The role of charge in the toxicity of polymer-coated cerium oxide nanomaterials to Caenorhabditis elegans

This study examined the impact of surface functionalization and charge on ceria nanomaterial toxicity to Caenorhabditis elegans. The examined endpoints included mortality, reproduction, protein expression, and protein oxidation profiles. Caenorhabditis elegans were exposed to identical 2–5 nm ceria nanomaterial cores which were coated with cationic (diethylaminoethyl dextran; DEAE), anionic (carboxymethyl dextran; CM), and non-ionic (dextran; DEX) polymers. Mortality and reproductive toxicity of DEAE-CeO2 was approximately two orders of magnitude higher than for CM-CeO2 or DEX-CeO2. Two-dimensional gel electrophoresis with orbitrap mass spectrometry identification revealed changes in the expression profiles of several mitochondrial-related proteins and proteins that are expressed in the C. elegans intestine. However, each type of CeO2 material exhibited a distinct protein expression profile. Increases in protein carbonyls and protein-bound 3-nitrotyrosine were also observed for some proteins, indicating oxidative and nitrosative damage. Taken together the results indicate that the magnitude of toxicity and toxicity pathways vary greatly due to surface functionalization of CeO2 nanomaterials

kNN Classification of Epilepsy Brainwaves

Epilepsy is a disorder of the normal brain function by the existence of abnormal synchronous discharges in large groups of neurons in brain structures and it is estimated about 1% of the world’s population suffers from this disease [Tzallas et al., 2009]. It has been reported that the brainwave of Epilepsy patient mostly in sharp, spike and complex wave pattern [Tzallas et al., 2009]. In addition, Epilepsy brainwaves pattern lies in wide variety of Electroencephalogram (EEG) signals in formed of low-amplitude and polyspikes activity [Vargas et al., 2011]. Generally, this disease was examined through the brainwaves or EEG signals by clinical neurulogists. An EEG is a device to record the brainwaves in term of electrical activity from the brain. Brain patterns from wave shapes that are commonly sinusoidal and measured from peak to peak that range from 0.5 μV to 100 μV in amplitude. Moreover, the brainwaves have been categorized into four frequency bands, Beta (>13 Hz), Alpha (8-13 Hz), Theta (4-8 Hz) and Delta (0.5-4 Hz). All the frequency bands will be used to characterize the Epilepsy brainwave in terms of amplitude (voltage) and frequency [Mustafa et al., 2013]. The Epilepsy brainwaves were downloaded from http://www.vis.caltech.edu/~rodri/data.htm of Fp1 and Fp2 channels which is from rats. The brainwaves consists Epilepsy and non-Epilepsy samples. Then, the brainwaves were pre-processed to remove artefact (noise). Various methods had been introduced to detect spike-wave discharge in Epilepsy patient brainwave. Brainwave is nonstationary signal, therefore, time-frequency analysis is appropriate methods to analyse the signals[Tzallas et al., 2009, Vargas et al., 2011]. One of the most popular time-frequency analyses is ShortTime Fourier Transform (STFT). After the brainwaves were pre-processed, STFT was employed to the clean brainwaves. The STFT spectrogram was generated for four frequency bands of the samples

Aluminum and Phthalates in Calcium Gluconate: Contribution from Glass and Plastic Packaging

Introduction: Aluminum contamination of parenteral nutrition solutions has been documented for three decades. It can result in elevated blood, bone, and whole body aluminum levels associated with neurotoxicity, reduced bone mass and mineral content, and perhaps hepatotoxicity. The primary aluminum source among parenteral nutrition components is glass-packaged calcium gluconate, in which aluminum concentration the past three decades has averaged~ 4000 [mu]g/L, compared to \u3c 200 [mu]g/L in plastic container-packaged calcium gluconate. A concern about plastic packaging is leaching of plasticizers, including phthalates, which have the potential to cause endocrine (male reproductive system) disruption and neurotoxicity. Methods: Aluminum was quantified in samples collected periodically over more than two years from three calcium gluconate sources used to prepare parenteral nutrition solutions; two packaged in glass (from France and the US) and one in plastic (from Germany); in a recently released plastic-packaged solution (from the US);and in the two glass containers. Phthalate concentration was determined in selected samples of each product and leachate of the plastic containers. Results: The initial aluminum concentration was ~ 5000 [mu]g/L in the two glass-packaged products and ~ 20 [mu]g/L in the plastic-packaged product, and increased ~ 30, 50 and 100% over 2 years, respectively. The aluminum concentration in a recently released Calcium Gluconate Injection USP was ~ 320 [mu]g/L. Phthalates were not detected in any calcium gluconate solutions or leachates. Conclusion: Plastic packaging greatly reduces the contribution of aluminum to parenteral nutrition solutions from calcium gluconate compared to the glass-packaged product

Environmental release, fate and ecotoxicological effects of manufactured ceria nanomaterials

