Micromachined nanocalorimetric sensor for ultra-low-volume cell-based assays.

PubMed

Johannessen, Erik A; Weaver, John M R; Bourova, Lenka; Svoboda, Petr; Cobbold, Peter H; Cooper, Jonathan M

2002-05-01

Current strategies for cell-based screening generally focus on the development of highly specific assays, which require an understanding of the nature of the signaling molecules and cellular pathways involved. In contrast, changes in temperature of cells provides a measure of altered cellular metabolism that is not stimulus specific and hence could have widespread applications in cell-based screening of receptor agonists and antagonists, as well as in the assessment of toxicity of new lead compounds. Consequently, we have developed a micromachined nanocalorimetric biological sensor using a small number of isolated living cells integrated within a subnanoliter format, which is capable of detecting 13 nW of generated power from the cells, upon exposure to a chemical or pharmaceutical stimulus. The sensor comprises a 10-junction gold and nickel thermopile, integrated on a silicon chip which was back-etched to span a 800-nm-thick membrane of silicon nitride. The thin-film membrane, which supported the sensing junctions of the thermoelectric transducer, gave the system a temperature resolution of 0.125 mK, a low heat capacity of 1.2 nJ mK(-1), and a rapid (unfiltered) response time of 12 ms. The application of the system in ultra-low-volume cell-based assays could provide a rapid endogenous screen. It offers important additional advantages over existing methods in that it is generic in nature, it does not require the use of recombinant cell lines or of detailed assay development, and finally, it can enable the use of primary cell lines or tissue biopsies.

Putting a finishing touch on GECIs

PubMed Central

Rose, Tobias; Goltstein, Pieter M.; Portugues, Ruben; Griesbeck, Oliver

2014-01-01

More than a decade ago genetically encoded calcium indicators (GECIs) entered the stage as new promising tools to image calcium dynamics and neuronal activity in living tissues and designated cell types in vivo. From a variety of initial designs two have emerged as promising prototypes for further optimization: FRET (Förster Resonance Energy Transfer)-based sensors and single fluorophore sensors of the GCaMP family. Recent efforts in structural analysis, engineering and screening have broken important performance thresholds in the latest generation for both classes. While these improvements have made GECIs a powerful means to perform physiology in living animals, a number of other aspects of sensor function deserve attention. These aspects include indicator linearity, toxicity and slow response kinetics. Furthermore creating high performance sensors with optically more favorable emission in red or infrared wavelengths as well as new stably or conditionally GECI-expressing animal lines are on the wish list. When the remaining issues are solved, imaging of GECIs will finally have crossed the last milestone, evolving from an initial promise into a fully matured technology. PMID:25477779

Improved Cell Sensitivity and Longevity in a Rapid Impedance-based Toxicity Sensor

DTIC Science & Technology

2009-01-06

sensitivity and longevity in a rapid impedance-based toxicity sensor† Improved cell sensitivity and longevityTheresa M. Curtis,a** Joel Tabb,a Lori...Romeo,a Steven J. Schwager,b Mark W. Widderc* and William H. van der Schaliec ABSTRACT: A number of toxicity sensors for testing field water using a...range of eukaryotic cell types have been proposed, but it has been difficult to identify sensors with both appropriate sensitivity to toxicants and the

Aquatic Toxicity Screening of Fire Fighting Agents; 2003 Report

DTIC Science & Technology

2003-06-02

Aqueous Film Forming Foam ( AFFF ), the reference toxicant. The aquatic toxicity screening consisted of an acute, static, range-finding...five concentrations of 3M Light Water Brand Aqueous Film Forming Foam ( AFFF ), the reference toxicant. The aquatic toxicity screening consisted of an...experimental foam concentrates against current Military Specification MIL-F-24385F Fire Extinguishing Agent, Aqueous Film Forming Foam

Nanogravimetric and voltammetric DNA-hybridization biosensors for studies of DNA damage by common toxicants and pollutants.

PubMed

Nowicka, Anna M; Kowalczyk, Agata; Stojek, Zbigniew; Hepel, Maria

2010-01-01

Electrochemical and nanogravimetric DNA-hybridization biosensors have been developed for sensing single mismatches in the probe-target ssDNA sequences. The voltammetric transduction was achieved by coupling ferrocene moiety to streptavidin linked to biotinylated tDNA. The mass-related frequency transduction was implemented by immobilizing the sensory pDNA on a gold-coated quartz crystal piezoresonators oscillating in the 10MHz band. The high sensitivity of these sensors enabled us to study DNA damage caused by representative toxicants and environmental pollutants, including Cr(VI) species, common pesticides and herbicides. We have found that the sensor responds rapidly to any damage caused by Cr(VI) species, with more severe DNA damage observed for Cr(2)O(7)(2-) and for CrO(4)(2-) in the presence of H(2)O(2) as compared to CrO(4)(2-) alone. All herbicides and pesticides examined caused DNA damage or structural alterations leading to the double-helix unwinding. Among these compounds, paraoxon-ethyl and atrazine caused the fastest and most severe damage to DNA. The physico-chemical mechanism of damaging interactions between toxicants and DNA has been proposed. The methodology of testing voltammetric and nanogravimetric DNA-hybridization biosensors developed in this work can be employed as a simple protocol to obtain rapid comparative data concerning DNA damage caused by herbicide, pesticides and other toxic pollutants. The DNA-hybridization biosensor can, therefore, be utilized as a rapid screening device for classifying environmental pollutants and to evaluate DNA damage induced by these compounds.

eUnaG: a new ligand-inducible fluorescent reporter to detect drug transporter activity in live cells

PubMed Central

Yeh, Johannes T.-H.; Nam, Kwangho; Yeh, Joshua T.-H.; Perrimon, Norbert

2017-01-01

The absorption, distribution, metabolism and excretion (ADME) of metabolites and toxic organic solutes are orchestrated by the ATP-binding cassette (ABC) transporters and the organic solute carrier family (SLC) proteins. A large number of ABC and SLC transpoters exist; however, only a small number have been well characterized. To facilitate the analysis of these transporters, which is important for drug safety and physiological studies, we developed a sensitive genetically encoded bilirubin (BR)-inducible fluorescence sensor (eUnaG) to detect transporter-coupled influx/efflux of organic compounds. This sensor can be used in live cells to measure transporter activity, as excretion of BR depends on ABC and SLC transporters. Applying eUnaG in functional RNAi screens, we characterize l(2)03659 as a Drosophila multidrug resistant-associated ABC transporter. PMID:28176814

Carbon nanotubes and graphene modified screen-printed carbon electrodes as sensitive sensors for the determination of phytochelatins in plants using liquid chromatography with amperometric detection.

PubMed

Dago, Àngela; Navarro, Javier; Ariño, Cristina; Díaz-Cruz, José Manuel; Esteban, Miquel

2015-08-28

Nanomaterials are of great interest for the development of electrochemical sensors. Multi-walled carbon nanotubes and graphene were used to modify the working electrode surface of different screen-printed carbon electrodes (SPCE) with the aim of improving the sensitivity of the SPCE and comparing it with the conventional glassy carbon electrode. To assay the usability of these sensors, a HPLC methodology with amperometric detection was developed to analyze several phytochelatins in plants of Hordeum vulgare and Glycine max treated with Hg(II) or Cd(II) giving detection limits in the low μmolL(-1) range. Phytochelatins are low molecular weight peptides with the general structure γ-(Glu-Cys)n-Gly (n=2-5) which are synthesized in plants in the presence of heavy metal ions. These compounds can chelate heavy metal ions by the formation of complexes which, are transported to the vacuoles, where the toxicity is not threatening. For this reason phytochelatins are essential in the detoxification of heavy metal ions in plants. The developed HPLC method uses a mobile phase of 1% of formic acid in water with KNO3 or NaCl (pH=2.00) and 1% of formic acid in acetonitrile. Electrochemical detection at different carbon-based electrodes was used. Among the sensors tested, the conventional glassy carbon electrode offers the best sensitivity although modification improves the sensitivity of the SPCE. Glutathione and several isoforms of phytochelatin two were found in plant extracts of both studied species. Copyright © 2015 Elsevier B.V. All rights reserved.

Mammalian Cell-Based Sensor System

NASA Astrophysics Data System (ADS)

Banerjee, Pratik; Franz, Briana; Bhunia, Arun K.

Use of living cells or cellular components in biosensors is receiving increased attention and opens a whole new area of functional diagnostics. The term "mammalian cell-based biosensor" is designated to biosensors utilizing mammalian cells as the biorecognition element. Cell-based assays, such as high-throughput screening (HTS) or cytotoxicity testing, have already emerged as dependable and promising approaches to measure the functionality or toxicity of a compound (in case of HTS); or to probe the presence of pathogenic or toxigenic entities in clinical, environmental, or food samples. External stimuli or changes in cellular microenvironment sometimes perturb the "normal" physiological activities of mammalian cells, thus allowing CBBs to screen, monitor, and measure the analyte-induced changes. The advantage of CBBs is that they can report the presence or absence of active components, such as live pathogens or active toxins. In some cases, mammalian cells or plasma membranes are used as electrical capacitors and cell-cell and cell-substrate contact is measured via conductivity or electrical impedance. In addition, cytopathogenicity or cytotoxicity induced by pathogens or toxins resulting in apoptosis or necrosis could be measured via optical devices using fluorescence or luminescence. This chapter focuses mainly on the type and applications of different mammalian cell-based sensor systems.

40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... toxicity screening test. 799.9355 Section 799.9355 Protection of Environment ENVIRONMENTAL PROTECTION... AND MIXTURE TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9355 TSCA reproduction/developmental toxicity screening test. (a) Scope—(1) Applicability. This section is intended to meet testing...

40 CFR 799.9355 - TSCA reproduction/developmental toxicity screening test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... toxicity screening test. 799.9355 Section 799.9355 Protection of Environment ENVIRONMENTAL PROTECTION... AND MIXTURE TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9355 TSCA reproduction/developmental toxicity screening test. (a) Scope—(1) Applicability. This section is intended to meet testing...

The biofilm electrode sensor system for acute toxicity and viral screening

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holodnick, S.E.

1988-01-01

The biofilm electrode sensor (BFE) is designed for the rapid and sensitive detection of toxic and pathogenic environmental contaminants and industrial effluents. It includes a dissolved oxygen electrode which senses respiration changes induced in a biomass film. This study assessed the effects of five chemical on biofilms of Saccharomyces cerevisiae, and polio virus on biofilms of Buffalo Green Monkey kidney cells (BGMk). Acute toxicity was assessed in 30 min, and viral infectivity in 15-20 hr. Potassium cyanide and cupric nitrate inhibited respiration in a similar manner, 2.5-68.2 %I and 30.2-68.8 %I, respectively. The response of the BFE to cyanide andmore » cupric ions occurred within 5-20 sec. Cadmium ions affected the BFE over the range of 50.0-1000 mg/l, but complexed with components in the support medium at lower concentrations. 2,4-dinitrophenol enhanced respiration in the concentration range of 10.0-50.0 mg/l and inhibited respiration in the concentration range of 85.0-100.0 mg/l. A maximum response of 19 %I was noted at 1200 mg/l phenol, before dissolution of the polysulfone membrane filter occurred. Detection of viruses utilized BGMk cells exposed to 4.7 {times} 10{sup 4}{minus}4.7 {times} 10{sup 8} ID{sub 50}/ml poliovirus for 2 hr prior to immobilization. The response of the BFE was optimal at 15-20 hr, with a %I range of 5-40%.« less

Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Hvastkovs, Eli, G.; Schenkman, John B.; Rusling, James, F.

2012-07-01

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography-mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates.

TOXICITY SCREENING WITH ZEBRAFISH ASSAY

EPA Science Inventory

The proposed toxicity screening will help EPA to prioritize chemicals for further testing, and it may also alert chemical manufacturers that some of their commercial products may be toxic. The proposed toxicity pathway studies will improve the research community’s abi...

Toxicity Screening of the ToxCast Chemical Library Using a Zebrafish Developmental Assay

EPA Science Inventory

As part of the chemical screening and prioritization research program of the U.S. Environmental Protection Agency, the toxicity of the 320 ToxCast™ Phase I chemicals were assessed using a vertebrate screen of developmental toxicity. Zebrafish embryos/larvae (Danio rerio) were exp...

The ToxCast Pathway Database for Identifying Toxicity Signatures and Potential Modes of Action from Chemical Screening Data

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA), through its ToxCast program, is developing predictive toxicity approaches that will use in vitro high-throughput screening (HTS), high-content screening (HCS) and toxicogenomic data to predict in vivo toxicity phenotypes. There are ...

A miniaturized bismuth-based sensor to evaluate the marine organism Styela plicata bioremediation capacity toward heavy metal polluted seawater.

PubMed

Colozza, Noemi; Gravina, Maria Flavia; Amendola, Luca; Rosati, Modesto; Akretche, Djamal Eddine; Moscone, Danila; Arduini, Fabiana

2017-04-15

Cadmium and lead are highly toxic heavy metals which cause a severe worldwide pollution. In addition to the toxic effect produced by the direct exposure, they can be bioconcentrated and accumulated in living organisms, including humans. Herein, a miniaturized and disposable electrochemical sensor was improved for the simultaneous detection of cadmium and lead ions to study the bioremediation of polluted seawater in presence of the filter-feeding marine organism Styela plicata. A screen-printed electrode modified in situ with a bismuth film was selected using the anodic stripping analysis as detection technique. This sensor was coupled with a portable potentiostat and the detection of cadmium and lead ions was carried out by Square Wave Anodic Stripping Voltammetry, allowing the simultaneous detection of both heavy metals at ppb level (LOD=0.3ppb for lead, 1.5ppb for cadmium). This analytical tool was then applied to assess the bioremediation capacity of S. plicata through a bioremediation experiment, in which the organism has been exposed to seawater artificially polluted with 1000ppb of Cd 2+ and Pb 2+ . The matrix effect of both seawater and acid digested biological samples was evaluated. A bioconcentration phenomenon was observed for both heavy metals through the analysis of S. plicata tissues. In details, Pb 2+ resulted to be about 2.5 times more bioconcentrated than Cd 2+ , giving an effective bioremediation level in seawater of 13% and 40% for Cd 2+ and Pb 2+ , respectively. Thus, our results demonstrate the capability of S. plicata to bioremediate Cd 2+ and Pb 2+ polluted seawater as well as the suitability of the electrochemical sensor for contaminated marine environment monitoring and bioremediation evaluation. Copyright © 2017 Elsevier B.V. All rights reserved.

A microcantilever-based silver ion sensor using DNA-functionalized gold nanoparticles as a mass amplifier

NASA Astrophysics Data System (ADS)

You, Juneseok; Song, Yeongjin; Park, Chanho; Jang, Kuewhan; Na, Sungsoo

2017-06-01

Silver ions have been used to sterilize many products, however, it has recently been demonstrated that silver ions can be toxic. This toxicity has been studied over many years with the lethal concentration at 10 μM. Silver ions can accumulate through the food chain, causing serious health problems in many species. Hence, there is a need for a commercially available silver ion sensor, with high detection sensitivity. In this work, we develop an ultra-sensitive silver ion sensor platform, using cytosine based DNA and gold nanoparticles as the mass amplifier. We achieve a lower detection limit for silver ions of 10 pM; this detection limit is one million times lower than the toxic concentration. Using our sensor platform we examine highly selective characteristics of other typical ions in water from natural sources. Furthermore, our sensor platform is able to detect silver ions in a real practical sample of commercially available drinking water. Our sensor platform, which we have termed a ‘MAIS’ (mass amplifier ion sensor), with a simple detection procedure, high sensitivity, selectivity and real practical applicability has shown potential as an early toxicity assessment of silver ions in the environment.

Metabolic Toxicity Screening Using Electrochemiluminescence Arrays Coupled with Enzyme-DNA Biocolloid Reactors and Liquid Chromatography–Mass Spectrometry

PubMed Central

Hvastkovs, Eli G.; Schenkman, John B.; Rusling, James F.

2012-01-01

New chemicals or drugs must be guaranteed safe before they can be marketed. Despite widespread use of bioassay panels for toxicity prediction, products that are toxic to a subset of the population often are not identified until clinical trials. This article reviews new array methodologies based on enzyme/DNA films that form and identify DNA-reactive metabolites that are indicators of potentially genotoxic species. This molecularly based methodology is designed in a rapid screening array that utilizes electrochemiluminescence (ECL) to detect metabolite-DNA reactions, as well as biocolloid reactors that provide the DNA adducts and metabolites for liquid chromatography–mass spectrometry (LC-MS) analysis. ECL arrays provide rapid toxicity screening, and the biocolloid reactor LC-MS approach provides a valuable follow-up on structure, identification, and formation rates of DNA adducts for toxicity hits from the ECL array screening. Specific examples using this strategy are discussed. Integration of high-throughput versions of these toxicity-screening methods with existing drug toxicity bioassays should allow for better human toxicity prediction as well as more informed decision making regarding new chemical and drug candidates. PMID:22482786

XPS and NRA investigations during the fabrication of gold nanostructured functionalized screen-printed sensors for the detection of metallic pollutants

NASA Astrophysics Data System (ADS)

Jasmin, Jean-Philippe; Miserque, Frédéric; Dumas, Eddy; Vickridge, Ian; Ganem, Jean-Jacques; Cannizzo, Caroline; Chaussé, Annie

2017-03-01

An all covalent nanostructured lead sensor was built by the successive grafting of gold nanoparticles and carboxylic ligands at the surface of self-adhesive carbon screen-printed electrodes (SPEs). Surface analysis techniques were used in each step in order to investigate the structuration of this sensor. The self-adhesive surfaces were made from the electrochemical grafting of p-phenylenediamine at the surface of the SPEs via diazonium salts chemistry. The quantity of grafted aniline functions, estimated by Nuclear Reaction Analysis (NRA) performed with p-phenylenediamine labelled with 15N isotope, is in agreement with an almost complete coverage of the electrode surface. The subsequent diazotization of the aniline functions at the surface of the SPEs was performed; X-ray Photoelectron Spectroscopy (XPS) allowed us to consider a quantitative conversion of the aniline functions into diazonium moieties. The spontaneous grafting of gold nanoparticles on the as-obtained reactive surfaces ensures the nanostructuration of the material, and XPS studies showed that the covalent bonding of the gold nanoparticles at the surface of the SPEs induces a change both in the Au-4f (gold nanoparticles) and Cl-2p (carbon ink) core level signals. These unusual observations are explained by an interaction between the carbon ink constituting the substrate and the gold nanoparticles. Heavy and toxic metals are considered of major environmental concern because of their non-biodegradability. In a final step, the grafting of the carboxylic ligands at the surface of the SPEs and an accumulation step in the presence of lead(II) cations allowed us to evidence the interest of nanostructured materials as metallic pollutants sensors.

Study of non-stoichiometric BaSrTiFeO3 oxide dedicated to semiconductor gas sensors

NASA Astrophysics Data System (ADS)

Fasquelle, D.; Verbrugghe, N.; Deputier, S.

2016-11-01

Developing instrumentation systems compatible with the European RoHS directive (restriction of hazardous substances) to monitor our environment is of great interest for our society. Our research therefore aims at developing innovating integrated systems of detection dedicated to the characterization of various environmental exposures. These systems, which integrate new gas sensors containing lead-free oxides, are dedicated to the detection of flammable and toxic gases. We have firstly chosen to study semiconductor gas sensors implemented with lead-free oxides in view to develop RoHS devices. Therefore thick films deposited by spin-coating and screen-printing have been chosen for their robustness, ease to realize and ease to finally obtain cost-effective sensors. As crystalline defects and ionic vacancies are of great interest for gas detection, we have decided to study a non-stoichiometric composition of the BaSrTiFeO3 sensible oxide. Nonstoichiometric BaSrTiFeO3 lead-free oxide thick films were deposited by screen-printing on polycrystalline AFO3 substrates covered by a layer of Ag-Pd acting as bottom electrode. The physical characterizations have revealed a crystalline structure mainly composed of BaTiO3 pseudo-cubic phase and Ba4Ti12O27 monoclinic phase for the powder, and a porous microstructure for the thick films. When compared to a BSTF thick film with a stoichiometric composition, a notable increase in the BSTF dielectric constant value was observed when taking into account of a similar microstructure and grain size. The loss tangent mean value varies more softly for the non-stoichiometric BaSrTiFeO3 films than for the perovskite BSTF film as tanδ decreases from 0.45 to 0.04 when the frequency increases from 100 Hz to 1 MHz.

Noise reducing screen devices for in-flow pressure sensors

NASA Technical Reports Server (NTRS)

Schmitz, Fredric (Inventor); Liu, Sandy (Inventor); Jaeger, Stephen (Inventor); Horne, W. Clifton (Inventor)

1997-01-01

An acoustic sensor assembly is provided for sensing acoustic signals in a moving fluid such as high speed fluid stream. The assembly includes one or more acoustic sensors and a porous, acoustically transparent screen supported between the moving fluid stream and the sensor and having a major surface disposed so as to be tangent to the moving fluid. A layer of reduced velocity fluid separating the sensor from the porous screen. This reduced velocity fluid can comprise substantially still air. A foam filler material attenuates acoustic signals arriving at the assembly from other than a predetermined range of incident angles.

Marine Invertebrate Xenobiotic-Activated Nuclear Receptors: Their Application as Sensor Elements in High-Throughput Bioassays for Marine Bioactive Compounds

PubMed Central

Richter, Ingrid; Fidler, Andrew E.

2014-01-01

Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors are particularly well-suited to act as sensors in such bioassays. More specifically, xenobiotic-activated nuclear receptors (XANRs) regulate transcription of genes involved in xenobiotic detoxification. XANR ligand-binding domains (LBDs) may adaptively evolve to bind those bioactive, and potentially toxic, compounds to which organisms are normally exposed to through their specific diets. A brief overview of the function and taxonomic distribution of both vertebrate and invertebrate XANRs is first provided. Proof-of-concept experiments are then described which confirm that a filter-feeding marine invertebrate XANR LBD is activated by marine bioactive compounds. We speculate that increasing access to marine invertebrate genome sequence data, in combination with the expression of functional recombinant marine invertebrate XANR LBDs, will facilitate the generation of high-throughput bioassays/biosensors of widely differing specificities, but all based on activation of XANR LBDs. Such assays may find application in screening marine extracts for bioactive compounds that could act as drug lead compounds. PMID:25421319

Disposable Screen Printed Electrochemical Sensors: Tools for Environmental Monitoring

PubMed Central

Hayat, Akhtar; Marty, Jean Louis

2014-01-01

Screen printing technology is a widely used technique for the fabrication of electrochemical sensors. This methodology is likely to underpin the progressive drive towards miniaturized, sensitive and portable devices, and has already established its route from “lab-to-market” for a plethora of sensors. The application of these sensors for analysis of environmental samples has been the major focus of research in this field. As a consequence, this work will focus on recent important advances in the design and fabrication of disposable screen printed sensors for the electrochemical detection of environmental contaminants. Special emphasis is given on sensor fabrication methodology, operating details and performance characteristics for environmental applications. PMID:24932865

Tandem screening of toxic compounds on GFP-labeled bacteria and cancer cells in microtiter plates.

PubMed

Montoya, Jessica; Varela-Ramirez, Armando; Shanmugasundram, Muthian; Martinez, Luis E; Primm, Todd P; Aguilera, Renato J

2005-09-23

A 96-well fluorescence-based assay has been developed for the rapid screening of potential cytotoxic and bacteriocidal compounds. The assay is based on detection of green fluorescent protein (GFP) in HeLa human carcinoma cells as well as gram negative (Escherichia coli) and gram positive bacteria (Mycobacterium avium). Addition of a toxic compound to the GFP marked cells resulted in the loss of the GFP fluorescence which was readily detected by fluorometry. Thirty-nine distinct naphthoquinone derivatives were screened and several of these compounds were found to be toxic to all cell types. Apart from differences in overall toxicity, two general types of toxic compounds were detected, those that exhibited toxicity to two or all three of the cell types and those that were primarily toxic to the HeLa cells. Our results demonstrate that the parallel screening of both eukaryotic and prokaryotic cells is not only feasible and reproducible but also cost effective.

Electrochromic Molecular Imprinting Sensor for Visual and Smartphone-Based Detections.

PubMed

Capoferri, Denise; Álvarez-Diduk, Ruslan; Del Carlo, Michele; Compagnone, Dario; Merkoçi, Arben

2018-05-01

Electrochromic effect and molecularly imprinted technology have been used to develop a sensitive and selective electrochromic sensor. The polymeric matrices obtained using the imprinting technology are robust molecular recognition elements and have the potential to mimic natural recognition entities with very high selectivity. The electrochromic behavior of iridium oxide nanoparticles (IrOx NPs) as physicochemical transducer together with a molecularly imprinted polymer (MIP) as recognition layer resulted in a fast and efficient translation of the detection event. The sensor was fabricated using screen-printing technology with indium tin oxide as a transparent working electrode; IrOx NPs where electrodeposited onto the electrode followed by thermal polymerization of polypyrrole in the presence of the analyte (chlorpyrifos). Two different approaches were used to detect and quantify the pesticide: direct visual detection and smartphone imaging. Application of different oxidation potentials for 10 s resulted in color changes directly related to the concentration of the analyte. For smartphone imaging, at fixed potential, the concentration of the analyte was dependent on the color intensity of the electrode. The electrochromic sensor detects a highly toxic compound (chlorpyrifos) with a 100 fM and 1 mM dynamic range. So far, to the best of our knowledge, this is the first work where an electrochromic MIP sensor uses the electrochromic properties of IrOx to detect a certain analyte with high selectivity and sensitivity.

Compounds with species and cell type specific toxicity identified in a 2000 compound drug screen of neural stem cells and rat mixed cortical neurons.

PubMed

Malik, Nasir; Efthymiou, Anastasia G; Mather, Karly; Chester, Nathaniel; Wang, Xiantao; Nath, Avindra; Rao, Mahendra S; Steiner, Joseph P

2014-12-01

Human primary neural tissue is a vital component for the quick and simple determination of chemical compound neurotoxicity in vitro. In particular, such tissue would be ideal for high-throughput screens that can be used to identify novel neurotoxic or neurotherapeutic compounds. We have previously established a high-throughput screening platform using human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) and neurons. In this study, we conducted a 2000 compound screen with human NSCs and rat cortical cells to identify compounds that are selectively toxic to each group. Approximately 100 of the tested compounds showed specific toxicity to human NSCs. A secondary screen of a small subset of compounds from the primary screen on human iPSCs, NSC-derived neurons, and fetal astrocytes validated the results from >80% of these compounds with some showing cell specific toxicity. Amongst those compounds were several cardiac glycosides, all of which were selectively toxic to the human cells. As the screen was able to reliably identify neurotoxicants, many with species and cell-type specificity, this study demonstrates the feasibility of this NSC-driven platform for higher-throughput neurotoxicity screens. Published by Elsevier B.V.

Cross-species extrapolation of toxicity information using the ...

EPA Pesticide Factsheets

In the United States, the Endocrine Disruptor Screening Program (EDSP) was established to identify chemicals that may lead to adverse effects via perturbation of the endocrine system (i.e., estrogen, androgen, and thyroid hormone systems). In the mid-1990s the EDSP adopted a two tiered approach for screening chemicals that applied standardized in vitro and in vivo toxicity tests. The Tier 1 screening assays were designed to identify substances that have the potential of interacting with the endocrine system and Tier 2 testing was developed to identify adverse effects caused by the chemical, with documentation of dose-response relationships. While this tiered approach was effective in identifying possible endocrine disrupting chemicals, the cost and time to screen a single chemical was significant. Therefore, in 2012 the EDSP proposed a transition to make greater use of computational approaches (in silico) and high-throughput screening (HTS; in vitro) assays to more rapidly and cost-efficiently screen chemicals for endocrine activity. This transition from resource intensive, primarily in vivo, screening methods to more pathway-based approaches aligns with the simultaneously occurring transformation in toxicity testing termed “Toxicity Testing in the 21st Century” which shifts the focus to the disturbance of the biological pathway predictive of the observable toxic effects. An example of such screening tools include the US Environmental Protection Agency’s

Development of an NDIR CO2 Sensor-Based System for Assessing Soil Toxicity Using Substrate-Induced Respiration

PubMed Central

Kaur, Jasmeen; Adamchuk, Viacheslav I.; Whalen, Joann K.; Ismail, Ashraf A.

2015-01-01

The eco-toxicological indicators used to evaluate soil quality complement the physico-chemical criteria employed in contaminated site remediation, but their cost, time, sophisticated analytical methods and in-situ inapplicability pose a major challenge to rapidly detect and map the extent of soil contamination. This paper describes a sensor-based approach for measuring potential (substrate-induced) microbial respiration in diesel-contaminated and non-contaminated soil and hence, indirectly evaluates their microbial activity. A simple CO2 sensing system was developed using an inexpensive non-dispersive infrared (NDIR) CO2 sensor and was successfully deployed to differentiate the control and diesel-contaminated soils in terms of CO2 emission after glucose addition. Also, the sensor system distinguished glucose-induced CO2 emission from sterile and control soil samples (p ≤ 0.0001). Significant effects of diesel contamination (p ≤ 0.0001) and soil type (p ≤ 0.0001) on glucose-induced CO2 emission were also found. The developed sensing system can provide in-situ evaluation of soil microbial activity, an indicator of soil quality. The system can be a promising tool for the initial screening of contaminated environmental sites to create high spatial density maps at a relatively low cost. PMID:25730479

Screen-printed back-to-back electroanalytical sensors.

PubMed

Metters, Jonathan P; Randviir, Edward P; Banks, Craig E

2014-11-07

We introduce the concept of screen-printed back-to-back electroanalytical sensors where in this facile and generic approach, screen-printed electrodes are printed back-to-back with a common electrical connection to the two working electrodes with the counter and reference electrodes for each connected in the same manner as a normal "traditional" screen-printed sensor would be. This approach utilises the usually redundant back of the screen-printed sensor, converting this "dead-space" into a further electrochemical sensor which results in improvements in the analytical performance. In the use of the back-to-back design, the electrode area is consequently doubled with improvements in the analytical performance observed with the analytical sensitivity (gradient of a plot of peak height/analytical signal against concentration) doubling and the corresponding limit-of-detection being reduced. We also demonstrate that through intelligent electrode design, a quadruple in the observed analytical sensitivity can also be realised when double microband electrodes are used in the back-to-back configuration as long as they are placed sufficiently apart such that no diffusional interaction occurs. Such work is generic in nature and can be facilely applied to a plethora of screen-printed (and related) sensors utilising the commonly overlooked redundant back of the electrode providing facile improvements in the electroanalytical performance.

Metabolomics Approach for Toxicity Screening of Volatile Substances

EPA Science Inventory

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However, the ch...

A screen-printed flexible flow sensor

NASA Astrophysics Data System (ADS)

Moschos, A.; Syrovy, T.; Syrova, L.; Kaltsas, G.

2017-04-01

A thermal flow sensor was printed on a flexible plastic substrate using exclusively screen-printing techniques. The presented device was implemented with custom made screen-printed thermistors, which allows simple, cost-efficient production on a variety of flexible substrates while maintaining the typical advantages of thermal flow sensors. Evaluation was performed for both static (zero flow) and dynamic conditions using a combination of electrical measurements and IR imaging techniques in order to determine important characteristics, such as temperature response, output repeatability, etc. The flow sensor was characterized utilizing the hot-wire and calorimetric principles of operation, while the preliminary results appear to be very promising, since the sensor was successfully evaluated and displayed adequate sensitivity in a relatively wide flow range.

Analytical instrumentation infrastructure for combinatorial and high-throughput development of formulated discrete and gradient polymeric sensor materials arrays

NASA Astrophysics Data System (ADS)

Potyrailo, Radislav A.; Hassib, Lamyaa

2005-06-01

Multicomponent polymer-based formulations of optical sensor materials are difficult and time consuming to optimize using conventional approaches. To address these challenges, our long-term goal is to determine relationships between sensor formulation and sensor response parameters using new scientific methodologies. As the first step, we have designed and implemented an automated analytical instrumentation infrastructure for combinatorial and high-throughput development of polymeric sensor materials for optical sensors. Our approach is based on the fabrication and performance screening of discrete and gradient sensor arrays. Simultaneous formation of multiple sensor coatings into discrete 4×6, 6×8, and 8×12 element arrays (3-15μL volume per element) and their screening provides not only a well-recognized acceleration in the screening rate, but also considerably reduces or even eliminates sources of variability, which are randomly affecting sensors response during a conventional one-at-a-time sensor coating evaluation. The application of gradient sensor arrays provides additional capabilities for rapid finding of the optimal formulation parameters.

In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System#

EPA Science Inventory

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However the cha...

Exploiting NanoLuc luciferase for smartphone-based bioluminescence cell biosensor for (anti)-inflammatory activity and toxicity.

PubMed

Cevenini, Luca; Calabretta, Maria Maddalena; Lopreside, Antonia; Tarantino, Giuseppe; Tassoni, Annalisa; Ferri, Maura; Roda, Aldo; Michelini, Elisa

2016-12-01

The availability of smartphones with high-performance digital image sensors and processing power has completely reshaped the landscape of point-of-need analysis. Thanks to the high maturity level of reporter gene technology and the availability of several bioluminescent proteins with improved features, we were able to develop a bioluminescence smartphone-based biosensing platform exploiting the highly sensitive NanoLuc luciferase as reporter. A 3D-printed smartphone-integrated cell biosensor based on genetically engineered Hek293T cells was developed. Quantitative assessment of (anti)-inflammatory activity and toxicity of liquid samples was performed with a simple and rapid add-and-measure procedure. White grape pomace extracts, known to contain several bioactive compounds, were analyzed, confirming the suitability of the smartphone biosensing platform for analysis of untreated complex biological matrices. Such approach could meet the needs of small medium enterprises lacking fully equipped laboratories for first-level safety tests and rapid screening of new bioactive products. Graphical abstract Smartphone-based bioluminescence cell biosensor.

Identifying Toxicity Pathways with ToxCast High-Throughput Screening and Applications to Predicting Developmental Toxicity

EPA Science Inventory

Results from rodent and non-rodent prenatal developmental toxicity tests for over 300 chemicals have been curated into the relational database ToxRefDB. These same chemicals have been run in concentration-response format through over 500 high-throughput screening assays assessin...

Validation of Microtox as a first screening tool for waste classification.

PubMed

Weltens, R; Deprez, K; Michiels, L

2014-12-01

The Waste Framework Directive (WFD; 2008/98/EG) describes how waste materials are to be classified as hazardous or not. For complex waste materials chemical analyses are often not conclusive and the WFD provides the possibility to assess the hazardous properties by testing on the waste materials directly. As a methodology WFD refers to the protocols described in the CLP regulation (regulation on Classification, Labeling and Packaging of chemicals) but the toxicity tests on mammals are not acceptable for waste materials. The DISCRISET project was initiated to investigate the suitability of alternative toxicity tests that are already in use in pharmaceutical applications, for the toxicological hazard assessment of complex waste materials. Results indicated that Microtox was a good candidate as a first screening test in a tiered approached hazard assessment. This is now further validated in the present study. The toxic responses measured in Microtox were compared to biological responses in other bioassays for both organic and inorganic fractions of the wastes. Both fractions contribute to the toxic load of waste samples. Results show that the Microtox test is indeed a good and practical screening tool for the organic fraction. A screening threshold (ST) of 5 geq/l as the EC50 value in Microtox is proposed as this ST allows to recognize highly toxic samples in the screening test. The data presented here show that the Microtox toxicity response at this ST is not only predictive for acute toxicity in other organisms but also for sub lethal toxic effects of the organic fraction. This limit value has to be further validated. For the inorganic fraction no specific biotest can be recommended as a screening test, but the use of direct toxicity assessment is also preferable for this fraction as metal speciation is an important issue to define the toxic load of elutriate fractions. A battery of 3 tests (Microtox, Daphnia and Algae) for direct toxicity assessment of this fraction is recommended in literature, but including tests for mechanistic toxicity might be useful. Copyright © 2014 Elsevier Ltd. All rights reserved.

Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening.

PubMed

Takayama, Kazuo; Mizuguchi, Hiroyuki

2017-02-01

Because drug-induced liver injury is one of the main reasons for drug development failures, it is important to perform drug toxicity screening in the early phase of pharmaceutical development. Currently, primary human hepatocytes are most widely used for the prediction of drug-induced liver injury. However, the sources of primary human hepatocytes are limited, making it difficult to supply the abundant quantities required for large-scale drug toxicity screening. Therefore, there is an urgent need for a novel unlimited, efficient, inexpensive, and predictive model which can be applied for large-scale drug toxicity screening. Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are able to replicate indefinitely and differentiate into most of the body's cell types, including hepatocytes. It is expected that hepatocyte-like cells generated from human ES/iPS cells (human ES/iPS-HLCs) will be a useful tool for drug toxicity screening. To apply human ES/iPS-HLCs to various applications including drug toxicity screening, homogenous and functional HLCs must be differentiated from human ES/iPS cells. In this review, we will introduce the current status of hepatocyte differentiation technology from human ES/iPS cells and a novel method to predict drug-induced liver injury using human ES/iPS-HLCs. Copyright © 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Zebrafish Developmental Screening of the ToxCast™ Phase I Chemical Library

EPA Science Inventory

Zebrafish (Danio rerio) is an emerging toxicity screening model for both human health and ecology. As part of the Computational Toxicology Research Program of the U.S. EPA, the toxicity of the 309 ToxCast™ Phase I chemicals was assessed using a zebrafish screen for developmental ...

The U.S. EPA's ToxCast Chemical Screening Program and Predictive Modeling of Toxicity

EPA Science Inventory

The ToxCast program was developed by the U.S. EPA's National Center for Computational Toxicology to provide cost-effective high-throughput screening for the potential toxicity of thousands of chemicals. Phase I screened 309 compounds in over 500 assays to evaluate concentration-...

Dose response screening of the Toxcast chemical library using a Zebrafish developmental assay

EPA Science Inventory

As part of the chemical screening and prioritization research program of the U.S. Environmental Protection Agency, the toxicity of the 320 ToxCaspM Phase I chemicals was assessed using a vertebrate screen of developmental toxicity. Zebrafish embryos/larvae (Danio rerio) were expo...

A novel microbial fuel cell sensor with a gas diffusion biocathode sensing element for water and air quality monitoring.

PubMed

Jiang, Yong; Liang, Peng; Huang, Xia; Ren, Zhiyong Jason

2018-07-01

Toxicity monitoring is essential for the protection of public health and ecological safety. Microbial fuel cell (MFC) sensors demonstrated good potential in toxicity monitoring, but current MFC sensors can only be used for anaerobic water monitoring. In this study, a novel gas diffusion (GD)-biocathode sensing element was fabricated using a simple method. The GD-biocathode MFC sensor can directly be used for formaldehyde detection (from 0.0005% to 0.005%) in both aerobic and anaerobic water bodies. Electrochemical analysis indicated that the response by the sensor was caused by the toxic inhibition to the microbial activity for the oxygen reduction reaction (ORR). This study for the first time demonstrated that the GD-biocathode MFC sensor has a detection limit of 20 ppm for formaldehyde and can be used to monitor air pollution. Selective sensitivity to formaldehyde was not achieved as the result of using a mixed-culture, which confirms that it can serve as a generic biosensor for monitoring gaseous pollutants. This study expands the realm of knowledge for MFC sensor applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation and Testing of Impedance-based Fluidic Biochips with RTgill-W1 Cells for Rapid Evaluation of Drinking Water Samples for Toxicity

PubMed Central

Brennan, Linda M.; Widder, Mark W.; McAleer, Michael K.; Mayo, Michael W.; Greis, Alex P.; van der Schalie, William H.

2016-01-01

This manuscript describes how to prepare fluidic biochips with Rainbow trout gill epithelial (RTgill-W1) cells for use in a field portable water toxicity sensor. A monolayer of RTgill-W1 cells forms on the sensing electrodes enclosed within the biochips. The biochips are then used for testing in a field portable electric cell-substrate impedance sensing (ECIS) device designed for rapid toxicity testing of drinking water. The manuscript further describes how to run a toxicity test using the prepared biochips. A control water sample and the test water sample are mixed with pre-measured powdered media and injected into separate channels of the biochip. Impedance readings from the sensing electrodes in each of the biochip channels are measured and compared by an automated statistical software program. The screen on the ECIS instrument will indicate either "Contamination Detected" or "No Contamination Detected" within an hour of sample injection. Advantages are ease of use and rapid response to a broad spectrum of inorganic and organic chemicals at concentrations that are relevant to human health concerns, as well as the long-term stability of stored biochips in a ready state for testing. Limitations are the requirement for cold storage of the biochips and limited sensitivity to cholinesterase-inhibiting pesticides. Applications for this toxicity detector are for rapid field-portable testing of drinking water supplies by Army Preventative Medicine personnel or for use at municipal water treatment facilities. PMID:27023147

Preparation and Testing of Impedance-based Fluidic Biochips with RTgill-W1 Cells for Rapid Evaluation of Drinking Water Samples for Toxicity.

PubMed

Brennan, Linda M; Widder, Mark W; McAleer, Michael K; Mayo, Michael W; Greis, Alex P; van der Schalie, William H

2016-03-07

This manuscript describes how to prepare fluidic biochips with Rainbow trout gill epithelial (RTgill-W1) cells for use in a field portable water toxicity sensor. A monolayer of RTgill-W1 cells forms on the sensing electrodes enclosed within the biochips. The biochips are then used for testing in a field portable electric cell-substrate impedance sensing (ECIS) device designed for rapid toxicity testing of drinking water. The manuscript further describes how to run a toxicity test using the prepared biochips. A control water sample and the test water sample are mixed with pre-measured powdered media and injected into separate channels of the biochip. Impedance readings from the sensing electrodes in each of the biochip channels are measured and compared by an automated statistical software program. The screen on the ECIS instrument will indicate either "Contamination Detected" or "No Contamination Detected" within an hour of sample injection. Advantages are ease of use and rapid response to a broad spectrum of inorganic and organic chemicals at concentrations that are relevant to human health concerns, as well as the long-term stability of stored biochips in a ready state for testing. Limitations are the requirement for cold storage of the biochips and limited sensitivity to cholinesterase-inhibiting pesticides. Applications for this toxicity detector are for rapid field-portable testing of drinking water supplies by Army Preventative Medicine personnel or for use at municipal water treatment facilities.

Increased Fire and Toxic Contaminant Detection Responsibility by Use of Distributed, Aspirating Sensors

NASA Technical Reports Server (NTRS)

Youngblood, Wallace W.

1990-01-01

Viewgraphs of increased fire and toxic contaminant detection responsivity by use of distributed, aspirating sensors for space station are presented. Objectives of the concept described are (1) to enhance fire and toxic contaminant detection responsivity in habitable regions of space station; (2) to reduce system weight and complexity through centralized detector/monitor systems; (3) to increase fire signature information from selected locations in a space station module; and (4) to reduce false alarms.

Evaluation and refinement of a field-portable drinking water toxicity sensor utilizing electric cell-substrate impedance sensing and a fluidic biochip.

PubMed

Widder, Mark W; Brennan, Linda M; Hanft, Elizabeth A; Schrock, Mary E; James, Ryan R; van der Schalie, William H

2015-07-01

The US Army's need for a reliable and field-portable drinking water toxicity sensor was the catalyst for the development and evaluation of an electric cell-substrate impedance sensing (ECIS) device. Water testing technologies currently available to soldiers in the field are analyte-specific and have limited capabilities to detect broad-based water toxicity. The ECIS sensor described here uses rainbow trout gill epithelial cells seeded on fluidic biochips to measure changes in impedance for the detection of possible chemical contamination of drinking water supplies. Chemicals selected for testing were chosen as representatives of a broad spectrum of toxic industrial compounds. Results of a US Environmental Protection Agency (USEPA)-sponsored evaluation of the field portable device were similar to previously published US Army testing results of a laboratory-based version of the same technology. Twelve of the 18 chemicals tested following USEPA Technology Testing and Evaluation Program procedures were detected by the ECIS sensor within 1 h at USEPA-derived human lethal concentrations. To simplify field-testing methods further, elimination of a procedural step that acclimated cells to serum-free media streamlined the test process with only a slight loss of chemical sensitivity. For field use, the ECIS sensor will be used in conjunction with an enzyme-based sensor that is responsive to carbamate and organophosphorus pesticides. Copyright © 2014 John Wiley & Sons, Ltd.

A novel microbial fuel cell sensor with biocathode sensing element.

PubMed

Jiang, Yong; Liang, Peng; Liu, Panpan; Wang, Donglin; Miao, Bo; Huang, Xia

2017-08-15

The traditional microbial fuel cell (MFC) sensor with bioanode as sensing element delivers limited sensitivity to toxicity monitoring, restricted application to only anaerobic and organic rich water body, and increased potential fault warning to the combined shock of organic matter/toxicity. In this study, the biocathode for oxygen reduction reaction was employed for the first time as the sensing element in MFC sensor for toxicity monitoring. The results shown that the sensitivity of MFC sensor with biocathode sensing element (7.4±2.0 to 67.5±4.0mA% -1 cm -2 ) was much greater than that showed by bioanode sensing element (3.4±1.5 to 5.5±0.7mA% -1 cm -2 ). The biocathode sensing element achieved the lowest detection limit reported to date using MFC sensor for formaldehyde detection (0.0005%), while the bioanode was more applicable for higher concentration (>0.0025%). There was a quicker response of biocathode sensing element with the increase of conductivity and dissolved oxygen (DO). The biocathode sensing element made the MFC sensor directly applied to clean water body monitoring, e.g., drinking water and reclaimed water, without the amending of background organic matter, and it also decreased the warning failure when challenged by a combined shock of organic matter/toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Application of Targeted Functional Assays to Assess a Putative Vascular Disruption Developmental Toxicity Pathway Informed By ToxCast High-Throughput Screening Data

EPA Science Inventory

Chemical perturbation of vascular development is a putative toxicity pathway which may result in developmental toxicity. EPA’s high-throughput screening (HTS) ToxCast program contains assays which measure cellular signals and biological processes critical for blood vessel develop...

Development of a detection sensor for lethal H2S gas.

