasing atmospheric concentration). For PM10 mortality, the highest two quintiles concentrations were significantly increased (p < 0.001) with univariate ORs of 1.30. For SO2, the ORs were 1.32, 1.39, and 1.46, for the top three quintiles. There was also a strong relationship between the underlying respiratory function; with forced expiratory volume (FEV1) in 1 second (FEV1) ≥ 2.0L at the lowest PM10 quintile, mortality was 6.5% (95% CI: 6.1, 6.9) increasing to 9.5% (95% CI: 9.0, 10.0) at the highest PM10 quintile. For patients with FEV1 < 2.0L, the mortality at the lowest PM10 quintile was 9.9% (95% CI: 8.8, 10.9) increasing to 14.2% (95% CI: 12.8, 15.6) at the highest quintile. Conclusion: Despite air quality improvement, there was a clear relationship between pollutant concentration and outcomes for respiratory emergency admissions; additionally, the underlying level of pulmonary function was predictive of in-hospital mortality. Full article
Open AccessCommentary
Toxicovigilance Systems and Practices in Africa
Toxics 2016, 4(3), 13; doi:10.3390/toxics4030013 -
Abstract
African consumers and citizens are growingly aware of the wide range of toxic poisoning scenarios from different products and hazards. Recurrent episodes on poisoning that have been reported in Africa include toxic hazards in consumers’ products ranging from food to herbal medicine, [...] Read more.
African consumers and citizens are growingly aware of the wide range of toxic poisoning scenarios from different products and hazards. Recurrent episodes on poisoning that have been reported in Africa include toxic hazards in consumers’ products ranging from food to herbal medicine, drugs, and cosmetics. Chemical poisoning remains an issue that is overlooked by public health stakeholders in Africa. Available information on toxicovigilance systems and practices in African countries is reviewed in terms of increasing development, organization and articulation levels. Less than nine out of 54 African countries have a legally recognized toxicovigilance system. Of these, the majority have created toxicovigilance systems recently, and are facing many challenges in developing them, at regional and country levels. Basic structures for a good toxicovigilance system include a phone line service (available 24/7), and hospital facilities. Pesticides emerge as the hazard recognized by all of the toxicovigilance systems, and may represent a prototypic toxicant towards a toxicovigilance system that is inclusive of a wider spectrum of toxicological hazards for the protection of community health. Toxicovigilance today is more reactive than preventive in Africa, but some milestones are present that constitute some promising seminal efforts. Full article
Open AccessEditorial
Toxicities of Therapeutic Agents Used in Medicine
Toxics 2016, 4(3), 14; doi:10.3390/toxics4030014 -
Abstract This Special Issue on “Toxicities of Therapeutic Agents Used in Medicine” reports on some peculiar cases of toxicities related to widely and commonly employed drugs.[...] Full article
Open AccessArticle
Household Air Pollution: Sources and Exposure Levels to Fine Particulate Matter in Nairobi Slums
Toxics 2016, 4(3), 12; doi:10.3390/toxics4030012 -
Abstract
With 2.8 billion biomass users globally, household air pollution remains a public health threat in many low- and middle-income countries. However, little evidence on pollution levels and health effects exists in low-income settings, especially slums. This study assesses the levels and sources [...] Read more.