Recent interest in the environmental fate and effects of manufactured CeO2 nanomaterials (nanoceria) has stemmed from its expanded use for a variety of applications including fuel additives, catalytic converters, chemical and mechanical planarization media and other uses. This has led to a wave of publications on the toxicological effects of nanoceria in ecological receptor species, but only limited information is available on possible environmental releases, concentrations in environmental media, or environmental transformations. In this paper, we make initial estimates of likely environmental releases and exposure concentrations in soils and water and compare them to published toxicity values. Insufficient information was available to estimate aquatic exposures, but we estimated inputs to a hypothetical wastewater treatment plant that could result in effluent concentrations that would result in acute toxicity to the most sensitive aquatic organisms tested so far, cyanobacteria. The purpose of this exercise is to identify which areas are lacking in data to perform either regional or site specific ecological risk assessments. While estimates can be made for releases from use as a diesel fuel additive, and predicted toxicity is low in most terrestrial species tested to date, estimates for releases from other uses are difficult at this stage. We recommend that future studies focus on environmentally realistic exposures that take into account potential environmental transformations of the nanoceria surface as well as chronic toxicity studies in benthic aquatic organisms, soil invertebrates and microorgansims

Evidence of Nickel and Other Trace Elements and Their Relationship to Clinical Findings in Acute Mesoamerican Nephropathy: A Case-Control Analysis

BACKGROUND: Although there are several hypothesized etiologies of Mesoamerican Nephropathy (MeN), evidence has not yet pointed to the underlying cause. Exposure to various trace elements can cause the clinical features observed in MeN. METHODS AND FINDINGS: We measured 15 trace elements, including heavy metals, in renal case-patients (n = 18) and healthy controls (n = 36) in a MeN high-risk region of Nicaragua. Toenails clippings from study participants were analyzed using inductively coupled plasma mass spectrometry. A case-control analysis was performed, and concentrations were also analyzed over participant characteristics and clinical parameters. Nickel (Ni) concentrations were significantly higher in toenails from cases (1.554 mg/kg [0.176–42.647]) than controls (0.208 mg/kg [0.055–51.235]; p \u3c 0.001). Ni concentrations correlated positively with serum creatinine levels (p = 0.001) and negatively with eGFR (p = 0.001). Greater Ni exposure was also associated with higher leukocyte (p = 0.001) and neutrophil (p = 0.003) counts, fewer lymphocytes (p = 0.003), and lower hemoglobin (p = 0.004) and hematocrit (p = 0.011). CONCLUSIONS: Low-dose, chronic environmental exposure to Ni is a possible health risk in this setting. Ni intoxication and resulting systemic and renal effects could explain the clinical signs observed during early MeN. This study provides compelling evidence for a role of Ni in the acute renal impairment observed in this MeN high-risk population. Additional work to assess exposure levels in a larger and heterogeneous population, identify environmental sources of Ni and exposure pathways, and evaluate the link between Ni and MeN pathogenesis are urgently needed

Controlling silver nanoparticle exposure in algal toxicity testing - A matter of timing

The aquatic ecotoxicity testing of nanoparticles is complicated by unstable exposure conditions resulting from various transformation processes of nanoparticles in aqueous suspensions. In this study, we investigated the influence of exposure timing on the algal test response to silver nanoparticles (AgNPs), by reducing the incubation time and by aging the AgNPs in algal medium prior to testing. The freshwater green algae Pseudokirchneriella subcapitata were exposed to AgNO(3), NM-300 K (a representative AgNP) and citrate stabilized AgNPs from two different manufacturers (AgNP1 and AgNP2) in a standard algal growth inhibition test (ISO 8692:2004) for 48 h and a short-term (2 h) (14)C-assimilation test. For AgNO(3), similar responses were obtained in the two tests, whereas freshly prepared suspensions of citrate stabilized AgNPs were less toxic in the 2-h tests compared to the 48-h tests. The 2-h test was found applicable for dissolved silver, but yielded non-monotonous concentration–response relationships and poor reproducibility for freshly prepared AgNP suspensions. However, when aging AgNPs in algal medium 24 h prior to testing, clear concentration–response patterns emerged and reproducibility increased. Prolonged aging to 48 h increased toxicity in the 2-h tests whereas aging beyond 48 h reduced toxicity. Our results demonstrate that the outcome of algal toxicity testing of AgNPs is highly influenced not only by the test duration, but also by the time passed from the moment AgNPs are added to the test medium. This time-dependency should be considered when nanomaterial dispersion protocols for ecotoxicity testing are developed

Toxic and Essential Trace Element Content of Commonly Administered Pediatric Oral Medications

OBJECTIVES: The aim of this study was to test the hypothesis that commonly administered pediatric oral medications are a significant source of toxic elements. The concentrations of 16 elements were determined in 14 frequently used pediatric oral medications. METHODS: Samples were prepared for analysis by dilution or nitric acid microwave-assisted digestion and analyzed by inductively coupled plasma mass spectrometry. The intake of each element from administration for 1 week of the medication\u27s maximum recommended daily dose to 6-month-olds was calculated and compared to an exposure guideline for that element. Exposure guidelines used for adverse effects were minimal risk levels, oral reference dose, permissible or permitted daily exposure, provisional tolerable weekly intake, and tolerable upper intake concentrations. Exposure guidelines utilized for desired effect were adequate intake and recommended dietary allowance. RESULTS: Intake of the maximum recommended daily dose by 6-month-olds for 1 week would not deliver more than the exposure guideline of any of the elements, with the exceptions of chromium in several medications and zinc in the pediatric electrolyte solution, if it was consumed for 1 week. CONCLUSIONS: Consumed alone, these frequently administered pediatric oral medications would not deliver amounts of toxic elements that exceed established exposure guidelines for adverse effects, nor would most significantly contribute to adequate intake of essential elements