PubMed

Park, Young-Ho; Kim, Yong-Jae; Lee, Chang-Seop

2012-07-01

The gas which may be lethal to human body with short-term exposure in common industrial fields or workplaces in LAB may paralyze the olfactory sense and impose severe damages to central nervous system and lung. This study is concerned with the gas sensor which allows individuals to avoid the toxic gas that may be generated in the space with residues of organic wastes under 50 degrees C or above. This study investigates response and selectivity of the sensor to hydrogen sulfide gas with operating temperatures and catalysts. The thick-film semiconductor sensor for hydrogen sulfide gas detection was fabricated WO3/SnO2 prepared by sol-gel and precipitation methods. The nanosized SnO2 powder mixed with the various metal oxides (WO3, TiO2, and ZnO) and doped with transition metals (Au, Ru, Pd Ag and In). Particle sizes, specific surface areas and phases of sensor materials were investigated by SEM, BET and XRD analyses. The metal-WO3/SnO2 thick films were prepared by screen-printing method. The measured response to hydrogen sulfide gas is defined as the ratio (Ra/R,) of the resistance of WO3ISnO2 film in air to the resistance of WO3/SnO2 film in a hydrogen sulfide gas. It was shown that the highest response and selectivity of the sensor for hydrogen sulfide by doping with 1 wt% Ru and 10 wt% WO3 to SnO2 at the optimum operating temperature of 200 degrees C.

The Effect of Cerium Oxide Nanoparticle Valence State on Reactive Oxygen Species and Toxicity.

PubMed

Dunnick, Katherine M; Pillai, Rajalekshmi; Pisane, Kelly L; Stefaniak, Aleksandr B; Sabolsky, Edward M; Leonard, Stephen S

2015-07-01

Cerium oxide (CeO2) nanoparticles, which are used in a variety of products including solar cells, gas sensors, and catalysts, are expected to increase in industrial use. This will subsequently lead to additional occupational exposures, making toxicology screenings crucial. Previous toxicology studies have presented conflicting results as to the extent of CeO2 toxicity, which is hypothesized to be due to the ability of Ce to exist in both a +3 and +4 valence state. Thus, to study whether valence state and oxygen vacancy concentration are important in CeO2 toxicity, CeO2 nanoparticles were doped with gadolinium to adjust the cation (Ce, Gd) and anion (O) defect states. The hypothesis that doping would increase toxicity and decrease antioxidant abilities as a result of increased oxygen vacancies and inhibition of +3 to +4 transition was tested. Differences in toxicity and reactivity based on valence state were determined in RLE-6TN rat alveolar epithelial and NR8383 rat alveolar macrophage cells using enhanced dark field microscopy, electron paramagnetic resonance (EPR), and annexin V/propidium iodide cell viability stain. Results from EPR indicated that as doping increased, antioxidant potential decreased. Alternatively, doping had no effect on toxicity at 24 h. The present results imply that as doping increases, thus subsequently increasing the Ce(3+)/Ce(4+) ratio, antioxidant potential decreases, suggesting that differences in reactivity of CeO2 are due to the ability of Ce to transition between the two valence states and the presence of increased oxygen vacancies, rather than dependent on a specific valence state.

Toxicity Screening of the ToxCast Phase II Chemical Library Using a Zebrafish Developmental Assay (SOT)

EPA Science Inventory

As part of the chemical screening and prioritization research program of the US EPA, the ToxCast Phase II chemicals were assessed using a vertebrate screen for developmental toxicity. Zebrafish embryos (Danio rerio) were exposed in 96-well plates from late-blastula stage (6hr pos...

Adaptive electric potential sensors for smart signal acquisition and processing

NASA Astrophysics Data System (ADS)

Prance, R. J.; Beardsmore-Rust, S.; Prance, H.; Harland, C. J.; Stiffell, P. B.

2007-07-01

Current applications of the Electric Potential Sensor operate in a strongly (capacitively) coupled limit, with the sensor physically close to or touching the source. This mode of operation screens the sensor effectively from the majority of external noise. To date however the full capability of these sensors operating in a remote mode has not been realised outside of a screened environment (Faraday cage). This paper describes the results of preliminary work in tailoring the response of the sensors to particular signals and so reject background noise, thereby enhancing both the dynamic range and signal to noise ratio significantly.

Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry

PubMed Central

Pick, Neora; Cameron, Scott; Arad, Dorit

2004-01-01

The worldwide rapid increase in bacterial resistance to numerous antibiotics requires on-going development of new drugs to enter the market. As the development of new antibiotics is lengthy and costly, early monitoring of compound's toxicity is essential in the development of novel agents. Our interest is in a rapid, simple, high throughput screening method to assess cytotoxicity induced by potential agents. Some intracellular pathogens, such as Mycobacterium tuberculosis primary site of infection is human alveolar macrophages. Thus, evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for high throughput drug toxicity screening of macrophages using flow cytometry are lacking in the literature. For this application we modified a preexisting technique, propidium iodide (PI) exclusion staining and utilized it for rapid toxicity tests. Samples were prepared in 96 well plates and analyzed by flow cytometry, which allowed for rapid, inexpensive and precise assessment of compound's toxicity associated with cell death. PMID:15472722

A new sensor for the assessment of personal exposure to volatile organic compounds

NASA Astrophysics Data System (ADS)

Chen, Cheng; Driggs Campbell, Katherine; Negi, Indira; Iglesias, Rodrigo A.; Owens, Patrick; Tao, Nongjian; Tsow, Francis; Forzani, Erica S.

2012-07-01

To improve our understanding of indoor and outdoor personal exposures to common environmental toxicants released into the environment, new technologies that can monitor and quantify the toxicants anytime anywhere are needed. This paper presents a wearable sensor to provide such capabilities. The sensor can communicate with a common smart phone and provides accurate measurement of volatile organic compound concentration at a personal level in real-time, providing environmental toxicants data every three minutes. The sensor has high specificity and sensitivity to aromatic, alkyl, and chlorinated hydrocarbons with a resolution as low as 4 parts-per-billion (ppb), with a detection range of 4 ppb-1000 ppm (parts-per-million). The sensor's performance was validated using Gas Chromatography and Selected Ion Flow Tube - Mass Spectrometry reference methods in a variety of environments and activities with overall accuracy higher than 81% (r2 > 0.9). Field tests examined personal exposure in various scenarios including: indoor and outdoor environments, traffic exposure in different cities which vary from 0 to 50 ppmC (part-per-million carbon from hydrocarbons), and pollutants near the 2010 Deepwater Horizon's oil spill. These field tests not only validated the performance but also demonstrated unprecedented high temporal and spatial toxicant information provided by the new technology.

A New Sensor for the Assessment of Personal Exposure to Volatile Organic Compounds

PubMed Central

Chen, Cheng; Campbell, Katherine Driggs; Negi, Indira; Iglesias, Rodrigo A.; Owens, Patrick; Tao, Nongjian; Tsow, Francis; Forzani, Erica

2012-01-01

To improve our understanding of indoor and outdoor personal exposures to common environmental toxicants released into the environment, new technologies that can monitor and quantify the toxicants anytime anywhere are needed. This paper presents a wearable sensor to provide such capabilities. The sensor can communicate with a common smart phone and provides accurate measurement of volatile organic compound concentration at a personal level in real time, providing environmental toxicants data every three minutes. The sensor has high specificity and sensitivity to aromatic, alkyl, and chlorinated hydrocarbons with a resolution as low as 4 parts per billion (ppb), with a detection range of 4 ppb to 1000 ppm (parts per million). The sensor's performance was validated using Gas Chromatography and Selected Ion Flow Tube - Mass Spectrometry reference methods in a variety of environments and activities with overall accuracy higher than 81% (r2 > 0.9). Field tests examined personal exposure in various scenarios including: indoor and outdoor environments, traffic exposure in different cities which vary from 0 to 50 ppmC (part-per-million carbon from hydrocarbons), and pollutants near the 2010 Deepwater Horizon's oil spill. These field tests not only validated the performance but also demonstrated unprecedented high temporal and spatial toxicant information provided by the new technology. PMID:22736952

A portable cell-based impedance sensor for toxicity testing of drinking water.

PubMed

Curtis, Theresa M; Widder, Mark W; Brennan, Linda M; Schwager, Steven J; van der Schalie, William H; Fey, Julien; Salazar, Noe

2009-08-07

A major limitation to using mammalian cell-based biosensors for field testing of drinking water samples is the difficulty of maintaining cell viability and sterility without an on-site cell culture facility. This paper describes a portable automated bench-top mammalian cell-based toxicity sensor that incorporates enclosed fluidic biochips containing endothelial cells monitored by Electric Cell-substrate Impedance Sensing (ECIS) technology. Long-term maintenance of cells on the biochips is made possible by using a compact, self-contained disposable media delivery system. The toxicity sensor monitors changes in impedance of cell monolayers on the biochips after the introduction of water samples. The fluidic biochip includes an ECIS electronic layer and a polycarbonate channel layer, which together reduce initial impedance disturbances seen in commercially available open well ECIS chips caused by the mechanics of pipetting while maintaining the ability of the cells to respond to toxicants. A curve discrimination program was developed that compares impedance values over time between the control and treatment channels on the fluidic biochip and determines if they are significantly different. Toxicant responses of bovine pulmonary artery endothelial cells grown on fluidic biochips are similar to cells on commercially-available open well chips, and these cells can be maintained in the toxicity sensor device for at least nine days using an automated media delivery system. Longer-term cell storage is possible; bovine lung microvessel endothelial cells survive for up to four months on the fluidic biochips and remain responsive to a model toxicant. This is the first demonstration of a portable bench top system capable of both supporting cell health over extended periods of time and obtaining impedance measurements from endothelial cell monolayers after toxicant exposure.

Priority screening of toxic chemicals and industry sectors in the U.S. toxics release inventory: a comparison of the life cycle impact-based and risk-based assessment tools developed by U.S. EPA.

PubMed

Lim, Seong-Rin; Lam, Carl W; Schoenung, Julie M

2011-09-01

Life Cycle Impact Assessment (LCIA) and Risk Assessment (RA) employ different approaches to evaluate toxic impact potential for their own general applications. LCIA is often used to evaluate toxicity potentials for corporate environmental management and RA is often used to evaluate a risk score for environmental policy in government. This study evaluates the cancer, non-cancer, and ecotoxicity potentials and risk scores of chemicals and industry sectors in the United States on the basis of the LCIA- and RA-based tools developed by U.S. EPA, and compares the priority screening of toxic chemicals and industry sectors identified with each method to examine whether the LCIA- and RA-based results lead to the same prioritization schemes. The Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI) is applied as an LCIA-based screening approach with a focus on air and water emissions, and the Risk-Screening Environmental Indicator (RSEI) is applied in equivalent fashion as an RA-based screening approach. The U.S. Toxic Release Inventory is used as the dataset for this analysis, because of its general applicability to a comprehensive list of chemical substances and industry sectors. Overall, the TRACI and RSEI results do not agree with each other in part due to the unavailability of characterization factors and toxic scores for select substances, but primarily because of their different evaluation approaches. Therefore, TRACI and RSEI should be used together both to support a more comprehensive and robust approach to screening of chemicals for environmental management and policy and to highlight substances that are found to be of concern from both perspectives. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recent Advances in the Fabrication and Application of Screen-Printed Electrochemical (Bio)Sensors Based on Carbon Materials for Biomedical, Agri-Food and Environmental Analyses

PubMed Central

Hughes, Gareth; Westmacott, Kelly; Honeychurch, Kevin C.; Crew, Adrian; Pemberton, Roy M.; Hart, John P.

2016-01-01

This review describes recent advances in the fabrication of electrochemical (bio)sensors based on screen-printing technology involving carbon materials and their application in biomedical, agri-food and environmental analyses. It will focus on the various strategies employed in the fabrication of screen-printed (bio)sensors, together with their performance characteristics; the application of these devices for the measurement of selected naturally occurring biomolecules, environmental pollutants and toxins will be discussed. PMID:27690118

A colorimetric sensor array for identification of toxic gases below permissible exposure limits†

PubMed Central

Feng, Liang; Musto, Christopher J.; Kemling, Jonathan W.; Lim, Sung H.; Suslick, Kenneth S.

2010-01-01

A colorimetric sensor array has been developed for the rapid and sensitive detection of 20 toxic industrial chemicals (TICs) at their PELs (permissible exposure limits). The color changes in an array of chemically responsive nanoporous pigments provide facile identification of the TICs with an error rate below 0.7%. PMID:20221484

Screening of Toxic Effects of Bisphenol A and Products of Its Degradation: Zebrafish (Danio rerio) Embryo Test and Molecular Docking.

PubMed

Makarova, Katerina; Siudem, Pawel; Zawada, Katarzyna; Kurkowiak, Justyna

2016-10-01

Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated. The docking experiments showed that 4-isopropylphenol could have similar toxicity to that of BPA due to its high affinity to ERRγ and ERRγB and high octanol-water partitioning coefficient. The least toxic compounds were hydroquinone and phenol. Those compounds as well as BPA were screened in the zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA caused the delay in development, multiple deformations, and low heartbeats (30 bps), whereas hydroquinone had no impact on the development of the zebrafish embryo. Thus, the results of zebrafish screening are in good agreement with our docking experiment. The molecular docking could be used to screen the toxicity of other xenoestrogens and their products of degradation.

Proposal of Screening Method of Sleep Disordered Breathing Using Fiber Grating Vision Sensor

NASA Astrophysics Data System (ADS)

Aoki, Hirooki; Nakamura, Hidetoshi; Nakajima, Masato

Every conventional respiration monitoring technique requires at least one sensor to be attached to the body of the subject during measurement, thereby imposing a sense of restraint that results in aversion against measurements that would last over consecutive days. To solve this problem, we developed a respiration monitoring system for sleepers, and it uses a fiber-grating vision sensor, which is a type of active image sensor to achieve non-contact respiration monitoring. In this paper, we verified the effectiveness of the system, and proposed screening method of the sleep disordered breathing. It was shown that our system could equivalently measure the respiration with thermistor and accelerograph. And, the respiratory condition of sleepers can be grasped by our screening method in one look, and it seems to be useful for the support of the screening of sleep disordered breathing.

The Texas-Indiana Virtual STAR Center: Zebrafish Models for Developmental Toxicity Screening

EPA Pesticide Factsheets

The Texas-Indiana Virtual STAR Center: Zebrafish Models for Developmental Toxicity Screening (Presented by Maria Bondesson Bolin, Ph.D, University of Houston, Center for Nuclear Receptors and Cell Signaling) (3/22/2012)

Toxicity ForeCaster (ToxCast™) Data

EPA Pesticide Factsheets

Data is organized into different data sets and includes descriptions of ToxCast chemicals and assays and files summarizing the screening results, a MySQL database, chemicals screened through Tox21, and available data generated from animal toxicity studies.

TOWARDS REFINED USE OF TOXICITY DATA IN ...

EPA Pesticide Factsheets

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants. In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

Tactical Network Load Balancing in Multi-Gateway Wireless Sensor Networks

DTIC Science & Technology

2013-12-01

writeup scrsz = get( 0 ,’ScreenSize’); %Creation of the random Sensor Network fig = figure(1); set(fig, ’Position’,[1 scrsz( 4 )*.25 scrsz(3)*.7...thesis writeup scrsz = get( 0 ,’ScreenSize’); %Creation of the random Sensor Network fig = figure(1); set(fig, ’Position’,[1 scrsz( 4 )*.25 scrsz(3)*.7...TYPE AND DATES COVERED Master’s Thesis 4 . TITLE AND SUBTITLE TACTICAL NETWORK LOAD BALANCING IN MULTI-GATEWAY WIRELESS SENSOR NETWORKS 5

High Throughput Screening For Hazard and Risk of Environmental Contaminants

EPA Science Inventory

High throughput toxicity testing provides detailed mechanistic information on the concentration response of environmental contaminants in numerous potential toxicity pathways. High throughput screening (HTS) has several key advantages: (1) expense orders of magnitude less than an...

Evaluation of the smoke density chamber as an apparatus for fire toxicity screening tests

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Labossiere, L. A.

1976-01-01

The smoke density chamber is perhaps the most widely used apparatus for smoke measurements. Because of its availability, it has been proposed as an apparatus for evaluating fire toxicity. The standard apparatus and procedure were not found suitable for toxicity screening tests using laboratory animals, because not enough materials of interest produced animal mortality or even incapacitation under standard test conditions. With modifications, the chamber offers greater promise as a screening tool, but other tests specifically designed to measure relative toxicity may be more cost-effective. Where one-dimensional heat flux is a requirement, the chamber is the most suitable apparatus available. It should be improved in regard to visibility of animals and ease of cleaning.

Gas Sensor Evaluations in Polymer Combustion Product Atmospheres

NASA Technical Reports Server (NTRS)

Delgado, Rafael H.; Davis, Dennis D.; Beeson, Harold D.

1999-01-01

Toxic gases produced by the combustion or thermo-oxidative degradation of materials such as wire insulation, foam, plastics, or electronic circuit boards in space shuttle or space station crew cabins may pose a significant hazard to the flight crew. Toxic gas sensors are routinely evaluated in pure gas standard mixtures, but the possible interferences from polymer combustion products are not routinely evaluated. The NASA White Sands Test Facility (WSTF) has developed a test system that provides atmospheres containing predetermined quantities of target gases combined with the coincidental combustion products of common spacecraft materials. The target gases are quantitated in real time by infrared (IR) spectroscopy and verified by grab samples. The sensor responses are recorded in real time and are compared to the IR and validation analyses. Target gases such as carbon monoxide, hydrogen cyanide, hydrogen chloride, and hydrogen fluoride can be generated by the combustion of poly(vinyl chloride), polyimide-fluoropolymer wire insulation, polyurethane foam, or electronic circuit board materials. The kinetics and product identifications for the combustion of the various materials were determined by thermogravimetric-IR spectroscopic studies. These data were then scaled to provide the required levels of target gases in the sensor evaluation system. Multisensor toxic gas monitors from two manufacturers were evaluated using this system. In general, the sensor responses satisfactorily tracked the real-time concentrations of toxic gases in a dynamic mixture. Interferences from a number of organic combustion products including acetaldehyde and bisphenol-A were minimal. Hydrogen bromide in the products of circuit board combustion registered as hydrogen chloride. The use of actual polymer combustion atmospheres for the evaluation of sensors can provide additional confidence in the reliability of the sensor response.

Laser photoacoustic sensor for air toxicity measurements

NASA Astrophysics Data System (ADS)

Prasad, Coorg R.; Lei, Jie; Shi, Wenhui; Li, Guangkun; Dunayevskiy, Ilya; Patel, C. Kumar N.

2012-06-01

US EPA's Clean Air Act lists 187 hazardous air pollutants (HAP) or airborne toxics that are considered especially harmful to health, and hence the measurement of their concentration is of great importance. Numerous sensor systems have been reported for measuring these toxic gases and vapors. However, most of these sensors are specific to a single gas or able to measure only a few of them. Thus a sensor capable of measuring many of the toxic gases simultaneously is desirable. Laser photoacoustic spectroscopy (LPAS) sensors have the potential for true broadband measurement when used in conjunction with one or more widely tunable laser sources. An LPAS gas analyzer equipped with a continuous wave, room temperature IR Quantum Cascade Laser tunable over the wavelength range of 9.4 μm to 9.7 μm was used for continuous real-time measurements of multiple gases/chemical components. An external cavity grating tuner was used to generate several (75) narrow line output wavelengths to conduct photoacoustic absorption measurements of gas mixtures. We have measured various HAPs such as Benzene, Formaldehyde, and Acetaldehyde in the presence of atmospheric interferents water vapor, and carbon dioxide. Using the preliminary spectral pattern recognition algorithm, we have shown our ability to measure all these chemical compounds simultaneously in under 3 minutes. Sensitivity levels of a few part-per-billion (ppb) were achieved with several of the measured compounds with the preliminary laboratory system.

A Stretchable Radio-Frequency Strain Sensor Using Screen Printing Technology

PubMed Central

Jeong, Heijun; Lim, Sungjoon

2016-01-01

In this paper, we propose a stretchable radio-frequency (RF) strain sensor fabricated with screen printing technology. The RF sensor is designed using a half-wavelength patch that resonates at 3.7 GHz. The resonant frequency is determined by the length of the patch, and it therefore changes when the patch is stretched. Polydimethylsiloxane (PDMS) is used to create the substrate, because of its stretchable and screen-printable surface. In addition, Dupont PE872 (Dupont, NC, American) silver conductive ink is used to create the stretchable conductive patterns. The sensor performance is demonstrated both with full-wave simulations and with measurements carried out on a fabricated sample. When the length of the patch sensor is increased by a 7.8% stretch, the resonant frequency decreases from 3.7 GHz to 3.43 GHz, evidencing a sensitivity of 3.43 × 107 Hz/%. Stretching the patch along its width does not change the resonant frequency. PMID:27827833

Pulsed Polarization-Based NOx Sensors of YSZ Films Produced by the Aerosol Deposition Method and by Screen-Printing

PubMed Central

Exner, Jörg; Albrecht, Gaby; Schönauer-Kamin, Daniela; Kita, Jaroslaw; Moos, Ralf

2017-01-01

The pulsed polarization technique on solid electrolytes is based on alternating potential pulses interrupted by self-discharge pauses. Since even small concentrations of nitrogen oxides (NOx) in the ppm range significantly change the polarization and discharge behavior, pulsed polarization sensors are well suited to measure low amounts of NOx. In contrast to all previous investigations, planar pulsed polarization sensors were built using an electrolyte thick film and platinum interdigital electrodes on alumina substrates. Two different sensor layouts were investigated, the first with buried Pt electrodes under the electrolyte and the second one with conventional overlying Pt electrodes. Electrolyte thick films were either formed by aerosol deposition or by screen-printing, therefore exhibiting a dense or porous microstructure, respectively. For screen-printed electrolytes, the influence of the electrolyte resistance on the NOx sensing ability was investigated as well. Sensors with buried electrodes showed little to no response even at higher NOx concentrations, in good agreement with the intended sensor mechanism. Electrolyte films with overlying electrodes, however, allowed the quantitative detection of NOx. In particular, aerosol deposited electrolytes exhibited high sensitivities with a sensor output signal ΔU of 50 mV and 75 mV for 3 ppm of NO and NO2, respectively. For screen-printed electrolytes, a clear trend indicated a decrease in sensitivity with increased electrolyte resistance. PMID:28933736

Pulsed Polarization-Based NOx Sensors of YSZ Films Produced by the Aerosol Deposition Method and by Screen-Printing.

PubMed

Exner, Jörg; Albrecht, Gaby; Schönauer-Kamin, Daniela; Kita, Jaroslaw; Moos, Ralf

2017-07-26

The pulsed polarization technique on solid electrolytes is based on alternating potential pulses interrupted by self-discharge pauses. Since even small concentrations of nitrogen oxides (NO x ) in the ppm range significantly change the polarization and discharge behavior, pulsed polarization sensors are well suited to measure low amounts of NO x . In contrast to all previous investigations, planar pulsed polarization sensors were built using an electrolyte thick film and platinum interdigital electrodes on alumina substrates. Two different sensor layouts were investigated, the first with buried Pt electrodes under the electrolyte and the second one with conventional overlying Pt electrodes. Electrolyte thick films were either formed by aerosol deposition or by screen-printing, therefore exhibiting a dense or porous microstructure, respectively. For screen-printed electrolytes, the influence of the electrolyte resistance on the NO x sensing ability was investigated as well. Sensors with buried electrodes showed little to no response even at higher NO x concentrations, in good agreement with the intended sensor mechanism. Electrolyte films with overlying electrodes, however, allowed the quantitative detection of NO x . In particular, aerosol deposited electrolytes exhibited high sensitivities with a sensor output signal Δ U of 50 mV and 75 mV for 3 ppm of NO and NO₂, respectively. For screen-printed electrolytes, a clear trend indicated a decrease in sensitivity with increased electrolyte resistance.

Picking Cell Lines for High-Throughput Transcriptomic Toxicity Screening (SOT)

EPA Science Inventory

High throughput, whole genome transcriptomic profiling is a promising approach to comprehensively evaluate chemicals for potential biological effects. To be useful for in vitro toxicity screening, gene expression must be quantified in a set of representative cell types that captu...

Toward the integration of optical sensors in smartphone screens using femtosecond laser writing.

PubMed

Lapointe, Jerome; Parent, Francois; de Lima Filho, Elton Soares; Loranger, Sébastien; Kashyap, Raman

2015-12-01

We demonstrate a new type of sensor incorporated directly into Corning Gorilla glass, an ultraresistant glass widely used in the screen of popular devices such as smartphones, tablets, and smart watches. Although physical space is limited in portable devices, the screens have been so far neglected in regard to functionalization. Our proof-of-concept shows a new niche for photonics device development, in which the screen becomes an active component integrated into the device. The sensor itself is a near-surface waveguide, sensitive to refractive index changes, enabling the analysis of liquids directly on the screen of a smartphone, without the need for any add-ons, thus opening this part of the device to advanced functionalization. The primary function of the screen is unaffected, since the sensor and waveguide are effectively invisible to the naked eye. We fabricated a waveguide just below the glass surface, directly written without any surface preparation, in which the change in refractive index on the surface-air interface changes the light guidance, thus the transmission of light. This work reports on sensor fabrication, using a femtosecond pulsed laser, and the light-interaction model of the beam propagating at the surface is discussed and compared with experimental measurement for refractive indexes in the range 1.3-1.7. A new and improved model, including input and output reflections due to the effective mode index change, is also proposed and yields a better match with our experimental measurements and also with previous measurements reported in the literature.

Electrochemical properties of the acetaminophen on the screen printed carbon electrode towards the high performance practical sensor applications.

PubMed

Karikalan, Natarajan; Karthik, Raj; Chen, Shen-Ming; Velmurugan, Murugan; Karuppiah, Chelladurai

2016-12-01

Acetaminophen is a non-steroidal anti-inflammatory drug used as an antipyretic agent for the alternative to aspirin. Conversely, the overdoses of acetaminophen can cause hepatic toxicity and kidney damage. Hence, the determination of acetaminophen receives much more attention in biological samples and also in pharmaceutical formulations. Here, we report a rapid and sensitive detection of the acetaminophen based on the bare (unmodified) screen printed carbon electrode (BSPCE) and its electrochemistry was studied in various pHs. From the observed results, the mechanism of the electro-oxidation of acetaminophen was derived for various pHs. The acetaminophen is not stable in strong acidic and strong alkaline media, which is hydrolyzed and hydroxylated. However, it is stable in intermediate pHs due to the dimerization of acetaminophen. The kinetics of the acetaminophen oxidation was briefly studied and documented in the schemes. In addition, the surface morphology and disorders of BSPCE was probed by scanning electron microscope (SEM) and Raman spectroscopy. Moreover, the BSPCE determined the acetaminophen with the linear concentration ranging from 0.05 to 190μM and the lower detection limit of 0.013μM. Besides that it reveals the good recoveries towards the pharmaceutical samples and shows the excellent selectivity, sensitivity and stability. To the best of our knowledge, this is the better performance compare to the previously reported unmodified acetaminophen sensors. Copyright © 2016 Elsevier Inc. All rights reserved.

Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward Melanoma Screening.

PubMed

Ciui, Bianca; Martin, Aida; Mishra, Rupesh K; Brunetti, Barbara; Nakagawa, Tatsuo; Dawkins, Thomas J; Lyu, Mengjia; Cristea, Cecilia; Sandulescu, Robert; Wang, Joseph

2018-04-01

Wearable bendable bandage-based sensor and a minimally invasive microneedle biosensor are described toward rapid screening of skin melanoma. These wearable electrochemical sensors are capable of detecting the presence of the tyrosinase (TYR) enzyme cancer biomarker in the presence of its catechol substrate, immobilized on the transducer surface. In the presence of the surface TYR biomarker, the immobilized catechol is rapidly converted to benzoquinone that is detected amperometrically, with a current signal proportional to the TYR level. The flexible epidermal bandage sensor relies on printing stress-enduring inks which display good resiliency against mechanical deformations, whereas the hollow microneedle device is filled with catechol-coated carbon paste for assessing tissue TYR levels. The bandage sensor can thus be used directly on the skin whereas microneedle device can reach melanoma tissues under the skin. Both wearable sensors are interfaced to an ultralight flexible electronic board, which transmits data wirelessly to a mobile device. The analytical performance of the resulting bandage and microneedle sensing systems are evaluated using TYR-containing agarose phantom gel and porcine skin. The new integrated conformal portable sensing platforms hold considerable promise for decentralized melanoma screening, and can be extended to the screening of other key biomarkers in skin moles. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Implementation of recommendations for the screening of hydroxychloroquine retinopathy: poor adherence of rheumatologists and ophthalmologists.

PubMed

Shulman, S; Wollman, J; Brikman, S; Padova, H; Elkayam, O; Paran, D

2017-03-01

The American Academy of Ophthalmology published in 2011 revised recommendations regarding screening for hydroxychloroquine (HCQ) toxicity. We aimed to assess implementation of these recommendations by rheumatologists and ophthalmologists. A questionnaire regarding screening practices for HCQ toxicity was distributed among all members of the Israeli societies of Rheumatology and Ophthalmology. A total of 128 physicians responded to the questionnaire (rheumatologists: 60, ophthalmologists: 68). Only 5% of the rheumatologists and 15% of the ophthalmologists are aware of ophthalmologic assessments recommended for baseline and follow-up evaluation. When an abnormal test is detected, even if inappropriate for HCQ toxicity screening, 60% of the responders recommend cessation of therapy. Only 13% of the responders recommend first follow-up after five years for patients without risk factors; the remainder recommend more frequent testing. Ninety-six percent of the responders are not aware of all of the known risk factors for HCQ toxicity. Use of inappropriate tests to detect HCQ retinal toxicity may lead to unnecessary cessation of beneficial treatment with risk of disease flare, while lack of consideration of risk factors may put patients at risk for toxicity. These results emphasize the importance of implementing the recommendations to ensure safe and effective use of this drug.

Toxicity of leachate from weathering plastics: An exploratory screening study with Nitocra spinipes.

PubMed

Bejgarn, Sofia; MacLeod, Matthew; Bogdal, Christian; Breitholtz, Magnus

2015-08-01

Between 60% and 80% of all marine litter is plastic. Leachate from plastics has previously been shown to cause acute toxicity in the freshwater species Daphnia magna. Here, we present an initial screening of the marine environmental hazard properties of leachates from weathering plastics to the marine harpacticoid copepod [Crustacea] Nitocra spinipes. Twenty-one plastic products made of different polymeric materials were leached and irradiated with artificial sunlight. Eight of the twenty-one plastics (38%) produced leachates that caused acute toxicity. Differences in toxicity were seen for different plastic products, and depending on the duration of irradiation. There was no consistent trend in how toxicity of leachate from plastics changed as a function of irradiation time. Leachate from four plastics became significantly more toxic after irradiation, two became significantly less toxic and two did not change significantly. Analysis of leachates from polyvinyl chloride (PVC) by liquid chromatography coupled to a full-scan high-resolution mass spectrometer showed that the leachates were a mixture of substances, but did not show evidence of degradation of the polymer backbone. This screening study demonstrates that leachates from different plastics differ in toxicity to N. spinipes and that the toxicity varies under simulated weathering. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System@@

EPA Science Inventory

In 2007, the National Research Council envisioned the need for inexpensive, rapid, cell-based toxicity testing methods relevant to human health. in vitro screening approaches have largely addressed these problems by using robotics and automation. However, the challenge is that ma...

Identifying Structural Alerts Based on Zebrafish Developmental Morphological Toxicity (TDS)

EPA Science Inventory

Zebrafish constitute a powerful alternative animal model for chemical hazard evaluation. To provide an in vivo complement to high-throughput screening data from the ToxCast program, zebrafish developmental toxicity screens were conducted on the ToxCast Phase I (Padilla et al., 20...

Integration of Dosimetry, Exposure and High-Throughput Screening Data in Chemical Toxicity Assessment

EPA Science Inventory

High-throughput in vitro toxicity screening can provide an efficient way to identify potential biological targets for chemicals. However, relying on nominal assay concentrations may misrepresent potential in vivo effects of these chemicals due to differences in bioavailability, c...

Recent Developments in Toxico-Cheminformatics; Supporting a New Paradigm for Predictive Toxicology

EPA Science Inventory

EPA's National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-content and high-thoughput screening d...

Advances in Toxico-Cheminformatics: Supporting a New Paradigm for Predictive Toxicology

EPA Science Inventory

EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-throughput screening (HTS) data. The D...

Tox21 Enricher: Web-based Chemical/Biological Functional Annotation Analysis Tool Based on Tox21 Toxicity Screening Platform.

PubMed

Hur, Junguk; Danes, Larson; Hsieh, Jui-Hua; McGregor, Brett; Krout, Dakota; Auerbach, Scott

2018-05-01

The US Toxicology Testing in the 21st Century (Tox21) program was established to develop more efficient and human-relevant toxicity assessment methods. The Tox21 program screens >10,000 chemicals using quantitative high-throughput screening (qHTS) of assays that measure effects on toxicity pathways. To date, more than 70 assays have yielded >12 million concentration-response curves. The patterns of activity across assays can be used to define similarity between chemicals. Assuming chemicals with similar activity profiles have similar toxicological properties, we may infer toxicological properties based on its neighbourhood. One approach to inference is chemical/biological annotation enrichment analysis. Here, we present Tox21 Enricher, a web-based chemical annotation enrichment tool for the Tox21 toxicity screening platform. Tox21 Enricher identifies over-represented chemical/biological annotations among lists of chemicals (neighbourhoods), facilitating the identification of the toxicological properties and mechanisms in the chemical set. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a Contingency Gas Analyzer for the Orion Crew Exploration Vehicle

NASA Technical Reports Server (NTRS)

Niu, Bill; Carney, Kenneth; Steiner, George; OHarra, William; Lewis, John

2010-01-01

NASA's experience with electrochemical sensors in a hand-held toxic gas monitor serves as a basis for the development of a fixed on-board instrument, the Contingency Gas Analyzer (CGA), for monitoring selected toxic combustion products as well as oxygen and carbon dioxide on the Orion Crew Exploration Vehicle (CEV). Oxygen and carbon dioxide are major components of the cabin environment and accurate measurement of these compounds is critical to maintaining a safe working environment for the crew. Fire or thermal degradation events may produce harmful levels of toxic products, including carbon monoxide (CO), hydrogen cyanide (HCN), and hydrogen chloride (HCl) in the environment. These three components, besides being toxic in their own right, can serve as surrogates for a panoply of hazardous combustion products. On orbit monitoring of these surrogates provides for crew health and safety by indicating the presence of toxic combustion products in the environment before, during and after combustion or thermal degradation events. Issues identified in previous NASA experiences mandate hardening the instrument and components to endure the mechanical and operational stresses of the CEV environment while maintaining high analytical fidelity. Specific functional challenges involve protecting the sensors from various anticipated events- such as rapid pressure changes, low cabin pressures, and extreme vibration/shock exposures- and extending the sensor lifetime and calibration periods far beyond the current state of the art to avoid the need for on-orbit calibration. This paper focuses on lessons learned from the earlier NASA hardware, current testing results, and engineering solutions to the identified problems. Of particular focus will be the means for protecting the sensors, addressing well known cross-sensitivity issues and the efficacy of a novel self monitoring mechanism for extending sensor calibration periods.

Patients Undergoing Radiation Therapy Are at Risk of Financial Toxicity: A Patient-based Prospective Survey Study.

PubMed

Palmer, Joshua D; Patel, Tejash T; Eldredge-Hindy, Harriet; Keith, Scott W; Patel, Tapas; Malatesta, Theresa; DiNome, Jessie; Lowther, Anne; Ferguson, Linda; Wagenborg, Sally; Smyles, John; Babaria, Usha; Stabile, Richard; Gressen, Eric; Rudoler, Shari; Fisher, Scot A

2018-06-01

Little is known about the financial burden experienced by patients receiving radiation therapy. Furthermore, currently, no financial toxicity screening tools have been validated for use in radiation oncology. Physician surveys were used to gauge provider understanding of treatment costs and their willingness to adopt the use of financial toxicity screening tools. Post-treatment patient surveys were used to investigate the covariates of treatment-induced financial risk. Of the 210 radiation oncologists who completed our survey, 53% reported being "very concerned" with treatment-related costs negatively affecting their patients, and 80% believed that a financial toxicity screening tool would be useful in practice. An analysis of patient surveys using logistic regression found age and cancer site to be the most important variables associated with financial toxicity. Thirty-four patients (22%) experienced financial toxicity related to treatment. The financial toxicities experienced were loss of job (28%), loss of income (24%), difficulty paying their rent or mortgage (20%), difficulty paying for transportation (15%), and difficulty paying for meals (13%). Financial toxicity is an important measure for patients and providers and is experienced by approximately one quarter of patients. Further studies to improve models to predict financial toxicity and how financial toxicity is related to patient outcomes and quality of life are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

Towards toxicity detection using a lab-on-chip based on the integration of MOEMS and whole-cell sensors.

PubMed

Elman, Noel M; Ben-Yoav, Hadar; Sternheim, Marek; Rosen, Rachel; Krylov, Slava; Shacham-Diamand, Yosi

2008-06-15

A lab-on-chip consisting of a unique integration of whole-cell sensors, a MOEMS (Micro-Opto-Electro-Mechanical-System) modulator, and solid-state photo-detectors was implemented for the first time. Whole-cell sensors were genetically engineered to express a bioluminescent reporter (lux) as a function of the lac promoter. The MOEMS modulator was designed to overcome the inherent low frequency noise of solid-state photo-detectors by means of a previously reported modulation technique, named IHOS (Integrated Heterodyne Optical System). The bio-reporter signals were modulated prior to photo-detection, increasing the SNR of solid-state photo-detectors at least by three orders of magnitude. Experiments were performed using isopropyl-beta-d-thiogalactopyranoside (IPTG) as a preliminary step towards testing environmental toxicity. The inducer was used to trigger the expression response of the whole-cell sensors testing the sensitivity of the lab-on-chip. Low intensity bio-reporter optical signals were measured after the whole-cell sensors were exposed to IPTG concentrations of 0.1, 0.05, and 0.02mM. The experimental results reveal the potential of this technology for future implementation as an inexpensive massive method for rapid environmental toxicity detection.

Potentially toxic elements and environmentally-related pollutants recognition using colorimetric and ratiometric fluorescent probes.

PubMed

Rasheed, Tahir; Li, Chuanlong; Bilal, Muhammad; Yu, Chunyang; Iqbal, Hafiz M N

2018-05-30

A safer detection or sensing of toxic pollutants is one among several environmental contamination issues, across the globe. The ever-increasing industrial practices and controlled or uncontrolled release of toxic pollutants from various industrial sectors is a key source of this environmental problem. Significant research efforts have been or being made to tackle this problematic issue to fulfill the growing needs of the modern world. Despite many useful aspects, heavy metals are posing noteworthy toxicological concerns and human-health related issues at various levels of the ecosystem. In this context, notable efforts from various regulatory authorities, the increase in the concentration of these toxic heavy metals in the environment is of serious concern, so real-time monitoring is urgently required. Herein, we reviewed fluorescent sensor based models and their potentialities to address the detection fate of hazardous pollutants including chromium, manganese, cobalt, nickel, copper, and zinc as model elements. The novel aspects of turn-on/off fluorescent sensors have also been discussed from a state of the art viewpoint. In summary, comprehensive literature regarding fluorescent sensor based models and their potentialities to detect various types of toxic pollutants is reviewed. Copyright © 2018 Elsevier B.V. All rights reserved.

The Toxicant-Target Paradigm for Toxicity Screening – Pharmacophore Based Constraints

EPA Science Inventory

There is a compelling need to develop information for the screening and prioritization of the health and environmental effects of large numbers of man-made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the preliminary evaluation of ris...

Screening for Developmental Neurotoxicity in Zebrafish Larvae: Assessment of Behavior and Malformations.

EPA Science Inventory

The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity. As part of this approach, it is important to be able to separate overt toxicity (Le., malformed larvae) from the more specific neurotoxic...

Developmental neurotoxicity testing in vitro: Models for assessing chemical effects on neurite outgrowth

EPA Science Inventory

In vitro models may be useful for the rapid toxicological screening of large numbers of chemicals for their potential to produce toxicity. Such screening could facilitate prioritization of resources needed for in vivo toxicity testing towards those chemicals most likely to resul...

Nanomaterial Toxicity Screening in Developing Zebrafish Embryos

EPA Science Inventory

To assess nanomaterial vertebrate toxicity, a high-content screening assay was created using developing zebrafish, Danio rerio. This included a diverse group of nanomaterials (n=42 total) ranging from metallic (Ag, Au) and metal oxide (CeO2, CuO, TiO2, ZnO) nanoparticles, to non...

[Express diagnostics of bovine leucosis by immune sensor based on surface plasmon resonance].

PubMed

Pyrohova, L V; Starodub, M F; Artiukh, V P; Nahaieva, L I; Dobrosol, H I

2002-01-01

An immune sensor based on the surface plasmon resonance (SPR) was developed for express diagnostics of bovine leucosis. The sensor was used for detection of the level of antibodies against bovine leukaemia virus (BLV) in the blood serum. The industrially manufactured BLV antigen for screening test in the agar gel immunodiffusion (AGID) required the additional purification in order to be used in immune sensor analysis. It was shown that immune sensor analysis was more sensitive, rapid and simple in comparison with the traditional AGID test. It was stated that the developed immune sensor was capable to be used for performance of bovine leucosis screening at the farms and the minimal dilution of the serum should be 1:500.

Challenges and the state of the technology for printed sensor arrays for structural monitoring

NASA Astrophysics Data System (ADS)

Joshi, Shiv; Bland, Scott; DeMott, Robert; Anderson, Nickolas; Jursich, Gregory

2017-04-01

Printed sensor arrays are attractive for reliable, low-cost, and large-area mapping of structural systems. These sensor arrays can be printed on flexible substrates or directly on monitored structural parts. This technology is sought for continuous or on-demand real-time diagnosis and prognosis of complex structural components. In the past decade, many innovative technologies and functional materials have been explored to develop printed electronics and sensors. For example, an all-printed strain sensor array is a recent example of a low-cost, flexible and light-weight system that provides a reliable method for monitoring the state of aircraft structural parts. Among all-printing techniques, screen and inkjet printing methods are well suited for smaller-scale prototyping and have drawn much interest due to maturity of printing procedures and availability of compatible inks and substrates. Screen printing relies on a mask (screen) to transfer a pattern onto a substrate. Screen printing is widely used because of the high printing speed, large selection of ink/substrate materials, and capability of making complex multilayer devices. The complexity of collecting signals from a large number of sensors over a large area necessitates signal multiplexing electronics that need to be printed on flexible substrate or structure. As a result, these components are subjected to same deformation, temperature and other parameters for which sensor arrays are designed. The characteristics of these electronic components, such as transistors, are affected by deformation and other environmental parameters which can lead to erroneous sensed parameters. The manufacturing and functional challenges of the technology of printed sensor array systems for structural state monitoring are the focus of this presentation. Specific examples of strain sensor arrays will be presented to highlight the technical challenges.

An RF Sensor for Gauging Screen-Channel Liquid Acquisition Devices for Cryogenic Propellants

NASA Technical Reports Server (NTRS)

Zimmerli, Gregory A.; Metzger, Scott; Asipauskas, Marius

2014-01-01

A key requirement of a low-gravity screen-channel liquid acquisition device (LAD) is the need to retain 100% liquid in the channel in response to propellant outflow and spacecraft maneuvers. The point at which a screen-channel LAD ingests vapor is known as breakdown, and can be measured several different ways such as: visual observation of bubbles in the LAD channel outflow; a sudden change in pressure drop between the propellant tank and LAD sump outlet; or, an indication by wet-dry sensors placed in the LAD channel or outflow stream. Here we describe a new type of sensor for gauging a screen-channel LAD, the Radio Frequency Mass Gauge (RFMG). The RFMG measures the natural electromagnetic modes of the screen-channel LAD, which is very similar to an RF waveguide, to determine the amount of propellant in the channel. By monitoring several of the RF modes, we show that the RFMG acts as a global sensor of the LAD channel propellant fill level, and enables detection of LAD breakdown even in the absence of outflow. This paper presents the theory behind the RFMG-LAD sensor, measurements and simulations of the RF modes of a LAD channel, and RFMG detection of LAD breakdown in a channel using a simulant fluid during inverted outflow and long-term stability tests.

[Comparative Sensitivity of the Luminescent Photobacterium phosphoreum, Escherichia coli, and Bacillus subtilis Strains to Toxic Effects of Carbon-Based Nanomaterials and Metal Nanoparticles].

PubMed

Deryabina, D G; Efremova, L V; Karimov, I F; Manukhov, I V; Gnuchikh, E Yu; Miroshnikov, S A

2016-01-01

A comparative analysis of the four commercially available and laboratory luminescent sensor strains to the toxic effect of 10 carbon-based nanomatherials (CBNs) and 10 metal nanoparticles (MNPs) was carried out in this study. The bioluminescence inhibition assays with marine Photobacterium phosphoreum and recombinant Escherichia coli strains were varied in minimal toxic concentrations and EC50 values but led to well correlated biotoxicity evaluation for the most active compounds were ranked as Cu > (MgO, CuO) > (fullerenol, graphene oxide). The novel sensor strain Bacillus subtilis EG 168-1 exhibited the highest sensitivity to CBNs and MNPs that increased significantly number of toxic compounds causing the bacterial bioluminescence inhibition effect.

The U.S. Environmental Protection Agency strategic plan for evaluating the toxicity of chemicals.

PubMed

Firestone, Michael; Kavlock, Robert; Zenick, Hal; Kramer, Melissa

2010-02-01

In the 2007 report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences envisioned a major transition in toxicity testing from cumbersome, expensive, and lengthy in vivo testing with qualitative endpoints, to in vitro robotic high-throughput screening with mechanistic quantitative parameters. Recognizing the need for agencies to partner and collaborate to ensure global harmonization, standardization, quality control and information sharing, the U.S. Environmental Protection Agency is leading by example and has established an intra-agency Future of Toxicity Testing Workgroup (FTTW). This workgroup has produced an ambitious blueprint for incorporating this new scientific paradigm to change the way chemicals are screened and evaluated for toxicity. Four main components of this strategy are discussed, as follows: (1) the impact and benefits of various types of regulatory activities, (2) chemical screening and prioritization, (3) toxicity pathway-based risk assessment, and (4) institutional transition. The new paradigm is predicated on the discovery of molecular perturbation pathways at the in vitro level that predict adverse health effects from xenobiotics exposure, and then extrapolating those events to the tissue, organ, or whole organisms by computational models. Research on these pathways will be integrated and compiled using the latest technology with the cooperation of global agencies, industry, and other stakeholders. The net result will be that chemical toxicity screening will become more efficient and cost-effective, include real-world exposure assessments, and eliminate currently used uncertainty factors.