With 2.8 billion biomass users globally, household air pollution remains a public health threat in many low- and middle-income countries. However, little evidence on pollution levels and health effects exists in low-income settings, especially slums. This study assesses the levels and sources of household air pollution in the urban slums of Nairobi. This cross-sectional study was embedded in a prospective cohort of pregnant women living in two slum areas—Korogocho and Viwandani—in Nairobi. Data on fuel and stove types and ventilation use come from 1058 households, while air quality data based on the particulate matters (PM2.5) level were collected in a sub-sample of 72 households using the DustTrak™ II Model 8532 monitor. We measured PM2.5 levels mainly during daytime and using sources of indoor air pollutions. The majority of the households used kerosene (69.7%) as a cooking fuel. In households where air quality was monitored, the mean PM2.5 levels were high and varied widely, especially during the evenings (124.6 µg/m3 SD: 372.7 in Korogocho and 82.2 µg/m3 SD: 249.9 in Viwandani), and in households using charcoal (126.5 µg/m3 SD: 434.7 in Korogocho and 75.7 µg/m3 SD: 323.0 in Viwandani). Overall, the mean PM2.5 levels measured within homes at both sites (Korogocho = 108.9 µg/m3 SD: 371.2; Viwandani = 59.3 µg/m3 SD: 234.1) were high. Residents of the two slums are exposed to high levels of PM2.5 in their homes. We recommend interventions, especially those focusing on clean cookstoves and lighting fuels to mitigate indoor levels of fine particles. Full article
Open AccessArticle
UNMIX Methods Applied to Characterize Sources of Volatile Organic Compounds in Toronto, Ontario
Toxics 2016, 4(2), 11; doi:10.3390/toxics4020011 -
Abstract
UNMIX, a sensor modeling routine from the U.S. Environmental Protection Agency (EPA), was used to model volatile organic compound (VOC) receptors in four urban sites in Toronto, Ontario. VOC ambient concentration data acquired in 2000–2009 for 175 VOC species in four air [...] Read more.
UNMIX, a sensor modeling routine from the U.S. Environmental Protection Agency (EPA), was used to model volatile organic compound (VOC) receptors in four urban sites in Toronto, Ontario. VOC ambient concentration data acquired in 2000–2009 for 175 VOC species in four air quality monitoring stations were analyzed. UNMIX, by performing multiple modeling attempts upon varying VOC menus—while rejecting the results that were not reliable—allowed for discriminating sources by their most consistent chemical characteristics. The method assessed occurrences of VOCs in sources typical of the urban environment (traffic, evaporative emissions of fuels, banks of fugitive inert gases), industrial point sources (plastic-, polymer-, and metalworking manufactures), and in secondary sources (releases from water, sediments, and contaminated urban soil). The remote sensing and robust modeling used here produces chemical profiles of putative VOC sources that, if combined with known environmental fates of VOCs, can be used to assign physical sources’ shares of VOCs emissions into the atmosphere. This in turn provides a means of assessing the impact of environmental policies on one hand, and industrial activities on the other hand, on VOC air pollution. Full article
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Open AccessArticle
Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure
Toxics 2016, 4(2), 10; doi:10.3390/toxics4020010 -
Abstract
Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker [...] Read more.
Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents’ exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%–54%) in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents’ study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended. Full article
Open AccessArticle
Assessing Potential Vulnerability and Response of Fish to Simulated Avian Predation after Exposure to Psychotropic Pharmaceuticals
Toxics 2016, 4(2), 9; doi:10.3390/toxics4020009 -
Abstract
Psychotropic pharmaceuticals present in the environment may impact organisms both directly and via interaction strengths with other organisms, including predators; therefore, this study examined the potential effects of pharmaceuticals on behavioral responses of fish to avian predators. Wild-caught juvenile perch (Perca[...] Read more.
Psychotropic pharmaceuticals present in the environment may impact organisms both directly and via interaction strengths with other organisms, including predators; therefore, this study examined the potential effects of pharmaceuticals on behavioral responses of fish to avian predators. Wild-caught juvenile perch (Perca fluviatilis) were assayed using a striking bird model after a seven-day exposure to psychotropic pharmaceuticals (the antidepressants fluoxetine or sertraline, or the β-blocker propranolol) under the hypotheses that exposure would increase vulnerability to avian predation via increasing the probability of predator encounter as well as degrading evasive behaviors upon encounter. None of the substances significantly affected swimming activity of the fish, nor did they increase vulnerability by affecting encounter probability or evasive endpoints compared to control treatments. Counter to our expectations, fish exposed to 100 μg/L fluoxetine (but no other concentrations or pharmaceuticals) were less likely to enter the open area of the arena, i.e., less likely to engage in risky behavior that could lead to predator encounters. Additionally, all fish exposed to environmentally relevant, low concentrations of sertraline (0.12 μg/L) and propranolol (0.1 μg/L) sought refuge after the simulated attack. Our unexpected results warrant further research as they have interesting implications on how these psychotropic pharmaceuticals may affect predator-prey interactions spanning the terrestrial-aquatic interface. Full article
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Open AccessCommunication
Current Status of Air Toxics Management and Its Strategies for Controlling Emissions in Taiwan
Toxics 2016, 4(2), 8; doi:10.3390/toxics4020008 -
Abstract
Since the 1970s, hazardous air pollutants (HAPs), so-called air toxics, have been of great concern because they can cause serious human health effects and have adverse effects on the environment. More noticeably, some of them are known to be human carcinogens. The [...] Read more.