Uptake and depuration of gold nanoparticles in Daphnia magna

This study presents a series of short-term studies (total duration 48 h) of uptake and depuration of engineered nanoparticles (ENP) in neonate Daphnia magna. Gold nanoparticles (Au NP) were used to study the influence of size, stabilizing agent and feeding on uptake and depuration kinetics and animal body burdens. 10 and 30 nm Au NP with different stabilizing agents [citrate (CIT) and mercaptoundecanoic acid (MUDA)] were tested in concentrations around 0.5 mg Au/L. Fast initial uptake was observed for all studied Au NP, with CIT stabilized Au NP showing similar rates independent of size and MUDA showing increased uptake for the smaller Au NP (MUDA 10 nm > CIT 10 nm, 30 nm > MUDA 30 nm). However, upon transfer to clean media no clear trend on depuration rates was found in terms of stabilizing agent or size. Independent of stabilizing agent, 10 nm Au NP resulted in higher residual whole-animal body burdens after 24 h depuration than 30 nm Au NP with residual body burdens about one order of magnitude higher of animals exposed to 10 nm Au NP. The presence of food (P. subcapitata) did not significantly affect the body burden after 24 h of exposure, but depuration was increased. While food addition is not necessary to ensure D. magna survival in the presented short-term test design, the influence of food on uptake and depuration kinetics is essential to consider in long term studies of ENP where food addition is necessary. This study demonstrates the feasibility of a short-term test design to assess the uptake and depuration of ENP in D. magna. The findings underlines that the assumptions behind the traditional way of quantifying bioconcentration are not fulfilled when ENPs are studied.Peer reviewed: YesNRC publication: Ye

Global DNA Adenine Methylation in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e after Multigenerational Exposure to Silver Nanoparticles and Silver Nitrate

Multigenerational and transgenerational reproductive toxicity in a model nematode Caenorhabditis elegans has been shown previously after exposure to silver nanoparticles (Ag-NPs) and silver ions (AgNO3 ). However, there is a limited understanding on the transfer mechanism of the increased reproductive sensitivity to subsequent generations. This study examines changes in DNA methylation at epigenetic mark N6-methyl-20 -deoxyadenosine (6mdA) after multigenerational exposure of C. elegans to pristine and transformed-via-sulfidation Ag-NPs and AgNO3 . Levels of 6mdA were measured as 6mdA/dA ratios prior to C. elegans exposure (F0) after two generations of exposure (F2) and two generations of rescue (F4) using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Although both AgNO3 and Ag-NPs induced multigenerational reproductive toxicity, only AgNO3 exposure caused a significant increase in global 6mdA levels after exposures (F2). However, after two generations of rescue (F4), the 6mdA levels in AgNO3 treatment returned to F0 levels, suggesting other epigenetic modifications may be also involved. No significant changes in global DNA methylation levels were observed after exposure to pristine and sulfidized sAg-NPs. This study demonstrates the involvement of an epigenetic mark in AgNO3 reproductive toxicity and suggests that AgNO3 and Ag-NPs may have different toxicity mechanism

Putting biomonitors to work: native moss as a screening tool for solid waste incineration

Solid waste incineration (SWI) can release numerous air pollutants although the geographic reach of emissions is not routinely monitored. While many studies use moss and lichens for biomonitoring trace elements, including around SWIs, few investigate the complex, multi-element footprint expected from SWI emissions. This study develops using native moss as a screening tool for SWI while also informing community concerns about an aging incinerator in rural Oregon, USA. Trained community volunteers helped collect 36 composite samples of epiphytic moss (Orthotrichum s.l.) along a 32-km transect from the SWI. We used ICP-MS to measure 40 elements in moss, including 14 rare earth elements (REEs) previously unexplored for SWI. We compared the elemental signatures of samples with an emissions profile for SWI and mod- eled relationships between element concentrations and distance from the facility using nonparametric regres- sion. The chemical signatures in moss pointed to SWI as a source, potentially through both stack and fugitive dust emissions. The strongest models described farther- dispersing elements, including mercury and cadmium (xR2 = 0.65 and 0.62, respectively), and suggested most deposition occurs within 5 to 10 km of the facility. Ele- ments often associated with soil and dust, like arsenic and chromium, exhibited localized peaks within 0.2 km of the incinerator (xR2 = 0.14–0.3). Three novel ele- ments—cesium and REEs europium and gadolinium— also showed promise as atmospheric tracers for SWI. Gadolinium, a contrast reagent for MRIs, could reflect medical waste incineration by the facility. We include additional analysis and discussion to help stakeholders use results effectively