Shack-Hartmann and Interferometric Hybrid Wavefront Sensor

DTIC Science & Technology

2011-03-24

focused spots from those measured for a reference surface [45]. In 1971 B. C. Platt and R. V. Shack proposed using a lenticular screen made with two...Shack-Hartmann WFS. Modern Shack-Hartmann sensors use a lenslet array formed from a solid piece of optical material instead of a lenticular screen [45

Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans

EPA Pesticide Factsheets

Development and Application of In Vitro Models for Screening Drugs and Environmental Chemicals that Predict Toxicity in Animals and Humans (Presented by James McKim, Ph.D., DABT, Founder and Chief Science Officer, CeeTox) (5/25/2012)

Species-Specific Predictive Signatures of Developmental Toxicity Using the ToxCast Chemical Library

EPA Science Inventory

EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive signatures that correlate with observed in vivo toxicity. In vitro profiling methods from ToxCast data consist of over 600 high-throughput screening (HTS) and high-content screening ...

Predictive Model of Rat Reproductive Toxicity from ToxCast High Throughput Screening

EPA Science Inventory

The EPA ToxCast research program uses high throughput screening for bioactivity profiling and predicting the toxicity of large numbers of chemicals. ToxCast Phase‐I tested 309 well‐characterized chemicals in over 500 assays for a wide range of molecular targets and cellular respo...

A Workflow for Identifying Metabolically Active Chemicals to Complement in vitro Toxicity Screening

EPA Science Inventory

The new paradigm of toxicity testing approaches involves rapid screening of thousands of chemicals across hundreds of biological targets through use of in vitro assays. Such assays may lead to false negatives when the complex metabolic processes that render a chemical bioactive i...

Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

EPA Science Inventory

Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive signature was constructed from U.S. EPA ToxCast high-throughput screening (HTS) assays that map to...

Recent Developments in Toxico-Cheminformatics and Progress Towards a New Paradigm for Predictive Toxicology (2)

EPA Science Inventory

EPAs National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through harnessing of legacy toxicity data, creation of data linkages, and generation of new in vitro screening data. In association with EPA...

Recent Developments in Toxico-Cheminformatics and Progress Towards a New Paradigm for Predictive Toxicology

EPA Science Inventory

EPA’s Computational Toxicology Center is building capabilities to support a new paradigm for toxicity screening and prediction through harnessing of legacy toxicity data, creation of data linkages, and generation of new in vitro screening data. In association with EPA’s ToxCastTM...

Photoactivated Mixed In-Plane and Edge-Enriched p-Type MoS2 Flake-Based NO2 Sensor Working at Room Temperature.

PubMed

Agrawal, Abhay V; Kumar, Rahul; Venkatesan, Swaminathan; Zakhidov, Alex; Yang, Guang; Bao, Jiming; Kumar, Mahesh; Kumar, Mukesh

2018-05-25

Toxic gases are produced during the burning of fossil fuels. Room temperature (RT) fast detection of toxic gases is still challenging. Recently, MoS 2 transition metal dichalcogenides have sparked great attention in the research community due to their performance in gas sensing applications. However, MoS 2 based gas sensors still suffer from long response and recovery times, especially at RT. Considering this challenge, here, we report photoactivated highly reversible and fast detection of NO 2 sensors at room temperature (RT) by using mixed in-plane and edge-enriched p-MoS 2 flakes (mixed MoS 2 ). The sensor showed fast response with good sensitivity of ∼10.36% for 10 ppm of NO 2 at RT without complete recovery. However, complete recovery was obtained with better sensor performance under UV light illumination at RT. The UV assisted NO 2 sensing showed improved performance in terms of fast response and recovery kinetics with enhanced sensitivity to 10 ppm NO 2 concentration. The sensor performance is also investigated under thermal energy, and a better sensor performance with reduced sensitivity and high selectivity toward NO 2 was observed. A detailed gas sensing mechanism based on the density functional theory (DFT) calculations for favorable NO 2 adsorption sites on in-plane and edge-enriched MoS 2 flakes is proposed. This study revealed the role of favorable adsorption sites in MoS 2 flakes for the enhanced interaction of target gases and developed a highly sensitive, reversible, and fast gas sensor for next-generation toxic gases at room temperature.

Electroanalytical applications of screen-printable surfactant-induced sol-gel graphite composites

DOEpatents

Guadalupe, Ana R.; Guo, Yizhu

2001-05-15

A process for preparing sol-gel graphite composite electrodes is presented. This process preferably uses the surfactant bis(2-ethylhexyl) sulfosuccinate (AOT) and eliminates the need for a cosolvent, an acidic catalyst, a cellulose binder and a thermal curing step from prior art processes. Fabrication of screen-printed electrodes by this process provides a simple approach for electroanalytical applications in aqueous and nonaqueous solvents. Examples of applications for such composite electrodes produced from this process include biochemical sensors such as disposable, single-use glucose sensors and ligand modified composite sensors for metal ion sensitive sensors.

Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review.

PubMed

Geamănu Pancă, A; Popa-Cherecheanu, A; Marinescu, B; Geamănu, C D; Voinea, L M

2014-09-15

Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.

Optically powered remote gas monitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dubaniewicz, T.H. Jr.; Chilton, J.E.

1995-12-31

Many mines rely on toxic gas sensors to help maintain a safe and healthy work environment. This report describes a prototype monitoring system developed by the US Bureau of Mines (USBM) that uses light to power and communicate with several remote toxic gas sensors. The design is based on state-of-art optical-to-electrical power converters, solid-state diode lasers, and fiber optics. This design overcomes several problems associated with conventional wire-based systems by providing complete electrical isolation between the remote sensors and the central monitor. The prototype performed well during a 2-week field trial in the USBM Pittsburgh Research Center Safety Research Coalmore » Mine.« less

75 FR 27434 - [alpha]-(p-Nonylphenol)-[omega]-hydroxypoly(oxyethylene) Sulfate and Phosphate Esters; Time...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

.... study with the reproduction/ developmental toxicity screening test in rats (NPEPSD) LOAEL = 300 mg/kg... toxicity screening test. In the Harmonized Guideline 870.3650 study with the nonylphenol ethoxylate... Guideline 870.3650 study in rats following pre- and post-natal exposure to NPEPSDs. E. Aggregate Risks and...

Unique Nanoparticle Optical Properties Confound Fluorescent Based Assays Widely Employed in Their In Vitro Toxicity Screening and Ranking

EPA Science Inventory

Nanoparticles (NPs) are novel materials having at least one dimension less than 100 nm and display unique physicochemical properties due to their nanoscale size. An emphasis has been placed on developing high throughput screening (HTS) assays to characterize and rank the toxiciti...

New Chemical/Biological Profiling and Informatics Approaches for Exploring Mutagenicity & Carcinogenicity: Updates of EPA ToxCast and Tox21 Programs

EPA Science Inventory

EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through harnessing of legacy toxicity data, creation of data linkages, and generation of new in vitro screening data. In association with EP...

High-throughput fabrication and screening improves gold nanoparticle chemiresistor sensor performance.

PubMed

Hubble, Lee J; Cooper, James S; Sosa-Pintos, Andrea; Kiiveri, Harri; Chow, Edith; Webster, Melissa S; Wieczorek, Lech; Raguse, Burkhard

2015-02-09

Chemiresistor sensor arrays are a promising technology to replace current laboratory-based analysis instrumentation, with the advantage of facile integration into portable, low-cost devices for in-field use. To increase the performance of chemiresistor sensor arrays a high-throughput fabrication and screening methodology was developed to assess different organothiol-functionalized gold nanoparticle chemiresistors. This high-throughput fabrication and testing methodology was implemented to screen a library consisting of 132 different organothiol compounds as capping agents for functionalized gold nanoparticle chemiresistor sensors. The methodology utilized an automated liquid handling workstation for the in situ functionalization of gold nanoparticle films and subsequent automated analyte testing of sensor arrays using a flow-injection analysis system. To test the methodology we focused on the discrimination and quantitation of benzene, toluene, ethylbenzene, p-xylene, and naphthalene (BTEXN) mixtures in water at low microgram per liter concentration levels. The high-throughput methodology identified a sensor array configuration consisting of a subset of organothiol-functionalized chemiresistors which in combination with random forests analysis was able to predict individual analyte concentrations with overall root-mean-square errors ranging between 8-17 μg/L for mixtures of BTEXN in water at the 100 μg/L concentration. The ability to use a simple sensor array system to quantitate BTEXN mixtures in water at the low μg/L concentration range has direct and significant implications to future environmental monitoring and reporting strategies. In addition, these results demonstrate the advantages of high-throughput screening to improve the performance of gold nanoparticle based chemiresistors for both new and existing applications.

Architecture of optical sensor for recognition of multiple toxic metal ions from water.

PubMed

Shenashen, M A; El-Safty, S A; Elshehy, E A

2013-09-15

Here, we designed novel optical sensor based on the wormhole hexagonal mesoporous core/multi-shell silica nanoparticles that enabled the selective recognition and removal of these extremely toxic metals from drinking water. The surface-coating process of a mesoporous core/double-shell silica platforms by several consequence decorations using a cationic surfactant with double alkyl tails (CS-DAT) and then a synthesized dicarboxylate 1,5-diphenyl-3-thiocarbazone (III) signaling probe enabled us to create a unique hierarchical multi-shell sensor. In this design, the high loading capacity and wrapping of the CS-DAT and III organic moieties could be achieved, leading to the formation of silica core with multi-shells that formed from double-silica, CS-DAT, and III dressing layers. In this sensing system, notable changes in color and reflectance intensity of the multi-shelled sensor for Cu(2+), Co(2+), Cd(2+), and Hg(2+) ions, were observed at pH 2, 8, 9.5 and 11.5, respectively. The multi-shelled sensor is added to enable accessibility for continuous monitoring of several different toxic metal ions and efficient multi-ion sensing and removal capabilities with respect to reversibility, selectivity, and signal stability. Copyright © 2013 Elsevier B.V. All rights reserved.

Whole-cell luminescence biosensor-based lab-on-chip integrated system for water toxicity analysis

NASA Astrophysics Data System (ADS)

Rabner, Arthur; Belkin, Shimshon; Rozen, Rachel; Shacham, Yosi

2006-01-01

A novel water chemical toxin sensor has been successfully developed and evaluated as a working portable laboratory prototype. This sensor relies on a disposable plastic biochip prepared with a 4x4 micro-laboratory (μLab) chambers array of Escherichia coli reporter cells and micro-fluidic channels for liquids translocation. Each bacterial strain has been genetically modified into a bioluminescent reporter that responds to a pre-determined class of chemical agents. When challenged with a water sample containing a toxic chemical, the sensor responds with an increased bioluminescent signal from the biochip that is monitored over time. The signal is received by a motorized photomultiplier-based analyzer and interpreted by signal processing software. We have performed several levels of analysis: (i) the change in the bioluminescent signal from the sensor bacteria serves as a rapid indication for the presence of toxic chemicals in the water sample; (ii) the intensity of the change indicates the toxin concentration level; and (iii) the pattern of the responses for the different members of the bacterial panel on the biochip characterizes the biological origin of the toxin. The analyzer contains housing mechanics, electro-optics for signal acquisition, motorized readout calibration accessories, hydro-pneumatics modules for water sample translocation into biochip micro laboratories, electronics for overall control and communication with the host computer. This prototype has a demonstrated sensitivity for broad classes of water-borne toxic chemicals including naladixic acid (a model genotoxic agent), botulinum and acetylcholine esterase inhibitors. This work has initiated an investigation of a novel handheld field-deployable Water Toxicity Analysis (WTA) device.

Flow Cytometry Enables Multiplexed Measurements of Genetically Encoded Intramolecular FRET Sensors Suitable for Screening.

PubMed

Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam

2016-07-01

Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections. © 2016 Society for Laboratory Automation and Screening.

Predictive simulations and optimization of nanowire field-effect PSA sensors including screening

NASA Astrophysics Data System (ADS)

Baumgartner, Stefan; Heitzinger, Clemens; Vacic, Aleksandar; Reed, Mark A.

2013-06-01

We apply our self-consistent PDE model for the electrical response of field-effect sensors to the 3D simulation of nanowire PSA (prostate-specific antigen) sensors. The charge concentration in the biofunctionalized boundary layer at the semiconductor-electrolyte interface is calculated using the propka algorithm, and the screening of the biomolecules by the free ions in the liquid is modeled by a sensitivity factor. This comprehensive approach yields excellent agreement with experimental current-voltage characteristics without any fitting parameters. Having verified the numerical model in this manner, we study the sensitivity of nanowire PSA sensors by changing device parameters, making it possible to optimize the devices and revealing the attributes of the optimal field-effect sensor.

QSAR models for reproductive toxicity and endocrine disruption in regulatory use – a preliminary investigation†

PubMed Central

Jensen, G.E.; Niemelä, J.R.; Wedebye, E.B.; Nikolov, N.G.

2008-01-01

A special challenge in the new European Union chemicals legislation, Registration, Evaluation and Authorisation of Chemicals, will be the toxicological evaluation of chemicals for reproductive toxicity. Use of valid quantitative structure–activity relationships (QSARs) is a possibility under the new legislation. This article focuses on a screening exercise by use of our own and commercial QSAR models for identification of possible reproductive toxicants. Three QSAR models were used for reproductive toxicity for the endpoints teratogenic risk to humans (based on animal tests, clinical data and epidemiological human studies), dominant lethal effect in rodents (in vivo) and Drosophila melanogaster sex-linked recessive lethal effect. A structure set of 57,014 European Inventory of Existing Chemical Substances (EINECS) chemicals was screened. A total of 5240 EINECS chemicals, corresponding to 9.2%, were predicted as reproductive toxicants by one or more of the models. The chemicals predicted positive for reproductive toxicity will be submitted to the Danish Environmental Protection Agency as scientific input for a future updated advisory classification list with advisory classifications for concern for humans owing to possible developmental toxic effects: Xn (Harmful) and R63 (Possible risk of harm to the unborn child). The chemicals were also screened in three models for endocrine disruption. PMID:19061080

Evaluation and Refinement of a Field-Portable Drinking Water Toxicity Sensor Utilizing Electric Cell-Substrate Impedance Sensing and a Fluidic Biochip

DTIC Science & Technology

2014-01-01

Potential interferences tested were chlorine and chloramine (commonly used for drinking water disinfection ), geosmin and 2-methyl-isoborneol (MIB...Protection Agency maximum residual disinfectant level for chlorine and chloramine is set at 4 mg l1 under the Safe Drinking Water Act and thus would...Evaluation and refinement of a field-portable drinking water toxicity sensor utilizing electric cell–substrate impedance sensing and a fluidic

Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review

PubMed Central

Geamănu (Pancă), A; Popa-Cherecheanu, A; Marinescu, B; Geamănu, CD; Voinea, LM

2014-01-01

Abstract Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects. PMID:25408748

Wireless sensors and sensor networks for homeland security applications.

PubMed

Potyrailo, Radislav A; Nagraj, Nandini; Surman, Cheryl; Boudries, Hacene; Lai, Hanh; Slocik, Joseph M; Kelley-Loughnane, Nancy; Naik, Rajesh R

2012-11-01

New sensor technologies for homeland security applications must meet the key requirements of sensitivity to detect agents below risk levels, selectivity to provide minimal false-alarm rates, and response speed to operate in high throughput environments, such as airports, sea ports, and other public places. Chemical detection using existing sensor systems is facing a major challenge of selectivity. In this review, we provide a brief summary of chemical threats of homeland security importance; focus in detail on modern concepts in chemical sensing; examine the origins of the most significant unmet needs in existing chemical sensors; and, analyze opportunities, specific requirements, and challenges for wireless chemical sensors and wireless sensor networks (WSNs). We further review a new approach for selective chemical sensing that involves the combination of a sensing material that has different response mechanisms to different species of interest, with a transducer that has a multi-variable signal-transduction ability. This new selective chemical-sensing approach was realized using an attractive ubiquitous platform of battery-free passive radio-frequency identification (RFID) tags adapted for chemical sensing. We illustrate the performance of RFID sensors developed in measurements of toxic industrial materials, humidity-independent detection of toxic vapors, and detection of chemical-agent simulants, explosives, and strong oxidizers.

Nanocomposite electrodes for smartphone enabled healthcare garments: e-bra and smart vest

NASA Astrophysics Data System (ADS)

Kumar, Prashanth S.; Rai, Pratyush; Oh, Sechang; Kwon, Hyeokjun; Varadan, Vijay K.

2012-10-01

The financial burden of hospital readmissions and treatment of chronic cardiac diseases are global concerns. Point of Care (POC) has been presented as an elegant solution for healthcare cost reduction. However, large scale adoption of POC systems requires an intuitive, unobtrusive and easy to use health monitoring system from patient's perspective. Healthcare textiles are sensor systems mounted on textile platform that function as wearable unobtrusive health monitoring systems. Although much work has been done in the development and demonstration of textile mounted monitoring systems, material and production costs are still high. Nanomaterials based devices and technology can be employed in these healthcare textiles for improved electrical characteristics of the sensors, lowered cost due to less material consumption and compatibility to varied manufacturing techniques. Carbon nanotube composite ink based printable conductive electrodes is such a textile adaptable nanomaterial technology. Screen printed Nanocomposite electrodes made of carbon nanotubes and an acrylic polymer can be used in undergarments like vests and brassieres, for cardiac biopotential (Electrocardiography, ECG) sensing. A Bluetooth module and a smartphone can then be used to provide cyber-infrastructure connectivity for the healthcare data from these healthcare garments. They can be used to monitor young or elderly recuperating /convalescent patients either in hospital or at home, or they can be used by young athletes to monitor important physiological parameters to better design their training or fitness program. In this study, we evaluate screen printed CNT-acrylic Nanocomposite electrodes for ECG signal quality and any CNT leaching hazard that might lead to skin toxicity.

DSSTOX (DISTRIBUTED STRUCTURE-SEARCHABLE ...

EPA Pesticide Factsheets

Distributed Structure-Searchable Toxicity Database Network Major trends affecting public toxicity information resources have the potential to significantly alter the future of predictive toxicology. Chemical toxicity screening is undergoing shifts towards greater use of more fundamental information on gene/protein expression patterns and bioactivity and bioassay profiles, the latter generated with highthroughput screening technologies. Curated, systematically organized, and webaccessible toxicity and biological activity data in association with chemical structures, enabling the integration of diverse data information domains, will fuel the next frontier of advancement for QSAR (quantitative structure-activity relationship) and data mining technologies. The DSSTox project is supporting progress towards these goals on many fronts, promoting the use of formalized and structure-annotated toxicity data models, helping to interface these efforts with QSAR modelers, linking data from diverse sources, and creating a large, quality reviewed, central chemical structure information resource linked to various toxicity data sources

High-throughput Screening of ToxCast™ Phase I Chemicals in a Mouse Embryonic Stem Cell (mESC) Assay Reveals Disruption of Potential Toxicity Pathways

EPA Science Inventory

Little information is available regarding the potential for many commercial chemicals to induce developmental toxicity. The mESC Adherent Cell Differentiation and Cytoxicity (ACDC) assay is a high-throughput screen used to close this data gap. Thus, ToxCast™ Phase I chemicals wer...

Biological screening of selected Pacific Northwest forest plants using the brine shrimp (Artemia salina) toxicity bioassay

Treesearch

Yvette M. Karchesy; Rick G. Kelsey; George Constantine; Joseph J. Karchesy

2016-01-01

The brine shrimp (Artemia salina) bioassay was used to screen 211 methanol extracts from 128 species of Pacific Northwest plants in search of general cytotoxic activity. Strong toxicity (LC50 < 100 μg/ml) was found for 17 extracts from 13 species, with highest activity observed for Angelica arguta...

SCREENING FOR TOXIC INDUSTRIAL CHEMICALS USING SEMIPERMEABLE MEMBRANE DEVICES WITH RAPID TOXICITY ASSAYS

EPA Science Inventory

A time-integrated sampling device interfaced with two toxicity-based assays is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethylsulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

Review: Endogenously Produced Volatiles for In Vitro Toxicity Testing Using Cell Lines

EPA Science Inventory

Due to the approximately 86,000 chemicals registered under the Toxic Substances Control Act and increasing ethical concerns regarding animal testing, it is not economically or technically feasible to screen every registered chemical for toxicity using animal-based toxicity assays...

Exposure Science for Chemical Prioritization and Toxicity Testing

EPA Science Inventory

Currently, a significant research effort is underway to apply new technologies to screen and prioritize chemicals for toxicity testing as well as to improve understanding of toxicity pathways (Dix et al. 2007, Toxicol Sci; NRC, 2007, Toxicity Testing in the 21st Century; Collins ...

A quartz-based micro catalytic methane sensor by high resolution screen printing

NASA Astrophysics Data System (ADS)

Lu, Wenshuai; Jing, Gaoshan; Bian, Xiaomeng; Yu, Hongyan; Cui, Tianhong

2016-02-01

A micro catalytic methane sensor was proposed and fabricated on a bulk fused quartz substrate using a high resolution screen printing technique for the first time, with reduced power consumption and optimized sensitivity. The sensor was designed by the finite element method and quartz was chosen as the substrate material and alumina support with optimized dimensions. Fabrication of the sensor consisted of two MEMS processes, lift-off and high resolution screen printing, with the advantages of high yield and uniformity. When the sensor’s regional working temperature changes from 250 °C to 470 °C, its sensitivity increases, as well as the power consumption. The highest sensitivity can reach 1.52 mV/% CH4. A temperature of 300 °C was chosen as the optimized working temperature, and the sensor’s sensitivity, power consumption, nonlinearity and response time are 0.77 mV/% CH4, 415 mW, 2.6%, and 35 s, respectively. This simple, but highly uniform fabrication process and the reliable performance of this sensor may lead to wide applications for methane detection.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens.

PubMed

Morgens, David W; Wainberg, Michael; Boyle, Evan A; Ursu, Oana; Araya, Carlos L; Tsui, C Kimberly; Haney, Michael S; Hess, Gaelen T; Han, Kyuho; Jeng, Edwin E; Li, Amy; Snyder, Michael P; Greenleaf, William J; Kundaje, Anshul; Bassik, Michael C

2017-05-05

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens

PubMed Central

Morgens, David W.; Wainberg, Michael; Boyle, Evan A.; Ursu, Oana; Araya, Carlos L.; Tsui, C. Kimberly; Haney, Michael S.; Hess, Gaelen T.; Han, Kyuho; Jeng, Edwin E.; Li, Amy; Snyder, Michael P.; Greenleaf, William J.; Kundaje, Anshul; Bassik, Michael C.

2017-01-01

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens. PMID:28474669

Synthesis, toxicity, biocompatibility, and biomedical applications of graphene and graphene-related materials.

PubMed

Gurunathan, Sangiliyandi; Kim, Jin-Hoi

2016-01-01

Graphene is a two-dimensional atomic crystal, and since its development it has been applied in many novel ways in both research and industry. Graphene possesses unique properties, and it has been used in many applications including sensors, batteries, fuel cells, supercapacitors, transistors, components of high-strength machinery, and display screens in mobile devices. In the past decade, the biomedical applications of graphene have attracted much interest. Graphene has been reported to have antibacterial, antiplatelet, and anticancer activities. Several salient features of graphene make it a potential candidate for biological and biomedical applications. The synthesis, toxicity, biocompatibility, and biomedical applications of graphene are fundamental issues that require thorough investigation in any kind of applications related to human welfare. Therefore, this review addresses the various methods available for the synthesis of graphene, with special reference to biological synthesis, and highlights the biological applications of graphene with a focus on cancer therapy, drug delivery, bio-imaging, and tissue engineering, together with a brief discussion of the challenges and future perspectives of graphene. We hope to provide a comprehensive review of the latest progress in research on graphene, from synthesis to applications.

Synthesis, toxicity, biocompatibility, and biomedical applications of graphene and graphene-related materials

PubMed Central

Gurunathan, Sangiliyandi; Kim, Jin-Hoi

2016-01-01

Graphene is a two-dimensional atomic crystal, and since its development it has been applied in many novel ways in both research and industry. Graphene possesses unique properties, and it has been used in many applications including sensors, batteries, fuel cells, supercapacitors, transistors, components of high-strength machinery, and display screens in mobile devices. In the past decade, the biomedical applications of graphene have attracted much interest. Graphene has been reported to have antibacterial, antiplatelet, and anticancer activities. Several salient features of graphene make it a potential candidate for biological and biomedical applications. The synthesis, toxicity, biocompatibility, and biomedical applications of graphene are fundamental issues that require thorough investigation in any kind of applications related to human welfare. Therefore, this review addresses the various methods available for the synthesis of graphene, with special reference to biological synthesis, and highlights the biological applications of graphene with a focus on cancer therapy, drug delivery, bio-imaging, and tissue engineering, together with a brief discussion of the challenges and future perspectives of graphene. We hope to provide a comprehensive review of the latest progress in research on graphene, from synthesis to applications. PMID:27226713

Behavioral Screening for Toxicology | Science Inventory | US ...

EPA Pesticide Factsheets

Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols used in pharmacology, toxicology, and psychology. Although there is a range of protocols in use today, all focus on detailed observations and specific tests of reflexes and responses. Several neurological functions are typically assessed, including autonomic, neuromuscular, and sensory, as well as levels of activity and excitability. The tests have been shown to be valid in detecting expected effects of known neurotoxicants, and reliable and reproducible whn compared across laboratories. Regardless of the specific protocol used, proper conduct and statistical analyses of the data are critical. Interpretation is based on the information from individual end points as well as the profile, or pattern, of effects observed. As long as continual refinements are made, behavioral screening methods will continue to be important tools with which to protect human health in the future.autonomic function; behavior; behavioral phenotypes; behavioral toxicity; excitability; functional observational battery ; motor activity; mouse; neuromuscular function; positive controls; rat; screening battery ; sensory function Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; how

[Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish].

PubMed

Wang, Mo; Ling, Jie; Chen, Ying; Song, Jie; Sun, E; Shi, Zi-Qi; Feng, Liang; Jia, Xiao-Bin; Wei, Ying-Jie

2017-11-01

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad literature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can't achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis. Copyright© by the Chinese Pharmaceutical Association.

Screen printing of a capacitive cantilever-based motion sensor on fabric using a novel sacrificial layer process for smart fabric applications

NASA Astrophysics Data System (ADS)

Wei, Yang; Torah, Russel; Yang, Kai; Beeby, Steve; Tudor, John

2013-07-01

Free-standing cantilevers have been fabricated by screen printing sacrificial and structural layers onto a standard polyester cotton fabric. By printing additional conductive layers, a complete capacitive motion sensor on fabric using only screen printing has been fabricated. This type of free-standing structure cannot currently be fabricated using conventional fabric manufacturing processes. In addition, compared to conventional smart fabric fabrication processes (e.g. weaving and knitting), screen printing offers the advantages of geometric design flexibility and the ability to simultaneously print multiple devices of the same or different designs. Furthermore, a range of active inks exists from the printed electronics industry which can potentially be applied to create many types of smart fabric. Four cantilevers with different lengths have been printed on fabric using a five-layer structure with a sacrificial material underneath the cantilever. The sacrificial layer is subsequently removed at 160 °C for 30 min to achieve a freestanding cantilever above the fabric. Two silver electrodes, one on top of the cantilever and the other on top of the fabric, are used to capacitively detect the movement of the cantilever. In this way, an entirely printed motion sensor is produced on a standard fabric. The motion sensor was initially tested on an electromechanical shaker rig at a low frequency range to examine the linearity and the sensitivity of each design. Then, these sensors were individually attached to a moving human forearm to evaluate more representative results. A commercial accelerometer (Microstrain G-link) was mounted alongside for comparison. The printed sensors have a similar motion response to the commercial accelerometer, demonstrating the potential of a printed smart fabric motion sensor for use in intelligent clothing applications.

Development of a Modular, Provider Customized Airway Trainer

DTIC Science & Technology

2015-11-25

Instructions for Airway Model with sensors and computer ( Raspberry PI ) ........................................ 31 Appendix B: Instructions for...Appendix A: Instructions for Airway Model with sensors and computer ( Raspberry PI ) RASPBERRY PI INSTRUCTIONS 1. Connect multicolor sensor...cable and two blue sensor cables (blue sensor cable orientation does not matter) 2. Plug in power to the screen and raspberry pi ( two separate

Recent Progress in Optical Chemical Sensors

PubMed Central

Qazi, Hummad Habib; Mohammad, Abu Bakar bin; Akram, Muhammad

2012-01-01

Optical chemical sensors have promoted escalating interest in the determination of various pollutants in the environment, which are creating toxicity and may cause serious health problems. This review paper focuses particularly on the recent progress and developments in this field; the working principles and basic classes of optical chemical sensors have been briefly described. PMID:23443392

TOWARDS REFINED USE OF TOXICITY DATA IN STATISTICALLY BASED SAR MODELS FOR DEVELOPMENTAL TOXICITY.

EPA Science Inventory

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

In Vitro Toxicity Assessment Technique for Volatile ...

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency is tasked with evaluating the human health, environmental, and wildlife effects of over 80,000 chemicals registered for use in the environment and commerce. The challenge is that sparse chemical data exists; traditional toxicity testing methods are slow, costly, involve animal studies, and cannot keep up with a chemical registry that typically grows by at least 1000 chemicals every year. In recent years, High Throughput Screening (HTS) has been used in order to prioritize chemicals for traditional toxicity screening or to complement traditional toxicity studies. HTS is an in vitro approach of rapidly assaying a large number of chemicals for biochemical activity using robotics and automation. However, no method currently exists for screening volatile chemicals such as air pollutants in a HTS fashion. Additionally, significant uncertainty regarding in vitro to in in vivo extrapolation (IVIVE) remains. An approach to bridge the IVIVE gap and the current lack of ability to screen volatile chemicals in a HTS fashion is by using a probe molecule (PrM) technique. The proposed technique uses chemicals with empirical human pharmacokinetic data as PrMs to study toxicity of molecules with no known data for gas-phase analysis. We are currently studying the xenobiotic-metabolizing enzyme CYP2A6 using transfected BEAS-2B bronchial epithelial cell line. The CYP2A6 pathway activity is studied by the formation of cotinine from nicot

CATSI EDM: recent advances in the development and validation of a ruggedized passive standoff CWA sensor

NASA Astrophysics Data System (ADS)

Lavoie, Hugo; Thériault, Jean-Marc; Bouffard, François; Puckrin, Eldon; Turcotte, Caroline S.; Lacasse, Paul

2008-04-01

Defence Research and Development Canada (DRDC) - Valcartier is currently developing a ruggedized passive standoff sensor for the detection of chemical warfare agents (CWAs) based on differential Fourier-transform infrared (FTIR) radiometry. This system is referred to as the Compact ATmospheric Sounding Interferometer (CATSI) Engineering Development Model (EDM). The CATSI EDM sensor is based on the use of a double-beam FTIR spectrometer that is optimized for optical subtraction. A description of the customized sensor is given along with a discussion on the detection and identification approaches that have been developed. Preliminary results of validation from a number of laboratory measurements and open-air trials are analyzed to establish the capability of detection and identification of various toxic and non-toxic chemical vapor plumes. These results clearly demonstrate the capability of the passive differential radiometric approach for the standoff detection and identification of chemical vapors at distances up to a few kilometers from the sensor.

EPA’s ToxCast Program for Predicting Toxicity and Prioritizing Chemicals for Further Screening and Testing

EPA Science Inventory

Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challengin...

Toxicity of selected insecticides applied to western spruce budworm

Treesearch

Jacqueline L. Robertson; Nancy L. Gillette; Melvin Look; Barbara A. Lucas; Robert L. Lyon

1975-01-01

The contact toxicity of 100 insecticides to last stage larvae of Choristoneura occidentalis Freeman was tested by topical application in a 10-yr series of screening experiments. Pyrethroids were generally the most toxic group of chemicals tested. Compounds more toxic than the standard, mexacarbate, at Ld50 were:...

Research and Development of Hazardous/Toxic Waste Analytical Screening Procedures. Available Field Methods for Rapid Screening of Hazardous Waste Materials at Waste Sites (Class A Poisons).

DTIC Science & Technology

1982-01-01

bromide is listed as a positive interference. Nitric oxide and nitrogen dioxide can be detected by using the Draeger nitrous fumes detector tube. A... fumes exhibit a delay from the time of exposure to the onset of symptoms. This time delay would not be conducive for a rapid field screening test. It...Dangerous when strongly heated, emits highly toxic fumes . THRESHOLD LIMIT VALUE: No information available PHYSIOLOGICAL EFFECTS: A. Intensely irritating to

A Call for Nominations of Quantitative High-Throughput ...

EPA Pesticide Factsheets

The National Research Council of the United States National Academies of Science has recently released a document outlining a long-range vision and strategy for transforming toxicity testing from largely whole animal-based testing to one based on in vitro assays. “Toxicity Testing in the 21st Century: A Vision and a Strategy” advises a focus on relevant human toxicity pathway assays. Toxicity pathways are defined in the document as “Cellular response pathways that, when sufficiently perturbed, are expected to result in adverse health effects”. Results of such pathway screens would serve as a filter to drive selection of more specific, targeted testing that will complement and validate the pathway assays. In response to this report, the US EPA has partnered with two NIH organizations, the National Toxicology Program and the NIH Chemical Genomics Center (NCGC), in a program named Tox21. A major goal of this collaboration is to screen chemical libraries consisting of known toxicants, chemicals of environmental and occupational exposure concern, and human pharmaceuticals in cell-based pathway assays. Currently, approximately 3000 compounds (increasing to 9000 by the end of 2009) are being validated and screened in quantitative high-throughput (qHTS) format at the NCGC producing extensive concentration-response data for a diverse set of potential toxicity pathways. The Tox21 collaboration is extremely interested in accessing additional toxicity pathway assa

A Multi-Modality CMOS Sensor Array for Cell-Based Assay and Drug Screening.

PubMed

Chi, Taiyun; Park, Jong Seok; Butts, Jessica C; Hookway, Tracy A; Su, Amy; Zhu, Chengjie; Styczynski, Mark P; McDevitt, Todd C; Wang, Hua

2015-12-01

In this paper, we present a fully integrated multi-modality CMOS cellular sensor array with four sensing modalities to characterize different cell physiological responses, including extracellular voltage recording, cellular impedance mapping, optical detection with shadow imaging and bioluminescence sensing, and thermal monitoring. The sensor array consists of nine parallel pixel groups and nine corresponding signal conditioning blocks. Each pixel group comprises one temperature sensor and 16 tri-modality sensor pixels, while each tri-modality sensor pixel can be independently configured for extracellular voltage recording, cellular impedance measurement (voltage excitation/current sensing), and optical detection. This sensor array supports multi-modality cellular sensing at the pixel level, which enables holistic cell characterization and joint-modality physiological monitoring on the same cellular sample with a pixel resolution of 80 μm × 100 μm. Comprehensive biological experiments with different living cell samples demonstrate the functionality and benefit of the proposed multi-modality sensing in cell-based assay and drug screening.

Risk-Screening Environmental Indicators (RSEI)

EPA Pesticide Factsheets

EPA's Risk-Screening Environmental Indicators (RSEI) is a geographically-based model that helps policy makers and communities explore data on releases of toxic substances from industrial facilities reporting to EPA??s Toxics Release Inventory (TRI). By analyzing TRI information together with simplified risk factors, such as the amount of chemical released, its fate and transport through the environment, each chemical??s relative toxicity, and the number of people potentially exposed, RSEI calculates a numeric score, which is designed to only be compared to other scores calculated by RSEI. Because it is designed as a screening-level model, RSEI uses worst-case assumptions about toxicity and potential exposure where data are lacking, and also uses simplifying assumptions to reduce the complexity of the calculations. A more refined assessment is required before any conclusions about health impacts can be drawn. RSEI is used to establish priorities for further investigation and to look at changes in potential impacts over time. Users can save resources by conducting preliminary analyses with RSEI.

Plants used in Guatemala for the treatment of protozoal infections. I. Screening of activity to bacteria, fungi and American trypanosomes of 13 native plants.

PubMed

Cáceres, A; López, B; González, S; Berger, I; Tada, I; Maki, J

1998-10-01

Extracts were prepared from 13 native plants used for the treatment of protozoal infections. Activity against bacteria and fungi was demonstrated by dilution procedures; Trypanosoma cruzi was evaluated in vitro against epimastigote and trypomastigotes and in vivo against trypomastigotes. In active extracts, toxicity was evaluated by Artemia salina nauplii, oral acute toxicity (1-5 g/kg) and oral and intraperitoneal subacute toxicity in mice (500 mg/kg). From the plants screened, six showed activity (< or = 2 mg/ml) against bacteria, three against yeasts, five against Microsporum gypseum and five against T. cruzi in vitro and/or in vivo. In vitro and in vivo activity was demonstrated by Neurolaena lobata and Solanum americanum; in vitro or in vivo activity was shown by Acalypha guatemalensis, Petiveria alliacea and Tridax procumbens. Toxicity studies showed that extracts from S. americanum are toxic to A. salina (aqueous, 160 ppm). None showed acute or oral toxicity to mice; S. americanum showed intraperitoneal subacute toxicity.

Bioassay selection, experimental design and quality control/assurance for use in effluent assessment and control.

PubMed

Johnson, Ian; Hutchings, Matt; Benstead, Rachel; Thain, John; Whitehouse, Paul

2004-07-01

In the UK Direct Toxicity Assessment Programme, carried out in 1998-2000, a series of internationally recognised short-term toxicity test methods for algae, invertebrates and fishes, and rapid methods (ECLOX and Microtox) were used extensively. Abbreviated versions of conventional tests (algal growth inhibition tests, Daphnia magna immobilisation test and the oyster embryo-larval development test) were valuable for toxicity screening of effluent discharges and the identification of causes and sources of toxicity. Rapid methods based on chemiluminescence and bioluminescence were not generally useful in this programme, but may have a role where the rapid test has been shown to be an acceptable surrogate for a standardised test method. A range of quality assurance and control measures were identified. Requirements for quality control/assurance are most stringent when deriving data for characterising the toxic hazards of effluents and monitoring compliance against a toxicity reduction target. Lower quality control/assurance requirements can be applied to discharge screening and the identification of causes and sources of toxicity.

Spectral domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the "flying saucer" sign).

PubMed

Chen, Eric; Brown, David M; Benz, Matthew S; Fish, Richard H; Wong, Tien P; Kim, Rosa Y; Major, James C

2010-10-21

While the long-term incidence of hydroxychloroquine (HCQ) retinopathy is low, there remains no definitive clinical screening test to recognize HCQ toxicity before ophthalmoscopic fundus changes or visual symptoms. Patients receiving HCQ were evaluated with spectral domain optical coherence tomography (SD OCT) to assess the feasibility of identifying HCQ retinopathy at an early stage. Twenty-five patients referred for the evaluation of hydroxychloroquine toxicity underwent a comprehensive ocular examination, Humphrey visual field (HVF) perimetry, time domain OCT, and SD OCT. Some patients with screening abnormalities also underwent further diagnostic testing at the discretion of the treating providers. Five patients were found to have SD OCT findings corresponding to HCQ toxicity and retinal damage as seen by clinical exam and/or HVF perimetry. Two patients with advanced toxicity were found to have significant outer retina disruption in the macula on SD OCT. Three patients with early HCQ toxicity and HVF 10-2 perifoveal defects were found to have loss of the perifoveal photoreceptor inner segment/outer segment (IS/OS) junction with intact outer retina directly under the fovea, creating the "flying saucer" sign. While two of these three patients had early ophthalmoscopic fundus changes, one had none. Outer retinal abnormalities including perifoveal photoreceptor IS/OS junction disruption can be identified by SD OCT in early HCQ toxicity, sometimes even before ophthalmoscopic fundus changes are apparent. SD OCT may have a potential complementary role in screening for HCQ retinopathy due to its quick acquisition and because it is more objective than automated perimetry.

Optical detection of chemical warfare agents and toxic industrial chemicals

NASA Astrophysics Data System (ADS)

Webber, Michael E.; Pushkarsky, Michael B.; Patel, C. Kumar N.

2004-12-01

We present an analytical model evaluating the suitability of optical absorption based spectroscopic techniques for detection of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in ambient air. The sensor performance is modeled by simulating absorption spectra of a sample containing both the target and multitude of interfering species as well as an appropriate stochastic noise and determining the target concentrations from the simulated spectra via a least square fit (LSF) algorithm. The distribution of the LSF target concentrations determines the sensor sensitivity, probability of false positives (PFP) and probability of false negatives (PFN). The model was applied to CO2 laser based photoacosutic (L-PAS) CWA sensor and predicted single digit ppb sensitivity with very low PFP rates in the presence of significant amount of interferences. This approach will be useful for assessing sensor performance by developers and users alike; it also provides methodology for inter-comparison of different sensing technologies.

Colorimetric sensor array for determination and identification of toxic industrial chemicals.

PubMed

Feng, Liang; Musto, Christopher J; Kemling, Jonathan W; Lim, Sung H; Zhong, Wenxuan; Suslick, Kenneth S

2010-11-15

A low-cost yet highly sensitive colorimetric sensor array for the detection and identification of toxic industrial chemicals (TICs) has been developed. The sensor consists of a disposable array of cross-responsive nanoporous pigments whose colors are changed by diverse chemical interactions with analytes. Clear differentiation among 20 different TICs has been easily achieved at both their IDLH (immediately dangerous to life or health) concentration within 2 min of exposure and PEL (permissible exposure limit) concentration within 5 min of exposure with no errors or misclassifications. Detection limits are generally well below the PEL (in most cases below 5% of PEL) and are typically in the low ppb range. The colorimetric sensor array is not responsive to changes in humidity or temperature over a substantial range. The printed arrays show excellent batch to batch reproducibility and long shelf life (greater than 3 months).

Integrated Magneto-Electrochemical Sensor for Exosome Analysis.

PubMed

Jeong, Sangmoo; Park, Jongmin; Pathania, Divya; Castro, Cesar M; Weissleder, Ralph; Lee, Hakho

2016-02-23

Extracellular vesicles, including exosomes, are nanoscale membrane particles that carry molecular information on parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magneto-electrochemical assay: exosomes are immunomagnetically captured from patient samples and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables (i) highly sensitive, cell-specific exosome detection and (ii) sensor miniaturization and scale-up for high-throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the simultaneous profiling of multiple protein markers within an hour, outperforming conventional methods in assay sensitivity and speed.

Integrated Magneto-Electrochemical Sensor for Exosome Analysis

PubMed Central

Jeong, Sangmoo; Park, Jongmin; Pathania, Divya; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho

2016-01-01

Extracellular vesicles, including exosomes, are nanoscale vesicles that carry molecular information of parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magnetic-electrochemical assay: exosomes are immunomagnetically captured from patient samples, and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables i) highly sensitive, cell-specific exosome detection, and ii) sensor miniaturization and scale-up for high throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device, and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the profiling of multiple protein markers simultaneously within an hour, outperforming conventional methods in assay sensitivity and speed. PMID:26808216

Toxico-Cheminformatics: New and Expanding Public Resources to Support Chemical Toxicity Assessments

EPA Science Inventory

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve information gathering efforts for chemical assessments and p...

Comparative study of different alcohol sensors based on Screen-Printed Carbon Electrodes.

PubMed

Costa Rama, Estefanía; Biscay, Julien; González García, María Begoña; Julio Reviejo, A; Pingarrón Carrazón, José Manuel; Costa García, Agustín

2012-05-30

Different very simple single-use alcohol enzyme sensors were developed using alcohol oxidase (AOX) from three different yeast, Hansenula sp., Pichia pastoris and Candida boidinii, and employing three different commercial mediator-based Screen-Printed Carbon Electrodes as transducers. The mediators tested, Prussian Blue, Ferrocyanide and Co-phthalocyanine were included into the ink of the working electrode. The procedure to obtain these sensors consists of the immobilization of the enzyme on the electrode surface by adsorption. For the immobilization, an AOX solution is deposited on the working electrode and left until dried (1h) at room temperature. The best results were obtained with the biosensor using Screen-Printed Co-phthalocyanine/Carbon Electrode and AOX from Hansenula sp. The reduced cobalt-phthalocyanine form is amperometrically detected at +0.4V (vs. Ag pseudo reference electrode). This sensor shows good sensitivity (1211 nA mM(-1)), high precision (2.1% RSD value for the slope value of the calibration plot) and wide linear response (0.05-1.00 mM) for ethanol determination. The sensor provides also accurate results for ethanol quantification in alcoholic drinks. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of a Hydrogen Peroxide Sensor Based on Screen-Printed Electrodes Modified with Inkjet-Printed Prussian Blue Nanoparticles

PubMed Central

Cinti, Stefano; Arduini, Fabiana; Moscone, Danila; Palleschi, Giuseppe; Killard, Anthony J.

2014-01-01

A sensor for the simple and sensitive measurement of hydrogen peroxide has been developed which is based on screen printed electrodes (SPEs) modified with Prussian blue nanoparticles (PBNPs) deposited using piezoelectric inkjet printing. PBNP-modified SPEs were characterized using physical and electrochemical techniques to optimize the PBNP layer thickness and electroanalytical conditions for optimum measurement of hydrogen peroxide. Sensor optimization resulted in a limit of detection of 2 × 10−7 M, a linear range from 0 to 4.5 mM and a sensitivity of 762 μA·mM−1·cm−2 which was achieved using 20 layers of printed PBNPs. Sensors also demonstrated excellent reproducibility (<5% rsd). PMID:25093348

Evaluation of Impermeant, DNA-Binding Dye Fluorescence as a Real-Time Readout of Eukaryotic Cell Toxicity in a High Throughput Screening Format

PubMed Central

Chiaraviglio, Lucius

2014-01-01

Abstract Interpretation of high throughput screening (HTS) data in cell-based assays may be confounded by cytotoxic properties of screening compounds. Therefore, assessing cell toxicity in real time during the HTS process itself would be highly advantageous. Here, we investigate the potential of putatively impermeant, fluorescent, DNA-binding dyes to give cell toxicity readout during HTS. Amongst 19 DNA-binding dyes examined, three classes were identified that were (1) permeant, (2) cytotoxic, or (3) neither permeant nor cytotoxic during 3-day incubation with a macrophage cell line. In the last class, four dyes (SYTOX Green, CellTox Green, GelGreen, and EvaGreen) gave highly robust cytotoxicity data in 384-well screening plates. As proof of principle, successful combination with a luminescence-based assay in HTS format was demonstrated. Here, both intracellular growth of Legionella pneumophila (luminescence) and host cell viability (SYTOX Green exclusion) were assayed in the same screening well. Incorporation of membrane-impermeant, DNA-binding, fluorescent dyes in HTS assays should prove useful by allowing evaluation of cytotoxicity in real time, eliminating reagent addition steps and effort associated with endpoint cell viability analysis, and reducing the need for follow-up cytotoxicity screening. PMID:24831788

Urine Multi-drug Screening with GC-MS or LC-MS-MS Using SALLE-hybrid PPT/SPE.