Since the 1970s, hazardous air pollutants (HAPs), so-called air toxics, have been of great concern because they can cause serious human health effects and have adverse effects on the environment. More noticeably, some of them are known to be human carcinogens. The objective of this paper is to investigate the regulatory systems and human health effects of air toxics which have been designated by the Taiwan government under the Air Pollution Control Act. These toxic air pollutants include acutely toxic gas (i.e., ammonia, chlorine, fluorides, hydrochloric acid, hydrogen cyanide, hydrogen sulfide, nitric acid, phosphoric acid and sulfuric acid), gas containing heavy metals, and carcinogenic chemicals (including formaldehyde, vinyl chloride, asbestos and matter containing asbestos, dioxins and furans, volatile organic compounds, polycyclic aromatic hydrocarbons, and polychlorinated biphenyls). In line with international concern about the carcinogenic risk and environmental persistence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) and heavy metals in recent years, the current status in monitoring and reducing the emissions of PCDDs/PCDFs from stationary sources was analyzed as a case study in the present study. Furthermore, the control strategies for reducing emissions of air toxics from stationary sources in Taiwan were also addressed. Full article
Open AccessArticle
Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy
Toxics 2016, 4(1), 7; doi:10.3390/toxics4010007 -
Abstract
People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects [...] Read more.
People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites). Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes. Full article
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Open AccessArticle
Transcriptional Suppression of Renal Antioxidant Enzyme Systems in Guinea Pigs Exposed to Polymerized Cell-Free Hemoglobin
Toxics 2016, 4(1), 6; doi:10.3390/toxics4010006 -
Abstract
Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury has raised safety concerns. Using a guinea pig exchange transfusion model, we examined the effects of polymerized bovine hemoglobin (HbG) on [...] Read more.
Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury has raised safety concerns. Using a guinea pig exchange transfusion model, we examined the effects of polymerized bovine hemoglobin (HbG) on the transcriptional regulation, activity, and expression of the renal antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). HbG infusion downregulated the mRNA levels for genes encoding SOD isoforms 1-3, GPx1, GPx3, GPx4, and CAT. This transcriptional suppression correlated with decreased enzymatic activities for SOD, CAT, and GPx. Immunostaining revealed decreased protein expression of SOD1, CAT, and GPx1 primarily in renal cortical tubules. DNA methylation analyses identified CpG hypermethylation in the gene promoters for SOD1-3, GPx1, GPx3, and GPx4, suggesting an epigenetic-based mechanism underlying the observed gene repression. HbG also induced oxidative stress as evidenced by increased renal lipid peroxidation end-products and 4-HNE immunostaining, which could be the result of the depleted antioxidant defenses and/or serve as a trigger for increased DNA methylation. Together, these findings provide evidence that the renal exposure to HbG suppresses the function of major antioxidant defense systems which may have relevant implications for understanding the safety of hemoglobin-based products. Full article
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Open AccessReview
Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS): A New Tool for the Analysis of Toxicological Effects on Single Cell Level
Toxics 2016, 4(1), 5; doi:10.3390/toxics4010005 -
Abstract
Single cell imaging mass spectrometry opens up a complete new perspective for strategies in toxicological risk assessment and drug discovery. In particular, time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial and depth resolution is becoming part of the imaging mass [...] Read more.