PubMed

Lee, Junhui; Park, Jiwon; Go, Ahra; Moon, Heesung; Kim, Sujin; Jung, Sohee; Jeong, Wonjoon; Chung, Heesun

2018-05-14

To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC-MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect. The results of the screening analysis were compared with patient medical records to check the reliability of the screen. Urine samples collected from an emergency room were extracted through a combination of salting-out assisted liquid-liquid extraction (SALLE) and hybrid protein precipitation/solid phase extraction (hybrid PPT/SPE) plates and examined by GC-MS and LC-MS-MS. GC-MS analysis was performed as unknown drug screen and LC-MS-MS analysis was conducted as targeted drug screen. After analysis by GC-MS, a library search was conducted using an in-house library established with the automated mass spectral deconvolution and identification system (AMDISTM). LC-MS-MS used Cliquid®2.0 software for data processing and acquisition in MRM mode. An UmDS method by GC-MS and LC-MS-MS was developed by using a SALLE-hybrid PPT/SPE and in-house library. The results of UmDS by GC-MS and LC-MS-MS showed that toxicants could be identified from 185 emergency room patient samples containing unknown toxicants. Zolpidem, acetaminophen and citalopram were the most frequently encountered drugs in emergency room patients. The UmDS analysis developed in this study can be used effectively to detect toxic substances in a short time. Hence, it could be utilized in clinical and forensic toxicology practices.

Pesticides sensing by surface plasmon resonance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalabina, N.A.; Ksenevich, T.I.; Beloglazov, A.A.

1995-12-31

High toxicity of pesticides and their wide use in agriculture, represent a general danger for environmental welfare and could become a real threat to life. Screening of pesticides in the environment has become very important during last years due to low threshold values for pesticides in drinking water. An optical biosensor has been developed for detection of pesticides, based on surface plasmon resonance (SPR) technique. Concentration of the pesticides was measured in liquid or gas. The authors specially originated organic film on a disposable element. A setup on the base of the Kretschmann arrangement was improved by using a computer-controlledmore » angular scanning system. The detection concentration limit of dinitrophenole (DNP) was 10{sup {minus}9} M. Some samples exhibited effect down to 10{sup {minus}11} M of DNP. The results obtained provide reason for further development of SPR sensor as applied to pesticides monitoring.« less

Hyalella IQ Toxicity Test{trademark} as a predictor of whole sediment toxicity with diversely contaminated sediments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Douglas, W.S.; Hayes, K.R.

1994-12-31

The IQ TOXICITY TEST{trademark} is a toxicity screening test that evaluates the organism`s galactosidase enzyme system functionality as a predictor of acute toxicity. Organisms are exposed to a potentially toxic solution for approximately one hour. Following the exposure, the organisms are exposed to a slurry of a galactoside sugar tagged with a fluorescent marker (methylumbelliferyl galactoside) for 15--20 minutes. A black light can then be used to examine whether the hemolymph of the organism contains free umbelliferone, which brightly fluoresces. The organisms are then scored as ``on`` or ``off`` with respect to free umbelliferone. This endpoint can then be usedmore » to calculate an EC50, which is comparable to a whole effluent, pure compound, or sediment toxicity test. Slightly different methodologies are used for different toxicity test organisms. The objective of this presentation is to discuss the use of the IQ{trademark} methodology with porewater extract exposures of the amphipod Hyalella azteca as a predictor of results of whole sediment toxicity tests. The results of over thirty 10 and 28-day whole sediment toxicity tests and the concurrent Hyalella azteca 10 TOXICITY TESTS{trademark} are compared and discussed. The use of screening tests as a reduced cost method for initial site assessment will be discussed.« less

INTERNATIONAL SOURCE WATER TOXICITY MONITORING CONSORTIUM

EPA Science Inventory

Many researchers in the field of time-relevant, on-line toxicity monitors for source water protection believe that some mechanism to guide and prioritize research in this emerging field would be beneficial. On-line toxicity monitors are tools designed to screen water quality and ...

ToxCast Workflow: High-throughput screening assay data processing, analysis and management (SOT)

EPA Science Inventory

US EPA’s ToxCast program is generating data in high-throughput screening (HTS) and high-content screening (HCS) assays for thousands of environmental chemicals, for use in developing predictive toxicity models. Currently the ToxCast screening program includes over 1800 unique c...

Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

PubMed

Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

2016-04-01

Abnormal tau accumulations were observed and documented in post-mortem brains of patients affected by Alzheimer's disease (AD) long before the identification of mutations in the Microtubule-associated protein tau (MAPT) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). The discovery of mutations in the MAPT gene associated with FTDP-17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over-expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large-scale screens have been performed using Drosophila, to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes including, but not limited to, phosphorylation, cytoskeleton organization, axonal transport, regulation of cellular proteostasis, transcription, RNA metabolism, cell cycle regulation, and apoptosis. We discuss the utility and application of invertebrate models in elucidating the cellular and molecular functions of novel and uncharacterized disease modifiers identified in large-scale screens as well as for investigating the function of genes identified as risk factors in genome-wide association studies from human patients in the post-genomic era. In this review, we combined and summarized several large-scale modifier screens performed in invertebrate models to identify modifiers of tau toxicity. A summary of the screens show that diverse cellular processes are implicated in the modification of tau toxicity. Kinases and phosphatases are the most predominant class of modifiers followed by components required for cellular proteostasis and axonal transport and cytoskeleton elements. © 2016 International Society for Neurochemistry.

Feasibility of using a bacteriophage-based structural color sensor for screening the geographical origins of agricultural products

NASA Astrophysics Data System (ADS)

Seol, Daun; Moon, Jong-Sik; Lee, Yujin; Han, Jiye; Jang, Daeil; Kang, Dong-Jin; Moon, Jiyoung; Jang, Eunjin; Oh, Jin-Woo; Chung, Hoeil

2018-05-01

An M13 bacteriophage-based color sensor, which can change its structural color upon interaction with a gaseous molecule, was evaluated as a screening tool for the discrimination of the geographical origins of three different agricultural products (garlic, onion, and perilla). Exposure of the color sensor to sample odors induced the self-assembled M13 bacteriophage bundles to swell by the interaction of amino acid residues (repeating units of four glutamates) on the bacteriophage with the odor components, resulting in a change in the structural color of the sensor. When the sensor was exposed to the odors of garlic and onion samples, the RGB color changes were considerable because of the strong interactions of the odor components such as disulfides with the glutamate residues on the sensor. Although the patterns of the color variations were generally similar between the domestic and imported samples, some degrees of dissimilarities in their intensities were also observed. Although the magnitude of color change decreased for perilla, the color change patterns between the two groups were somewhat different. With the acquired RGB data, a support vector machine was employed to distinguish the domestic and imported samples, and the resulting accuracies in the measurements of garlic, onion, and perilla samples were 94.1, 88.7, and 91.6%, respectively. The differences in the concentrations of the odor components between both groups and/or the presence of specific components exclusively in the odor of one group allowed the color sensor-based discrimination. The demonstrated color sensor was thus shown to be a potentially versatile and simple as an on-site screening tool. Strategies able to further improve the sensor performance were also discussed.

Feasibility of using a bacteriophage-based structural color sensor for screening the geographical origins of agricultural products.

PubMed

Seol, Daun; Moon, Jong-Sik; Lee, Yujin; Han, Jiye; Jang, Daeil; Kang, Dong-Jin; Moon, Jiyoung; Jang, Eunjin; Oh, Jin-Woo; Chung, Hoeil

2018-05-15

An M13 bacteriophage-based color sensor, which can change its structural color upon interaction with a gaseous molecule, was evaluated as a screening tool for the discrimination of the geographical origins of three different agricultural products (garlic, onion, and perilla). Exposure of the color sensor to sample odors induced the self-assembled M13 bacteriophage bundles to swell by the interaction of amino acid residues (repeating units of four glutamates) on the bacteriophage with the odor components, resulting in a change in the structural color of the sensor. When the sensor was exposed to the odors of garlic and onion samples, the RGB color changes were considerable because of the strong interactions of the odor components such as disulfides with the glutamate residues on the sensor. Although the patterns of the color variations were generally similar between the domestic and imported samples, some degrees of dissimilarities in their intensities were also observed. Although the magnitude of color change decreased for perilla, the color change patterns between the two groups were somewhat different. With the acquired RGB data, a support vector machine was employed to distinguish the domestic and imported samples, and the resulting accuracies in the measurements of garlic, onion, and perilla samples were 94.1, 88.7, and 91.6%, respectively. The differences in the concentrations of the odor components between both groups and/or the presence of specific components exclusively in the odor of one group allowed the color sensor-based discrimination. The demonstrated color sensor was thus shown to be a potentially versatile and simple as an on-site screening tool. Strategies able to further improve the sensor performance were also discussed. Copyright © 2018. Published by Elsevier B.V.

Behavioral Screening for Toxicology

EPA Science Inventory

Screening for behavioral toxicity, or neurotoxicity, has been in use for decades; however, only in the past 20 years has this become a standard practice in toxicology. Current screening batteries, such as the functional observational battery (FOB), are derived from protocols use...

Bio-oils from biomass slow pyrolysis: a chemical and toxicological screening.

PubMed

Cordella, Mauro; Torri, Cristian; Adamiano, Alessio; Fabbri, Daniele; Barontini, Federica; Cozzani, Valerio

2012-09-15

Bio-oils were produced from bench-scale slow-pyrolysis of three different biomass samples (corn stalks, poplar and switchgrass). Experimental protocols were developed and applied in order to screen their chemical composition. Several hazardous compounds were detected in the bio-oil samples analysed, including phenols, furans and polycyclic aromatic hydrocarbons. A procedure was outlined and applied to the assessment of toxicological and carcinogenic hazards of the bio-oils. The following hazardous properties were considered: acute toxicity; ecotoxicity; chronic toxicity; carcinogenicity. Parameters related to these properties were quantified for each component identified in the bio-oils and overall values were estimated for the bio-oils. The hazard screening carried out for the three bio-oils considered suggested that: (i) hazards to human health could be associated with chronic exposures to the bio-oils; (ii) acute toxic effects on humans and eco-toxic effects on aquatic ecosystems could also be possible in the case of loss of containment; and (iii) bio-oils may present a marginal potential carcinogenicity. The approach outlined allows the collection of screening information on the potential hazards posed by the bio-oils. This can be particularly useful when limited time and analytical resources reduce the possibility to obtain detailed specific experimental data. Copyright © 2012 Elsevier B.V. All rights reserved.

Toxicity of pyrolysis gases from polyether sulfone

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Olcomendy, E. M.

1979-01-01

A sample of polyether sulfone was evaluated for toxicity of pyrolysis gases, using the toxicity screening test method developed at the University of San Francisco. Animal response times were relatively short at pyrolysis temperatures of 600 to 800 C, with death occurring within 6 min. The principal toxicant appeared to be a compound other than carbon monoxide.

Screening methods for chemical warfare agents in environmental samples at the Edgewood area of Aberdeen Proving Ground, Maryland

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakubowski, E.M.; Borland, M.M.; Norris, L.

1995-06-01

The U.S. Army Edgewood Research, Development and Engineering Center, the U.S. Army Aberdeen Proving Ground Support Activity, Directorate of Safety, Health and the Environment and SciTech Services Inc., an independent contractor, have developed an approach for screening environmental samples for the presence of chemical warfare agents. Since 1918, the Edgewood area of Aberdeen Proving Ground has been a research and testing ground for toxic agent compounds. Since these materials are considered highly toxic, screening for their presence in environmental samples is necessary for safe shipment to contract laboratories for testing by EPA guidelines. The screening ensures worker safety and maintainsmore » U.S. Army standards for transportation of materials potentially contaminated with chemical warfare agents. This paper describes the screening methodology.« less

Highly Sensitive Aluminium(III) Ion Sensor Based on a Self-assembled Monolayer on a Gold Nanoparticles Modified Screen-printed Carbon Electrode.

PubMed

See, Wong Pooi; Heng, Lee Yook; Nathan, Sheila

2015-01-01

A new approach for the development of a highly sensitive aluminium(III) ion sensor via the preconcentration of aluminium(III) ion with a self-assembled monolayer on a gold nanoparticles modified screen-printed carbon electrode and current mediation by potassium ferricyanide redox behavior during aluminium(III) ion binding has been attempted. A monolayer of mercaptosuccinic acid served as an effective complexation ligand for the preconcentration of trace aluminium; this led to an enhancement of aluminium(III) ion capture and thus improved the sensitivity of the sensor with a detection limit of down to the ppb level. Under the optimum experimental conditions, the sensor exhibited a wide linear dynamic range from 0.041 to 12.4 μM. The lower detection limit of the developed sensor was 0.037 μM (8.90 ppb) using a 10 min preconcentration time. The sensor showed excellent selectivity towards aluminium(III) ion over other interference ions.

Intelligent detection of cracks in metallic surfaces using a waveguide sensor loaded with metamaterial elements.

PubMed

Ali, Abdulbaset; Hu, Bing; Ramahi, Omar

2015-05-15

This work presents a real life experiment of implementing an artificial intelligence model for detecting sub-millimeter cracks in metallic surfaces on a dataset obtained from a waveguide sensor loaded with metamaterial elements. Crack detection using microwave sensors is typically based on human observation of change in the sensor's signal (pattern) depicted on a high-resolution screen of the test equipment. However, as demonstrated in this work, implementing artificial intelligence to classify cracked from non-cracked surfaces has appreciable impact in terms of sensing sensitivity, cost, and automation. Furthermore, applying artificial intelligence for post-processing data collected from microwave sensors is a cornerstone for handheld test equipment that can outperform rack equipment with large screens and sophisticated plotting features. The proposed method was tested on a metallic plate with different cracks and the obtained experimental results showed good crack classification accuracy rates.

Intelligent Detection of Cracks in Metallic Surfaces Using a Waveguide Sensor Loaded with Metamaterial Elements

PubMed Central

Ali, Abdulbaset; Hu, Bing; Ramahi, Omar M.

2015-01-01

This work presents a real-life experiment implementing an artificial intelligence model for detecting sub-millimeter cracks in metallic surfaces on a dataset obtained from a waveguide sensor loaded with metamaterial elements. Crack detection using microwave sensors is typically based on human observation of change in the sensor's signal (pattern) depicted on a high-resolution screen of the test equipment. However, as demonstrated in this work, implementing artificial intelligence to classify cracked from non-cracked surfaces has appreciable impacts in terms of sensing sensitivity, cost, and automation. Furthermore, applying artificial intelligence for post-processing the data collected from microwave sensors is a cornerstone for handheld test equipment that can outperform rack equipment with large screens and sophisticated plotting features. The proposed method was tested on a metallic plate with different cracks, and the experimental results showed good crack classification accuracy rates. PMID:25988871

VAPOR SAMPLING DEVICE FOR INTERFACE WITH MICROTOX ASSAY FOR SCREENING TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor...

Fluorescent sensor based models for the detection of environmentally-related toxic heavy metals.

PubMed

Rasheed, Tahir; Bilal, Muhammad; Nabeel, Faran; Iqbal, Hafiz M N; Li, Chuanlong; Zhou, Yongfeng

2018-02-15

The quest for industrial and biotechnological revolution has been contributed in increasing environmental contamination issues, worldwide. The controlled or uncontrolled release of hazardous pollutants from various industrial sectors is one of the key problems facing humanity. Among them, adverse influences of lead, cadmium, and mercury on human health are well known to cause many disorders like reproductive, neurological, endocrine system, and cardiovascular, etc. Besides their presence at lower concentrations, most of these toxic heavy metals are posing noteworthy toxicological concerns. In this context, notable efforts from various regulatory authorities, the increase in the concentration of these toxic heavy metals in the environment is of serious concern, so real-time monitoring is urgently required. This necessitates the exploration for novel and efficient probes for recognition of these toxic agents. Among various methodologies adopted for tailoring such probes, generally the methodologies, in which changes associated with spectral properties, are preferred for the deceptive ease in the recognition process. Accordingly, a promising modality has emerged in the form of radiometric and colorimetric monitoring of these toxic agents. Herein, we review fluorescent sensor based models and their potentialities to address the detection fate of hazardous pollutants for a cleaner environment. Second, recent advances regarding small molecule and rhodamine-based fluorescent sensors, radiometric and colorimetric probes are discussed. The information is also given on the photoinduced electron transfer (PET) mechanism, chelation enhancement fluorescence (CHEF) effect and spirocyclic ring opening mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

Defect Functionalization of MoS2 nanostructures as toxic gas sensors: A review

NASA Astrophysics Data System (ADS)

Ramanathan, A. A.

2018-02-01

Toxic gas sensing plays an important role in many parts of our life from environmental protection, human health, agriculture to biomedicine. The importance of detecting toxic gases in the environment cannot be minimised in today’s highly polluted world and the reality of global warming. Carbon monoxide and NO gas are highly toxic air pollutants and can cause serious health problems. Therefore, materials able to detect these toxic gases are urgently needed. Doping and defect substitution is a versatile and new tool for changing the chemical and electronic properties of 2D layered materials and boosting the applications of these materials. Molybdenum disulphide (MoS2) as a 2D layered material has unique properties and applications due its semiconducting nature, bandgap and layered structure. In the past decade, although, extensive research of Graphene as a gas sensor was conducted, the zero bandgap limited its potential and applicability. This is overcome in MoS2 nanostructures (MSNs) and the current focus is defect engineering of MSNs. The large surface to volume ratio, bandgap and cheapness makes MSNs very attractive for gas sensor applications. The idea is fuelled by the recent finding of Ding et al [16] of successful doping strategies on monolayer MoS2 for enhanced NO detection. Moreover, the work of Luo et al [17] shows that substitutional doping is the new way of boosting and engineering the properties of ML MoS2. A short and focused report in this exciting field is presented in this review.

CHRONIC ZINC SCREENING WATER EFFECT RATIO FOR THE H-12 OUTFALL, SAVANNAH RIVER SITE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coughlin, D.; Looney, B.; Millings, M.

2009-01-13

In response to proposed Zn limits for the NPDES outfall H-12, a Zn screening Water Effects Ratio (WER) study was conducted to determine if a full site-specific WER is warranted. Using standard assumptions for relating the lab results to the stream, the screening WER data were consistent with the proposed Zn limit and suggest that a full WER would result in a similar limit. Addition of a humate amendment to the outfall water reduced Zn toxicity, but the toxicity reduction was relatively small and unlikely to impact proposed Zn limits. The screening WER data indicated that the time and expensemore » required to perform a full WER for Zn is not warranted.« less

Behavioral screening for toxicology and safety pharmacology

EPA Science Inventory

Screening for behavioral toxicity, or neurotoxicity, has been in use for many decades; however, only in the past 20 years has this become a standard practice in toxicology and safety pharmacology. Current screening batteries, such as the functional observational battery (FOB) and...

Sequential assessment via daphnia and zebrafish for systematic toxicity screening of heterogeneous substances.

PubMed

Jang, Gun Hyuk; Park, Chang-Beom; Kang, Benedict J; Kim, Young Jun; Lee, Kwan Hyi

2016-09-01

Environment and organisms are persistently exposed by a mixture of various substances. However, the current evaluation method is mostly based on an individual substance's toxicity. A systematic toxicity evaluation of heterogeneous substances needs to be established. To demonstrate toxicity assessment of mixture, we chose a group of three typical ingredients in cosmetic sunscreen products that frequently enters ecosystems: benzophenone-3 (BP-3), ethylhexyl methoxycinnamate (EHMC), and titanium dioxide nanoparticle (TiO2 NP). We first determined a range of nominal toxic concentration of each ingredient or substance using Daphnia magna, and then for the subsequent organismal level phenotypic assessment, chose the wild-type zebrafish embryos. Any phenotype change, such as body deformation, led to further examinations on the specific organs of transgenic zebrafish embryos. Based on the systematic toxicity assessments of the heterogeneous substances, we offer a sequential environmental toxicity assessment protocol that starts off by utilizing Daphnia magna to determine a nominal concentration range of each substance and finishes by utilizing the zebrafish embryos to detect defects on the embryos caused by the heterogeneous substances. The protocol showed additive toxic effects of the mixtures. We propose a sequential environmental toxicity assessment protocol for the systematic toxicity screening of heterogeneous substances from Daphnia magna to zebrafish embryo in-vivo models. Copyright © 2016 Elsevier Ltd. All rights reserved.

Medium-Throughput Screen of Microbially Produced Serotonin via a G-Protein-Coupled Receptor-Based Sensor.

PubMed

Ehrenworth, Amy M; Claiborne, Tauris; Peralta-Yahya, Pamela

2017-10-17

Chemical biosensors, for which chemical detection triggers a fluorescent signal, have the potential to accelerate the screening of noncolorimetric chemicals produced by microbes, enabling the high-throughput engineering of enzymes and metabolic pathways. Here, we engineer a G-protein-coupled receptor (GPCR)-based sensor to detect serotonin produced by a producer microbe in the producer microbe's supernatant. Detecting a chemical in the producer microbe's supernatant is nontrivial because of the number of other metabolites and proteins present that could interfere with sensor performance. We validate the two-cell screening system for medium-throughput applications, opening the door to the rapid engineering of microbes for the increased production of serotonin. We focus on serotonin detection as serotonin levels limit the microbial production of hydroxystrictosidine, a modified alkaloid that could accelerate the semisynthesis of camptothecin-derived anticancer pharmaceuticals. This work shows the ease of generating GPCR-based chemical sensors and their ability to detect specific chemicals in complex aqueous solutions, such as microbial spent medium. In addition, this work sets the stage for the rapid engineering of serotonin-producing microbes.

Fabrication and Characterization of Flexible and Miniaturized Humidity Sensors Using Screen-Printed TiO2 Nanoparticles as Sensitive Layer

PubMed Central

Dubourg, Georges; Segkos, Apostolos; Katona, Jaroslav; Radović, Marko; Savić, Slavica; Crnojević-Bengin, Vesna

2017-01-01

This paper describes the fabrication and the characterization of an original example of a miniaturized resistive-type humidity sensor, printed on flexible substrate in a large-scale manner. The fabrication process involves laser ablation for the design of interdigitated electrodes on PET (Poly-Ethylene Terephthalate) substrate and a screen-printing process for the deposition of the sensitive material, which is based on TiO2 nanoparticles. The laser ablation process was carefully optimized to obtain micro-scale and well-resolved electrodes on PET substrate. A functional paste based on cellulose was prepared in order to allow the precise screen-printing of the TiO2 nanoparticles as sensing material on the top of the electrodes. The current against voltage (I–V) characteristic of the sensor showed good linearity and potential for low-power operation. The results of a humidity-sensing investigation and mechanical testing showed that the fabricated miniaturized sensors have excellent mechanical stability, sensing characteristics, good repeatability, and relatively fast response/recovery times operating at room temperature. PMID:28800063

Phytochemical screening and toxicity studies on the methanol extract of the seeds of moringa oleifera.

PubMed

Ajibade, Temitayo Olabisi; Arowolo, Ruben; Olayemi, Funsho Olakitike

2013-05-07

The seeds of Moringa oleifera were collected, air-dried, pulverized, and subjected to cold extraction with methanol. The methanol extract was screened phytochemically for its chemical components and used for acute and sub-acute toxicity studies in rats. The phytochemical screening revealed the presence of saponins, tannins, terpenes, alkaloids, flavonoids, carbohydrates, and cardiac glycosides but the absence of anthraquinones. Although signs of acute toxicity were observed at a dose of 4,000 mg kg-1 in the acute toxicity test, and mortality was recorded at 5,000 mg kg-1, no adverse effect was observed at concentrations lower than 3,000 mg kg-1. The median lethal dose of the extract in rat was 3,873 mg kg-1. Sub-acute administration of the seed extract caused significant (p<0.05) increase in the levels of alanine and aspartate transferases (ALT and AST), and significant (p<0.05) decrease in weight of experimental rats, at 1,600 mg kg-1. The study concludes that the extract of seeds of M. oleifera is safe both for medicinal and nutritional uses.

NANOSTRUCTURED POROUS SILICON AND LUMINESCENT POLYSILOLES AS CHEMICAL SENSORS FOR CARCINOGENIC CHROMIUM(VI) AND ARSENIC(V)

EPA Science Inventory

The chief goal is to develop new selective solid state sensors for carcinogenic and toxic chromium(VI) and arsenic(V) in water based on redox quenching of the luminescence from nanostructured porous silicon and polysiloles.

Functional Genomic Screening Approaches in Mechanistic Toxicology and Potential Future Applications of CRISPR-Cas9

PubMed Central

Shen, Hua; McHale, Cliona M.; Smith, Martyn T; Zhang, Luoping

2015-01-01

Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. Chemical toxicants act by many different mechanisms, however, and the genes involved in adverse outcome pathways (AOPs) and AOP networks are not yet characterized. Functional genomic approaches can reveal both toxicity pathways and susceptibility genes, through knockdown or knockout of all non-essential genes in a cell of interest, and identification of genes associated with a toxicity phenotype following toxicant exposure. Screening approaches in yeast and human near-haploid leukemic KBM7 cells, have identified roles for genes and pathways involved in response to many toxicants but are limited by partial homology among yeast and human genes and limited relevance to normal diploid cells. RNA interference (RNAi) suppresses mRNA expression level but is limited by off-target effects (OTEs) and incomplete knockdown. The recently developed gene editing approach called clustered regularly interspaced short palindrome repeats-associated nuclease (CRISPR)-Cas9, can precisely knock-out most regions of the genome at the DNA level with fewer OTEs than RNAi, in multiple human cell types, thus overcoming the limitations of the other approaches. It has been used to identify genes involved in the response to chemical and microbial toxicants in several human cell types and could readily be extended to the systematic screening of large numbers of environmental chemicals. CRISPR-Cas9 can also repress and activate gene expression, including that of non-coding RNA, with near-saturation, thus offering the potential to more fully characterize AOPs and AOP networks. Finally, CRISPR-Cas9 can generate complex animal models in which to conduct preclinical toxicity testing at the level of individual genotypes or haplotypes. Therefore, CRISPR-Cas9 is a powerful and flexible functional genomic screening approach that can be harnessed to provide unprecedented mechanistic insight in the field of modern toxicology. PMID:26041264

Validation of Screening Assays for Developmental Toxicity: An Exposure-Based Approach

EPA Science Inventory

There continue to be widespread efforts to develop assay methods for developmental toxicity that are shorter than the traditional Segment 2 study and use fewer or no animals. As with any alternative test method, novel developmental toxicity assays must be validated by evaluating ...

A comparison of relative toxicity rankings by some small-scale laboratory tests

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Cumming, H. J.

1977-01-01

Small-scale laboratory tests for fire toxicity, suitable for use in the average laboratory hood, are needed for screening and ranking materials on the basis of relative toxicity. The performance of wool, cotton, and aromatic polyamide under several test procedures is presented.

Disposable screen-printed sensors for determination of duloxetine hydrochloride

PubMed Central

2012-01-01

A screen-printed disposable electrode system for the determination of duloxetine hydrochloride (DL) was developed using screen-printing technology. Homemade printing has been characterized and optimized on the basis of effects of the modifier and plasticizers. The fabricated bi-electrode potentiometric strip containing both working and reference electrodes was used as duloxetine hydrochloride sensor. The proposed sensors worked satisfactorily in the concentration range from 1.0 × 10-6-1.0 × 10-2 mol L-1 with detection limit reaching 5.0 × 10-7 mol L-1 and adequate shelf life of 6 months. The method is accurate, precise and economical. The proposed method has been applied successfully for the analysis of the drug in pure and in its dosage forms. In this method, there is no interference from any common pharmaceutical additives and diluents. Results of the analysis were validated statistically by recovery studies. PMID:22264225

Zeolite-based Impedimetric Gas Sensor Device in Low-cost Technology for Hydrocarbon Gas Detection

PubMed Central

Reiß, Sebastian; Hagen, Gunter; Moos, Ralf

2008-01-01

Due to increasing environmental concerns the need for inexpensive selective gas sensors is increasing. This work deals with transferring a novel zeolite-based impedimetric hydrocarbon gas sensor principle, which has been originally manufactured in a costly combination of photolithography, thin-film processes, and thick-film processes to a low-cost technology comprising only thick-film processes and one electroplating step. The sensing effect is based on a thin chromium oxide layer between the interdigital electrodes and a Pt-loaded ZSM-5 zeolite film. When hydrocarbons are present in the sensor ambient, the electrical sensor impedance increases strongly and selectively. In the present work, the chromium oxide film is electroplated on Au screen-printed interdigital electrodes and then oxidized to Cr2O3. The electrode area is covered with the screen-printed zeolite. The sensor device is self-heated utilizing a planar platinum heater on the backside. The best sensor performance is obtained at a frequency of 3 Hz at around 350 °C. The good selectivity of the original sensor setup could be confirmed, but a strong cross-sensitivity to ammonia occurs, which might prohibit its original intention for use in automotive exhausts. PMID:27873966

Product-induced gene expression, a product-responsive reporter assay used to screen metagenomic libraries for enzyme-encoding genes.

PubMed

Uchiyama, Taku; Miyazaki, Kentaro

2010-11-01

A reporter assay-based screening method for enzymes, which we named product-induced gene expression (PIGEX), was developed and used to screen a metagenomic library for amidases. A benzoate-responsive transcriptional activator, BenR, was placed upstream of the gene encoding green fluorescent protein and used as a sensor. Escherichia coli sensor cells carrying the benR-gfp gene cassette fluoresced in response to benzoate concentrations as low as 10 μM but were completely unresponsive to the substrate benzamide. An E. coli metagenomic library consisting of 96,000 clones was grown in 96-well format in LB medium containing benzamide. The library cells were then cocultivated with sensor cells. Eleven amidase genes were recovered from 143 fluorescent wells; eight of these genes were homologous to known bacterial amidase genes while three were novel genes. In addition to their activity toward benzamide, the enzymes were active toward various substrates, including d- and l-amino acid amides, and displayed enantioselectivity. Thus, we demonstrated that PIGEX is an effective approach for screening novel enzymes based on product detection.

Using pre-screening methods for an effective and reliable site characterization at megasites.

PubMed

Algreen, Mette; Kalisz, Mariusz; Stalder, Marcel; Martac, Eugeniu; Krupanek, Janusz; Trapp, Stefan; Bartke, Stephan

2015-10-01

This paper illustrates the usefulness of pre-screening methods for an effective characterization of polluted sites. We applied a sequence of site characterization methods to a former Soviet military airbase with likely fuel and benzene, toluene, ethylbenzene, and xylene (BTEX) contamination in shallow groundwater and subsoil. The methods were (i) phytoscreening with tree cores; (ii) soil gas measurements for CH4, O2, and photoionization detector (PID); (iii) direct-push with membrane interface probe (MIP) and laser-induced fluorescence (LIF) sensors; (iv) direct-push sampling; and (v) sampling from soil and from groundwater monitoring wells. Phytoscreening and soil gas measurements are rapid and inexpensive pre-screening methods. Both indicated subsurface pollution and hot spots successfully. The direct-push sensors yielded 3D information about the extension and the volume of the subsurface plume. This study also expanded the applicability of tree coring to BTEX compounds and tested the use of high-resolution direct-push sensors for light hydrocarbons. Comparison of screening results to results from conventional soil and groundwater sampling yielded in most cases high rank correlation and confirmed the findings. The large-scale application of non- or low-invasive pre-screening can be of help in directing and focusing the subsequent, more expensive investigation methods. The rapid pre-screening methods also yielded useful information about potential remediation methods. Overall, we see several benefits of a stepwise screening and site characterization scheme, which we propose in conclusion.

Interspecies quantitative structure-activity relationships (QSARs) for eco-toxicity screening of chemicals: the role of physicochemical properties.

PubMed

Furuhama, A; Hasunuma, K; Aoki, Y

2015-01-01

In addition to molecular structure profiles, descriptors based on physicochemical properties are useful for explaining the eco-toxicities of chemicals. In a previous study we reported that a criterion based on the difference between the partition coefficient (log POW) and distribution coefficient (log D) values of chemicals enabled us to identify aromatic amines and phenols for which interspecies relationships with strong correlations could be developed for fish-daphnid and algal-daphnid toxicities. The chemicals that met the log D-based criterion were expected to have similar toxicity mechanisms (related to membrane penetration). Here, we investigated the applicability of log D-based criteria to the eco-toxicity of other kinds of chemicals, including aliphatic compounds. At pH 10, use of a log POW - log D > 0 criterion and omission of outliers resulted in the selection of more than 100 chemicals whose acute fish toxicities or algal growth inhibition toxicities were almost equal to their acute daphnid toxicities. The advantage of log D-based criteria is that they allow for simple, rapid screening and prioritizing of chemicals. However, inorganic molecules and chemicals containing certain structural elements cannot be evaluated, because calculated log D values are unavailable.

A Simple Metallothionein-Based Biosensor for Enhanced Detection of Arsenic and Mercury

PubMed Central

Irvine, Gordon W.; Tan, Swee Ngin; Stillman, Martin J.

2017-01-01

Metallothioneins (MTs) are a family of cysteine-rich proteins whose biological roles include the regulation of essential metal ions and protection against the harmful effects of toxic metals. Due to its high affinity for many toxic, soft metals, recombinant human MT isoform 1a was incorporated into an electrochemical-based biosensor for the detection of As3+ and Hg2+. A simple design was chosen to maximize its potential in environmental monitoring and MT was physically adsorbed onto paper discs placed on screen-printed carbon electrodes (SPCEs). This system was tested with concentrations of arsenic and mercury typical of contaminated water sources ranging from 5 to 1000 ppb. The analytical performance of the MT-adsorbed paper discs on SPCEs demonstrated a greater than three-fold signal enhancement and a lower detection limit compared to blank SPCEs, 13 ppb for As3+ and 45 ppb for Hg2+. While not being as low as some of the recommended drinking water limits, the sensitivity of the simple MT-biosensor would be potentially useful in monitoring of areas of concern with a known contamination problem. This paper describes the ability of the metal binding protein metallothionein to enhance the effectiveness of a simple, low-cost electrochemical sensor. PMID:28335390

Effects of Langmuir-Blodgett-film gas sensors with integrated optical interferometers

NASA Astrophysics Data System (ADS)

Fushen, Chen; Yunqi, Liu; Yu, Xu; Qu, Liang

1996-10-01

Novel Langmuir-Blodgett-film toxic-gas sensors that have a Ti:LiNbO 3 integrated optical Mach-Zehnder interferometer structure are experimentally investigated. The gas-sensing properties of the sensors are obtained for NO 2, Cl2, NH3, and H2S by means of the detection of optical output changes. All the optical connections are made with optical fiber pigtails.

Recent Developments in Toxico-Cheminformatics; Supporting ...

EPA Pesticide Factsheets

EPA's National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction through the harnessing of legacy toxicity data, creation of data linkages, and generation of new high-content and high-thoughput screening data. In association with EPA's ToxCast, ToxRefDB, and ACToR projects, the DSSTox project provides cheminformatics support and, in addition, is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than traditionally employed in SAR modeling, and in ways that facilitate data-mining and data read-across. The latest DSSTox version of the Carcinogenic Potency Database file (CPDBAS) illustrates ways in which various summary definitions of carcinogenic activity can be employed in modeling and data mining. DSSTox Structure-Browser provides structure searchability across all published DSSTox toxicity-related inventory, and is enabling linkages between previously isolated toxicity data resources associated with environmental and industrial chemicals. The public DSSTox inventory also has been integrated into PubChem, allowing a user to take full advantage of PubChem structure-activity and bioassay clustering features. Phase I of the ToxCast project is generating high-throughput screening data from several hundred biochemical and cell-based assays for a set of 320 chemicals, mostly pesticide actives with rich toxicology profiles. Incorporating

Numerical evaluation of moiré pattern in touch sensor module with electrode mesh structure in oblique view

NASA Astrophysics Data System (ADS)

Pournoury, M.; Zamiri, A.; Kim, T. Y.; Yurlov, V.; Oh, K.

2016-03-01

Capacitive touch sensor screen with the metal materials has recently become qualified for substitution of ITO; however several obstacles still have to be solved. One of the most important issues is moiré phenomenon. The visibility problem of the metal-mesh, in touch sensor module (TSM) is numerically considered in this paper. Based on human eye contract sensitivity function (CSF), moiré pattern of TSM electrode mesh structure is simulated with MATLAB software for 8 inch screen display in oblique view. Standard deviation of the generated moiré by the superposition of electrode mesh and screen image is calculated to find the optimal parameters which provide the minimum moiré visibility. To create the screen pixel array and mesh electrode, rectangular function is used. The filtered image, in frequency domain, is obtained by multiplication of Fourier transform of the finite mesh pattern (product of screen pixel and mesh electrode) with the calculated CSF function for three different observer distances (L=200, 300 and 400 mm). It is observed that the discrepancy between analytical and numerical results is less than 0.6% for 400 mm viewer distance. Moreover, in the case of oblique view due to considering the thickness of the finite film between mesh electrodes and screen, different points of minimum standard deviation of moiré pattern are predicted compared to normal view.

Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data

EPA Science Inventory

EPA's ToxCast™ project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database wou...

A Call for Nominations of Quantitative High-Throughput Screening Assays from Relevant Human Toxicity Pathways

EPA Science Inventory

The National Research Council of the United States National Academies of Science has recently released a document outlining a long-range vision and strategy for transforming toxicity testing from largely whole animal-based testing to one based on in vitro assays. “Toxicity Testin...

Toxicity of selected insecticides applied to western spruce budworm

Treesearch

Jacqueline E. Robertson; Nancy L. Gillette; Barbara A. Lucas; Robert L. Lyon

1976-01-01

The contact toxlaty of 100 insecticides to last stage larvae of Choristoneura occidentalis Freeman was tested by topical application in a 10-yr series of screening experiments. Pyrethroids were generally the most toxic group of chemicals tested. Compounds more toxic than the standard, mexacarbate, at LD90 were:...

EPAs ToxCast Program for Predicting Toxcity and Prioritizing Chemicals for Further Screening and Testing

EPA Science Inventory

Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challengin...

Integrated display scanner

DOEpatents

Veligdan, James T.

2004-12-21

A display scanner includes an optical panel having a plurality of stacked optical waveguides. The waveguides define an inlet face at one end and a screen at an opposite end, with each waveguide having a core laminated between cladding. A projector projects a scan beam of light into the panel inlet face for transmission from the screen as a scan line to scan a barcode. A light sensor at the inlet face detects a return beam reflected from the barcode into the screen. A decoder decodes the return beam detected by the sensor for reading the barcode. In an exemplary embodiment, the optical panel also displays a visual image thereon.

Detection of Antibiotics and Evaluation of Antibacterial Activity with Screen-Printed Electrodes

PubMed Central

Titoiu, Ana Maria; Marty, Jean-Louis

2018-01-01

This review provides a brief overview of the fabrication and properties of screen-printed electrodes and details the different opportunities to apply them for the detection of antibiotics, detection of bacteria and antibiotic susceptibility. Among the alternative approaches to costly chromatographic or ELISA methods for antibiotics detection and to lengthy culture methods for bacteria detection, electrochemical biosensors based on screen-printed electrodes present some distinctive advantages. Chemical and (bio)sensors for the detection of antibiotics and assays coupling detection with screen-printed electrodes with immunomagnetic separation are described. With regards to detection of bacteria, the emphasis is placed on applications targeting viable bacterial cells. While the electrochemical sensors and biosensors face many challenges before replacing standard analysis methods, the potential of screen-printed electrodes is increasingly exploited and more applications are anticipated to advance towards commercial analytical tools. PMID:29562637

Fluid dynamic design and experimental study of an aspirated temperature measurement platform used in climate observation.

PubMed

Yang, Jie; Liu, Qingquan; Dai, Wei; Ding, Renhui

2016-08-01

Due to the solar radiation effect, current air temperature sensors inside a thermometer screen or radiation shield may produce measurement errors that are 0.8 °C or higher. To improve the observation accuracy, an aspirated temperature measurement platform is designed. A computational fluid dynamics (CFD) method is implemented to analyze and calculate the radiation error of the aspirated temperature measurement platform under various environmental conditions. Then, a radiation error correction equation is obtained by fitting the CFD results using a genetic algorithm (GA) method. In order to verify the performance of the temperature sensor, the aspirated temperature measurement platform, temperature sensors with a naturally ventilated radiation shield, and a thermometer screen are characterized in the same environment to conduct the intercomparison. The average radiation errors of the sensors in the naturally ventilated radiation shield and the thermometer screen are 0.44 °C and 0.25 °C, respectively. In contrast, the radiation error of the aspirated temperature measurement platform is as low as 0.05 °C. This aspirated temperature sensor allows the radiation error to be reduced by approximately 88.6% compared to the naturally ventilated radiation shield, and allows the error to be reduced by a percentage of approximately 80% compared to the thermometer screen. The mean absolute error and root mean square error between the correction equation and experimental results are 0.032 °C and 0.036 °C, respectively, which demonstrates the accuracy of the CFD and GA methods proposed in this research.

Fluid dynamic design and experimental study of an aspirated temperature measurement platform used in climate observation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Jie, E-mail: yangjie396768@163.com; School of Atmospheric Physics, Nanjing University of Information Science and Technology, Nanjing 210044; Liu, Qingquan

Due to the solar radiation effect, current air temperature sensors inside a thermometer screen or radiation shield may produce measurement errors that are 0.8 °C or higher. To improve the observation accuracy, an aspirated temperature measurement platform is designed. A computational fluid dynamics (CFD) method is implemented to analyze and calculate the radiation error of the aspirated temperature measurement platform under various environmental conditions. Then, a radiation error correction equation is obtained by fitting the CFD results using a genetic algorithm (GA) method. In order to verify the performance of the temperature sensor, the aspirated temperature measurement platform, temperature sensors withmore » a naturally ventilated radiation shield, and a thermometer screen are characterized in the same environment to conduct the intercomparison. The average radiation errors of the sensors in the naturally ventilated radiation shield and the thermometer screen are 0.44 °C and 0.25 °C, respectively. In contrast, the radiation error of the aspirated temperature measurement platform is as low as 0.05 °C. This aspirated temperature sensor allows the radiation error to be reduced by approximately 88.6% compared to the naturally ventilated radiation shield, and allows the error to be reduced by a percentage of approximately 80% compared to the thermometer screen. The mean absolute error and root mean square error between the correction equation and experimental results are 0.032 °C and 0.036 °C, respectively, which demonstrates the accuracy of the CFD and GA methods proposed in this research.« less

Pesticide Toxicity Index: a tool for assessing potential toxicity of pesticide mixtures to freshwater aquatic organisms

USGS Publications Warehouse

Nowell, Lisa H.; Norman, Julia E.; Moran, Patrick W.; Martin, Jeffrey D.; Stone, Wesley W.

2014-01-01

Pesticide mixtures are common in streams with agricultural or urban influence in the watershed. The Pesticide Toxicity Index (PTI) is a screening tool to assess potential aquatic toxicity of complex pesticide mixtures by combining measures of pesticide exposure and acute toxicity in an additive toxic-unit model. The PTI is determined separately for fish, cladocerans, and benthic invertebrates. This study expands the number of pesticides and degradates included in previous editions of the PTI from 124 to 492 pesticides and degradates, and includes two types of PTI for use in different applications, depending on study objectives. The Median-PTI was calculated from median toxicity values for individual pesticides, so is robust to outliers and is appropriate for comparing relative potential toxicity among samples, sites, or pesticides. The Sensitive-PTI uses the 5th percentile of available toxicity values, so is a more sensitive screening-level indicator of potential toxicity. PTI predictions of toxicity in environmental samples were tested using data aggregated from published field studies that measured pesticide concentrations and toxicity to Ceriodaphnia dubia in ambient stream water. C. dubia survival was reduced to ≤ 50% of controls in 44% of samples with Median-PTI values of 0.1–1, and to 0% in 96% of samples with Median-PTI values > 1. The PTI is a relative, but quantitative, indicator of potential toxicity that can be used to evaluate relationships between pesticide exposure and biological condition.

Reduced graphene oxide-ZnO composites based gas sensors: A review

NASA Astrophysics Data System (ADS)

Thakare, N. B.; Raghuwanshi, F. C.; Kalyamwar, V. S.; Tamgadge, Y. S.

2018-05-01

The need to monitor and control life threatening gases has led to research and development of a wide variety of sensors using different materials and technologies. Recently rGO (reduced graphene oxide)-MOS (Metal Oxide Semiconductor) architectures have been studied for efficient and cost effective gas sensors that will operate at low temperature. In this review paper, we review latest findings and progress in rGO-ZnO composites as sensors to detect volatile and toxic gases.

An evaluation of inorganic toxicity reference values for use in assessing hazards to American robins (Turdus migratorius)

USGS Publications Warehouse

Beyer, W. Nelson; Sample, Bradley E.

2017-01-01

When performing screening-level and baseline risk assessments, assessors usually compare estimated exposures of wildlife receptor species with toxicity reference values (TRVs). We modeled the exposure of American robins (Turdus migratorius) to 10 elements (As, Cd, Cr, Cu, Hg, Mn, Pb, Se, Zn, and V) in spring and early summer, a time when earthworms are the preferred prey. We calculated soil benchmarks associated with possible toxic effects to these robins from 6 sets of published TRVs. Several of the resulting soil screening-level benchmarks were inconsistent with each other and less than soil background concentrations. Accordingly, we examined the derivations of the TRVs as a possible source of error. In the case of V, a particularly toxic chemical compound (ammonium vanadate) containing V, not normally present in soil, had been used to estimate a TRV. In the cases of Zn and Cu, use of uncertainty values of 10 in estimating TRVs led to implausibly low soil screening values. In the case of Pb, a TRV was calculated from studies demonstrating reductions in egg production in Japanese quail (Coturnix coturnix japonica) exposed to Pb concentrations well below than those causing toxic effects in other species of birds. The results on quail, which were replicated in additional trials, are probably not applicable to other, unrelated species, although we acknowledge that only a small fraction of all species of birds has been tested. These examples underscore the importance of understanding the derivation and relevance of TRVs before selecting them for use in screening or in ecological risk assessment.

RFC 18001 – Regional Screening Level Tables – Anthraquinone

EPA Pesticide Factsheets

9,10-Anthraquinone (CASRN 84-65-1) in Provisional Peer-Reviewed Toxicity Values, EPA/690/R-11/007F, Final 2-17-2011, and EPA Regional Screening Level (RSL) Tables at: https://www.epa.gov/risk/regional-screening-levels-rsls-generic-tables-november-2017

Evaluation of the Occupational Risks from Jet Fuel (Toxicity Screening Battery)

DTIC Science & Technology

2012-09-01

1α may serve as a marker of epidermal damage or stress due to irritation in this in vitro model. As an alternative to the 3-dimensional human skin...AFRL-RH-FS-SR-2013-0003 Final Report: Evaluation of the Occupational Risks from Jet Fuel (Toxicity Screening Battery) David R. Mattie...2. REPORT TYPE Special Report 3. DATES COVERED (From - To) Oct 2010 – Dec 2011 4. TITLE AND SUBTITLE Evaluation of the Occupational Risks from

In vivo analgesic activity, toxicity and phytochemical screening of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine.

PubMed

Alvarenga, Felipe Queiroz; Mota, Bárbara C F; Leite, Marcel N; Fonseca, Jaciara M S; Oliveira, Dario A; Royo, Vanessa de Andrade; e Silva, Márcio L A; Esperandim, Viviane; Borges, Alexandre; Laurentiz, Rosangela S

2013-10-28

Psidium cattleianum Sabine is extensively used in Brazilian traditional medicine to treat several diseases including painful disorders. Aim of the study to investigate the toxicity and the possible analgesic activities of the hydroalcoholic extract from the leaves of Psidium cattleianum Sabine (ELPCS), to support its use in folk medicine. To screen the major phytochemical constituents of this extract and evaluate their antioxidant activity. ELPCS was assessed for its antioxidant activity using the DPPH model. Its analgesic activity was examined using mouse models of acetic acid-induced writhing and hot plate paw licking models. The major phytochemical constituents of the extract were screened; their toxicity on LLC-MK2 mammalian cells was evaluated. ELPCS exhibited significant peripheral analgesic activity at doses of 60, 80, 100, 200 and 400mg/kg in mice, but it did not display central analgesic activity and not was toxic to LLC-MK2 cell (LD50>400 µg/mL). The extract exhibited free radical scavenging activity as evidenced by IC50 values (15.9 µg/mL) obtained by the DPPH method. Phytochemical screening detected flavonoids, saponins, cardiac glycosides, anthraquinones, and tannins. The results of the experimental studies proved the analgesic activity of ELPCS and supported the traditional use of this plant. © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluating Zeolite-Modified Sensors: towards a faster set of chemical sensors

NASA Astrophysics Data System (ADS)

Berna, A. Z.; Vergara, A.; Trincavelli, M.; Huerta, R.; Afonja, A.; Parkin, I. P.; Binions, R.; Trowell, S.

2011-09-01

The responses of zeolite-modified sensors, prepared by screen printing layers of chromium titanium oxide (CTO), were compared to unmodified tin oxide sensors using amplitude and transient responses. For transient responses we used a family of features, derived from the exponential moving average (EMA), to characterize chemo-resistive responses. All sensors were tested simultaneously against 20 individual volatile compounds from four chemical groups. The responses of the two types of sensors showed some independence. The zeolite-modified CTO sensors discriminated compounds better using either amplitude response or EMA features and CTO-modified sensors also responded three times faster.

Environmental Toxin Screening Using Human-Derived 3D Bioengineered Liver and Cardiac Organoids.

PubMed

Forsythe, Steven D; Devarasetty, Mahesh; Shupe, Thomas; Bishop, Colin; Atala, Anthony; Soker, Shay; Skardal, Aleksander

2018-01-01

Environmental toxins, such as lead and other heavy metals, pesticides, and other compounds, represent a significant health concern within the USA and around the world. Even in the twenty-first century, a plethora of cities and towns in the U.S. have suffered from exposures to lead in drinking water or other heavy metals in food or the earth, while there is a high possibility of further places to suffer such exposures in the near future. We employed bioengineered 3D human liver and cardiac organoids to screen a panel of environmental toxins (lead, mercury, thallium, and glyphosate), and charted the response of the organoids to these compounds. Liver and cardiac organoids were exposed to lead (10 µM-10 mM), mercury (200 nM-200 µM), thallium (10 nM-10 µM), or glyphosate (25 µM-25 mM) for a duration of 48 h. The impacts of toxin exposure were then assessed by LIVE/DEAD viability and cytotoxicity staining, measuring ATP activity and determining IC50 values, and determining changes in cardiac organoid beating activity. As expected, all of the toxins induced toxicity in the organoids. Both ATP and LIVE/DEAD assays showed toxicity in both liver and cardiac organoids. In particular, thallium was the most toxic, with IC50 values of 13.5 and 1.35 µM in liver and cardiac organoids, respectively. Conversely, glyphosate was the least toxic of the four compounds, with IC50 values of 10.53 and 10.85 mM in liver and cardiac organoids, respectively. Additionally, toxins had a negative influence on cardiac organoid beating activity as well. Thallium resulting in the most significant decreases in beating rate, followed by mercury, then glyphosate, and finally, lead. These results suggest that the 3D organoids have significant utility to be deployed in additional toxicity screening applications, and future development of treatments to mitigate exposures. 3D organoids have significant utility to be deployed in additional toxicity screening applications, such as future development of treatments to mitigate exposures, drug screening, and environmental toxin detection.

NEW PUBLIC DATA AND INTERNET RESOURCES ...

EPA Pesticide Factsheets

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve predictive capabilities in toxicology. Internet Resource

DEVELOPMENT OF EPA'S TOXCAST PROGRAM FOR PRIORITIZING THE TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS.

EPA Science Inventory

EPA is developing methods for utilizing computational chemistry, high-throughput screening (HTS)and genomic technologies to predict potential toxicity and prioritize the use of limited testing resources.

WILDLIFE TOXICITY REFERENCE VALUES FOR POLYNUCLEAR AROMATIC HYDROCARBONS AND DDT

EPA Science Inventory

The presentation will provide an overview of the procedures used in deriving mammalian and avian wildlife toxicity reference values to be used in development of ecological soil screening levels (Eco-SSLs).

Compound toxicity screening and structure-activity relationship modeling in Escherichia coli.

PubMed

Planson, Anne-Gaëlle; Carbonell, Pablo; Paillard, Elodie; Pollet, Nicolas; Faulon, Jean-Loup

2012-03-01

Synthetic biology and metabolic engineering are used to develop new strategies for producing valuable compounds ranging from therapeutics to biofuels in engineered microorganisms. When developing methods for high-titer production cells, toxicity is an important element to consider. Indeed the production rate can be limited due to toxic intermediates or accumulation of byproducts of the heterologous biosynthetic pathway of interest. Conversely, highly toxic molecules are desired when designing antimicrobials. Compound toxicity in bacteria plays a major role in metabolic engineering as well as in the development of new antibacterial agents. Here, we screened a diversified chemical library of 166 compounds for toxicity in Escherichia coli. The dataset was built using a clustering algorithm maximizing the chemical diversity in the library. The resulting assay data was used to develop a toxicity predictor that we used to assess the toxicity of metabolites throughout the metabolome. This new tool for predicting toxicity can thus be used for fine-tuning heterologous expression and can be integrated in a computational-framework for metabolic pathway design. Many structure-activity relationship tools have been developed for toxicology studies in eukaryotes [Valerio (2009), Toxicol Appl Pharmacol, 241(3): 356-370], however, to the best of our knowledge we present here the first E. coli toxicity prediction web server based on QSAR models (EcoliTox server: http://www.issb.genopole.fr/∼faulon/EcoliTox.php). Copyright © 2011 Wiley Periodicals, Inc.

Using in vivo oxidation status of one- and two-component redox relays to determine H2O2 levels linked to signaling and toxicity.

PubMed

Domènech, Alba; Ayté, José; Antunes, Fernando; Hidalgo, Elena

2018-06-01

Hydrogen peroxide (H 2 O 2 ) is generated as a by-product of metabolic reactions during oxygen use by aerobic organisms, and can be toxic or participate in signaling processes. Cells, therefore, need to be able to sense and respond to H 2 O 2 in an appropriate manner. This is often accomplished through thiol switches: Cysteine residues in proteins that can act as sensors, and which are both scarce and finely tuned. Bacteria and eukaryotes use different types of such sensors-either a one-component (OxyR) or two-component (Pap1-Tpx1) redox relay, respectively. However, the biological significance of these two different signaling modes is not fully understood, and the concentrations and peroxides driving those types of redox cascades have not been determined, nor the intracellular H 2 O 2 levels linked to toxicity. Here we elucidate the characteristics, rates, and dynamic ranges of both systems. By comparing the activation of both systems in fission yeast, and applying mathematical equations to the experimental data, we estimate the toxic threshold of intracellular H 2 O 2 able to halt aerobic growth, and the temporal gradients of extracellular to intracellular peroxides. By calculating both the oxidation rates of OxyR and Tpx1 by peroxides, and their reduction rates by the cellular redoxin systems, we propose that, while Tpx1 is a sensor and an efficient H 2 O 2 scavenger because it displays fast oxidation and reduction rates, OxyR is strictly a H 2 O 2 sensor, since its reduction kinetics are significantly slower than its oxidation by peroxides, and therefore, it remains oxidized long enough to execute its transcriptional role. We also show that these two paradigmatic H 2 O 2 -sensing models are biologically similar at pre-toxic peroxide levels, but display strikingly different activation behaviors at toxic doses. Both Tpx1 and OxyR contain thiol switches, with very high reactivity towards peroxides. Nevertheless, the fast reduction of Tpx1 defines it as a scavenger, and this efficient recycling dramatically changes the Tpx1-Pap1 response to H 2 O 2 and connects H 2 O 2 sensing to the redox state of the cell. In contrast, OxyR is a true H 2 O 2 sensor but not a scavenger, being partially insulated from the cellular electron donor capacity.

Piezoresistive cantilever array sensor for consolidated bioprocess monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Seonghwan Sam; Rahman, Touhidur; Senesac, Larry R

2009-01-01

Cellulolytic microbes occur in diverse natural niches and are being screened for industrial modification and utility. A microbe for Consolidated bioprocessing (CBP) development can rapidly degrade pure cellulose and then ferment the resulting sugars into fuels. To identify and screen for novel microbes for CBP, we have developed a piezoresistive cantilever array sensor which is capable of simultaneous monitoring of glucose and ethanol concentration changes in a phosphate buffer solution. 4-mercaptophenylboronic acid (4-MPBA) and polyethyleneglycol (PEG)-thiol are employed to functionalize each piezoresistive cantilever for glucose and ethanol sensing, respectively. Successful concentration measurements of glucose and ethanol with minimal interferences aremore » obtained with our cantilever array sensor.« less

In vitro screening of 50 highly prescribed drugs for thiol adduct formation--comparison of potential for drug-induced toxicity and extent of adduct formation.

PubMed

Gan, Jinping; Ruan, Qian; He, Bing; Zhu, Mingshe; Shyu, Wen C; Humphreys, W Griffith

2009-04-01

Reactive metabolite formation has been associated with drug-induced liver, skin, and hematopoietic toxicity of many drugs that has resulted in serious clinical toxicity, leading to clinical development failure, black box warnings, or, in some cases, withdrawal from the market. In vitro and in vivo screening for reactive metabolite formation has been proposed and widely adopted in the pharmaceutical industry with the aim of minimizing the property and thus the risk of drug-induced toxicity (DIT). One of the most common screening methods is in vitro thiol trapping of reactive metabolites. Although it is well-documented that many hepatotoxins form thiol adducts, there is no literature describing the adduct formation potential of safer drugs that are widely used. The objective of this study was to quantitatively assess the thiol adduct formation potential of 50 drugs (10 associated with DIT and 40 not associated) and document apparent differences in adduct formation between toxic and safer drugs. Dansyl glutathione was used as a trapping agent to aid the quantitation of adducts following in vitro incubation of drugs with human liver microsomes in the presence and absence of NADPH. Metabolic turnover of these drugs was also monitored by LC/UV. Overall, 15 out of the 50 drugs screened formed detectable levels of thiol adducts. There were general trends toward more positive findings in the DIT group vs the non-DIT group. These trends became more marked when the relative amount of thiol adducts was taken into account and improved further when dose and total daily reactive metabolite burdens were considered. In conclusion, there appears to be a general trend between the extent of thiol adduct formation and the potential for DIT, which would support the preclinical measurement and minimization of the property through screening of thiol adduct formation as part of an overall discovery optimization paradigm.

Evaluation of a Microbial Sensor as a Tool for Antimicrobial Activity Test of Cosmetic Preservatives.

PubMed

Gomyo, Hideyuki; Ookawa, Masaki; Oshibuchi, Kota; Sugamura, Yuriko; Hosokawa, Masahito; Shionoiri, Nozomi; Maeda, Yoshiaki; Matsunaga, Tadashi; Tanaka, Tsuyoshi

2015-01-01

For high-throughput screening of novel cosmetic preservatives, a rapid and simple assay to evaluate the antimicrobial activities should be developed because the conventional agar dilution method is time-consuming and labor-intensive. To address this issue, we evaluated a microbial sensor as a tool for rapid antimicrobial activity testing. The sensor consists of an oxygen electrode and a filter membrane that holds the test microorganisms, Staphylococcus aureus and Candida albicans. The antimicrobial activity of the tested cosmetic preservative was evaluated by measuring the current increases corresponding to the decreases in oxygen consumption in the microbial respiration. The current increases detected by the sensor showed positive correlation to the concentrations of two commercially used preservatives, chlorphenesin and 2-phenoxyethanol. The same tendency was also observed when a model cosmetic product was used as a preservative solvent, indicating the feasibility in practical use. Furthermore, the microbial sensor and microfluidic flow-cell was assembled to achieve sequential measurements. The sensor system presented in this study could be useful in large-scale screening experiments.

Perceptions of environmental health risks among residents in the “Toxic Doughnut”: Opportunities for risk screening and community mobilization

EPA Science Inventory

Surrounded by landfills, and toxic and hazardous facilities, Altgeld Gardens is located in a “toxic doughnut.” With high rates of environmentally-related conditions, residents have called for a community-based environmental health assessment to improve overall health in their com...

Aquatic Toxicity Screening of Fire Fighting Agents

DTIC Science & Technology

2005-09-21

Aqueous Film Forming Foam ( AFFF ), the reference toxicant. The aquatic toxicity...Specification MIL-F-24385F Fire Extinguishing Agent, Aqueous Film Forming Foam ( AFFF ) Liquid Concentrate, For Fresh and Sea Water (MIL SPEC AFFF ). This...extinguish liquid hydrocarbon fuel fires involving aircraft operations. Several types of foam exist including protein, fluoroprotein and aqueous film

Cell-based approaches for screening and prioritization of chemicals that may cause developmental neurotoxicity

EPA Science Inventory

The National Academies report on Toxicity Testing in the 21st Century envisioned the use of in vitro toxicity tests using cells of human origin to predict the ability of chemicals to cause toxicity in vivo. Successful implementation of this strategy will ultimately result in fast...

Cytotoxicity screening of 23 engineered nanomaterials using a test matrix of ten cell lines and three different assays

PubMed Central

2011-01-01

Background Engineered nanomaterials display unique properties that may have impact on human health, and thus require a reliable evaluation of their potential toxicity. Here, we performed a standardized in vitro screening of 23 engineered nanomaterials. We thoroughly characterized the physicochemical properties of the nanomaterials and adapted three classical in vitro toxicity assays to eliminate nanomaterial interference. Nanomaterial toxicity was assessed in ten representative cell lines. Results Six nanomaterials induced oxidative cell stress while only a single nanomaterial reduced cellular metabolic activity and none of the particles affected cell viability. Results from heterogeneous and chemically identical particles suggested that surface chemistry, surface coating and chemical composition are likely determinants of nanomaterial toxicity. Individual cell lines differed significantly in their response, dependent on the particle type and the toxicity endpoint measured. Conclusion In vitro toxicity of the analyzed engineered nanomaterials cannot be attributed to a defined physicochemical property. Therefore, the accurate identification of nanomaterial cytotoxicity requires a matrix based on a set of sensitive cell lines and in vitro assays measuring different cytotoxicity endpoints. PMID:21345205

Optimized ratiometric calcium sensors for functional in vivo imaging of neurons and T lymphocytes.

PubMed

Thestrup, Thomas; Litzlbauer, Julia; Bartholomäus, Ingo; Mues, Marsilius; Russo, Luigi; Dana, Hod; Kovalchuk, Yuri; Liang, Yajie; Kalamakis, Georgios; Laukat, Yvonne; Becker, Stefan; Witte, Gregor; Geiger, Anselm; Allen, Taylor; Rome, Lawrence C; Chen, Tsai-Wen; Kim, Douglas S; Garaschuk, Olga; Griesinger, Christian; Griesbeck, Oliver

2014-02-01

The quality of genetically encoded calcium indicators (GECIs) has improved dramatically in recent years, but high-performing ratiometric indicators are still rare. Here we describe a series of fluorescence resonance energy transfer (FRET)-based calcium biosensors with a reduced number of calcium binding sites per sensor. These 'Twitch' sensors are based on the C-terminal domain of Opsanus troponin C. Their FRET responses were optimized by a large-scale functional screen in bacterial colonies, refined by a secondary screen in rat hippocampal neuron cultures. We tested the in vivo performance of the most sensitive variants in the brain and lymph nodes of mice. The sensitivity of the Twitch sensors matched that of synthetic calcium dyes and allowed visualization of tonic action potential firing in neurons and high resolution functional tracking of T lymphocytes. Given their ratiometric readout, their brightness, large dynamic range and linear response properties, Twitch sensors represent versatile tools for neuroscience and immunology.

Making Waves: New Developments in Toxicology With the Zebrafish.

PubMed

Horzmann, Katharine A; Freeman, Jennifer L

2018-05-01

The laboratory zebrafish (Danio rerio) is now an accepted model in toxicologic research. The zebrafish model fills a niche between in vitro models and mammalian biomedical models. The developmental characteristics of the small fish are strategically being used by scientists to study topics ranging from high-throughput toxicity screens to toxicity in multi- and transgenerational studies. High-throughput technology has increased the utility of zebrafish embryonic toxicity assays in screening of chemicals and drugs for toxicity or effect. Additionally, advances in behavioral characterization and experimental methodology allow for observation of recognizable phenotypic changes after xenobiotic exposure. Future directions in zebrafish research are predicted to take advantage of CRISPR-Cas9 genome editing methods in creating models of disease and interrogating mechanisms of action with fluorescent reporters or tagged proteins. Zebrafish can also model developmental origins of health and disease and multi- and transgenerational toxicity. The zebrafish has many advantages as a toxicologic model and new methodologies and areas of study continue to expand the usefulness and application of the zebrafish.

Statistical studies of animal response data from USF toxicity screening test method

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Machado, A. M.

1978-01-01

Statistical examination of animal response data obtained using Procedure B of the USF toxicity screening test method indicates that the data deviate only slightly from a normal or Gaussian distribution. This slight departure from normality is not expected to invalidate conclusions based on theoretical statistics. Comparison of times to staggering, convulsions, collapse, and death as endpoints shows that time to death appears to be the most reliable endpoint because it offers the lowest probability of missed observations and premature judgements.

Sensitive detection of chemical agents and toxic industrial chemicals using active open-path FTIRs

NASA Astrophysics Data System (ADS)

Walter, William T.

2004-03-01

Active open-path FTIR sensors provide more sensitive detection of chemical agents than passive FTIRs, such as the M21 RSCAAL and JSLSCAD, and at the same time identify and quantify toxic industrial chemicals (TIC). Passive FTIRs are bistatic sensors relying on infrared sources of opportunity. Utilization of earth-based sources of opportunity limits the source temperatures available for passive chemical-agent FTIR sensors to 300° K. Active FTIR chemical-agent sensors utilize silicon carbide sources, which can be operated at 1500° K. The higher source temperature provides more than an 80-times increase in the infrared radiant flux emitted per unit area in the 7 to 14 micron spectral fingerprint region. Minimum detection limits are better than 5 μgm/m3 for GA, GB, GD, GF and VX. Active FTIR sensors can (1) assist first responders and emergency response teams in their assessment of and reaction to a terrorist threat, (2) provide information on the identification of the TIC present and their concentrations and (3) contribute to the understanding and prevention of debilitating disorders analogous to the Gulf War Syndrome for military and civilian personnel.

Unbound bilirubin measurements by a novel probe in preterm infants.

PubMed

Hegyi, Thomas; Kleinfeld, Alan; Huber, Andrew; Weinberger, Barry; Memon, Naureen; Shih, Weichung; Carayannopoulos, Mary; Oh, William

2018-03-12

Hyperbilirubinemia occurs in over 80% of newborns and severe bilirubin toxicity can lead to neurological dysfunction and death, especially in preterm infants. Currently, the risk of bilirubin toxicity is assessed by measuring the levels of total serum bilirubin (TSB), which are used to direct treatments including immunoglobulin administration, phototherapy, and exchange transfusion. However, free, unbound bilirubin levels (Bf) predict the risk of bilirubin neurotoxicity more accurately than TSB. To examine Bf levels in preterm infants and determine the frequency with which they exceed reported neurotoxic thresholds. One hundred thirty preterm infants (BW 500-2000 g; GA 23-34 weeks) were enrolled and Bf levels measured during the first week of life by the fluorescent Bf sensor BL22P1B11-Rh. TSB and plasma albumin were measured by standard techniques. Bilirubin-albumin dissociation constants (K d ) were calculated based on Bf and plasma albumin. Five hundred eighty samples were measured during the first week of life, with an overall mean Bf of 13.6 ± 9.0 nM. A substantial number of measurements exceeded potential toxic thresholds levels as reported in the literature. The correlation between Bf and TSB was statistically significant (r 2 0.17), but this weak relationship was lost at high Bf levels. Infants <28-week gestations had more hearing screening failures than infants ≥28-week gestation. Unbound (free) bilirubin values are extremely variable during the first week of life in preterm infants. A significant proportion of these values exceeded reported neurotoxic thresholds.

20180312 - Evaluating the applicability of read-across tools and high throughput screening data for food relevant chemicals (SOT)

EPA Science Inventory

Alternative toxicity assessment methods to characterize the hazards of chemical substances have been proposed to reduce animal testing and screen thousands of chemicals in an efficient manner. Resources to accomplish these goals include utilizing large in vitro chemical screening...

DEVELOPMENT OF AN OBJECTIVE AND QUANTIFIABLE TERATOLOGICAL SCREEN FOR USE IN ZEBRAFISH LARVAE.

EPA Science Inventory

To address EPA’s need to prioritize large numbers of chemicals for testing, a rapid, cost-effective in vivo screen for potential developmental toxicity using an alternative vertebrate species (zebrafish;Danio rerio) has been developed. A component of that screen is the observatio...

Evaluating the Impact of Uncertainties in Clearance and Exposure When Prioritizing Chemicals Screened in High-Throughput Assays

EPA Science Inventory

The toxicity-testing paradigm has evolved to include high-throughput (HT) methods for addressing the increasing need to screen hundreds to thousands of chemicals rapidly. Approaches that involve in vitro screening assays, in silico predictions of exposure concentrations, and phar...

The Toxicity Estimation Software Tool (T.E.S.T.)

EPA Science Inventory

The Toxicity Estimation Software Tool (T.E.S.T.) has been developed to estimate toxicological values for aquatic and mammalian species considering acute and chronic endpoints for screening purposes within TSCA and REACH programs.

National Air Toxics Assessment

EPA Pesticide Factsheets

NATA is an ongoing comprehensive evaluation of air toxics in the U.S. As a screening tool, it helps air agencies prioritize pollutants, emission sources and locations of interest for further study to gain a better understanding of risks.

MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: I. SYSTEMIC TOXICITY

EPA Science Inventory

The toxicity of 10 chemicals (carbaryl, carbon tetrachloride, chlordane, ethylhexylphthalate, dichloromethane, heptachlor, phenol, tetrachloroethylene, triadimefon, and trichloroethylene were examined in the liver, kidney, spleen, thymus, and adrenal of female F-344 rats. cute le...

NEW PUBLIC DATA AND INTERNET RESOURCES IMPACTING PREDICTIVE TOXICOLOGY.

EPA Science Inventory

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve predictive capabilities in toxicology.

Soil criteria to protect terrestrial wildlife and open-range livestock from metal toxicity at mining sites.

PubMed

Ford, Karl L; Beyer, W Nelson

2014-03-01

Thousands of hard rock mines exist in the western USA and in other parts of the world as a result of historic and current gold, silver, lead, and mercury mining. Many of these sites in the USA are on public lands. Typical mine waste associated with these sites are tailings and waste rock dumps that may be used by wildlife and open-range livestock. This report provides wildlife screening criteria levels for metals in soil and mine waste to evaluate risk and to determine the need for site-specific risk assessment, remediation, or a change in management practices. The screening levels are calculated from toxicity reference values based on maximum tolerable levels of metals in feed, on soil and plant ingestion rates, and on soil to plant uptake factors for a variety of receptors. The metals chosen for this report are common toxic metals found at mining sites: arsenic, cadmium, copper, lead, mercury, and zinc. The resulting soil screening values are well above those developed by the US Environmental Protection Agency. The difference in values was mainly a result of using toxicity reference values that were more specific to the receptors addressed rather than the most sensitive receptor.

Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

PubMed

Singh, Pankaj Kumar; Negi, Arvind; Gupta, Pawan Kumar; Chauhan, Monika; Kumar, Raj

2016-08-01

Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

Soil criteria to protect terrestrial wildlife and open-range livestock from metal toxicity at mining sites

USGS Publications Warehouse

Ford, Karl L; Beyer, W. Nelson

2014-01-01

Thousands of hard rock mines exist in the western USA and in other parts of the world as a result of historic and current gold, silver, lead, and mercury mining. Many of these sites in the USA are on public lands. Typical mine waste associated with these sites are tailings and waste rock dumps that may be used by wildlife and open-range livestock. This report provides wildlife screening criteria levels for metals in soil and mine waste to evaluate risk and to determine the need for site-specific risk assessment, remediation, or a change in management practices. The screening levels are calculated from toxicity reference values based on maximum tolerable levels of metals in feed, on soil and plant ingestion rates, and on soil to plant uptake factors for a variety of receptors. The metals chosen for this report are common toxic metals found at mining sites: arsenic, cadmium, copper, lead, mercury, and zinc. The resulting soil screening values are well above those developed by the US Environmental Protection Agency. The difference in values was mainly a result of using toxicity reference values that were more specific to the receptors addressed rather than the most sensitive receptor.

Biosensor development.

PubMed

Ziegler, C; Göpel, W

1998-10-01

Current biosensor developments can be summarised by different trends. For traditional enzymatic biosensors such as glucose sensors, steady improvements of well known basic principles have been made in order to achieve better sensor stability. On the other hand, new affinity sensors such as nucleic acid sensors, transmembrane sensors, and sensors utilising whole cells or even cell networks have become of increasing interest. New ways to miniaturise biosensors and to control their interfaces down to the molecular level have been introduced (the bioelectronics approach). High-throughput screening based on various signal transduction principles has become of increasing importance.

Mixture toxicity of wood preservative products in the fish embryo toxicity test.

PubMed

Coors, Anja; Dobrick, Jan; Möder, Monika; Kehrer, Anja

2012-06-01

Wood preservative products are used globally to protect wood from fungal decay and insects. We investigated the aquatic toxicity of five commercial wood preservative products, the biocidal active substances and some formulation additives contained therein, as well as six generic binary mixtures of the active substances in the fish embryo toxicity test (FET). Median lethal concentrations (LC50) of the single substances, the mixtures, and the products were estimated from concentration-response curves and corrected for concentrations measured in the test medium. The comparison of the experimentally observed mixture toxicity with the toxicity predicted by the concept of concentration addition (CA) showed less than twofold deviation for all binary mixtures of the active substances and for three of the biocidal products. A more than 60-fold underestimation of the toxicity of the fourth product by the CA prediction was detected and could be explained fully by the toxicity of one formulation additive, which had been labeled as a hazardous substance. The reason for the 4.6-fold underestimation of toxicity of the fifth product could not be explained unambiguously. Overall, the FET was found to be a suitable screening tool to verify whether the toxicity of formulated wood preservatives can reliably be predicted by CA. Applied as a quick and simple nonanimal screening test, the FET may support approaches of applying component-based mixture toxicity predictions within the environmental risk assessment of biocidal products, which is required according to European regulations. Copyright © 2012 SETAC.

A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis

PubMed Central

Golanski, Jacek; Lukasiak, Magdalena; Redzynia, Malgorzata; Dastych, Jaroslaw; Watala, Cezary

2017-01-01

The toxicity of in vitro tested compounds is usually evaluated based on AC50 values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating AC50. In the present study, 22 polyphenol-rich compounds were prioritized from the least to the most toxic based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The studied compounds were ranked across three key cell indicators (mitochondrial membrane potential, cell membrane integrity and nuclear size) in a panel of five cell lines (HepG2, Caco-2, A549, HMEC-1, and 3T3), using a high-content screening (HCS) assay. Regarding AUOC score values, naringin (negative control) was the least toxic phenolic compound. Aronox, spent hop extract and kale leaf extract had very low cytotoxicity with regard to mitochondrial membrane potential and cell membrane integrity, as well as nuclear morphology (nuclear area). Kaempferol (positive control) exerted strong cytotoxic effects on the mitochondrial and nuclear compartments. Extracts from buckthorn bark, walnut husk and hollyhock flower were highly cytotoxic with regard to the mitochondrion and cell membrane, but not the nucleus. We propose an alternative algorithm for the screening of a large number of agents and for identifying those with adverse cellular effects at an early stage of drug discovery, using high content screening analysis. This approach should be recommended for series of compounds producing a non-sigmoidal cell response, and for agents with unknown toxicity or mechanisms of action. PMID:28662177

An evaluation of inorganic toxicity reference values for use in assessing hazards to American robins (Turdus migratorius).

PubMed

Beyer, W Nelson; Sample, Bradley E

2017-03-01

When performing screening-level and baseline risk assessments, assessors usually compare estimated exposures of wildlife receptor species with toxicity reference values (TRVs). We modeled the exposure of American robins (Turdus migratorius) to 10 elements (As, Cd, Cr, Cu, Hg, Mn, Pb, Se, Zn, and V) in spring and early summer, a time when earthworms are the preferred prey. We calculated soil benchmarks associated with possible toxic effects to these robins from 6 sets of published TRVs. Several of the resulting soil screening-level benchmarks were inconsistent with each other and less than soil background concentrations. Accordingly, we examined the derivations of the TRVs as a possible source of error. In the case of V, a particularly toxic chemical compound (ammonium vanadate) containing V, not normally present in soil, had been used to estimate a TRV. In the cases of Zn and Cu, use of uncertainty values of 10 in estimating TRVs led to implausibly low soil screening values. In the case of Pb, a TRV was calculated from studies demonstrating reductions in egg production in Japanese quail (Coturnix coturnix japonica) exposed to Pb concentrations well below than those causing toxic effects in other species of birds. The results on quail, which were replicated in additional trials, are probably not applicable to other, unrelated species, although we acknowledge that only a small fraction of all species of birds has been tested. These examples underscore the importance of understanding the derivation and relevance of TRVs before selecting them for use in screening or in ecological risk assessment. Integr Environ Assess Manag 2017;13:352-359. © 2016 SETAC. © 2016 SETAC.

US EPA Office of Research and Development Community-Focused Exposure and Risk Screening Tool (C-FERST) Air web mapping service

EPA Pesticide Factsheets

This map service displays all air-related layers used in the USEPA Community/Tribal-Focused Exposure and Risk Screening Tool (C/T-FERST) mapping application (https://www.epa.gov/c-ferst). The following data sources (and layers) are contained in this service:USEPA's 2005 National-Scale Air Toxic Assessment (NATA) data. Data are shown at the census tract level (2000 census tract boundaries, US Census Bureau) for Cumulative Cancer and Non-Cancer risks (Neurological and Respiratory) from 139 air toxics. In addition, individual pollutant estimates of Ambient Concentration, Exposure Concentration, Cancer, and Non-Cancer risks (Neurological and Respiratory) are provided for: Acetaldehyde, Acrolein, Arsenic, Benzene, 1,3-Butadiene, Chromium, Diesel PM, Formaldehyde, Lead, Naphthalene, and Polycyclic Aromatic Hydrocarbon (PAH). The original Access tables were downloaded from USEPA's Office of Air and Radiation (OAR) https://www.epa.gov/national-air-toxics-assessment/2005-national-air-toxics-assessment. The data classification (defined interval) for this map service was developed for USEPA's Office of Research and Development's (ORD) Community-Focused Exposure and Risk Screening Tool (C-FERST) per guidance provided by OAR.The 2005 NATA provides information on 177 of the 187 Clean Air Act air toxics (https://www.epa.gov/sites/production/files/2015-10/documents/2005-nata-pollutants.pdf) plus diesel particulate matter (diesel PM was assessed for non-cancer only). For addit

Derivation of soil screening thresholds to protect chisel-toothed kangaroo rat from uranium mine waste in northern Arizona

USGS Publications Warehouse

Hinck, Jo E.; Linder, Greg L.; Otton, James K.; Finger, Susan E.; Little, Edward E.; Tillitt, Donald E.

2013-01-01

Chemical data from soil and weathered waste material samples collected from five uranium mines north of the Grand Canyon (three reclaimed, one mined but not reclaimed, and one never mined) were used in a screening-level risk analysis for the Arizona chisel-toothed kangaroo rat (Dipodomys microps leucotis); risks from radiation exposure were not evaluated. Dietary toxicity reference values were used to estimate soil-screening thresholds presenting risk to kangaroo rats. Sensitivity analyses indicated that body weight critically affected outcomes of exposed-dose calculations; juvenile kangaroo rats were more sensitive to the inorganic constituent toxicities than adult kangaroo rats. Species-specific soil-screening thresholds were derived for arsenic (137 mg/kg), cadmium (16 mg/kg), copper (1,461 mg/kg), lead (1,143 mg/kg), nickel (771 mg/kg), thallium (1.3 mg/kg), uranium (1,513 mg/kg), and zinc (731 mg/kg) using toxicity reference values that incorporate expected chronic field exposures. Inorganic contaminants in soils within and near the mine areas generally posed minimal risk to kangaroo rats. Most exceedances of soil thresholds were for arsenic and thallium and were associated with weathered mine wastes.

Identification of compounds protective against G93A-SOD1 toxicity for the treatment of amyotrophic lateral sclerosis.

PubMed

Benmohamed, Radhia; Arvanites, Anthony C; Kim, Jinho; Ferrante, Robert J; Silverman, Richard B; Morimoto, Richard I; Kirsch, Donald R

2011-03-01

The underlying cause of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder, remains unknown. However, there is strong evidence that one pathophysiological mechanism, toxic protein misfolding and/or aggregation, may trigger motor neuron dysfunction and loss. Since the clinical and pathological features of sporadic and familial ALS are indistinguishable, all forms of the disease may be better understood and ultimately treated by studying pathogenesis and therapy in models expressing mutant forms of SOD1. We developed a cellular model in which cell death depended on the expression of G93A-SOD1, a mutant form of superoxide dismutase found in familial ALS patients that produces toxic protein aggregates. This cellular model was optimized for high throughput screening to identify protective compounds from a >50,000 member chemical library. Three novel chemical scaffolds were selected for further study following screen implementation, counter-screening and secondary testing, including studies with purchased analogs. All three scaffolds blocked SOD1 aggregation in high content screening assays and data on the optimization and further characterization of these compounds will be reported separately. These data suggest that optimization of these chemicals scaffolds may produce therapeutic candidates for ALS patients.

The effect of acetaminophen on ubiquitin homeostasis in Saccharomyces cerevisiae

PubMed Central

Huseinovic, Angelina; van Leeuwen, Jolanda S.; van Welsem, Tibor; Stulemeijer, Iris; van Leeuwen, Fred; Vermeulen, Nico P. E.; Kooter, Jan M.; Vos, J. Chris

2017-01-01

Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed. In this screen we identified genes related to the DNA damage response. Next, we investigated the link between genotype and APAP-induced toxicity or resistance by performing a more detailed screen with a library containing mutants of 1522 genes related to nuclear processes, like DNA repair and chromatin remodelling. We identified 233 strains that had an altered growth rate relative to wild type, of which 107 showed increased resistance to APAP and 126 showed increased sensitivity. Gene Ontology analysis identified ubiquitin homeostasis, regulation of transcription of RNA polymerase II genes, and the mitochondria-to-nucleus signalling pathway to be associated with APAP resistance, while histone exchange and modification, and vesicular transport were connected to APAP sensitivity. Indeed, we observed a link between ubiquitin levels and APAP resistance, whereby ubiquitin deficiency conferred resistance to APAP toxicity while ubiquitin overexpression resulted in sensitivity. The toxicity profile of various chemicals, APAP, and its positional isomer AMAP on a series of deletion strains with ubiquitin deficiency showed a unique resistance pattern for APAP. Furthermore, exposure to APAP increased the level of free ubiquitin and influenced the ubiquitination of proteins. Together, these results uncover a role for ubiquitin homeostasis in APAP-induced toxicity. PMID:28291796

Metabolic enzyme microarray coupled with miniaturized cell-culture array technology for high-throughput toxicity screening.

PubMed

Lee, Moo-Yeal; Dordick, Jonathan S; Clark, Douglas S

2010-01-01

Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug candidates to pharmaceuticals, it is important to develop high-throughput tools that can provide early-stage predictive toxicology data. In particular, in vitro cell-based systems that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process. The in vitro techniques that provide a high degree of human toxicity prediction will be perhaps more important in cosmetic and chemical industries in Europe, as animal toxicity testing is being phased out entirely in the immediate future.We have developed a metabolic enzyme microarray (the Metabolizing Enzyme Toxicology Assay Chip, or MetaChip) and a miniaturized three-dimensional (3D) cell-culture array (the Data Analysis Toxicology Assay Chip, or DataChip) for high-throughput toxicity screening of target compounds and their metabolic enzyme-generated products. The human or rat MetaChip contains an array of encapsulated metabolic enzymes that is designed to emulate the metabolic reactions in the human or rat liver. The human or rat DataChip contains an array of 3D human or rat cells encapsulated in alginate gels for cell-based toxicity screening. By combining the DataChip with the complementary MetaChip, in vitro toxicity results are obtained that correlate well with in vivo rat data.

The effect of acetaminophen on ubiquitin homeostasis in Saccharomyces cerevisiae.

PubMed

Huseinovic, Angelina; van Leeuwen, Jolanda S; van Welsem, Tibor; Stulemeijer, Iris; van Leeuwen, Fred; Vermeulen, Nico P E; Kooter, Jan M; Vos, J Chris

2017-01-01

Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed. In this screen we identified genes related to the DNA damage response. Next, we investigated the link between genotype and APAP-induced toxicity or resistance by performing a more detailed screen with a library containing mutants of 1522 genes related to nuclear processes, like DNA repair and chromatin remodelling. We identified 233 strains that had an altered growth rate relative to wild type, of which 107 showed increased resistance to APAP and 126 showed increased sensitivity. Gene Ontology analysis identified ubiquitin homeostasis, regulation of transcription of RNA polymerase II genes, and the mitochondria-to-nucleus signalling pathway to be associated with APAP resistance, while histone exchange and modification, and vesicular transport were connected to APAP sensitivity. Indeed, we observed a link between ubiquitin levels and APAP resistance, whereby ubiquitin deficiency conferred resistance to APAP toxicity while ubiquitin overexpression resulted in sensitivity. The toxicity profile of various chemicals, APAP, and its positional isomer AMAP on a series of deletion strains with ubiquitin deficiency showed a unique resistance pattern for APAP. Furthermore, exposure to APAP increased the level of free ubiquitin and influenced the ubiquitination of proteins. Together, these results uncover a role for ubiquitin homeostasis in APAP-induced toxicity.

Maritime Evaluation of Aerosol Fire Knock Down Tools. Part 2: Toxicity and Corrosion Potential

DTIC Science & Technology

2014-02-01

determined using paramagnetic sensor technology, while CO and CO2 concentrations were measured, respectively, via gas filter correlation and single...time response of each sensor in the unit. Since it is important to account for this delay in response during analysis and interpretation of measured...within, the compartment as well as confinement and extinguishment of the fire. 1 The initial response of the NOx analyzer and delay in sensor

Chip-based generation of carbon nanodots via electrochemical oxidation of screen printed carbon electrodes and the applications for efficient cell imaging and electrochemiluminescence enhancement

NASA Astrophysics Data System (ADS)

Xu, Yuanhong; Liu, Jingquan; Zhang, Jizhen; Zong, Xidan; Jia, Xiaofang; Li, Dan; Wang, Erkang

2015-05-01

A portable lab-on-a-chip methodology to generate ionic liquid-functionalized carbon nanodots (CNDs) was developed via electrochemical oxidation of screen printed carbon electrodes. The CNDs can be successfully applied for efficient cell imaging and solid-state electrochemiluminescence sensor fabrication on the paper-based chips.A portable lab-on-a-chip methodology to generate ionic liquid-functionalized carbon nanodots (CNDs) was developed via electrochemical oxidation of screen printed carbon electrodes. The CNDs can be successfully applied for efficient cell imaging and solid-state electrochemiluminescence sensor fabrication on the paper-based chips. Electronic supplementary information (ESI) available: Experimental section; Fig. S1. XPS spectra of the as-prepared CNDs after being dialyzed for 72 hours; Fig. S2. LSCM images showing time-dependent fluorescence signals of HeLa cells treated by the as-prepared CNDs; Tripropylamine analysis using the Nafion/CNDs modified ECL sensor. See DOI: 10.1039/c5nr01765c

THE TOXCAST PROGRAM FOR PRIORITIZING TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS

EPA Science Inventory

The United States Environmental Protection Agency (EPA) is developing methods for utilizing computational chemistry, high-throughput screening (HTS) and various toxicogenomic technologies to predict potential for toxicity and prioritize limited testing resources towards chemicals...

Fourier-transform infrared spectroscopy for rapid screening and live-cell monitoring: application to nanotoxicology.

PubMed

Sundaram, S K; Sacksteder, Colette A; Weber, Thomas J; Riley, Brian J; Addleman, R Shane; Harrer, Bruce J; Peterman, John W

2013-01-01

A significant challenge to realize the full potential of nanotechnology for therapeutic and diagnostic applications is to understand and evaluate how live cells interact with an external stimulus, such as a nanosized particle, and the toxicity and broad risk associated with these stimuli. It is difficult to capture the complexity and dynamics of these interactions by following omics-based approaches exclusively, which can be expensive and time-consuming. Attenuated total reflectance-Fourier transform infrared spectroscopy is well suited to provide noninvasive live-cell monitoring of cellular responses to potentially toxic nanosized particles or other stimuli. This alternative approach provides the ability to carry out rapid toxicity screenings and nondisruptive monitoring of live-cell cultures. We review the technical basis of the approach, the instrument configuration and interface with the biological media, the various effects that impact the data, subsequent data analysis and toxicity, and present some preliminary results on live-cell monitoring.

Toxicity studies of a polyurethane rigid foam

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Schneider, J. E.

1977-01-01

Relative toxicity tests were performed on a polyurethane foam containing a trimethylopropane-based polyol and an organophosphate flame retardant. The routine screening procedure involved the exposure of four Swiss albino male mice in a 4.2 liter hemispherical chamber to the products generated by pyrolyzing a 1.00 g sample at a heating rate of 40 deg C/min from 200 to 800 C in the absence of air flow. In addition to the routine screening, experiments were performed with a very rapid rise to 800 C, with nominal 16 and 48 ml/sec air flow and with varying sample rates. No unusual toxicity was observed with either gradual or rapid pyrolysis to 800 C. Convulsions and seizures similar to those previously reported were observed when the materials were essentially flash pyrolyzed at 800 C in the presence of air flow, and the toxicity appeared unusual because of low sample weights required to produce death.

The effect of changes in the USF/NASA toxicity screening test method on data from some cellular polymers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Miller, C. M.

1976-01-01

Rankings of relative toxicity can be markedly affected by changes in test variables. Revision of the USF/NASA toxicity screening test procedure to eliminate the connecting tube and supporting floor and incorporate a 1.0 g sample weight, 200 C starting temperature, and 800 C upper limit temperature for pyrolysis, reversed the rankings of flexible polyurethane and polychloroprene foams, not only in relation to each other, but also in relation to cotton and red oak. Much of the change is attributed to reduction of the distance between the sample and the test animals, and reduction of the sample weight charged. Elimination of the connecting tube increased the relative toxicity of the polyurethane foams. The materials tested were flexible polyurethane foam, without and with fire retardant; rigid polyurethane foam with fire retardant; flexible polychloroprene foam; cotton, Douglas fir, red oak, hemlock, hardboard, particle board, polystyrene, and polymethyl methacrylate.

A Systematic Strategy for Screening and Application of Specific Biomarkers in Hepatotoxicity Using Metabolomics Combined With ROC Curves and SVMs.

PubMed

Li, Yubo; Wang, Lei; Ju, Liang; Deng, Haoyue; Zhang, Zhenzhu; Hou, Zhiguo; Xie, Jiabin; Wang, Yuming; Zhang, Yanjun

2016-04-01

Current studies that evaluate toxicity based on metabolomics have primarily focused on the screening of biomarkers while largely neglecting further verification and biomarker applications. For this reason, we used drug-induced hepatotoxicity as an example to establish a systematic strategy for screening specific biomarkers and applied these biomarkers to evaluate whether the drugs have potential hepatotoxicity toxicity. Carbon tetrachloride (5 ml/kg), acetaminophen (1500 mg/kg), and atorvastatin (5 mg/kg) are established as rat hepatotoxicity models. Fifteen common biomarkers were screened by multivariate statistical analysis and integration analysis-based metabolomics data. The receiver operating characteristic curve was used to evaluate the sensitivity and specificity of the biomarkers. We obtained 10 specific biomarker candidates with an area under the curve greater than 0.7. Then, a support vector machine model was established by extracting specific biomarker candidate data from the hepatotoxic drugs and nonhepatotoxic drugs; the accuracy of the model was 94.90% (92.86% sensitivity and 92.59% specificity) and the results demonstrated that those ten biomarkers are specific. 6 drugs were used to predict the hepatotoxicity by the support vector machines model; the prediction results were consistent with the biochemical and histopathological results, demonstrating that the model was reliable. Thus, this support vector machine model can be applied to discriminate the between the hepatic or nonhepatic toxicity of drugs. This approach not only presents a new strategy for screening-specific biomarkers with greater diagnostic significance but also provides a new evaluation pattern for hepatotoxicity, and it will be a highly useful tool in toxicity estimation and disease diagnoses. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

Code of Federal Regulations, 2011 CFR

2011-07-01

... the control and the top dose group for observation of reversibility, persistence or delayed occurrence... toxicity. (2) Dosage. (i) Generally, at least three test groups and a control group should be used. If... administering the test substance, the control group should receive the vehicle in the highest volume used. (ii...

40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

Code of Federal Regulations, 2012 CFR

2012-07-01

... the control and the top dose group for observation of reversibility, persistence or delayed occurrence... toxicity. (2) Dosage. (i) Generally, at least three test groups and a control group should be used. If... administering the test substance, the control group should receive the vehicle in the highest volume used. (ii...