Single cell imaging mass spectrometry opens up a complete new perspective for strategies in toxicological risk assessment and drug discovery. In particular, time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial and depth resolution is becoming part of the imaging mass spectrometry toolbox used for single cell analysis. Recent instrumentation advancements in combination with newly developed cluster ion guns allow 3-dimensional reconstruction of single cells together with a spatially resolved compound location and quantification on nanoscale depth level. The exact location and quantification of a single compound or even of a set of compounds is no longer restricted to the two dimensional space within single cells, but is available for voxels, a cube-sized 3-dimensional space, rather than pixels. The information gathered from one voxel is further analysed using multivariate statistical methodology like maximum autocorrelation factors to co-locate the compounds of interest within intracellular organelles like nucleus, mitochondria or golgi apparatus. Furthermore, the cell membrane may be resolved, including adhering compounds and potential changes of the lipid patterns. The generated information can be used further for a first evaluation of intracellular target specifity of new drug candidates or for the toxicological risk assessment of environmental chemicals and their intracellular metabolites. Additionally, single cell lipidomics and metabolomics enable for the first time an in-depth understanding of the activation or inhibition of cellular biosynthesis and signalling pathways. Full article
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Open AccessArticle
Contributing Factors for Acute Illness/Injury from Childhood Pesticide Exposure in North Carolina, USA, 2007–2013
Toxics 2016, 4(1), 4; doi:10.3390/toxics4010004 -
Abstract
Between 2007 and 2013, there were 685 events with evidence of a relationship between pesticide exposure and acute illness/injury among persons less than 18 years old in North Carolina (United States). Median age of children affected was 4.3 years (range: 0.2–17.9). Distribution [...] Read more.
Between 2007 and 2013, there were 685 events with evidence of a relationship between pesticide exposure and acute illness/injury among persons less than 18 years old in North Carolina (United States). Median age of children affected was 4.3 years (range: 0.2–17.9). Distribution by gender was similar across all age groups. One fatality and four high severity events were observed. The greatest proportion (42%) of events had ocular exposures, followed by dermal (25%) and inhalation (18%) exposures. When more than one route of exposure occurred, dermal and ocular routes were the most common (46%). Almost all events took place indoors and 32 events involved contact with pets. Insecticides (53%) and insect repellants (31%) were the most frequent agents contributing to these events. Manual application of pesticides contributed to the greatest number of events (25%), while application through a pressurized can and use of a trigger pump were involved in 21% and 15% of events, respectively. Additional contributors were due to inappropriate storage of pesticides and improper use of the pesticide. These contributing factors can be removed or minimized if pesticides are stored outside the residence or out of the reach of children and pets, and adequate ventilation is ensured whenever pesticides are applied. Full article
Open AccessCommunication
Metal and Microelement Biomarkers of Neurodegeneration in Early Life Permethrin-Treated Rats
Toxics 2016, 4(1), 3; doi:10.3390/toxics4010003 -
Abstract
Hair is a non-invasive biological material useful in the biomonitoring of trace elements because it is a vehicle for substance excretion from the body, and it permits evaluating long-term metal exposure. Here, hair from an animal model of neurodegeneration, induced by early [...] Read more.
Hair is a non-invasive biological material useful in the biomonitoring of trace elements because it is a vehicle for substance excretion from the body, and it permits evaluating long-term metal exposure. Here, hair from an animal model of neurodegeneration, induced by early life permethrin treatment from the sixth to 21th day of life, has been analyzed with the aim to assess if metal and microelement content could be used as biomarkers. A hair trace element assay was performed by the ICP-MS technique in six- and 12-month-old rats. A significant increase of As, Mg, S and Zn was measured in the permethrin-treated group at 12 months compared to six months, while Si and Cu/Zn were decreased. K, Cu/Zn and S were increased in the treated group compared to age-matched controls at six and 12 months, respectively. Cr significantly decreased in the treated group at 12 months. PCA analysis showed both a best difference between treated and age-matched control groups at six months. The present findings support the evidence that the Cu/Zn ratio and K, measured at six months, are the best biomarkers for neurodegeneration. This study supports the use of hair analysis to identify biomarkers of neurodegeneration induced by early life permethrin pesticide exposure. Full article
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