40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

Code of Federal Regulations, 2010 CFR

2010-07-01

... the control and the top dose group for observation of reversibility, persistence or delayed occurrence... toxicity. (2) Dosage. (i) Generally, at least three test groups and a control group should be used. If... administering the test substance, the control group should receive the vehicle in the highest volume used. (ii...

40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

Code of Federal Regulations, 2013 CFR

2013-07-01

... the control and the top dose group for observation of reversibility, persistence or delayed occurrence... toxicity. (2) Dosage. (i) Generally, at least three test groups and a control group should be used. If... administering the test substance, the control group should receive the vehicle in the highest volume used. (ii...

40 CFR 799.9365 - TSCA combined repeated dose toxicity study with the reproduction/developmental toxicity screening...

Code of Federal Regulations, 2014 CFR

2014-07-01

... the control and the top dose group for observation of reversibility, persistence or delayed occurrence... toxicity. (2) Dosage. (i) Generally, at least three test groups and a control group should be used. If... administering the test substance, the control group should receive the vehicle in the highest volume used. (ii...

SCREENING BIOAVAILABLE HYDROPHOBIC TOXICANTS IN SURFACE WATERS WITH SEMIPERMEABLE MEMBRANE DEVICES: ROLE OF INHERENT OLEIC ACID IN TOXICITY EVALUATIONS

EPA Science Inventory

Semipermeable membrane devices (SPMDs) were deployed for 4 weeks in two rivers in Lithuania, The SPMD dialysates were tested in the Microtox assay and, surprisingly, the sample from the relatively clean (U) over bar la River exhibited three times more toxicity than the sample fro...

Group B Streptococcal Toxic Shock Syndrome and covR/S Mutations Revisited

PubMed Central

Sendi, Parham; el Hay, Muad Abd; Brandt, Claudia M.

2017-01-01

Gene mutations in the virulence regulator CovR/S of group A Streptococcus play a substantial role in the pathogenesis of streptococcal toxic shock syndrome. We screened 25 group B Streptococcus (GBS) isolates obtained from patients with streptococcal toxic shock syndrome and found only 1 GBS clone harboring this kind of mutation. PMID:27983484

Group B Streptococcal Toxic Shock Syndrome and covR/S Mutations Revisited.

PubMed

Sendi, Parham; El Hay, Muad Abd; Brandt, Claudia M; Spellerberg, Barbara

2017-01-01

Gene mutations in the virulence regulator CovR/S of group A Streptococcus play a substantial role in the pathogenesis of streptococcal toxic shock syndrome. We screened 25 group B Streptococcus (GBS) isolates obtained from patients with streptococcal toxic shock syndrome and found only 1 GBS clone harboring this kind of mutation.

Lead Toxicity and Iron Deficiency in Utah Migrant Children.

ERIC Educational Resources Information Center

Ratcliffe, Stephen D.; And Others

1989-01-01

Determines the frequency of presumptive iron deficiency and lead toxicity in 198 Utah migrant children, aged 9-72 months. There were no confirmed cases of lead toxicity. Thirteen percent of all children tested, and 30 percent of those aged 9-23 months, were iron deficient. Hematocrit determination is an insensitive screen for iron deficiency.…

Engineering dynamic pathway regulation using stress-response promoters.

PubMed

Dahl, Robert H; Zhang, Fuzhong; Alonso-Gutierrez, Jorge; Baidoo, Edward; Batth, Tanveer S; Redding-Johanson, Alyssa M; Petzold, Christopher J; Mukhopadhyay, Aindrila; Lee, Taek Soon; Adams, Paul D; Keasling, Jay D

2013-11-01

Heterologous pathways used in metabolic engineering may produce intermediates toxic to the cell. Dynamic control of pathway enzymes could prevent the accumulation of these metabolites, but such a strategy requires sensors, which are largely unknown, that can detect and respond to the metabolite. Here we applied whole-genome transcript arrays to identify promoters that respond to the accumulation of toxic intermediates, and then used these promoters to control accumulation of the intermediate and improve the final titers of a desired product. We apply this approach to regulate farnesyl pyrophosphate (FPP) production in the isoprenoid biosynthetic pathway in Escherichia coli. This strategy improved production of amorphadiene, the final product, by twofold over that from inducible or constitutive promoters, eliminated the need for expensive inducers, reduced acetate accumulation and improved growth. We extended this approach to another toxic intermediate to demonstrate the broad utility of identifying novel sensor-regulator systems for dynamic regulation.

An Optoelectronic Nose for Detection of Toxic Gases

PubMed Central

Lim, Sung H.; Feng, Liang; Kemling, Jonathan W.; Musto, Christopher J.; Suslick, Kenneth S.

2009-01-01

We have developed a simple colorimetric sensor array (CSA) for the detection of a wide range of volatile analytes and applied it to the detection of toxic gases. The sensor consists of a disposable array of cross-responsive nanoporous pigments whose colors are changed by diverse chemical interactions with analytes. Although no single chemically responsive pigment is specific for any one analyte, the pattern of color change for the array is a unique molecular fingerprint. Clear differentiation among 19 different toxic industrial chemicals (TICs) within two minutes of exposure at IDLH (immediately dangerous to life or health) concentration has been demonstrated. Quantification of each analyte is easily accomplished based on the color change of the array, and excellent detection limits have been demonstrated, generally below the PELs (permissible exposure limits). Identification of the TICs was readily achieved using a standard chemometric approach, i.e., hierarchical clustering analysis (HCA), with no misclassifications over 140 trials. PMID:20160982

The Wireless Sensor Network (WSN) Based Coal Ash Impoundments Safety Monitoring System

NASA Astrophysics Data System (ADS)

Sun, E. J.; Nieto, A.; Zhang, X. K.

2017-01-01

Coal ash impoundments are inevitable production of the coal-fired power plants. All coal ash impoundments in North Carolina USA that tested for groundwater contamination are leaking toxic heavy metals and other pollutants. Coal ash impoundments are toxic sources of dangerous pollutants that pose a danger to human and environmental health if the toxins spread to adjacent surface waters and drinking water wells. Coal ash impoundments failures accidents resulted in serious water contamination along with toxic heavy metals. To improve the design and stability of coal ash impoundments, the Development of a Coal Ash Impoundment Safety Monitoring System (CAISM) was proposed based on the implementation of a wireless sensor network (WSN) with the ability to monitor the stability of coal ash impoundments, water level, and saturation levels on-demand and remotely. The monitoring system based on a robust Ad-hoc network could be adapted to different safety conditions.

An optoelectronic nose for the detection of toxic gases.

PubMed

Lim, Sung H; Feng, Liang; Kemling, Jonathan W; Musto, Christopher J; Suslick, Kenneth S

2009-10-01

We have developed a simple colorimetric sensor array that detects a wide range of volatile analytes and then applied it to the detection of toxic gases. The sensor consists of a disposable array of cross-responsive nanoporous pigments with colours that are changed by diverse chemical interactions with analytes. Although no single chemically responsive pigment is specific for any one analyte, the pattern of colour change for the array is a unique molecular fingerprint. Clear differentiation among 19 different toxic industrial chemicals (TICs) within two minutes of exposure at concentrations immediately dangerous to life or health were demonstrated. Based on the colour change of the array, quantification of each analyte was accomplished easily, and excellent detection limits were achieved, generally below the permissible exposure limits. Different TICs were identified readily using a standard chemometric approach (hierarchical clustering analysis), with no misclassifications over 140 trials.

Non-invasive carboxyhemoglobin monitoring: screening emergency medical services patients for carbon monoxide exposure.

PubMed

Nilson, Douglas; Partridge, Robert; Suner, Selim; Jay, Gregory

2010-01-01

Carbon monoxide (CO) toxicity is a significant health problem. The use of non-invasive pulse CO-oximetry screening in the emergency department has demonstrated that the rapid screening of numerous individuals for CO toxicity is simple and capable of identifying occult cases of CO toxicity. The objective of this study was to extend the use of this handheld device to the prehospital arena, assess carboxyhemoglobin (SpCO) levels in emergency medical services (EMS) patients, and correlate these levels with clinical and demographic data. This was a retrospective, observational, chart review of adult patients transported to hospital emergency departments by urban fire department EMS ambulances during a six-week period. Each ambulance used a non-invasive pulse CO-oximeter (Rad-57, Masimo Inc.) to record patients' COHb concentrations (SpCO) along with the standard EMS assessment data. Spearman's Rank Correlation tests and Student's t-tests were used to analyze the data and calculate relationships between SpCO and other variables (age, gender, respiratory rate, heart rate, mean arterial pressure, and oxygen saturation measured by pulse oximetry). A total of 36.4% of the patients transported during the study had SpCO documented. Of the 1,017 adults included in this group, 11 (1.1%) had an SpCO >15%. There was no correlation between SpCO and heart rate, ventilatory rate, mean arterial pressure, and oxygen saturation. Screening for CO toxicity in the EMS setting is possible, and may aid in the early detection and treatment of CO-poisoned patients.

ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology.

PubMed

Richard, Ann M; Judson, Richard S; Houck, Keith A; Grulke, Christopher M; Volarath, Patra; Thillainadarajah, Inthirany; Yang, Chihae; Rathman, James; Martin, Matthew T; Wambaugh, John F; Knudsen, Thomas B; Kancherla, Jayaram; Mansouri, Kamel; Patlewicz, Grace; Williams, Antony J; Little, Stephen B; Crofton, Kevin M; Thomas, Russell S

2016-08-15

The U.S. Environmental Protection Agency's (EPA) ToxCast program is testing a large library of Agency-relevant chemicals using in vitro high-throughput screening (HTS) approaches to support the development of improved toxicity prediction models. Launched in 2007, Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay end points. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in the public release of screening data at the end of 2013. Subsequent expansion in Phase III has resulted in more than 3800 chemicals actively undergoing ToxCast screening, 96% of which are also being screened in the multi-Agency Tox21 project. The chemical library unpinning these efforts plays a central role in defining the scope and potential application of ToxCast HTS results. The history of the phased construction of EPA's ToxCast library is reviewed, followed by a survey of the library contents from several different vantage points. CAS Registry Numbers are used to assess ToxCast library coverage of important toxicity, regulatory, and exposure inventories. Structure-based representations of ToxCast chemicals are then used to compute physicochemical properties, substructural features, and structural alerts for toxicity and biotransformation. Cheminformatics approaches using these varied representations are applied to defining the boundaries of HTS testability, evaluating chemical diversity, and comparing the ToxCast library to potential target application inventories, such as used in EPA's Endocrine Disruption Screening Program (EDSP). Through several examples, the ToxCast chemical library is demonstrated to provide comprehensive coverage of the knowledge domains and target inventories of potential interest to EPA. Furthermore, the varied representations and approaches presented here define local chemistry domains potentially worthy of further investigation (e.g., not currently covered in the testing library or defined by toxicity "alerts") to strategically support data mining and predictive toxicology modeling moving forward.

Optimization of printing techniques for electrochemical biosensors

NASA Astrophysics Data System (ADS)

Zainuddin, Ahmad Anwar; Mansor, Ahmad Fairuzabadi Mohd; Rahim, Rosminazuin Ab; Nordin, Anis Nurashikin

2017-03-01

Electrochemical biosensors show great promise for point-of-care applications due to their low cost, portability and compatibility with microfluidics. The miniature size of these sensors provides advantages in terms of sensitivity, specificity and allows them to be mass produced in arrays. The most reliable fabrication technique for these sensors is lithography followed by metal deposition using sputtering or chemical vapor deposition techniques. This technique which is usually done in the cleanroom requires expensive masking followed by deposition. Recently, cheaper printing techniques such as screen-printing and ink-jet printing have become popular due to its low cost, ease of fabrication and mask-less method. In this paper, two different printing techniques namely inkjet and screen printing are demonstrated for an electrochemical biosensor. For ink-jet printing technique, optimization of key printing parameters, such as pulse voltages, drop spacing and waveform setting, in-house temperature and cure annealing for obtaining the high quality droplets, are discussed. These factors are compared with screen-printing parameters such as mesh size, emulsion thickness, minimum spacing of lines and curing times. The reliability and reproducibility of the sensors are evaluated using scotch tape test, resistivity and profile-meter measurements. It was found that inkjet printing is superior because it is mask-less, has minimum resolution of 100 µm compared to 200 µm for screen printing and higher reproducibility rate of 90% compared to 78% for screen printing.

77 FR 35745 - Highway Safety Programs; Conforming Products List of Screening Devices To Measure Alcohol in...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-14

..., battery powered device with a semiconductor sensor. (2) Alcohol Countermeasure Systems Corp., submitted...-0062] Highway Safety Programs; Conforming Products List of Screening Devices To Measure Alcohol in... Screening Devices to Measure Alcohol in Bodily Fluids dated, March 31, 2008 (73 FR 16956). DATES: Effective...

Influence of the UV radiation on the screen-printed pH-sensitive layers based on graphene and ruthenium dioxide

NASA Astrophysics Data System (ADS)

Pepłowski, A.; Grudziński, D.; Raczyński, T.; Wróblewski, G.; Janczak, D.; Jakubowska, M.

2017-08-01

Electrodes for measuring pH of the solution were fabricated by the means of screen-printing technology. Potentiometric sensors' layers comprised of composite with polymer matrix and graphene nanoplatelets/ruthenium (IV) oxide nanopowder as functional phase. Transceivers were printed on the elastic PMMA foil. Regarding potential application of the sensors in the wearable devices, dynamic response of the electrodes to changing ultraviolet radiation levels was assessed, since RuO2 is reported to be UV-sensitive. Observed changes of the electrodes' potential were of sub-millivolt magnitude, being comparable to simultaneously observed signal drift. Given this stability under varying UV conditions and previously verified good flexibility, fabricated sensors meet the requirements for wearable applications.

siRNA screen identifies QPCT as a druggable target for Huntington's disease.

PubMed

Jimenez-Sanchez, Maria; Lam, Wun; Hannus, Michael; Sönnichsen, Birte; Imarisio, Sara; Fleming, Angeleen; Tarditi, Alessia; Menzies, Fiona; Dami, Teresa Ed; Xu, Catherine; Gonzalez-Couto, Eduardo; Lazzeroni, Giulia; Heitz, Freddy; Diamanti, Daniela; Massai, Luisa; Satagopam, Venkata P; Marconi, Guido; Caramelli, Chiara; Nencini, Arianna; Andreini, Matteo; Sardone, Gian Luca; Caradonna, Nicola P; Porcari, Valentina; Scali, Carla; Schneider, Reinhard; Pollio, Giuseppe; O'Kane, Cahir J; Caricasole, Andrea; Rubinsztein, David C

2015-05-01

Huntington's disease (HD) is a currently incurable neurodegenerative condition caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We identified new modifiers of mutant HTT toxicity by performing a large-scale 'druggable genome' siRNA screen in human cultured cells, followed by hit validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one of the strongest effects on mutant HTT-induced toxicity and aggregation in the cell-based siRNA screen and also rescued these phenotypes in Drosophila. We found that QPCT inhibition induced the levels of the molecular chaperone αB-crystallin and reduced the aggregation of diverse proteins. We generated new QPCT inhibitors using in silico methods followed by in vitro screening, which rescued the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data reveal a new HD druggable target affecting mutant HTT aggregation and provide proof of principle for a discovery pipeline from druggable genome screen to drug development.

High-throughput Screening of ToxCast" Phase I Chemicals in an Embryonic Stem Cell Assay Reveals Potential Disruption of a Critical Developmental Signaling Pathway

EPA Science Inventory

Little is known about the developmental toxicity of the expansive chemical landscape in existence today. Significant efforts are being made to apply novel methods to predict developmental activity of chemicals utilizing high-throughput screening (HTS) and high-content screening (...

A multi-analyte profile of serum proteins to screen for toxicological effects of anticholinesterase insecticides in the rat

EPA Science Inventory

The development of high throughput biochemical screens could be useful to assess the broad spectrum of physiological effects of environmental toxicants. To explore the prospect of using a screen in an in vivo exposure scenario, we applied a commercially available multianalyte pro...

Real-time monitoring of the Trojan-horse effect of silver nanoparticles by using a genetically encoded fluorescent cell sensor.

PubMed

You, Fang; Tang, Wenqin; Yung, Lin-Yue Lanry

2018-04-26

Silver nanoparticles (AgNPs) are widely incorporated into commercial products due to their antimicrobial properties. As a consequence, concerns about the adverse effects induced by AgNPs to humans and the environment need to be carefully examined. The existing literature reveals that AgNPs exhibit certain toxic effects, but it remains to be proved whether AgNPs or the ionic silver (Ag+) released from AgNPs are the main toxic species. Here, a genetically encoded fluorescent protein sensor with high affinity to Ag+ was developed. The resulting sensor, MT2a-FRET, was found to be ratiometric, sensitive and selective toward only Ag+ but inert against AgNPs. This makes this sensor a potential useful tool for monitoring the real-time intracellular dissolutions of AgNPs. Our data supported that AgNPs display the "Trojan-horse" mechanism, where AgNPs are internalized by cells and undergo dissolution intracellularly. We further found that cells exhibited a detoxification ability to remove active Ag+ from cells in 48 hours.

ADDME – Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

PubMed Central

Tsaioun, Katya; Bottlaender, Michel; Mabondzo, Aloise

2009-01-01

The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity. PMID:19534730

ADMET in silico modelling: towards prediction paradise?

PubMed

van de Waterbeemd, Han; Gifford, Eric

2003-03-01

Following studies in the late 1990s that indicated that poor pharmacokinetics and toxicity were important causes of costly late-stage failures in drug development, it has become widely appreciated that these areas should be considered as early as possible in the drug discovery process. However, in recent years, combinatorial chemistry and high-throughput screening have significantly increased the number of compounds for which early data on absorption, distribution, metabolism, excretion (ADME) and toxicity (T) are needed, which has in turn driven the development of a variety of medium and high-throughput in vitro ADMET screens. Here, we describe how in silico approaches will further increase our ability to predict and model the most relevant pharmacokinetic, metabolic and toxicity endpoints, thereby accelerating the drug discovery process.

A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents

PubMed Central

Datta, Sandipan; Sahdeo, Sunil; Gray, Jennifer A.; Morriseau, Christophe; Hammock, Bruce D.; Cortopassi, Gino

2016-01-01

Mitochondrial toxicity is emerging as a major mechanism underlying serious human health consequences. This work performs a high-throughput screen (HTS) of 176 environmental chemicals for mitochondrial toxicity utilizing a previously reported biosensor platform. This established HTS confirmed known mitochondrial toxins and identified novel mitotochondrial uncouplers such as 2, 2′-Methylenebis(4-chlorophenol) and pentachlorophenol. It also identified a mitochondrial ‘structure activity relationship’ (SAR) in the sense that multiple environmental chlorophenols are mitochondrial inhibitors and uncouplers. This study demonstrates proof-of-concept that a mitochondrial HTS assay detects known and novel environmental mitotoxicants, and could be used to quickly evaluate human health risks from mitotoxicants in the environment. PMID:27717841

Using enzyme bioassays as a rapid screen for metal toxicity

USGS Publications Warehouse

Choate, LaDonna M.; Ross, P.E.; Blumenstein, E. P.; Ranville, James F.

2005-01-01

Mine tailings piles and abandoned mine soils are often contaminated by a suite of toxic metals, which were released in the mining process. Traditionally, toxicity of such areas has been determined by numerous chemical methods including the Toxicity Characteristic Leachate Procedure (TCLP) and traditional toxicity tests using organisms such as the cladoceran Ceriodaphnia dubia. Such tests can be expensive and time-consuming. Enzymatic bioassays may provide an easier, less costly, and more time-effective toxicity screening procedure for mine tailings and abandoned mine soil leachates. This study evaluated the commercially available MetPLATE™ enzymatic toxicity assay test kit. The MetPLATE™ assay uses a modified strain of Escherichia coli bacteria as the test organism. Toxicity is defined by the activity of β-galactosidase enzyme which is monitored colorometrically with a 96-well spectrophotometer. The study used water samples collected from North Fork Clear Creek, a mining influenced water (MIW) located in Colorado. A great benefit to using the MetPLATE™ assay over the TCLP is that it shows actual toxicity of a sample by taking into account the bioavailability of the toxicants rather than simply measuring the metal concentration present. Benefits of the MetPLATE™ assay over the use of C. dubia include greatly reduced time for the testing process (∼2 hours), a more continuous variable due to a greater number of organisms present in each sample (100,000+), and the elimination of need to maintain a culture of organisms at all times.

Reactive chromophores for sensitive and selective detection of chemical warfare agents and toxic industrial chemicals

NASA Astrophysics Data System (ADS)

Frye-Mason, Greg; Leuschen, Martin; Wald, Lara; Paul, Kateri; Hancock, Lawrence F.

2005-05-01

A reactive chromophore developed at MIT exhibits sensitive and selective detection of surrogates for G-class nerve agents. This reporter acts by reacting with the agent to form an intermediate that goes through an internal cyclization reaction. The reaction locks the molecule into a form that provides a strong fluorescent signal. Using a fluorescent sensor platform, Nomadics has demonstrated rapid and sensitive detection of reactive simulants such as diethyl chloro-phosphate (simulant for sarin, soman, and related agents) and diethyl cyanophosphate (simulant for tabun). Since the unreacted chromophore does not fluoresce at the excitation wavelength used for the cyclized reporter, the onset of fluo-rescence can be easily detected. This fluorescence-based detection method provides very high sensitivity and could enable rapid detection at permissible exposure levels. Tests with potential interferents show that the reporter is very selective, with responses from only a few highly toxic, electrophilic chemicals such as phosgene, thionyl chloride, and strong acids such as HF, HCl, and nitric acid. Dimethyl methyl phosphonate (DMMP), a common and inactive simu-lant for other CW detectors, is not reactive enough to generate a signal. The unique selectivity to chemical reactivity means that a highly toxic and hazardous chemical is present when the reporter responds and illustrates that this sensor can provide very low false alarm rates. Current efforts focus on demonstrating the sensitivity and range of agents and toxic industrial chemicals detected with this reporter as well as developing additional fluorescent reporters for a range of chemical reactivity classes. The goal is to produce a hand-held sensor that can sensitively detect a broad range of chemical warfare agent and toxic industrial chemical threats.

EPAS TOXCAST PROGRAM FOR PREDICTING HAZARD AND PRIORITIZING TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS(S).

EPA Science Inventory

EPAs National Center for Computational Toxicology is developing methods that apply computational chemistry, high-throughput screening (HTS) and genomic technologies to predict potential toxicity and prioritize the use of limited testing resources.

Toxico-Cheminformatics: A New Frontier for Predictive Toxicology

EPA Science Inventory

The DSSTox database network and efforts to improve public access to chemical toxicity information resources, coupled with high-throughput screening (HTS) data and efforts to systematize legacy toxicity studies, have the potential to significantly improve predictive capabilities i...

Electrochemical Sensors for the Detection of Lead and Other Toxic Heavy Metals: The Next Generation of Personal Exposure Biomonitors

PubMed Central

Yantasee, Wassana; Lin, Yuehe; Hongsirikarn, Kitiya; Fryxell, Glen E.; Addleman, Raymond; Timchalk, Charles

2007-01-01

To support the development and implementation of biological monitoring programs, we need quantitative technologies for measuring xenobiotic exposure. Microanalytical based sensors that work with complex biomatrices such as blood, urine, or saliva are being developed and validated and will improve our ability to make definitive associations between chemical exposures and disease. Among toxic metals, lead continues to be one of the most problematic. Despite considerable efforts to identify and eliminate Pb exposure sources, this metal remains a significant health concern, particularly for young children. Ongoing research focuses on the development of portable metal analyzers that have many advantages over current available technologies, thus potentially representing the next generation of toxic metal analyzers. In this article, we highlight the development and validation of two classes of metal analyzers for the voltammetric detection of Pb, including: a) an analyzer based on flow injection analysis and anodic stripping voltammetry at a mercury-film electrode, and b) Hg-free metal analyzers employing adsorptive stripping voltammetry and novel nanostructure materials that include the self-assembled monolayers on mesoporous supports and carbon nanotubes. These sensors have been optimized to detect Pb in urine, blood, and saliva as accurately as the state-of-the-art inductively coupled plasma-mass spectrometry with high reproducibility, and sensitivity allows. These improved and portable analytical sensor platforms will facilitate our ability to conduct biological monitoring programs to understand the relationship between chemical exposure assessment and disease outcomes. PMID:18087583

MR 201104: Evaluation of Discrimination Technologies and Classification Results and MR 201157: Demonstration of MetalMapper Static Data Acquisition and Data Analysis

DTIC Science & Technology

2016-09-23

Acquisition and Data Analysis). EMI sensors, MetalMapper, man-portable Time-domain Electromagnetic Multi-sensor Towed Array Detection System (TEMTADS...California Department of Toxic Substances Control EM61 EM61-MK2 EMI electromagnetic induction ESTCP Environmental Security Technology Certification...SOP Standard Operating Procedure v TEMTADS Time-domain Electromagnetic Multi-sensor Towed Array Detection System man-portable 2x2 TOI target(s

Fish freshness detection by a computer screen photoassisted based gas sensor array.

PubMed

Alimelli, Adriano; Pennazza, Giorgio; Santonico, Marco; Paolesse, Roberto; Filippini, Daniel; D'Amico, Arnaldo; Lundström, Ingemar; Di Natale, Corrado

2007-01-23

In the last years a large number of different measurement methodologies were applied to measure the freshness of fishes. Among them the connection between freshness and headspace composition has been considered by gas chromatographic analysis and from the last two decades by a number of sensors and biosensors aimed at measuring some characteristic indicators (usually amines). More recently also the so-called artificial olfaction systems gathering together many non-specific sensors have shown a certain capability to transduce the global composition of the fish headspace capturing the differences between fresh and spoiled products. One of the main objectives related to the introduction of sensor systems with respect to the analytical methods is the claimed possibility to distribute the freshness control since sensors are expected to be "portable" and "simple". In spite of these objectives, until now sensor systems did not result in any tool that may be broadly distributed. In this paper, we present a chemical sensor array where the optical features of layers of chemicals, sensitive to volatile compounds typical of spoilage processes in fish, are interrogated by a very simple platform based on a computer screen and a web cam. An array of metalloporphyrins is here used to classify fillets of thawed fishes according to their storage days and to monitor the spoilage in filleted anchovies for a time of 8 h. Results indicate a complete identification of the storage days of thawed fillets and a determination of the storage time of anchovies held at room temperature with a root mean square error of validation of about 30 min. The optical system produces a sort of spectral fingerprint containing information about both the absorbance and the emission of the sensitive layer. The system here illustrated, based on computer peripherals, can be easily scaled to any device endowed with a programmable screen and a camera such as cellular phones offering for the first time the possibility to fulfil the sensor expectation of diffused and efficient analytical capabilities.

Engineering Genetically Encoded FRET Sensors

PubMed Central

Lindenburg, Laurens; Merkx, Maarten

2014-01-01

Förster Resonance Energy Transfer (FRET) between two fluorescent proteins can be exploited to create fully genetically encoded and thus subcellularly targetable sensors. FRET sensors report changes in energy transfer between a donor and an acceptor fluorescent protein that occur when an attached sensor domain undergoes a change in conformation in response to ligand binding. The design of sensitive FRET sensors remains challenging as there are few generally applicable design rules and each sensor must be optimized anew. In this review we discuss various strategies that address this shortcoming, including rational design approaches that exploit self-associating fluorescent domains and the directed evolution of FRET sensors using high-throughput screening. PMID:24991940

Response of a Zn₂TiO₄ Gas Sensor to Propanol at Room Temperature.

PubMed

Gaidan, Ibrahim; Brabazon, Dermot; Ahad, Inam Ul

2017-08-31

In this study, three different compositions of ZnO and TiO₂ powders were cold compressed and then heated at 1250 °C for five hours. The samples were ground to powder form. The powders were mixed with 5 wt % of polyvinyl butyral (PVB) as binder and 1.5 wt % carbon black and ethylene-glyco-lmono-butyl-ether as a solvent to form screen-printed pastes. The prepared pastes were screen printed on the top of alumina substrates containing arrays of three copper electrodes. The three fabricated sensors were tested to detect propanol at room temperature at two different concentration ranges. The first concentration range was from 500 to 3000 ppm while the second concentration range was from 2500 to 5000 ppm, with testing taking place in steps of 500 ppm. The response of the sensors was found to increase monotonically in response to the increment in the propanol concentration. The surface morphology and chemical composition of the prepared samples were characterized by Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD). The sensors displayed good sensitivity to propanol vapors at room temperature. Operation under room-temperature conditions make these sensors novel, as other metal oxide sensors operate only at high temperature.

Microbial Biosensors for Selective Detection of Disaccharides

USDA-ARS?s Scientific Manuscript database

Seven microbial strains were screened for their ability to detect disaccharides as components of Clark-type oxygen biosensors. Sensors responded to varying degrees to maltose, cellobiose, sucrose, and melibiose, but none responded strongly to lactose. Although microbial sensors are relatively nons...

Frontiers in Chemical Sensors: Novel Principles and Techniques

NASA Astrophysics Data System (ADS)

Orellana, Guillermo; Moreno-Bondi, Maria Cruz

This third volume of Springer Series on Chemical Sensors and Biosensors aims to enable the researcher or technologist to become acquainted with the latest principles and techniques that keep on enlarging the applications in this fascinating field. It deals with the novel luminescence lifetime-based techniques for interrogation of sensor arrays in high-throughput screening, cataluminescence, chemical sensing with hollow waveguides, new ways in sensor design and fabrication by means of either combinatorial methods or engineered indicator/support couples.

EPA'S TOXCAST PROGRAM FOR PREDICTING HAZARD AND PRIORITIZING TOXICITY TESTING OF ENVIRONMENTAL CHEMICALS

EPA Science Inventory

EPA is developing methods for utilizing computational chemistry, high-throughput screening (HTS) and various toxicogenomic technologies to predict potential for toxicity and prioritize limited testing resources towards chemicals that likely represent the greatest hazard to human ...

Recent Developments in Toxico-Cheminformatics: A New Frontier for Predictive Toxicology

EPA Science Inventory

Efforts to improve public access to chemical toxicity information resources, coupled with new high-throughput screening (HTS) data and efforts to systematize legacy toxicity studies, have the potential to significantly improve predictive capabilities in toxicology. Important rec...

Volume balance and toxicity analysis for the cross lake bridge.

DOT National Transportation Integrated Search

2009-09-01

There were two overall objectives for this project: (1) to assess leakage from the bridge once repairs to the collection system were completed and (2) to investigate Microtox, a toxicity screening tool manufactured by Azur environmental, as a m...

MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: II. DEVELOPMENTAL TOXICITY

EPA Science Inventory

As part of the validation of an integrated bioassay for systemic, neuro-, and developmental toxicity, we evaluated the responses of Fischer-344 rats to four pesticides, four chlorinated solvents, and two other industrial chemicals. he pesticides included carbaryl, triadimefon, ch...

New Toxico-Cheminformatics & Computational Toxicology Initiatives At EPA

EPA Science Inventory

EPA’s National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction. The DSSTox project is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than tr...

Object detection system using SPAD proximity detectors

NASA Astrophysics Data System (ADS)

Stark, Laurence; Raynor, Jeffrey M.; Henderson, Robert K.

2011-10-01

This paper presents an object detection system based upon the use of multiple single photon avalanche diode (SPAD) proximity sensors operating upon the time-of-flight (ToF) principle, whereby the co-ordinates of a target object in a coordinate system relative to the assembly are calculated. The system is similar to a touch screen system in form and operation except that the lack of requirement of a physical sensing surface provides a novel advantage over most existing touch screen technologies. The sensors are controlled by FPGA-based firmware and each proximity sensor in the system measures the range from the sensor to the target object. A software algorithm is implemented to calculate the x-y coordinates of the target object based on the distance measurements from at least two separate sensors and the known relative positions of these sensors. Existing proximity sensors were capable of determining the distance to an object with centimetric accuracy and were modified to obtain a wide field of view in the x-y axes with low beam angle in z in order to provide a detection area as large as possible. Design and implementation of the firmware, electronic hardware, mechanics and optics are covered in the paper. Possible future work would include characterisation with alternative designs of proximity sensors, as this is the component which determines the highest achievable accur1acy of the system.

Effect of pyrolysis temperature and air flow on toxicity of gases from a polycarbonate polymer

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Brick, V. E.; Brauer, D. P.

1978-01-01

A polycarbonate polymer was evaluated for toxicity of pyrolysis gases generated at various temperatures without forced air flow and with 1 L/min air flow, using the toxicity screening test method developed at the University of San Francisco. Time to various animal responses decreased with increasing pyrolysis temperature over the range from 500 C to 800 C. There appeared to be no significant toxic effects at 400 C and lower temperatures.

The use of high-throughput screening techniques to evaluate mitochondrial toxicity.

PubMed

Wills, Lauren P

2017-11-01

Toxicologists and chemical regulators depend on accurate and effective methods to evaluate and predict the toxicity of thousands of current and future compounds. Robust high-throughput screening (HTS) experiments have the potential to efficiently test large numbers of chemical compounds for effects on biological pathways. HTS assays can be utilized to examine chemical toxicity across multiple mechanisms of action, experimental models, concentrations, and lengths of exposure. Many agricultural, industrial, and pharmaceutical chemicals classified as harmful to human and environmental health exert their effects through the mechanism of mitochondrial toxicity. Mitochondrial toxicants are compounds that cause a decrease in the number of mitochondria within a cell, and/or decrease the ability of mitochondria to perform normal functions including producing adenosine triphosphate (ATP) and maintaining cellular homeostasis. Mitochondrial dysfunction can lead to apoptosis, necrosis, altered metabolism, muscle weakness, neurodegeneration, decreased organ function, and eventually disease or death of the whole organism. The development of HTS techniques to identify mitochondrial toxicants will provide extensive databases with essential connections between mechanistic mitochondrial toxicity and chemical structure. Computational and bioinformatics approaches can be used to evaluate compound databases for specific chemical structures associated with toxicity, with the goal of developing quantitative structure-activity relationship (QSAR) models and mitochondrial toxicophores. Ultimately these predictive models will facilitate the identification of mitochondrial liabilities in consumer products, industrial compounds, pharmaceuticals and environmental hazards. Copyright © 2017 Elsevier B.V. All rights reserved.

Homogeneous plate based antibody internalization assay using pH sensor fluorescent dye.

PubMed

Nath, Nidhi; Godat, Becky; Zimprich, Chad; Dwight, Stephen J; Corona, Cesear; McDougall, Mark; Urh, Marjeta

2016-04-01

Receptor-mediated antibody internalization is a key mechanism underlying several anti-cancer antibody therapeutics. Delivering highly toxic drugs to cancer cells, as in the case of antibody drug conjugates (ADCs), efficient removal of surface receptors from cancer cells and changing the pharmacokinetics profile of the antibody drugs are some of key ways that internalization impacts the therapeutic efficacy of the antibodies. Over the years, several techniques have been used to study antibody internalization including radiolabels, fluorescent microscopy, flow cytometry and cellular toxicity assays. While these methods allow analysis of internalization, they have limitations including a multistep process and limited throughput and are generally endpoint assays. Here, we present a new homogeneous method that enables time and concentration dependent measurements of antibody internalization. The method uses a new hydrophilic and bright pH sensor dye (pHAb dye), which is not fluorescent at neutral pH but becomes highly fluorescent at acidic pH. For receptor mediated antibody internalization studies, antibodies against receptors are conjugated with the pHAb dye and incubated with the cells expressing the receptors. Upon binding to the receptor, the dyes conjugated to the antibody are not fluorescent because of the neutral pH of the media, but upon internalization and trafficking into endosomal and lysosomal vesicles the pH drops and dyes become fluorescent. The enabling attributes of the pHAb dyes are the hydrophilic nature to minimize antibody aggregation and bright fluorescence at acidic pH which allows development of simple plate based assays using a fluorescent reader. Using two different therapeutic antibodies--Trastuzumab (anti-HER2) and Cetuximab (anti-EGFR)--we show labeling with pHAb dye using amine and thiol chemistries and impact of chemistry and dye to antibody ration on internalization. We finally present two new approaches using the pHAb dye, which will be beneficial for screening a large number of antibody samples during early monoclonal development phase. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Combinatorial screening of potentiometric Pb(II) sensors from polysulfoaminoanthraquinone solid ionophore.

PubMed

Huang, Mei-Rong; Ding, Yong-Bo; Li, Xin-Gui

2014-03-10

A potentiometric Pb(II)-selective sensor was fabricated by a combinatorial screening of electrically conducting polysulfoaminoanthraquinone (PSA) nanoparticles as a solid ionophore, ion exchangers (oleic acid (OA) and NaTPB), plasticizers in a polyvinyl chloride (PVC) matrix, membrane thickness, inner filling ion species, and concentration. The membrane sensor with the composition of PSA/PVC/DOP (dioctyl phthalate)/OA (1.0:33:61:5.0) exhibited the best performance, including a slope of 29.3 mV decade(-1) in the concentration range 10(-6.3)-10(-1.6) M, detection limit of 1.6 × 10(-7) M, response time of 16 s, lifetime of five months, and good response reversibility. The proposed sensor has demonstrated good selectivity for Pb(II) over other monovalent, divalent and trivalent interfering ions, and could be used in a pH range of 3.62-5.22. The Pb(II) sensor has been successfully applied for the determination of Pb(II) concentration in real-world samples and also as an indicator electrode for potentiometric titration of lead ions.

Obstructive Sleep Apnea Screening Using a Piezo-Electric Sensor

PubMed Central

2017-01-01

In this study, we propose a novel method for obstructive sleep apnea (OSA) detection using a piezo-electric sensor. OSA is a relatively common sleep disorder. However, more than 80% of OSA patients remain undiagnosed. We investigated the feasibility of OSA assessment using a single-channel physiological signal to simplify the OSA screening. We detected both snoring and heartbeat information by using a piezo-electric sensor, and snoring index (SI) and features based on pulse rate variability (PRV) analysis were extracted from the filtered piezo-electric sensor signal. A support vector machine (SVM) was used as a classifier to detect OSA events. The performance of the proposed method was evaluated on 45 patients from mild, moderate, and severe OSA groups. The method achieved a mean sensitivity, specificity, and accuracy of 72.5%, 74.2%, and 71.5%; 85.8%, 80.5%, and 80.0%; and 70.3%, 77.1%, and 71.9% for the mild, moderate, and severe groups, respectively. Finally, these results not only show the feasibility of OSA detection using a piezo-electric sensor, but also illustrate its usefulness for monitoring sleep and diagnosing OSA. PMID:28480645

Recycling Metals from Spent Screen-Printed Electrodes While Learning the Fundamentals of Electrochemical Sensing

ERIC Educational Resources Information Center

González-Sánchez, María-Isabel; Gómez-Monedero, Beatriz; Agrisuelas, Jerónimo; Valero, Edelmira

2018-01-01

A laboratory experiment in which students recycle silver and platinum selectively from spent screen-printed platinum electrodes is described. The recovered silver in solution is used to show its spontaneous redox reaction with a copper sheet. The recovered platinum is electrodeposited onto a screen-printed carbon electrode to develop a sensor for…

Pluripotent stem cell derived hepatocyte like cells and their potential in toxicity screening.

PubMed

Greenhough, Sebastian; Medine, Claire N; Hay, David C

2010-12-30

Despite considerable progress in modelling human liver toxicity, the requirement still exists for efficient, predictive and cost effective in vitro models to reduce attrition during drug development. Thousands of compounds fail in this process, with hepatotoxicity being one of the significant causes of failure. The cost of clinical studies is substantial, therefore it is essential that toxicological screening is performed early on in the drug development process. Human hepatocytes represent the gold standard model for evaluating drug toxicity, but are a limited resource. Current alternative models are based on immortalised cell lines and animal tissue, but these are limited by poor function, exhibit species variability and show instability in culture. Pluripotent stem cells are an attractive alternative as they are capable of self-renewal and differentiation to all three germ layers, and thereby represent a potentially inexhaustible source of somatic cells. The differentiation of human embryonic stem cells and induced pluripotent stem cells to functional hepatocyte like cells has recently been reported. Further development of this technology could lead to the scalable production of hepatocyte like cells for liver toxicity screening and clinical therapies. Additionally, induced pluripotent stem cell derived hepatocyte like cells may permit in vitro modelling of gene polymorphisms and genetic diseases. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Adaptation of High-Throughput Screening in Drug Discovery—Toxicological Screening Tests

PubMed Central

Szymański, Paweł; Markowicz, Magdalena; Mikiciuk-Olasik, Elżbieta

2012-01-01

High-throughput screening (HTS) is one of the newest techniques used in drug design and may be applied in biological and chemical sciences. This method, due to utilization of robots, detectors and software that regulate the whole process, enables a series of analyses of chemical compounds to be conducted in a short time and the affinity of biological structures which is often related to toxicity to be defined. Since 2008 we have implemented the automation of this technique and as a consequence, the possibility to examine 100,000 compounds per day. The HTS method is more frequently utilized in conjunction with analytical techniques such as NMR or coupled methods e.g., LC-MS/MS. Series of studies enable the establishment of the rate of affinity for targets or the level of toxicity. Moreover, researches are conducted concerning conjugation of nanoparticles with drugs and the determination of the toxicity of such structures. For these purposes there are frequently used cell lines. Due to the miniaturization of all systems, it is possible to examine the compound’s toxicity having only 1–3 mg of this compound. Determination of cytotoxicity in this way leads to a significant decrease in the expenditure and to a reduction in the length of the study. PMID:22312262

State-of-the-art lab chip sensors for environmental water monitoring

NASA Astrophysics Data System (ADS)

Jang, Am; Zou, Zhiwei; Kug Lee, Kang; Ahn, Chong H.; Bishop, Paul L.

2011-03-01

As a result of increased water demand and water pollution, both surface water and groundwater quantity and quality are of major concern worldwide. In particular, the presence of nutrients and heavy metals in water is a serious threat to human health. The initial step for the effective management of surface waters and groundwater requires regular, continuous monitoring of water quality in terms of contaminant distribution and source identification. Because of this, there is a need for screening and monitoring measurements of these compounds at contaminated areas. However, traditional monitoring techniques are typically still based on laboratory analyses of representative field-collected samples; this necessitates considerable effort and expense, and the sample may change before analysis. Furthermore, currently available equipment is so large that it cannot usually be made portable. Alternatively, lab chip and electrochemical sensing-based portable monitoring systems appear well suited to complement standard analytical methods for a number of environmental monitoring applications. In addition, this type of portable system could save tremendous amounts of time, reagent, and sample if it is installed at contaminated sites such as Superfund sites (the USA's worst toxic waste sites) and Resource Conservation and Recovery Act (RCRA) facilities or in rivers and lakes. Accordingly, state-of-the-art monitoring equipment is necessary for accurate assessments of water quality. This article reviews details on our development of these lab-on-a-chip (LOC) sensors.

Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

PubMed

Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

2016-09-01

Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

[Investigation of metabolites of Triptergium wilfordii on liver toxicity by LC-MS].

PubMed

Zhao, Xiao-mei; Liu, Xin-ying; Xu, Chang; Ye, Tao; Jin, Cheng; Zhao, Kui-jun; Ma, Zhi-jie; Xiao, Xiao-he

2015-10-01

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.

Photonic sensor applications in transportation security

NASA Astrophysics Data System (ADS)

Krohn, David A.

2007-09-01

There is a broad range of security sensing applications in transportation that can be facilitated by using fiber optic sensors and photonic sensor integrated wireless systems. Many of these vital assets are under constant threat of being attacked. It is important to realize that the threats are not just from terrorism but an aging and often neglected infrastructure. To specifically address transportation security, photonic sensors fall into two categories: fixed point monitoring and mobile tracking. In fixed point monitoring, the sensors monitor bridge and tunnel structural health and environment problems such as toxic gases in a tunnel. Mobile tracking sensors are being designed to track cargo such as shipboard cargo containers and trucks. Mobile tracking sensor systems have multifunctional sensor requirements including intrusion (tampering), biochemical, radiation and explosives detection. This paper will review the state of the art of photonic sensor technologies and their ability to meet the challenges of transportation security.

A New Miniaturized Inkjet Printed Solid State Electrolyte Sensor for Applications in Life Support Systems - First Results

NASA Astrophysics Data System (ADS)

Hill, Christine; Stefanos Fasoulas, -; Eberhart, Martin; Berndt, Felix

New generations of integrated closed loop systems will combine life support systems (incl. biological components) and energy systems such as fuel cell and electrolysis systems. Those systems and their test beds also contain complex safety sensor monitoring systems. Especially in fuel cells and electrolysis systems, the hydrogen and oxygen flows and exchange into other areas due to diffusion processes or leaks need to be monitored. Knowledge of predominant gas concentrations at all times is essential to avoid explosive gas mixtures. Solid state electrolyte sensors are promising for use as safety sensors. They have already been developed and produced at various institutes, but the power consumption for heating an existing solid state electrolyte sensor element still lies between 1 to 1.5 W and the operational readiness still takes about 20 to 30 s. This is partially due to the current manufacturing process for the solid state electrolyte sensor elements that is based on screen printing technology. However this technology has strong limitations in flexibility of the layout and re-designs. It is therefore suitable for mass production, but not for a flexible development and the production of specific individual sensors, e.g. for space applications. Moreover a disadvantage is the relatively high material consumption, especially in combination with the sensors need of expensive noble metal and ceramic pastes, which leads to a high sensor unit price. The Inkjet technology however opens up completely new possibilities in terms of dimensions, geometries, structures, morphologies and materials of sensors. This new approach is capable of printing finer high-resolution layers without the necessity of meshes or masks for patterning. Using the Inkjet technology a design change is possible at any time on the CAD screen. Moreover the ink is only deposited where it is needed. Custom made sensors, as they are currently demanded in space sensor applications, are thus realized simply, economically and ecologically. Based on the knowledge of the screen printing sensor production a complete solid state electrolyte oxygen sensor could be produced using Inkjet technology. First measurements in oxygen environment already show promising results. A defined oxygen concentration could be seen during exposition of the Inkjet sensors in an oxygen environment. The obtained results demonstrate the potential to use the technology development in other applications such as in situ respiratory gas analysis systems for human spaceflight. Further approaches at the Institute of Space Systems include the implementation of Inkjet printed solid state electrolyte sensors for the use as redundant safety sensors for the Institute's hybrid life support test beds including fuel cells and algal photo bioreactor elements.

Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

PubMed

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

Humidity Sensors Printed on Recycled Paper and Cardboard

PubMed Central

Mraović, Matija; Muck, Tadeja; Pivar, Matej; Trontelj, Janez; Pleteršek, Anton

2014-01-01

Research, design, fabrication and results of various screen printed capacitive humidity sensors is presented in this paper. Two types of capacitive humidity sensors have been designed and fabricated via screen printing on recycled paper and cardboard, obtained from the regional paper and cardboard industry. As printing ink, commercially available silver nanoparticle-based conductive ink was used. A considerable amount of work has been devoted to the humidity measurement methods using paper as a dielectric material. Performances of different structures have been tested in a humidity chamber. Relative humidity in the chamber was varied in the range of 35%–80% relative humidity (RH) at a constant temperature of 23 °C. Parameters of interest were capacitance and conductance of each sensor material, as well as long term behaviour. Process reversibility has also been considered. The results obtained show a mainly logarithmic response of the paper sensors, with the only exception being cardboard-based sensors. Recycled paper-based sensors exhibit a change in value of three orders of magnitude, whereas cardboard-based sensors have a change in value of few 10s over the entire scope of relative humidity range (RH 35%–90%). Two different types of capacitor sensors have been investigated: lateral (comb) type sensors and modified, perforated flat plate type sensors. The objective of the present work was to identify the most important factors affecting the material performances with humidity, and to contribute to the development of a sensor system supported with a Radio Frequency Identification (RFID) chip directly on the material, for use in smart packaging applications. Therefore, the authors built a passive and a battery-supported wireless module based on SL900A smart sensory tag's IC to achieve UHF-RFID functionality with data logging capability. PMID:25072347

Resolution Properties of a Calcium Tungstate (CaWO4) Screen Coupled to a CMOS Imaging Detector

NASA Astrophysics Data System (ADS)

Koukou, Vaia; Martini, Niki; Valais, Ioannis; Bakas, Athanasios; Kalyvas, Nektarios; Lavdas, Eleftherios; Fountos, George; Kandarakis, Ioannis; Michail, Christos

2017-11-01

The aim of the current work was to assess the resolution properties of a calcium tungstate (CaWO4) screen (screen coating thickness: 50.09 mg/cm2, actual thickness: 167.2 μm) coupled to a high resolution complementary metal oxide semiconductor (CMOS) digital imaging sensor. A 2.7x3.6 cm2 CaWO4 sample was extracted from an Agfa Curix universal screen and was coupled directly with the active area of the active pixel sensor (APS) CMOS sensor. Experiments were performed following the new IEC 62220-1-1:2015 International Standard, using an RQA-5 beam quality. Resolution was assessed in terms of the Modulation Transfer Function (MTF), using the slanted-edge method. The CaWO4/CMOS detector configuration was found with linear response, in the exposure range under investigation. The final MTF was obtained through averaging the oversampled edge spread function (ESF), using a custom-made software developed by our team, according to the IEC 62220-1-1:2015. Considering the renewed interest in calcium tungstate for various applications, along with the resolution results of this work, CaWO4 could be also considered for use in X-ray imaging devices such as charged-coupled devices (CCD) and CMOS.

A facile electrochemical intercalation and microwave assisted exfoliation methodology applied to screen-printed electrochemical-based sensing platforms to impart improved electroanalytical outputs.

PubMed

Pierini, Gastón D; Foster, Christopher W; Rowley-Neale, Samuel J; Fernández, Héctor; Banks, Craig E

2018-06-12

Screen-printed electrodes (SPEs) are ubiquitous with the field of electrochemistry allowing researchers to translate sensors from the laboratory to the field. In this paper, we report an electrochemically driven intercalation process where an electrochemical reaction uses an electrolyte as a conductive medium as well as the intercalation source, which is followed by exfoliation and heating/drying via microwave irradiation, and applied to the working electrode of screen-printed electrodes/sensors (termed EDI-SPEs) for the first time. This novel methodology results in an increase of up to 85% of the sensor area (electrochemically active surface area, as evaluated using an outer-sphere redox probe). Upon further investigation, it is found that an increase in the electroactive area of the EDI-screen-printed based electrochemical sensing platforms is critically dependent upon the analyte and its associated electrochemical mechanism (i.e. adsorption vs. diffusion). Proof-of-concept for the electrochemical sensing of capsaicin, a measure of the hotness of chillies and chilli sauce, within both model aqueous solutions and a real sample (Tabasco sauce) is demonstrated in which the electroanalytical sensitivity (a plot of signal vs. concentration) is doubled when utilising EDI-SPEs over that of SPEs.

Elucidation of Adverse Bioactivity Profiles as Predictors of Toxicity Potential

EPA Science Inventory

Toxicity testing in vitro remains a formidable challenge due to lack of understanding of key molecular targets and pathways underlying many pathological events. The combination of genome sequencing and widespread application of high-throughput screening tools have provided the me...

ExpoCast: Exposure Science for Prioritization and Toxicity Testing (S)

EPA Science Inventory

The US EPA is completing the Phase I pilot for a chemical prioritization research program, called ToxCast. Here EPA is developing methods for using computational chemistry, high-throughput screening, and toxicogenomic technologies to predict potential toxicity and prioritize limi...

ExpoCast: Exposure Science for Prioritization and Toxicity Testing

EPA Science Inventory

The US EPA is completing the Phase I pilot for a chemical prioritization research program, called ToxCastTM. Here EPA is developing methods for using computational chemistry, high-throughput screening, and toxicogenomic technologies to predict potential toxicity and prioritize l...

THE DEVELOPMENTAL TOXICITY OF BROMOCHLOROACETONITRILE IN PREGNANT LONG-EVANS RATS

EPA Science Inventory

Bromochloroacetonitrile (BCAN) is a by-product of the chlorine disinfection of water containing natural organic material. Adverse effects of BCAN in an in vivo teratology screen (i.e. neonatal survival assay) gave reason for further investigation into the developmental toxicity o...

SURVEY OF HALONITROMETHANES AND IODOMETHANES: DISINFECTION BY-PRODUCTS IN DRINKING WATER

EPA Science Inventory

This project involves the study of two classes of chemicals, halonitromethanes and iodomethanes, which have been found to be drinking water disinfection by-products (DBPs). Both have been predicted to have toxicity. In toxicity screening tests, bromonitromethanes have been shown ...

In Vitro Toxicity Screening Technique for Volatile Substances ...

EPA Pesticide Factsheets

In 2007 the National Research Council envisioned the need for inexpensive, high throughput, cell based toxicity testing methods relevant to human health. High Throughput Screening (HTS) in vitro screening approaches have addressed these problems by using robotics. However the challenge is that many of these chemicals are volatile and not amenable to HTS robotic liquid handling applications. We assembled an in vitro cell culture apparatus capable of screening volatile chemicals for toxicity with potential for miniaturization for high throughput. BEAS-2B lung cells were grown in an enclosed culture apparatus under air-liquid interface (ALI) conditions, and exposed to an array of xenobiotics in 5% CO2. Use of ALI conditions allows direct contact of cells with a gas xenobiotic, as well as release of endogenous gaseous molecules without interference by medium on the apical surface. To identify potential xenobiotic-induced perturbations in cell homeostasis, we monitored for alterations of endogenously-produced gaseous molecules in air directly above the cells, termed “headspace”. Alterations in specific endogenously-produced gaseous molecules (e.g., signaling molecules nitric oxide (NO) and carbon monoxide (CO) in headspace is indicative of xenobiotic-induced perturbations of specific cellular processes. Additionally, endogenously produced volatile organic compounds (VOCs) may be monitored in a nonspecific, discovery manner to determine whether cell processes are

Hydrogel tissue construct-based high-content compound screening.

PubMed

Lam, Vy; Wakatsuki, Tetsuro

2011-01-01

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)-based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds--rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)--for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

Environmental and risk screening for prioritizing pollution prevention opportunities in the U.S. printed wiring board manufacturing industry.

PubMed

Lam, Carl W; Lim, Seong-Rin; Schoenung, Julie M

2011-05-15

Modern manufacturing of printed wiring boards (PWBs) involves extensive use of various hazardous chemicals in different manufacturing steps such as board preparation, circuit design transfer, etching and plating processes. Two complementary environmental screening methods developed by the U.S. EPA, namely: (i) the Tool for the Reduction and Assessment of Chemical and Other Environmental Impacts (TRACI) and (ii) Risk-Screening Environmental Indicators (RSEI), are used to quantify geographic and chemical environmental impacts in the U.S. PWB manufacturing industry based on Toxics Release Inventory (TRI) data. Although the release weight percentages of industrial chemicals such as methanol, glycol ethers and dimethylformamide comprise the larger fraction of reported air and water emissions, results indicate that lead, copper and their compounds' releases correspond to the highest environmental impact from toxicity potentials and risk-screening scores. Combining these results with further knowledge of PWB manufacturing, select alternative chemical processes and materials for pollution prevention are discussed. Examples of effective pollution prevention options in the PWB industry include spent etchant recovery technologies, and process and material substitutions. In addition, geographic assessment of environmental burden highlights states where promotion of pollution prevention strategies and emissions regulations can have the greatest effect to curb the PWB industry's toxic release impacts. Copyright © 2011 Elsevier B.V. All rights reserved.

Respirometric biomonitor for the control of industrial effluent toxicity

NASA Astrophysics Data System (ADS)

Campanella, Luigi; Favero, G.; Mastrofini, D.; Tomassetti, M.

1995-10-01

A yeast cell biosystem has been recently developed for the total toxicity testing of a sample that may contain a number of different polluting species. The method uses an amperometric gas diffusion oxygen sensor as indicating electrode and is based on the perturbation of the respiratory activity of the immobilized yeast Saccharomyces cerevisiae; glucose acts as substrate. Several toxic substances were tested: metal ions, phenol and cationic, anionic or nonionic surfactants. Some results of a monitoring program of an industrial wastewater are also reported and discussed.

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure

PubMed Central

Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Mahon, Sari B.; Kim, Sonia; Ryu, Justine H.; Werdich, Andreas; Januzzi, James L.; Boss, Gerry R.; Rockwood, Gary A.; MacRae, Calum A.; Brenner, Matthew; Gerszten, Robert E.; Peterson, Randall T.

2013-01-01

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.—Nath, A. K., Roberts, L. D., Liu, Y., Mahon, S. B., Kim, S., Ryu, J. H., Werdich, A., Januzzi, J. L., Boss, G. R., Rockwood, G. A., MacRae, C. A., Brenner, M., Gerszten, R. E., Peterson, R. T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. PMID:23345455

A systematic study of mitochondrial toxicity of environmental chemicals using quantitative high throughput screening

PubMed Central

Attene-Ramos, Matias S.; Huang, Ruili; Sakamuru, Srilatha; Witt, Kristine L.; Beeson, Gyda C.; Shou, Louie; Schnellmann, Rick G.; Beeson, Craig C.; Tice, Raymond R.; Austin, Christopher P.; Xia, Menghang

2014-01-01

A goal of the Tox21 program is to transit toxicity testing from traditional in vivo models to in vitro assays that assess how chemicals affect cellular responses and toxicity pathways. A critical contribution of the NIH Chemical Genomics center (NCGC) to the Tox21 program is the implementation of a quantitative high throughput screening (qHTS) approach, using cell- and biochemical-based assays to generate toxicological profiles for thousands of environmental compounds. Here, we evaluated the effect of chemical compounds on mitochondrial membrane potential in HepG2 cells by screening a library of 1,408 compounds provided by the National Toxicology Program (NTP) in a qHTS platform. Compounds were screened over 14 concentrations, and results showed that 91 and 88 compounds disrupted mitochondrial membrane potential after treatment for one or five h, respectively. Seventy-six compounds active at both time points were clustered by structural similarity, producing 11 clusters and 23 singletons. Thirty-eight compounds covering most of the active chemical space were more extensively evaluated. Thirty-six of the 38 compounds were confirmed to disrupt mitochondrial membrane potential using a fluorescence plate reader and 35 were confirmed using a high content imaging approach. Among the 38 compounds, 4 and 6 induced LDH release, a measure of cytotoxicity, at 1 or 5 h, respectively. Compounds were further assessed for mechanism of action (MOA) by measuring changes in oxygen consumption rate, which enabled identification of 20 compounds as uncouplers. This comprehensive approach allows for evaluation of thousands of environmental chemicals for mitochondrial toxicity and identification of possible MOAs. PMID:23895456

Investigating the binding properties of porous drug delivery systems using nuclear sensors (radiotracers) and positron annihilation lifetime spectroscopy--predicting conditions for optimum performance.

PubMed

Mume, Eskender; Lynch, Daniel E; Uedono, Akira; Smith, Suzanne V

2011-06-21

Understanding how the size, charge and number of available pores in porous material influences the uptake and release properties is important for optimising their design and ultimately their application. Unfortunately there are no standard methods for screening porous materials in solution and therefore formulations must be developed for each encapsulated agent. This study investigates the potential of a library of radiotracers (nuclear sensors) for assessing the binding properties of hollow silica shell materials. Uptake and release of Cu(2+) and Co(2+) and their respective complexes with polyazacarboxylate macrocycles (dota and teta) and a series of hexa aza cages (diamsar, sarar and bis-(p-aminobenzyl)-diamsar) from the hollow silica shells was monitored using their radioisotopic analogues. Coordination chemistry of the metal (M) species, subtle alterations in the molecular architecture of ligands (Ligand) and their resultant complexes (M-Ligand) were found to significantly influence their uptake over pH 3 to 9 at room temperature. Positively charged species were selectively and rapidly (within 10 min) absorbed at pH 7 to 9. Negatively charged species were preferentially absorbed at low pH (3 to 5). Rates of release varied for each nuclear sensor, and time to establish equilibrium varied from minutes to days. The subtle changes in design of the nuclear sensors proved to be a valuable tool for determining the binding properties of porous materials. The data support the development of a library of nuclear sensors for screening porous materials for use in optimising the design of porous materials and the potential of nuclear sensors for high through-put screening of materials.

AOPs & Biomarkers: Bridging High Throughput Screening and Regulatory Decision Making.

EPA Science Inventory

As high throughput screening (HTS) approaches play a larger role in toxicity testing, computational toxicology has emerged as a critical component in interpreting the large volume of data produced. Computational models for this purpose are becoming increasingly more sophisticated...

Functional Observational Battery Testing for Nervous System Effects of Drugs and Other Chemicals

EPA Science Inventory

Screening for behavioral toxicity, or neurotoxicity, has become standard practice in preclinical safety pharmacology and toxicology. Behavior represents the integrated sum of activities mediated by the nervous system. Current screening batteries, such as the functional observat...

Cheminformatic Analysis of the US EPA ToxCast Chemical Library

EPA Science Inventory

The ToxCast project is employing high throughput screening (HTS) technologies, along with chemical descriptors and computational models, to develop approaches for screening and prioritizing environmental chemicals for further toxicity testing. ToxCast Phase I generated HTS data f...

Response to “Accurate Risk-Based Chemical Screening Relies on Robust Exposure Estimates”

EPA Science Inventory

This is a correspondence (letter to the editor) with reference to comments by Rudel and Perovich on the article "Integration of Dosimetry, Exposure, and High-Throughput Screening Data in Chemical Toxicity Assessment". Article Reference: SI # 238882

Utilizing high throughput screening data for predictive toxicology models: protocols and application to MLSCN assays

NASA Astrophysics Data System (ADS)

Guha, Rajarshi; Schürer, Stephan C.

2008-06-01

Computational toxicology is emerging as an encouraging alternative to experimental testing. The Molecular Libraries Screening Center Network (MLSCN) as part of the NIH Molecular Libraries Roadmap has recently started generating large and diverse screening datasets, which are publicly available in PubChem. In this report, we investigate various aspects of developing computational models to predict cell toxicity based on cell proliferation screening data generated in the MLSCN. By capturing feature-based information in those datasets, such predictive models would be useful in evaluating cell-based screening results in general (for example from reporter assays) and could be used as an aid to identify and eliminate potentially undesired compounds. Specifically we present the results of random forest ensemble models developed using different cell proliferation datasets and highlight protocols to take into account their extremely imbalanced nature. Depending on the nature of the datasets and the descriptors employed we were able to achieve percentage correct classification rates between 70% and 85% on the prediction set, though the accuracy rate dropped significantly when the models were applied to in vivo data. In this context we also compare the MLSCN cell proliferation results with animal acute toxicity data to investigate to what extent animal toxicity can be correlated and potentially predicted by proliferation results. Finally, we present a visualization technique that allows one to compare a new dataset to the training set of the models to decide whether the new dataset may be reliably predicted.

Screening tests in toxicity or drug effect studies with use of centrifichem general-purpose spectrophotometeric analyzer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagy, B.; Bercz, J.P.

CentrifiChem System 400 general-purpose spectrophotometric analyzer which can process simultaneously 30 samples and reads the reactions within milliseconds was used for toxicity studies. Organic and inorganic chemicals were screened for inhibitory action of the hydrolytic activity of sarcoplasmic reticulum (SR) Ca,Mg-ATPase and that of the sacrolemmal (SL) Na,K-ATPase, or mitochondrial ATPase (M). SR and SL were prepared from rabbit muscles, Na,K-ATPase from pig kidneys, M from pig hearts. Pseudosubstrates of paranitrophenyl phosphate and 2,4-dinitrophenyl phosphate, both proven high energy phosphate substitutes for ATPase coupled ion transfer were used. The reaction rates were followed spectrophotometrically at 405 nm measuring the accumulationmore » of yellow nitrophenolate ions. The reported calcium transfer coupling ratio to hydrolysis of 2:1 was ascertained with use of /sup 45/Ca in case of SR. Inhibition constants (pI) on SR, SL, and M for the pseudosubstrate hydrolysis will be given for over 20 chemicals tested. The applicability of the system to general toxicity testing and to general cardio-effective drug screening will be presented.« less

Fourier-transform infrared spectroscopy for rapid screening and live-cell monitoring: application to nanotoxicology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundaram, S. K.; Sacksteder, Colette A.; Weber, T. J.

2013-01-01

A significant challenge to realize the full potential of nanotechnology for therapeutic and diagnostic applications is to understand and evaluate how live-cells interact with an external stimulus, e.g., a nanosized particle (NSP), and the toxicity and broad risk associated with these stimuli. NSPs are increasingly used in medicine with largely undetermined hazards in complex cell dynamics and environments. It is difficult to capture the complexity and dynamics of these interactions by following an omics-based approach exclusively, which are expensive and time-consuming. Additionally, this approach needs destructive sampling methods. Live-cell attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometry is well suited tomore » provide noninvasive approach to provide rapid screening of cellular responses to potentially toxic NSPs or any stimuli. Herein we review the technical basis of the approach, the instrument configuration and interface with the biological media, and various effects that impact the data, data analysis, and toxicity. Our preliminary results on live-cell monitoring show promise for rapid screening the NSPs.« less

Screening of agelasine D and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral leishmaniasis and Chagas disease.

PubMed

Vik, Anders; Proszenyák, Agnes; Vermeersch, Marieke; Cos, Paul; Maes, Louis; Gundersen, Lise-Lotte

2009-01-08

There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC(50) <0.5 microg/mL) while two others displayed IC(50) <1 microg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases (TDR), these compounds could be classified as hits for leishmaniasis and for Chagas disease, respectively. Identification of the hits as well as other SAR data from this initial screening will be valuable for design of more potent and selective potential drugs against these neglected tropical diseases.

Reviews Equipment: Data logger Book: Imagined Worlds Equipment: Mini data loggers Equipment: PICAXE-18M2 data logger Books: Engineering: A Very Short Introduction and To Engineer Is Human Book: Soap, Science, & Flat-Screen TVs Equipment: uLog and SensorLab Web Watch

NASA Astrophysics Data System (ADS)

2012-07-01

WE RECOMMEND Data logger Fourier NOVA LINK: data logging and analysis To Engineer is Human Engineering: essays and insights Soap, Science, & Flat-Screen TVs People, politics, business and science overlap uLog sensors and sensor adapter A new addition to the LogIT range offers simplicity and ease of use WORTH A LOOK Imagined Worlds Socio-scientific predictions for the future Mini light data logger and mini temperature data logger Small-scale equipment for schools SensorLab Plus LogIT's supporting software, with extra features HANDLE WITH CARE CAXE110P PICAXE-18M2 data logger Data logger 'on view' but disappoints Engineering: A Very Short Introduction A broad-brush treatment fails to satisfy WEB WATCH Two very different websites for students: advanced physics questions answered and a more general BBC science resource

Low-cost carbon thick-film strain sensors for implantable applications

NASA Astrophysics Data System (ADS)

Gutierrez, Christian A.; Meng, Ellis

2010-09-01

The suitability of low-cost carbon thick-film strain sensors embedded within a biomedical grade silicone rubber (Silastic® MDX4-4210) for implantable applications is investigated. These sensors address the need for robust cost-effective implantable strain sensing technology for the closed loop operation of function-restoring neural prosthetic systems. Design, fabrication and characterization of the sensors are discussed in the context of the application to strain/fullness measurements of the urinary bladder as part of the neuroprosthetic treatment of lower urinary tract dysfunction. The fabrication process, utilizing off-the-shelf screen-printing materials, is convenient and cost effective while achieving resolutions down to 75 µm. This method can also be extended to produce multilayer embedded devices by superposition of different screen-printable materials. Uniaxial loading performance, temperature dependence and long-term soak testing are used to validate suitability for implantation while proof-of-concept operation (up to 40% strain) is demonstrated on a bench-top latex balloon bladder model.

Highly selective dopamine electrochemical sensor based on electrochemically pretreated graphite and nafion composite modified screen printed carbon electrode.

PubMed

Ku, Shuhao; Palanisamy, Selvakumar; Chen, Shen-Ming

2013-12-01

Herein, we report a highly selective dopamine electrochemical sensor based on electrochemically pretreated graphite/nafion composite modified screen printed carbon (SPC) electrode. Electrochemically activated graphite/nafion composite was prepared by using a simple electrochemical method. Scanning electron microscope (SEM) used to characterize the surface morphology of the fabricated composite electrode. The SEM result clearly indicates that the graphitic basal planes were totally disturbed and leads to the formation of graphite nanosheets. The composite modified electrode showed an enhanced electrocatalytic activity toward the oxidation of DA when compared with either electrochemical pretreated graphite or nafion SPC electrodes. The fabricated composite electrode exhibits a good electrocatalytic oxidation toward DA in the linear response range from 0.5 to 70 μM with the detection limit of 0.023 μM. The proposed sensor also exhibits very good selectivity and stability, with the appreciable sensitivity. In addition, the proposed sensor showed satisfactory recovery results toward the commercial pharmaceutical DA samples. Copyright © 2013 Elsevier Inc. All rights reserved.

A flexible proximity sensor formed by duplex screen/screen-offset printing and its application to non-contact detection of human breathing

NASA Astrophysics Data System (ADS)

Nomura, Ken-Ichi; Kaji, Ryosaku; Iwata, Shiro; Otao, Shinobu; Imawaka, Naoto; Yoshino, Katsumi; Mitsui, Ryosuke; Sato, Junya; Takahashi, Seiya; Nakajima, Shin-Ichiro; Ushijima, Hirobumi

2016-01-01

We describe a flexible capacitance-type sensor that can detect an approaching human without contact, fabricated by developing and applying duplex conductive-ink printing to a film substrate. The results of our calculations show that the difference in size between the top and bottom electrodes of the sensor allows for the spatial extension of the electric field distribution over the electrodes. Hence, such a component functions as a proximity sensor. This thin and light device with a large form factor can be arranged at various places, including curved surfaces and the back of objects such that it is unnoticeable. In our experiment, we attached it to the back of a bed, and found that our device successfully detected the breathing of a subject on the bed without contacting his body. This should contribute to reducing the physical and psychological discomfort among patients during medical checks, or when their condition is being monitored.

A flexible proximity sensor formed by duplex screen/screen-offset printing and its application to non-contact detection of human breathing

PubMed Central

Nomura, Ken-ichi; Kaji, Ryosaku; Iwata, Shiro; Otao, Shinobu; Imawaka, Naoto; Yoshino, Katsumi; Mitsui, Ryosuke; Sato, Junya; Takahashi, Seiya; Nakajima, Shin-ichiro; Ushijima, Hirobumi

2016-01-01

We describe a flexible capacitance-type sensor that can detect an approaching human without contact, fabricated by developing and applying duplex conductive-ink printing to a film substrate. The results of our calculations show that the difference in size between the top and bottom electrodes of the sensor allows for the spatial extension of the electric field distribution over the electrodes. Hence, such a component functions as a proximity sensor. This thin and light device with a large form factor can be arranged at various places, including curved surfaces and the back of objects such that it is unnoticeable. In our experiment, we attached it to the back of a bed, and found that our device successfully detected the breathing of a subject on the bed without contacting his body. This should contribute to reducing the physical and psychological discomfort among patients during medical checks, or when their condition is being monitored. PMID:26795237

A FLUORESCENCE-BASED SCREENING ASSAY FOR DNA DAMAGE INDUCED BY GENOTOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

The possibility of deliberate or accidental release of toxic chemicals in industrial, commercial or residential settings has indicated a need for rapid, cost-effective and versatile monitoring methods to prevent exposures to humans and ecosystems. Because many toxic industrial c...

In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System

EPA Science Inventory

In 2007 the National Research Council envisioned the need for inexpensive, rapid, cell based toxicity testing methods relevant to human health. Recent advances in robotics, automation, and miniaturization have been used to address these problems. However, one challenge is that ma...

Integration into Big Data: First Steps to Support Reuse of Comprehensive Toxicity Model Modules (SOT)

EPA Science Inventory

Data surrounding the needs of human disease and toxicity modeling are largely siloed limiting the ability to extend and reuse modules across knowledge domains. Using an infrastructure that supports integration across knowledge domains (animal toxicology, high-throughput screening...

ADAPTING THE MEDAKA EMBRYO ASSAY TO A HIGH-THROUGHPUT APPROACH FOR DEVELOPMENTAL TOXICITY TESTING.

EPA Science Inventory

Chemical exposure during embryonic development may cause persistent effects, yet developmental toxicity data exist for very few chemicals. Current testing procedures are time consuming and costly, underlining the need for rapid and low cost screening strategies. While in vitro ...

ToxRefDB: Classifying ToxCast™ Phase I Chemicals Utilizing Structured Toxicity Information

EPA Science Inventory

There is an essential need for highly detailed chemicals classifications within the ToxCast™ research program. In order to develop predictive models and biological signatures utilizing high-throughput screening (HTS) and in vitro genomic data, relevant endpoints and toxicities m...

In Vitro Toxicity Screening Technique for Volatile Substances Using Flow-Through System##

EPA Science Inventory

In 2007 the National Research Council envisioned the need for inexpensive, rapid, cell based toxicity testing methods relevant to human health. Recent advances in robotics, automation, and miniaturization have been used to address this challenge. However, one drawback to currentl...

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 258.55 - Assessment monitoring program.

Code of Federal Regulations, 2013 CFR

2013-07-01

... upgradient edge of the MSWLF unit and downgradient monitoring well screen (minimum distance of travel); (5... effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or mutation. (ii) [Reserved] (j) In establishing ground-water protection...

40 CFR 258.55 - Assessment monitoring program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... upgradient edge of the MSWLF unit and downgradient monitoring well screen (minimum distance of travel); (5... effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or mutation. (ii) [Reserved] (j) In establishing ground-water protection...

40 CFR 258.55 - Assessment monitoring program.

Code of Federal Regulations, 2012 CFR

2012-07-01

... upgradient edge of the MSWLF unit and downgradient monitoring well screen (minimum distance of travel); (5... effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or mutation. (ii) [Reserved] (j) In establishing ground-water protection...

Optimization of high-throughput nanomaterial developmental toxicity testing in zebrafish embryos

EPA Science Inventory

Nanomaterial (NM) developmental toxicities are largely unknown. With an extensive variety of NMs available, high-throughput screening methods may be of value for initial characterization of potential hazard. We optimized a zebrafish embryo test as an in vivo high-throughput assay...

A possible early sign of hydroxychloroquine macular toxicity.

PubMed

Brandao, Livia M; Palmowski-Wolfe, Anja M

2016-02-01

Hydroxychloroquine (HCQ) has a low risk of retinal toxicity which increases dramatically with a cumulative dose of >1000 g. Here we report a case of HCQ macular toxicity presentation in a young patient with a cumulative dose of 438 g. A 15-year-old female started attending annual consultations for retinal toxicity screening in our clinic after 3 years of HCQ treatment for juvenile idiopathic dermatomyositis. She had been diagnosed at age 12 and had been on hydroxychloroquine 200 mg/day, cyclosporin 150 mg/day and vitamin D3 since. Screening consultations included: complete ophthalmologic examination, automated perimetry (AP, M Standard, Octopus 101, Haag-Streit), multifocal electroretinogram (VERIS 6.06™, FMSIII), optical coherence tomography (OCT, fast macular protocol, Cirrus SD-OCT, Carl Zeiss), fundus autofluorescence imaging (Spectralis OCT, Heidelberg Engineering Inc.) and color testing (Farnsworth-Panel-D-15). After 5 years of treatment, AP demonstrated reduced sensibility in only one extra-foveal point in each eye (p < 0.2). Even though other exams showed no alteration and the cumulative dose was only around 353 g, consultations were increased to every 6 months. After 2-year follow-up, that is, 7 years of HCQ, a bilateral paracentral macula thinning was evident on OCT, suggestive of bull's eye maculopathy. However, the retinal pigmented epithelium appeared intact and AP was completely normal in both eyes. Further evaluation with ganglion cell analysis (GCA = ganglion cell + inner plexiform layer, Cirrus SD-OCT, Carl Zeiss) showed a concentric thinning of this layer in the same area. Although daily and cumulative doses were still under the high toxicity risk parameters, HCQ was suspended. At a follow-up 1 year later, visual acuity was 20/16 without any further changes in OCT or on any other exam. This may be the first case report of insidious bull's eye maculopathy exclusively identified using OCT thickness analysis, in a patient in whom both cumulative and daily dosages were under the high-risk parameters for screening and the averages reported in studies. As ganglion cell analysis has only recently become available, further studies are needed to understand toxicity mechanisms and maybe review screening recommendations.

Application of Caenorhabditis elegans (nematode) and Danio rerio embryo (zebrafish) as model systems to screen for developmental and reproductive toxicity of Piperazine compounds.

PubMed

Racz, Peter I; Wildwater, Marjolein; Rooseboom, Martijn; Kerkhof, Engelien; Pieters, Raymond; Yebra-Pimentel, Elena Santidrian; Dirks, Ron P; Spaink, Herman P; Smulders, Chantal; Whale, Graham F

2017-10-01

To enable selection of novel chemicals for new processes, there is a recognized need for alternative toxicity screening assays to assess potential risks to man and the environment. For human health hazard assessment these screening assays need to be translational to humans, have high throughput capability, and from an animal welfare perspective be harmonized with the principles of the 3Rs (Reduction, Refinement, Replacement). In the area of toxicology a number of cell culture systems are available but while these have some predictive value, they are not ideally suited for the prediction of developmental and reproductive toxicology (DART). This is because they often lack biotransformation capacity, multicellular or multi- organ complexity, for example, the hypothalamus pituitary gonad (HPG) axis and the complete life cycle of whole organisms. To try to overcome some of these limitations in this study, we have used Caenorhabditis elegans (nematode) and Danio rerio embryos (zebrafish) as alternative assays for DART hazard assessment of some candidate chemicals being considered for a new commercial application. Nematodes exposed to Piperazine and one of the analogs tested showed a slight delay in development compared to untreated animals but only at high concentrations and with Piperazine as the most sensitive compound. Total brood size of the nematodes was also reduced primarily by Piperazine and one of the analogs. In zebrafish Piperazine and analogs showed developmental delays. Malformations and mortality in individual fish were also scored. Significant malformations were most sensitively identified with Piperazine, significant mortality was only observed in Piperazine and only at the higest dose. Thus, Piperazine seemed the most toxic compound for both nematodes and zebrafish. The results of the nematode and zebrafish studies were in alignment with data obtained from conventional mammalian toxicity studies indicating that these have potential as developmental toxicity screening systems. The results of these studies also provided reassurance that none of the Piperazines tested are likely to have any significant developmental and/or reproductive toxicity issues to humans when used in their commercial applications. Copyright © 2017. Published by Elsevier Ltd.

A Neuron-Based Screening Platform for Optimizing Genetically-Encoded Calcium Indicators

PubMed Central

Schreiter, Eric R.; Hasseman, Jeremy P.; Tsegaye, Getahun; Fosque, Benjamin F.; Behnam, Reza; Shields, Brenda C.; Ramirez, Melissa; Kimmel, Bruce E.; Kerr, Rex A.; Jayaraman, Vivek; Looger, Loren L.; Svoboda, Karel; Kim, Douglas S.

2013-01-01

Fluorescent protein-based sensors for detecting neuronal activity have been developed largely based on non-neuronal screening systems. However, the dynamics of neuronal state variables (e.g., voltage, calcium, etc.) are typically very rapid compared to those of non-excitable cells. We developed an electrical stimulation and fluorescence imaging platform based on dissociated rat primary neuronal cultures. We describe its use in testing genetically-encoded calcium indicators (GECIs). Efficient neuronal GECI expression was achieved using lentiviruses containing a neuronal-selective gene promoter. Action potentials (APs) and thus neuronal calcium levels were quantitatively controlled by electrical field stimulation, and fluorescence images were recorded. Images were segmented to extract fluorescence signals corresponding to individual GECI-expressing neurons, which improved sensitivity over full-field measurements. We demonstrate the superiority of screening GECIs in neurons compared with solution measurements. Neuronal screening was useful for efficient identification of variants with both improved response kinetics and high signal amplitudes. This platform can be used to screen many types of sensors with cellular resolution under realistic conditions where neuronal state variables are in relevant ranges with respect to timing and amplitude. PMID:24155972

Role of vacancy sites and UV-ozone treatment on few layered MoS2 nanoflakes for toxic gas detection

NASA Astrophysics Data System (ADS)

Burman, Debasree; Ghosh, Ruma; Santra, Sumita; Ray, Samit Kumar; Guha, Prasanta Kumar

2017-10-01

Various issues like global warming and environmental pollutions have led to the research of toxic gas detection worldwide. In this work, we have tried to develop a molybdenum disulfide (MoS2) based gas sensor to detect toxic gases like ammonia and NO. MoS2, an inorganic analog of graphene, has attracted lots of attention for many different applications recently. This paper reports the use of liquid exfoliated MoS2 nanoflakes as the sensing layer in a handheld, resistive toxic gas sensor. The nanoflakes were exfoliated from MoS2 bulk powder using a sonication based exfoliation technique at room temperature. The successful exfoliation of the nanoflakes was characterized using different techniques e.g., optical microscopy, atomic force microscopy, field emission scanning electron microscopy, high resolution transmission electron microscopy, x-ray diffraction, Raman spectroscopy, x-ray photoelectron spectroscopy and ultraviolet-visible spectrophotometry. The characterization results showed that few-layered nanoflakes have successfully been exfoliated. The MoS2 nanoflakes showed reasonable sensing towards ammonia and NO. In order to explore the effect of particle size on ammonia sensing, the MoS2 flakes were also exfoliated using different sonication times. We also observed that various factors like presence of vacancy sites, ambient oxygen, humidity, different contact electrodes have significant effect on the sensing characteristics. In fact, the response of the sensing layer against 400 ppm of ammonia increased from 54.1% to ˜80% when it was UV-ozone treated. This work holds promises to developing cost-effective, reliable and highly sensitive MoS2 based ammonia sensors.

[Detection of the level of antibodies against bovine leucosis virus in the cow milk by immune sensor].

PubMed

Pyrohova, L V; Starodub, M F; Nahaeva, L I

2005-01-01

An immune sensor based on the surface plasmon resonance (SPR) was developed for express diagnostics of bovine leucosis. Sensor used for detection of the level of antibodies against bovine leukaemia virus (BLV) in the milk serum. It was shown that immune sensor analysis is more sensitive, rapid and simple in comparison with the traditional AGID test. It was stated that the developed immune sensor may be used for performance of screening of bovine leucosis at the farms and the minimal dilution of the milk serum should be 1:20.

Studies on the Behavior of Larval Zebrafish for Developmental Neurotoxicity Screening

EPA Science Inventory

The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity. We are exploring methods to detect developmentally neurotoxic chemicals using zebrafish behavior at 6 days of age. The behavioral paradig...

Applying fiber optical methods for toxicological testing in vitro

NASA Astrophysics Data System (ADS)

Maerz, Holger K.; Buchholz, Rainer; Emmrich, Frank; Fink, Frank; Geddes, Clive L.; Pfeifer, Lutz; Raabe, Ferdinand; Scheper, Thomas-Helmut; Ulrich, Elizabeth; Marx, Uwe

1999-04-01

The new medical developments, e.g. immune therapy, patient oriented chemotherapy or even gene therapy, create a questionable doubt to the further requirement of animal test. Instead the call for humanitarian reproductive in vitro models becomes increasingly louder. Pharmaceutical usage of in vitro has a long proven history. In cancer research and therapy, the effect of chemostatica in vitro in the so-called oncobiogram is being tested; but the assays do not always correlate with in vivo-like drug resistance and sensitivity. We developed a drug test system in vitro, feasible for therapeutic drug monitoring by the combination of tissue cultivation in hollow fiber bioreactors and fiber optic sensors for monitoring the pharmaceutical effect. Using two fiber optic sensors - an optical oxygen sensor and a metabolism detecting Laserfluoroscope, we were able to successfully monitor the biological status of tissue culture and the drug or toxic effects of in vitro pharmaceutical testing. Furthermore, we developed and patented a system for monitoring the effect of minor toxic compounds which can induce Sick Building Syndrome.

Multicoloured fluorescent indicators for live-cell and in vivo imaging of inorganic mercury dynamics.

PubMed

Tao, Rongkun; Shi, Mei; Zou, Yejun; Cheng, Di; Wang, Qiaohui; Liu, Renmei; Wang, Aoxue; Zhu, Jiahuan; Deng, Lei; Hu, Hanyang; Chen, Xianjun; Du, Jiulin; Zhu, Weiping; Zhao, Yuzheng; Yang, Yi

2018-06-01

Engineered fluorescent indicators for visualizing mercury ion (Hg 2+ ) are powerful tools to illustrate the intracellular distribution and serious toxicity of the ion. However, the sensitive and specific detection of Hg 2+ in living cells and in vivo is challenging. This paper reported the development of fluorescent indicators for Hg 2+ in green or red color by inserting a circularly permuted fluorescent protein into a highly mercury-specific repressor. These sensors provided a rapid, sensitive, specific, and real-time read-out of Hg 2+ dynamics in solutions, bacteria, subcellular organelles of mammalian cells, and zebrafish, thereby providing a useful new method for Hg 2+ detection and bioimaging. In conjunction with the hydrogen peroxide sensor HyPer, we found mercury uptake would trigger subcellular oxidative events at the single-cell level, and provided visual evidence of the causality of mercury and oxidative damage. These sensors would paint the landscape of mercury toxicity to cell functions. Copyright © 2018 Elsevier Inc. All rights reserved.

Multisensor system for toxic gases detection generated on indoor environments

NASA Astrophysics Data System (ADS)

Durán, C. M.; Monsalve, P. A. G.; Mosquera, C. J.

2016-11-01

This work describes a wireless multisensory system for different toxic gases detection generated on indoor environments (i.e., Underground coal mines, etc.). The artificial multisensory system proposed in this study was developed through a set of six chemical gas sensors (MQ) of low cost with overlapping sensitivities to detect hazardous gases in the air. A statistical parameter was implemented to the data set and two pattern recognition methods such as Principal Component Analysis (PCA) and Discriminant Function Analysis (DFA) were used for feature selection. The toxic gases categories were classified with a Probabilistic Neural Network (PNN) in order to validate the results previously obtained. The tests were carried out to verify feasibility of the application through a wireless communication model which allowed to monitor and store the information of the sensor signals for the appropriate analysis. The success rate in the measures discrimination was 100%, using an artificial neural network where leave-one-out was used as cross validation method.

Effect of heating rate on toxicity of pyrolysis gases from some synthetic polymers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Soriano, J. A.; Kosola, K. L.

1977-01-01

The effect of heating rate on the toxicity of the pyrolysis gases from some synthetic polymers was investigate, using a screening test method. The synthetic polymers were polyethylene, polystyrene, polymethyl methacrylate, polycarbonate, ABS, polyaryl sulfone, polyether sulfone, and polyphenylene sulfide. The toxicants from the sulfur-containing polymers appeared to act more rapidly than the toxicants from the other polymers. It is not known whether this effect is due primarily to differences in concentration or in the nature of the toxicants. The carbon monoxide concentrations found do not account for the observed results.

Sensor array for toxic gas detection

DOEpatents

Stetter, Joseph R.; Zaromb, Solomon; Penrose, William R.

1987-01-01

A portable instrument for use in the field in detecting and identifying a hazardous component in air or other gas including an array of small sensors which upon exposure to the gas from a pattern of electrical responses, a source of standard response patterns characteristic of various components, and microprocessor means for comparing the sensor-formed response pattern with one or more standard patterns to thereby identify the component on a display. The number of responses may be increased beyond the number of sensors by changing the operating voltage, temperature or other condition associated with one or more sensors to provide a plurality of responses from each of one or more of the sensors. In one embodiment, the instrument is capable of identifying anyone of over 50-100 hazardous components.

Fabrication of bimetallic microfluidic surface-enhanced Raman scattering sensors on paper by screen printing.

PubMed

Qu, Lu-Lu; Song, Qi-Xia; Li, Yuan-Ting; Peng, Mao-Pan; Li, Da-Wei; Chen, Li-Xia; Fossey, John S; Long, Yi-Tao

2013-08-20

Au-Ag bimetallic microfluidic, dumbbell-shaped, surface enhanced Raman scattering (SERS) sensors were fabricated on cellulose paper by screen printing. These printed sensors rely on a sample droplet injection zone, and a SERS detection zone at either end of the dumbbell motif, fabricated by printing silver nanoparticles (Ag NPs) and gold nanoparticles (Au NPs) successively with microscale precision. The microfluidic channel was patterned using an insulating ink to connect these two zones and form a hydrophobic circuit. Owing to capillary action of paper in the millimeter-sized channels, the sensor could enable self-filtering of fluids to remove suspended particles within wastewater without pumping. This sensor also allows sensitive SERS detection, due to advantageous combination of the strong surface enhancement of Ag NPs and excellent chemical stability of Au NPs. The SERS performance of the sensors was investigated by employing the probe rhodamine 6G, a limit of detection (LOD) of 1.1×10(-13)M and an enhancement factor of 8.6×10(6) could be achieved. Moreover, the dumbbell-shaped bimetallic sensors exhibited good stability with SERS performance being maintained over 14 weeks in air, and high reproducibility with less than 15% variation in spot-to-spot SERS intensity. Using these dumbbell-shaped bimetallic sensors, substituted aromatic pollutants in wastewater samples could be quantitatively analyzed, which demonstrated their excellent capability for rapid trace pollutant detection in wastewater samples in the field without pre-separation. Copyright © 2013 Elsevier B.V. All rights reserved.

The toxicological properties of petroleum gases.

PubMed

McKee, Richard H; Herron, Deborah; Saperstein, Mark; Podhasky, Paula; Hoffman, Gary M; Roberts, Linda

2014-01-01

To characterize the toxicological hazards of petroleum gases, 90-day inhalation toxicity (Organization for Economic Cooperation and Development [OECD] 413) and developmental toxicity (OECD 414) tests were conducted with liquefied propane gas (LPG) at concentrations of 1000, 5000, or 10,000 ppm. A micronucleus test (OECD 474) of LPG was also conducted. No systemic or developmental effects were observed; the overall no observed adverse effect concentration (NOAEC) was 10,000 ppm. Further, there was no effect of LPG exposure at levels up to 10,000 ppm on micronucleus induction and no evidence of bone marrow toxicity. Other alkane gases (ethane, propane, n-butane, and isobutane) were then evaluated in combined repeated exposure studies with reproduction/development toxicity screening tests (OECD 422). There were no toxicologically important changes in parameters relating to systemic toxicity or neurotoxicity for any of these gases at concentrations ranging from 9000 to 16,000 ppm. There was no evidence of effects on developmental or reproductive toxicity in the studies of ethane, propane, or n-butane at the highest concentrations tested. However, there was a reduction in mating in the high-exposure group (9000 ppm) of the isobutane study, which although not significantly different was outside the range previously observed in the testing laboratory. Assuming the reduction in mating to have been toxicologically significant, the NOAEC for the isobutane reproductive toxicity screening test was 3000 ppm (7125 mg/m(3)). A method is proposed by which the toxicity of any of the 106 complex petroleum gas streams can be estimated from its composition.

Computational fluid dynamics analysis and experimental study of a low measurement error temperature sensor used in climate observation.

PubMed

Yang, Jie; Liu, Qingquan; Dai, Wei

2017-02-01

To improve the air temperature observation accuracy, a low measurement error temperature sensor is proposed. A computational fluid dynamics (CFD) method is implemented to obtain temperature errors under various environmental conditions. Then, a temperature error correction equation is obtained by fitting the CFD results using a genetic algorithm method. The low measurement error temperature sensor, a naturally ventilated radiation shield, a thermometer screen, and an aspirated temperature measurement platform are characterized in the same environment to conduct the intercomparison. The aspirated platform served as an air temperature reference. The mean temperature errors of the naturally ventilated radiation shield and the thermometer screen are 0.74 °C and 0.37 °C, respectively. In contrast, the mean temperature error of the low measurement error temperature sensor is 0.11 °C. The mean absolute error and the root mean square error between the corrected results and the measured results are 0.008 °C and 0.01 °C, respectively. The correction equation allows the temperature error of the low measurement error temperature sensor to be reduced by approximately 93.8%. The low measurement error temperature sensor proposed in this research may be helpful to provide a relatively accurate air temperature result.

Chalcogenide Glass for Active and Passive Mid-IR Applications

DTIC Science & Technology

2010-09-01

Reactive gas conversion • Chemical vapour deposition What is a Chalcogenide? – From Greek sulphur-loving for elements that frequently bond to sulphur...Predominately As or Se based (toxic!) ORC Research Focussed On – Gallium Lanthanum Sulphides (non-toxic) – Germanium Sulphides (non-toxic) – Capability to...770 2 hours Primary Screening 2 - 3 days Time Scale: one week Pioneering Technology: High Throughput Physical Vapour Deposition Material Discovery

A Novel Inhibitor Of Topoisomerase I is Selectively Toxic For A Subset of Non-Small Cell Lung Cancer Cell Lines | Office of Cancer Genomics

Cancer.gov

SW044248, identified through a screen for chemicals that are selectively toxic for NSCLC cell lines, was found to rapidly inhibit macromolecular synthesis in sensitive, but not in insensitive cells. SW044248 killed approximately 15% of a panel of 74 NSCLC cell lines and was non-toxic to immortalized human bronchial cell lines.

TOXICOLOGICAL HIGHLIGHT: SCREENING FOR DEVELOPMENTAL TOXICITY OF TOBACCO SMOKE CONSTITUENTS

EPA Science Inventory

Abstract
Cigarette smoking is unrivaled among developmental toxicants in terms of total adverse impact on the human population. According to the American Lung Association, smoking during pregnancy is estimated to account for 20 to 30 percent of low-weight babies, up to 14 per...

NEW METHODS TO SCREEN FOR DEVELOPMENTAL NEUROTOXICITY.

EPA Science Inventory

The development of alternative methods for toxicity testing is driven by the need for scientifically valid data (i.e. predictive of a toxic effect) that can be obtained in a rapid and cost-efficient manner. These predictions will enable decisions to be made as to whether further ...

A Redox Sensitive Pathway in the Mouse ES Cell Assay Modeled From ToxCast HTS Data

EPA Science Inventory

The broad chemical landscape coupled with the lack of developmental toxicity information across most environmental chemicals has motivated the need for high- throughput screening methods and predictive models of developmental toxicity. Towards this end, we used the mouse embryoni...

A Different Approach to Validating Screening Assays for Developmental Toxicity

EPA Science Inventory

BACKGROUND: There continues to be many efforts around the world to develop assays that are shorter than the traditional embryofetal developmental toxicity assay, or use fewer or no mammals, or use less compound, or have all three attributes. Each assay developer needs to test th...

SeqAPASS: Sequence alignment to predict across-species susceptibility

EPA Science Inventory

Efforts to shift the toxicity testing paradigm from whole organism studies to those focused on the initiation of toxicity and relevant pathways have led to increased utilization of in vitro and in silico methods. Hence the emergence of high through-put screening (HTS) programs, s...

Modeling Reproductive Toxicity for Chemical Prioritization into an Integrated Testing Strategy

EPA Science Inventory

The EPA ToxCast research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I tested 309 well-characterized chemicals in over 500 assays of different molecular targets, cellular responses and cell-states. Of th...

ToxiFly: Can Fruit Flies be Used to Identify Toxicity Pathways for Airborne Chemicals?

EPA Science Inventory

Current high-throughput and alternative screening assays for chemical toxicity are unable to test volatile organic compounds (VOCs), thus limiting their scope. Further, the data generated by these assays require mechanistic information to link effects at molecular targets to adve...

Some possible reference materials for fire toxicity tests

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Solis, A. N.

1977-01-01

Suitable reference materials need to be selected in order to standardize any test method. The evaluation of cotton, polyethylene, polyether sulfone, polycarbonate, polystyrene, and polyurethane flexible and rigid foams as possible reference materials for the University of San Francisco/NASA toxicity screening test method is discussed.

Pathway Profiling and Tissue Modeling of Developmental Toxicity

EPA Science Inventory

High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

VIRTUAL EMBRYO: SYSTEMS MODELING IN DEVELOPMENTAL TOXICITY - Symposium: SOT 2012

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. Chemical profiling in ToxCast covered 965 drugs-chemicals in over 500 diverse assays testing...

Virtual Embryo: Systems Modeling in Developmental Toxicity

EPA Science Inventory

High-throughput and high-content screening (HTS-HCS) studies are providing a rich source of data that can be applied to in vitro profiling of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition t...

Water quality criteria for hexachloroethane: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davidson, K.A.; Hovatter, P.S.; Ross, R.H.

1988-03-01

The available data regarding the environmental fate, aquatic toxicity, and mammalian toxicity of hexachloroethane, which is used in military screening smokes, were reviewed. The USEPA guidelines were used to generate water quality criteria for the protection of aquatic life and its uses and of human health. 16 tabs.

High-Content, High-Throughput Screening for the Identification of Cytotoxic Compounds Based on Cell Morphology and Cell Proliferation Markers

PubMed Central

Martin, Heather L.; Adams, Matthew; Higgins, Julie; Bond, Jacquelyn; Morrison, Ewan E.; Bell, Sandra M.; Warriner, Stuart; Nelson, Adam; Tomlinson, Darren C.

2014-01-01

Toxicity is a major cause of failure in drug discovery and development, and whilst robust toxicological testing occurs, efficiency could be improved if compounds with cytotoxic characteristics were identified during primary compound screening. The use of high-content imaging in primary screening is becoming more widespread, and by utilising phenotypic approaches it should be possible to incorporate cytotoxicity counter-screens into primary screens. Here we present a novel phenotypic assay that can be used as a counter-screen to identify compounds with adverse cellular effects. This assay has been developed using U2OS cells, the PerkinElmer Operetta high-content/high-throughput imaging system and Columbus image analysis software. In Columbus, algorithms were devised to identify changes in nuclear morphology, cell shape and proliferation using DAPI, TOTO-3 and phosphohistone H3 staining, respectively. The algorithms were developed and tested on cells treated with doxorubicin, taxol and nocodazole. The assay was then used to screen a novel, chemical library, rich in natural product-like molecules of over 300 compounds, 13.6% of which were identified as having adverse cellular effects. This assay provides a relatively cheap and rapid approach for identifying compounds with adverse cellular effects during screening assays, potentially reducing compound rejection due to toxicity in subsequent in vitro and in vivo assays. PMID:24505478

A Multiplexed High-Content Screening Approach Using the Chromobody Technology to Identify Cell Cycle Modulators in Living Cells.

PubMed

Schorpp, Kenji; Rothenaigner, Ina; Maier, Julia; Traenkle, Bjoern; Rothbauer, Ulrich; Hadian, Kamyar

2016-10-01

Many screening hits show relatively poor quality regarding later efficacy and safety. Therefore, small-molecule screening efforts shift toward high-content analysis providing more detailed information. Here, we describe a novel screening approach to identify cell cycle modulators with low toxicity by combining the Cell Cycle Chromobody (CCC) technology with the CytoTox-Glo (CTG) cytotoxicity assay. The CCC technology employs intracellularly functional single-domain antibodies coupled to a fluorescent protein (chromobodies) to visualize the cell cycle-dependent redistribution of the proliferating cell nuclear antigen (PCNA) in living cells. This image-based cell cycle analysis was combined with determination of dead-cell protease activity in cell culture supernatants by the CTG assay. We adopted this multiplex approach to high-throughput format and screened 960 Food and Drug Administration (FDA)-approved drugs. By this, we identified nontoxic compounds, which modulate different cell cycle stages, and validated selected hits in diverse cell lines stably expressing CCC. Additionally, we independently validated these hits by flow cytometry as the current state-of-the-art format for cell cycle analysis. This study demonstrates that CCC imaging is a versatile high-content screening approach to identify cell cycle modulators, which can be multiplexed with cytotoxicity assays for early elimination of toxic compounds during screening. © 2016 Society for Laboratory Automation and Screening.

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

PubMed

Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

2015-10-01

To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

ELECTROCHEMICAL TECHNIQUE FOR TNT USING DISPOSABLE SCREEN-PRINTED ELECTRODE

EPA Science Inventory

Screen-printed thick film electrodes are demonstrated as voltammetric sensors for measurement of 2,4,6-trinitrotoluene (TNT). The square wave voltammetric (SWV) scan technique is used to measure TNT in as little as 50 uL sample volumes. This electrochemical assay is coupled ...

Study and Control of Various Corona Modes in an Atmospheric Pressure Weakly Ionized Plasma Reactor Using a Current Sensor Characterized by a Broad Frequency Band

NASA Astrophysics Data System (ADS)

Islam, Rokibul; Pedrow, Patrick; Lekobou, William; Englund, Karl

2013-09-01

A broad band current sensor is being used to monitor the various phenomena (primary streamers, secondary streamers, back corona, etc.) associated with an atmospheric pressure needle-array-to-grounded-screen corona discharge. The reactor consists of a PVC tube and the needle array consists of nickel coated steel electrodes with radius of curvature about 50 μ . The grounded screen is made from stainless steel mesh and applied voltage has a frequency of 60 Hz with an RMS value ranging from 0 to 10 kV. The voltage sensor is a resistive divider and the current sensor is a viewing resistor with value 50 Ω. The feed gas stream is presently (argon + acetylene) or (argon + oxygen) with the argon acting as carrier gas and the acetylene and oxygen acting as precursor gases. Voltage and current are captured with a LeCroy 9350AL 500MHz oscilloscope and analyzed with Matlab using digital signal processing algorithms. The goals of the research are 1) to measure reactor electrical power on a real time basis; 2) to provide real time control of the applied voltage and thus avoid spark conditions; and 3) to identify the various corona modes present in the reactor. Processing of substrates takes place downstream from the grounded screen, outside of the harsh corona discharge environment.

High Throughput Exposure Prioritization of Chemicals Using a Screening-Level Probabilistic SHEDS-Lite Exposure Model

EPA Science Inventory

These novel modeling approaches for screening, evaluating and classifying chemicals based on the potential for biologically-relevant human exposures will inform toxicity testing and prioritization for chemical risk assessment. The new modeling approach is derived from the Stocha...

Neuronal models for evaluation of proliferation in vitro using high content screening

EPA Science Inventory

In vitro test methods can provide a rapid approach for the screening of large numbers of chemicals for their potential to produce toxicity (hazard identification). In order to identify potential developmental neurotoxicants, a battery of in vitro tests for neurodevelopmental proc...

Phenotypic Screening of Primary Human Cell Culture Systems to Identify Potential for Compound Toxicity (CHI Phenotypic Screening)

EPA Science Inventory

Addressing safety aspects of drugs and environmental chemicals has historically been undertaken through animal testing. However, the quantity of chemicals needing assessment and the challenge of species extrapolation require development of alternative approaches. Assessing phenot...

Gene Expression Changes in Developing Zebrafish as Potential Markers for Rapid Developmental Neurotoxicity Screening

EPA Science Inventory

Sparse information exists on many chemicals to guide developmental neurotoxicity (DNT) risk assessments. As DNT testing using rodents is laborious and expensive, alternative species such as zebrafish are being adapted for toxicity screening. Assessing the DNT potential of chem...

Incorporating Human Dosimetry and Exposure into High-Throughput In Vitro Toxicity Screening

EPA Science Inventory

Many chemicals in commerce today have undergone limited or no safety testing. To reduce the number of untested chemicals and prioritize limited testing resources, several governmental programs are using high-throughput in vitro screens for assessing chemical effects across multip...

AOPs and Biomarkers: Bridging High Throughput Screening and Regulatory Decision Making

EPA Science Inventory

As high throughput screening (HTS) plays a larger role in toxicity testing, camputational toxicology has emerged as a critical component in interpreting the large volume of data produced. Computational models designed to quantify potential adverse effects based on HTS data will b...

Functional Assays and Alternative Species: Using Larval Zebrafish in Developmental Neurotoxicity Screening**

EPA Science Inventory

The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity. As such, we are exploring a behavioral testing paradigm, which can assess the effect of sublethal and subteratogenic concentrations of de...

Functional Assays and Alternative Species: Using Larval Zebrafish in Developmental Neurotoxicity Screening

EPA Science Inventory

The U.S. Environmental Protection Agency is developing and evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity. Towards this goal, we are exploring methods to detect developmental neurotoxicants in very young larval zebrafish. We have...

High-throughput screening, predictive modeling and computational embryology

EPA Science Inventory

High-throughput screening (HTS) studies are providing a rich source of data that can be applied to profile thousands of chemical compounds for biological activity and potential toxicity. EPA’s ToxCast™ project, and the broader Tox21 consortium, in addition to projects worldwide,...

EPA's proposed land ban regulations. Hearing before the Subcommittee on Commerce, Transportation, and Tourism of the Committee on Energy and Commerce, House of Representatives, Ninety-Ninth Congress, Second Session, February 19, 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-01-01

Three representatives of the Environmental Protection Agency (EPA) testified in response to questions over the agency's apparent approval of the land disposal of toxic materials in contradiction to the ban implicit in the Hazardous and Solid Waste Amendments of 1984. In new regulations, EPA interprets the ban as applying only when migration of toxic materials exceeds its screening levels. EPA also cites its screening levels to place a cap on waste treatment. At issue was EPA's effort to avoid the mandate of the 1984 legislation and its acceptance of screening levels which may assume a lower threat than actually exists.more » EPA representatives explained the rulemaking, and defended the use of screening levels as a basis for treatment and exemption. Additional material submitted for the record by the agency and by the House committee follows the testimony.« less

Determining Performance Acceptability of Electrochemical Oxygen Sensors

NASA Technical Reports Server (NTRS)

Gonzales, Daniel

2012-01-01

A method has been developed to screen commercial electrochemical oxygen sensors to reduce the failure rate. There are three aspects to the method: First, the sensitivity over time (several days) can be measured and the rate of change of the sensitivity can be used to predict sensor failure. Second, an improvement to this method would be to store the sensors in an oxygen-free (e.g., nitrogen) environment and intermittently measure the sensitivity over time (several days) to accomplish the same result while preserving the sensor lifetime by limiting consumption of the electrode. Third, the second time derivative of the sensor response over time can be used to determine the point in time at which the sensors are sufficiently stable for use.

Abscisic acid dynamics in roots detected with genetically encoded FRET sensors

PubMed Central

Jones, Alexander M; Danielson, Jonas ÅH; ManojKumar, Shruti N; Lanquar, Viviane; Grossmann, Guido; Frommer, Wolf B

2014-01-01

Cytosolic hormone levels must be tightly controlled at the level of influx, efflux, synthesis, degradation and compartmentation. To determine ABA dynamics at the single cell level, FRET sensors (ABACUS) covering a range ∼0.2–800 µM were engineered using structure-guided design and a high-throughput screening platform. When expressed in yeast, ABACUS1 detected concentrative ABA uptake mediated by the AIT1/NRT1.2 transporter. Arabidopsis roots expressing ABACUS1-2µ (Kd∼2 µM) and ABACUS1-80µ (Kd∼80 µM) respond to perfusion with ABA in a concentration-dependent manner. The properties of the observed ABA accumulation in roots appear incompatible with the activity of known ABA transporters (AIT1, ABCG40). ABACUS reveals effects of external ABA on homeostasis, that is, ABA-triggered induction of ABA degradation, modification, or compartmentation. ABACUS can be used to study ABA responses in mutants and quantitatively monitor ABA translocation and regulation, and identify missing components. The sensor screening platform promises to enable rapid fine-tuning of the ABA sensors and engineering of plant and animal hormone sensors to advance our understanding of hormone signaling. DOI: http://dx.doi.org/10.7554/eLife.01741.001 PMID:24737862

Obstructive Sleep Apnea Screening Using a Piezo-Electric Sensor.

PubMed

Erdenebayar, Urtnasan; Park, Jong Uk; Jeong, Pilsoo; Lee, Kyoung Joung

2017-06-01

In this study, we propose a novel method for obstructive sleep apnea (OSA) detection using a piezo-electric sensor. OSA is a relatively common sleep disorder. However, more than 80% of OSA patients remain undiagnosed. We investigated the feasibility of OSA assessment using a single-channel physiological signal to simplify the OSA screening. We detected both snoring and heartbeat information by using a piezo-electric sensor, and snoring index (SI) and features based on pulse rate variability (PRV) analysis were extracted from the filtered piezo-electric sensor signal. A support vector machine (SVM) was used as a classifier to detect OSA events. The performance of the proposed method was evaluated on 45 patients from mild, moderate, and severe OSA groups. The method achieved a mean sensitivity, specificity, and accuracy of 72.5%, 74.2%, and 71.5%; 85.8%, 80.5%, and 80.0%; and 70.3%, 77.1%, and 71.9% for the mild, moderate, and severe groups, respectively. Finally, these results not only show the feasibility of OSA detection using a piezo-electric sensor, but also illustrate its usefulness for monitoring sleep and diagnosing OSA. © 2017 The Korean Academy of Medical Sciences.

Development and Validation of an On-Line Water Toxicity Sensor with Immobilized Luminescent Bacteria for On-Line Surface Water Monitoring

PubMed Central

Woutersen, Marjolijn; van der Gaag, Bram; Abrafi Boakye, Afua; Mink, Jan; Marks, Robert S.; Wagenvoort, Arco J.; Ketelaars, Henk A. M.; Brouwer, Bram; Heringa, Minne B.

2017-01-01

Surface water used for drinking water production is frequently monitored in The Netherlands using whole organism biomonitors, with for example Daphnia magna or Dreissena mussels, which respond to changes in the water quality. However, not all human-relevant toxic compounds can be detected by these biomonitors. Therefore, a new on-line biosensor has been developed, containing immobilized genetically modified bacteria, which respond to genotoxicity in the water by emitting luminescence. The performance of this sensor was tested under laboratory conditions, as well as under field conditions at a monitoring station along the river Meuse in The Netherlands. The sensor was robust and easy to clean, with inert materials, temperature control and nutrient feed for the reporter organisms. The bacteria were immobilized in sol-gel on either an optical fiber or a glass slide and then continuously exposed to water. Since the glass slide was more sensitive and robust, only this setup was used in the field. The sensor responded to spikes of genotoxic compounds in the water with a minimal detectable concentration of 0.01 mg/L mitomycin C in the laboratory and 0.1 mg/L mitomycin C in the field. With further optimization, which should include a reduction in daily maintenance, the sensor has the potential to become a useful addition to the currently available biomonitors. PMID:29165334

Development and Validation of an On-Line Water Toxicity Sensor with Immobilized Luminescent Bacteria for On-Line Surface Water Monitoring.

PubMed

Woutersen, Marjolijn; van der Gaag, Bram; Abrafi Boakye, Afua; Mink, Jan; Marks, Robert S; Wagenvoort, Arco J; Ketelaars, Henk A M; Brouwer, Bram; Heringa, Minne B

2017-11-22

Surface water used for drinking water production is frequently monitored in The Netherlands using whole organism biomonitors, with for example Daphnia magna or Dreissena mussels, which respond to changes in the water quality. However, not all human-relevant toxic compounds can be detected by these biomonitors. Therefore, a new on-line biosensor has been developed, containing immobilized genetically modified bacteria, which respond to genotoxicity in the water by emitting luminescence. The performance of this sensor was tested under laboratory conditions, as well as under field conditions at a monitoring station along the river Meuse in The Netherlands. The sensor was robust and easy to clean, with inert materials, temperature control and nutrient feed for the reporter organisms. The bacteria were immobilized in sol-gel on either an optical fiber or a glass slide and then continuously exposed to water. Since the glass slide was more sensitive and robust, only this setup was used in the field. The sensor responded to spikes of genotoxic compounds in the water with a minimal detectable concentration of 0.01 mg/L mitomycin C in the laboratory and 0.1 mg/L mitomycin C in the field. With further optimization, which should include a reduction in daily maintenance, the sensor has the potential to become a useful addition to the currently available biomonitors.

Toxicity of pyrolysis gases from synthetic polymers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Soriano, J. A.; Kosola, K. L.; Kourtides, D. A.; Parker, J. A.

1977-01-01

The screening test method was used to investigate toxicity in polyethylene, polystyrene, polymethyl methacrylate, polyaryl sulfone, polyether sulfone, polyphenyl sulfone, and polyphenylene sulfide. Changing from a rising temperature program to a fixed temperature program resulted on shorter times to animal responses. This effect was attributed in part to more rapid generation of toxicants. The toxicants from the sulfur containing polymers appeared to act more rapidly than the toxicants from the other polymers. It was not known whether this effect was due primarily to difference in concentration or in the nature of the toxicants. The carbon monoxide concentration found did not account for the results observed with the sulfur containing polymers. Polyphenyl sulfone appeared to exhibit the least toxicity among the sulfur containing polymers evaluated under these test conditions.

EPA's ToxCast Program for Predicting Hazard and Prioritizing the Toxicity Testing of Environmental Chemicals

EPA Science Inventory

An alternative is to perform a set of relatively inexpensive and rapid high throughput screening (HTS) assays, derive signatures predictive of effects or modes of chemical toxicity from the HTS data, then use these predictions to prioritize chemicals for more detailed analysis. T...

Evaluating the Zebrafish Embryo Toxicity Test for Pesticide Hazard Screening

EPA Science Inventory

Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more reso...

EPA Project Updates: DSSTox and ToxCast Generating New Data and Data Linkages for Use in Predictive Modeling

EPA Science Inventory

EPAs National Center for Computational Toxicology is building capabilities to support a new paradigm for toxicity screening and prediction. The DSSTox project is improving public access to quality structure-annotated chemical toxicity information in less summarized forms than tr...

Computational Modeling and Simulation of Developmental Toxicity. What can we learn from a virtual embryo? (FDA-CFSAN workshop)

EPA Science Inventory

SYNOPSIS: The question of how tissues and organs are shaped during development is crucial for understanding human birth defects. Data from high-throughput screening assays on human stem cells may be utilized predict developmental toxicity with reasonable accuracy. Other types of ...

DESIGN AND PERFORMANCE OF A XENOBIOTIC METABOLISM DATABASE MANAGER FOR METABOLIC SIMULATOR ENHANCEMENT AND CHEMICAL RISK ANALYSIS

EPA Science Inventory

A major uncertainty that has long been recognized in evaluating chemical toxicity is accounting for metabolic activation of chemicals resulting in increased toxicity. In silico approaches to predict chemical metabolism and to subsequently screen and prioritize chemicals for risk ...

CHEMICAL PRIORITIZATION FOR DEVELOPMENTAL TOXICITY USING LITERATURE MINING-BASED WEIGHTING OF TOXCAST ASSAYS

EPA Science Inventory

Defining a predictive model of developmental toxicity from in vitro and high-throughput screening (HTS) assays can be limited by the availability of developmental defects data. ToxRefDB (www.epa.gov/ncct/todrefdb) was built from animal studies on data-rich environmental chemicals...

Perspectives on Validation of High-Throughput Assays Supporting 21st Century Toxicity Testing

EPA Science Inventory

In vitro high-throughput screening (HTS) assays are seeing increasing use in toxicity testing. HTS assays can simultaneously test many chemicals but have seen limited use in the regulatory arena, in part because of the need to undergo rigorous, time-consuming formal validation. ...

Validation, acceptance, and extension of a predictive model of reproductive toxicity using ToxCast data

EPA Science Inventory

The EPA ToxCast research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I tested 309 well-characterized chemicals (mostly pesticides) in over 500 assays of different molecular targets, cellular responses an...

EPA DSSTox and ToxCast Project Updates: Generating New Data and Linkages in Support of Public Toxico-Cheminformatics Efforts

EPA Science Inventory

EPA’s National Center for Computational Toxicology is generating data and capabilities to support a new paradigm for toxicity screening and prediction. The DSSTox project is improving public access to quality structure-annotated chemical toxicity information in less summarized fo...

Framework for a Quantitative Systemic Toxicity Model (FutureToxII)

EPA Science Inventory

EPA’s ToxCast program profiles the bioactivity of chemicals in a diverse set of ~700 high throughput screening (HTS) assays. In collaboration with L’Oreal, a quantitative model of systemic toxicity was developed using no effect levels (NEL) from ToxRefDB for 633 chemicals with HT...

Developmental Exposure to a Dopaminergic Toxicant Produces Altered Locomotor Activity in Larval Zebrafish

EPA Science Inventory

In an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after developmental exposure to various classes of prototypic drugs that act on the central nervous system. ...

In Vitro Screening of Environmental Chemicals for Targeted Testing Prioritization: The ToxCast Project

EPA Science Inventory

Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency’s ToxCast program aims to address these concerns by ...

The US EPAs ToxCast Program for the Prioritization and Prediction of Environmental Chemical Toxicity

EPA Science Inventory

To meet the need for evaluating large numbers of chemicals for potential toxicity, the U.S. Environmental Protection Agency has initiated a research project call ToxCast that makes use of recent advances in molecular biology and high-throughput screening. These technologies have ...

Predictive Signatures of Developmental Toxicity Modeled with HTS Data from ToxCast™ Bioactivity Profiles

EPA Science Inventory

The EPA ToxCast™ research program uses a high-throughput screening (HTS) approach for predicting the toxicity of large numbers of chemicals. Phase-I contains 309 well-characterized chemicals which are mostly pesticides tested in over 600 assays of different molecular targets, cel...

Predictive Modeling of Apical Toxicity Endpoints Using Data From ToxCast

EPA Science Inventory

The US EPA and other regulatory agencies face a daunting challenge of evaluating potential toxicity for tens of thousands of environmental chemicals about which little is currently known. The EPA’s ToxCast program is testing a novel approach to this problem by screening compounds...

Utility of an improved model of amyloid-beta (Aβ1-42) toxicity in Caenorhabditis elegans for drug screening for Alzheimer’s disease

PubMed Central

2012-01-01

Background The definitive indicator of Alzheimer’s disease (AD) pathology is the profuse accumulation of amyloid-ß (Aß) within the brain. Various in vitro and cell-based models have been proposed for high throughput drug screening for potential therapeutic benefit in diseases of protein misfolding. Caenorhabditis elegans offers a convenient in vivo system for examination of Aß accumulation and toxicity in a complex multicellular organism. Ease of culturing and a short life cycle make this animal model well suited to rapid screening of candidate compounds. Results We have generated a new transgenic strain of C. elegans that expresses full length Aß1-42. This strain differs from existing Aß models that predominantly express amino-truncated Aß3-42. The Aß1-42 is expressed in body wall muscle cells, where it oligomerizes, aggregates and results in severe, and fully penetrant, age progressive-paralysis. The in vivo accumulation of Aß1-42 also stains positive for amyloid dyes, consistent with in vivo fibril formation. The utility of this model for identification of potential protective compounds was examined using the investigational Alzheimer’s therapeutic PBT2, shown to be neuroprotective in mouse models of AD and significantly improve cognition in AD patients. We observed that treatment with PBT2 provided rapid and significant protection against the Aß-induced toxicity in C. elegans. Conclusion This C. elegans model of full length Aß1-42 expression can now be adopted for use in screens to rapidly identify and assist in development of potential therapeutics and to study underlying toxic mechanism(s) of Aß. PMID:23171715

Micro-ring sensor used in the diagnosis of gastric cancer

NASA Astrophysics Data System (ADS)

Shi, Sichao; Cheng, Qing; Lin, Rong; Su, Da; Huang, Ying

2016-01-01

To find a detecting method that can be applied to the clinical screening and diagnosis, the cascaded micro-ring sensor with Vernier effect was used to distinguish gastric cancerous and normal cells. The simulation by FDTD of the cascaded microring sensor with different refractive indexes of the analyte (normal cells and gastric cancer cells) will be presented. In the simulation, with the refractive index's change Δn=0.02 for the two different analyte, the shift of sensor's resonant wavelength is 6.71nm. And the cascaded micro-ring sensor's sensitivity S is 335.5nm/RIU, and it is much larger compared to 19nm/RIU for a single ring sensor.

White balance tester with color sensor for industrial applications

NASA Astrophysics Data System (ADS)

Chen, Jiasheng; Zhu, XiaoSong

1996-12-01

The white balance tester is an instrument that adjusts the white balance for color TVs, monitors, and PC displays. We have designed a new white balance tester for use directly at the production line. It picks up the R (Red), G (Green), and B (Blue) signals for the screen using color sensors, compares the signals with the data previously stored in the internal memory, displays their differences with LED bars in the compare mode or displays x y Y, u v Y, JND (just noticeable difference) as well as correlated color temperature in the numerical mode. A built-in TV signal generator sets the luminance of the adjusting screen to the brightness of the reference white screen automatically. A 16-bit single chip microcomputer processes the measured values and controls the output levels of the TV signal generator.

Screen-printed nanoparticles as anti-counterfeiting tags

NASA Astrophysics Data System (ADS)

Campos-Cuerva, Carlos; Zieba, Maciej; Sebastian, Victor; Martínez, Gema; Sese, Javier; Irusta, Silvia; Contamina, Vicente; Arruebo, Manuel; Santamaria, Jesus

2016-03-01

Metallic nanoparticles with different physical properties have been screen printed as authentication tags on different types of paper. Gold and silver nanoparticles show unique optical signatures, including sharp emission bandwidths and long lifetimes of the printed label, even under accelerated weathering conditions. Magnetic nanoparticles show distinct physical signals that depend on the size of the nanoparticle itself. They were also screen printed on different substrates and their magnetic signals read out using a magnetic pattern recognition sensor and a vibrating sample magnetometer. The novelty of our work lies in the demonstration that the combination of nanomaterials with optical and magnetic properties on the same printed support is possible, and the resulting combined signals can be used to obtain a user-configurable label, providing a high degree of security in anti-counterfeiting applications using simple commercially-available sensors.

Screen-printed nanoparticles as anti-counterfeiting tags.

PubMed

Campos-Cuerva, Carlos; Zieba, Maciej; Sebastian, Victor; Martínez, Gema; Sese, Javier; Irusta, Silvia; Contamina, Vicente; Arruebo, Manuel; Santamaria, Jesus

2016-03-04

Metallic nanoparticles with different physical properties have been screen printed as authentication tags on different types of paper. Gold and silver nanoparticles show unique optical signatures, including sharp emission bandwidths and long lifetimes of the printed label, even under accelerated weathering conditions. Magnetic nanoparticles show distinct physical signals that depend on the size of the nanoparticle itself. They were also screen printed on different substrates and their magnetic signals read out using a magnetic pattern recognition sensor and a vibrating sample magnetometer. The novelty of our work lies in the demonstration that the combination of nanomaterials with optical and magnetic properties on the same printed support is possible, and the resulting combined signals can be used to obtain a user-configurable label, providing a high degree of security in anti-counterfeiting applications using simple commercially-available sensors.

Label-free screening of foodborne Salmonella using surface plasmon resonance imaging

USDA-ARS?s Scientific Manuscript database

Since 15 pathogens cause approximately 95% of the foodborne infections, it is desirable to develop rapid and simultaneous screening methods for these major pathogens. In this study, we developed an immunoassay for Salmonella based on surface plasmon resonance imaging (SPRi). The sensor surface modif...

High-Content Screening in Zebrafish Embryos Identifies Butafenacil as a Potent Inducer of Anemia

PubMed Central

Leet, Jessica K.; Lindberg, Casey D.; Bassett, Luke A.; Isales, Gregory M.; Yozzo, Krystle L.; Raftery, Tara D.; Volz, David C.

2014-01-01

Using transgenic zebrafish (fli1:egfp) that stably express enhanced green fluorescent protein (eGFP) within vascular endothelial cells, we recently developed and optimized a 384-well high-content screening (HCS) assay that enables us to screen and identify chemicals affecting cardiovascular development and function at non-teratogenic concentrations. Within this assay, automated image acquisition procedures and custom image analysis protocols are used to quantify body length, heart rate, circulation, pericardial area, and intersegmental vessel area within individual live embryos exposed from 5 to 72 hours post-fertilization. After ranking developmental toxicity data generated from the U.S. Environmental Protection Agency's (EPA's) zebrafish teratogenesis assay, we screened 26 of the most acutely toxic chemicals within EPA's ToxCast Phase-I library in concentration-response format (0.05–50 µM) using this HCS assay. Based on this screen, we identified butafenacil as a potent inducer of anemia, as exposure from 0.39 to 3.125 µM butafenacil completely abolished arterial circulation in the absence of effects on all other endpoints evaluated. Butafenacil is an herbicide that inhibits protoporphyrinogen oxidase (PPO) – an enzyme necessary for heme production in vertebrates. Using o-dianisidine staining, we then revealed that severe butafenacil-induced anemia in zebrafish was due to a complete loss of hemoglobin following exposure during early development. Therefore, six additional PPO inhibitors within the ToxCast Phase-I library were screened to determine whether anemia represents a common adverse outcome for these herbicides. Embryonic exposure to only one of these PPO inhibitors – flumioxazin – resulted in a similar phenotype as butafenacil, albeit not as severe as butafenacil. Overall, this study highlights the potential utility of this assay for (1) screening chemicals for cardiovascular toxicity and (2) prioritizing chemicals for future hypothesis-driven and mechanism-focused investigations within zebrafish and mammalian models. PMID:25090246

Amphibian (Xenopus sp.) iodothyronine deiodinase production for screening of thyroid-disrupting chemicals

EPA Science Inventory

The U.S. EPA-MED amphibian thyroid group is currently screening chemicals for inhibition of human iodothyronine deiodinase activity as components of the thyroid system important in human development. Amphibians are a bellwether taxonomic group to gauge toxicity of chemicals in th...

Defining the taxonomic domain of applicability for mammalian-based high-throughput screening assays

EPA Science Inventory

Cell-based high throughput screening (HTS) technologies are becoming mainstream in chemical safety evaluations. The US Environmental Protection Agency (EPA) Toxicity Forecaster (ToxCastTM) and the multi-agency Tox21 Programs have been at the forefront in advancing this science, m...

TOXICITY AND BIODEGRADABILITY SCREENING OF NONIONIC SURFACTANTS USING SEDIMENT-DERIVED METHANOGENIC CONSORTIA. (R825404)

EPA Science Inventory

Abstract

The objective of this study was to screen and select biologically-compatible surfactants for subsequent use in enhancing the bioavailability and reductive dechlorination of sorbed-phase chlorinated organic contaminants. Sixteen surfactants commonly used in sur...

QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

EPA Science Inventory

New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

Behavorial Screens for Detecting Developmental Neurotoxicity in Larval Zebrafish

EPA Science Inventory

As part of the EPA's effort to develop an in vivo, vertebrate screen for toxic chemicals, we have characterized basic behaviors of 6-day post-fertilization (dpf) zebrafish (Danio rerio) larvae in a microtiter plate format. Our main goal is to develop a convenient, reproducible me...

Studies of the Variables Affecting Behavior of Larval Zebrafish for Developmental Neurotoxicity Testing*

EPA Science Inventory

The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity. We are exploring methods to screen for developmentally neurotoxic chemicals using zebrafish behavior at 6 days of age. The behavioral par...

Aquatic Toxicity Screening of an ACWA Secondary Waste, GB-Hydrolysate

DTIC Science & Technology

2009-01-01

Toxicity Comparison for GB-hydrolysates, Acetone, and Malathion Using O’Bryan and Ross Chemical Scoring System for Hazard and Exposure Identification ...hydrolysates, Acetone, and Malathion Using O’Bryan and Ross Chemical Scoring System for Hazard and Exposure Identification (5) and the U.S. Fish and...WWTF) or a TSDF. The toxicity results were ranked using the Chemical Scoring System for Hazard and Exposure Identification (5). This system is

Ranking the in vivo toxicity of nanomaterials in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Vecchio, G.; Galeone, A.; Malvindi, M. A.; Cingolani, R.; Pompa, P. P.

2013-09-01

In this work, we propose a quantitative assessment of nanoparticles toxicity in vivo. We show a quantitative ranking of several types of nanoparticles (AuNPs, AgNPs, cadmium-based QDs, cadmium-free QDs, and iron oxide NPs, with different coating and/or surface chemistries), providing a categorization of their toxicity outcomes. This strategy may offer an innovative high-throughput screening tool of nanomaterials, of potential and broad interest to the nanoscience community.

PHYTOCHEMICAL SCREENING, ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF PENTANISIA PRUNELLOIDES FROM THE EASTERN CAPE PROVINCE, SOUTH AFRICA.

PubMed

Mathews, Miya Gugulethu; Ajayi, Oyemitan Idris; Opeoluwa, Oyedeji Oyehan; Oluwatobi, Oluwafemi Samuel; Benedicta N, Nkeh-Chungag; Phindile, Songca Sandile; Oyedeji; Omowumi, Adebola

2016-01-01

Pentanisia prunelloides is a medicinal plant widely used to remedy various ailments including infections, fever and rheumatism in Eastern Cape Province of South Africa. There is scanty report on the phytochemical and biological properties of the plant; hence various solvent extracts of the dried plant materials were phytochemically screened, and its aqueous extract evaluated for acute toxicity effect, analgesic and antiinflammatory properties in rodents. Different extracts of both leaf and rhizome were obtained separately with ethanol, methanol and water. Portions of the filtrate were used for qualitative screening of secondary metabolites and remaining portions were concentrated and dried. Dried grounded leaf and rhizome of the plant were also used for quantitative screening for some major components. The aqueous extract of the leaf and rhizome were used for acute toxicity (LD 50 ) test, antiinflammatory and analgesic activities in rodents. The qualitative phytochemical screening showed the presence of several phytoconstituents with saponins, flavonoids and alkaloids constituting highest constituents in the leaf and rhizome. The LD50: of the aqueous extracts (from leaf or rhizome) was found to be ≥5000 mg/kg orally. The leaf and rhizome aqueous extract (250-500 mg/kg) significantly (p<0.01) reduced egg albumin-induced paw oedema and paw licking in mice induced by formalin, signifying antinociceptive and antiinflammatory activities respectively. It is concluded that the leaf and rhizome of P. prunelloides are rich in various phytochemicals which could be associated with their medicinal uses. The aqueous leaf and rhizome extracts are similarly non-toxic orally, showed antiinflammatory and analgesic potentials thus rationalizing its use in folkloric medicine.

Discovery of a novel general anesthetic chemotype using high-throughput screening.

PubMed

McKinstry-Wu, Andrew R; Bu, Weiming; Rai, Ganesha; Lea, Wendy A; Weiser, Brian P; Liang, David F; Simeonov, Anton; Jadhav, Ajit; Maloney, David J; Eckenhoff, Roderic G

2015-02-01

The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures. Using a novel high-throughput screen employing the fluorescent anesthetic 1-aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein target(s), we screened a 350,000 compound library for competition with 1-aminoanthracene-apoferritin binding. Hit compounds meeting structural criteria had their binding affinities for apoferritin quantified with isothermal titration calorimetry and were tested for γ-aminobutyric acid type A receptor binding using a flunitrazepam binding assay. Chemotypes with a strong presence in the top 700 and exhibiting activity via isothermal titration calorimetry were selected for medicinal chemistry optimization including testing for anesthetic potency and toxicity in an in vivo Xenopus laevis tadpole assay. Compounds with low toxicity and high potency were tested for anesthetic potency in mice. From an initial chemical library of more than 350,000 compounds, we identified 2,600 compounds that potently inhibited 1-aminoanthracene binding to apoferritin. A subset of compounds chosen by structural criteria (700) was successfully reconfirmed using the initial assay. Based on a strong presence in both the initial and secondary screens the 6-phenylpyridazin-3(2H)-one chemotype was assessed for anesthetic activity in tadpoles. Medicinal chemistry efforts identified four compounds with high potency and low toxicity in tadpoles, two were found to be effective novel anesthetics in mice. The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.

Function-based Biosensor for Hazardous Waste Toxin Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

James J Hickman

There is a need for new types of toxicity sensors in the DOE and other agencies that are based on biological function as the toxins encountered during decontamination or waste remediation may be previously unknown or their effects subtle. Many times the contents of the environmental waste, especially the minor components, have not been fully identified and characterized. New sensors of this type could target unknown toxins that cause death as well as intermediate levels of toxicity that impair function or cause long term impairment that may eventually lead to death. The primary question posed in this grant was tomore » create an electronically coupled neuronal cellular circuit to be used as sensor elements for a hybrid non-biological/biological toxin sensor system. A sensor based on the electrical signals transmitted between two mammalian neurons would allow the marriage of advances in solid state electronics with a functioning biological system to develop a new type of biosensor. Sensors of this type would be a unique addition to the field of sensor technology but would also be complementary to existing sensor technology that depends on knowledge of what is to be detected beforehand. We integrated physics, electronics, surface chemistry, biotechnology, and fundamental neuroscience in the development of this biosensor. Methods were developed to create artificial surfaces that enabled the patterning of discrete cells, and networks of cells, in culture; the networks were then aligned with transducers. The transducers were designed to measure electromagnetic fields (EMF) at low field strength. We have achieved all of the primary goals of the project. We can now pattern neurons routinely in our labs as well as align them with transducers. We have also shown the signals between neurons can be modulated by different biochemicals. In addition, we have made another significant advance where we have repeated the patterning results with adult hippocampal cells. Finally, we demonstrated that patterned cardiac cells on microelectrode arrays could act as sensors as well.« less

Concentration-response data on toxicity of pyrolysis gases from some natural and synthetic polymers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Huttlinger, N. V.

1978-01-01

Concentration-response data are presented on the toxic effects of the pyrolysis gases from some natural and synthetic polymers, using the toxicity screening test method developed at the University of San Francisco. The pyrolysis gases from wool, red oak, Douglas fir, polycaprolactam, polyether sulfone, polyaryl sulfone, and polyphenylene sulfide appeared to exhibit the concentration-response relationships commonly encountered in toxicology. Carbon monoxide seemed to be an important toxicant in the pyrolysis gases from red oak, Douglas fir, and polycaprolactam, but did not appear to have been the principal toxicant in the pyrolysis gases from polyether sulfone and polyphenylene sulfide.

Handheld colorimeter for determination of heavy metal concentrations

NASA Astrophysics Data System (ADS)

López Ruiz, N.; Ariza, M.; Martínez Olmos, A.; Vukovic, J.; Palma, A. J.; Capitan-Vallvey, L. F.

2011-08-01

A portable instrument that measures heavy metal concentration from a colorimetric sensor array is presented. The use of eight sensing membranes, placed on a plastic support, allows to obtain the hue component of the HSV colour space of each one in order to determinate the concentration of metals present in a solution. The developed microcontroller-based system captures, in an ambient light environment, an image of the sensor array using an integrated micro-camera and shows the picture in a touch micro-LCD screen which acts as user interface. After image-processing of the regions of interest selected by the user, colour and concentration information are displayed on the screen.

Lopinavir up-regulates expression of the antiviral protein ribonuclease L in human papillomavirus-positive cervical carcinoma cells.

PubMed

Batman, Gavin; Oliver, Anthony W; Zehbe, Ingeborg; Richard, Christina; Hampson, Lynne; Hampson, Ian N

2011-01-01

We have previously shown that the HIV protease inhibitor lopinavir has selective toxicity against human papillomavirus (HPV)-positive cervical carcinoma cells via an unknown mechanism. SiHa cervical carcinoma cells were stably transfected with the proteasome sensor vector pZsProSensor-1 to confirm lopinavir inhibits the proteasome in these cells. The Panorama Xpress profiler 725 antibody array was then used to analyse specific changes in protein expression in lopinavir-treated versus control untreated SiHa cells followed by PCR and western blotting. Colorimetric growth assays of lopinavir-treated E6/E7 immortalised versus control human keratinocytes were performed. Targeted small interfering RNA gene silencing followed by growth assay comparison of lopinavir-treated/untreated SiHa cells was also used. Lopinavir induced an increase in the fluorescence of pZsProSensor-1 transfected SiHa cells, indicative of proteasomal inhibition. Ribonuclease L (RNASEL) protein was shown to be up-regulated in lopinavir-treated SiHa cells, which was confirmed by PCR and western blot. Targeted silencing of RNASEL reduced the sensitivity of SiHa cells to lopinavir. Selective toxicity against E6/E7 immortalised keratinocytes versus control cells was also seen with lopinavir and was associated with up-regulated RNASEL expression. These data are consistent with the toxicity of lopinavir against HPV-positive cervical carcinoma cells being related to its ability to block viral proteasome activation and induce an up-regulation of the antiviral protein RNASEL. This is supported by the drug's selective toxicity and up-regulation of RNASEL in E6/E7 immortalised keratinocytes combined with the increased resistance to lopinavir observed in SiHa cells following silencing of RNASEL gene expression.

Analytical applications of microbial fuel cells. Part II: Toxicity, microbial activity and quantification, single analyte detection and other uses.

PubMed

Abrevaya, Ximena C; Sacco, Natalia J; Bonetto, Maria C; Hilding-Ohlsson, Astrid; Cortón, Eduardo

2015-01-15

Microbial fuel cells were rediscovered twenty years ago and now are a very active research area. The reasons behind this new activity are the relatively recent discovery of electrogenic or electroactive bacteria and the vision of two important practical applications, as wastewater treatment coupled with clean energy production and power supply systems for isolated low-power sensor devices. Although some analytical applications of MFCs were proposed earlier (as biochemical oxygen demand sensing) only lately a myriad of new uses of this technology are being presented by research groups around the world, which combine both biological-microbiological and electroanalytical expertises. This is the second part of a review of MFC applications in the area of analytical sciences. In Part I a general introduction to biological-based analytical methods including bioassays, biosensors, MFCs design, operating principles, as well as, perhaps the main and earlier presented application, the use as a BOD sensor was reviewed. In Part II, other proposed uses are presented and discussed. As other microbially based analytical systems, MFCs are satisfactory systems to measure and integrate complex parameters that are difficult or impossible to measure otherwise, such as water toxicity (where the toxic effect to aquatic organisms needed to be integrated). We explore here the methods proposed to measure toxicity, microbial metabolism, and, being of special interest to space exploration, life sensors. Also, some methods with higher specificity, proposed to detect a single analyte, are presented. Different possibilities to increase selectivity and sensitivity, by using molecular biology or other modern techniques are also discussed here. Copyright © 2014 Elsevier B.V. All rights reserved.

Studies with the USF/NASA toxicity screening test method - Exercise wheels and oxygen replenishment

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Cumming, H. J.

1977-01-01

Continuing efforts to improve the University of San Francisco/NASA toxicity screening test method have included the addition of exercise wheels to provide a different measure of incapacitation, and oxygen replenishment to offset any effect of oxygen depletion by the test animals. The addition of exercise wheels limited the number of animals in each test and doubled the required number of tests without any significant improvement in reproducibility. Oxygen replenishment appears to have an effect on survival in the last 5 minutes of the 30-minute test, but the effect is expected to be similar for most materials.

Bridging the gap between high-throughput genetic and transcriptional data reveals cellular pathways responding to alpha-synuclein toxicity

PubMed Central

Yeger-Lotem, Esti; Riva, Laura; Su, Linhui Julie; Gitler, Aaron D.; Cashikar, Anil; King, Oliver D.; Auluck, Pavan K.; Geddie, Melissa L.; Valastyan, Julie S.; Karger, David R.; Lindquist, Susan; Fraenkel, Ernest

2009-01-01

Cells respond to stimuli by changes in various processes, including signaling pathways and gene expression. Efforts to identify components of these responses increasingly depend on mRNA profiling and genetic library screens, yet the functional roles of the genes identified by these assays often remain enigmatic. By comparing the results of these two assays across various cellular responses, we found that they are consistently distinct. Moreover, genetic screens tend to identify response regulators, while mRNA profiling frequently detects metabolic responses. We developed an integrative approach that bridges the gap between these data using known molecular interactions, thus highlighting major response pathways. We harnessed this approach to reveal cellular pathways related to alpha-synuclein, a small lipid-binding protein implicated in several neurodegenerative disorders including Parkinson disease. For this we screened an established yeast model for alpha-synuclein toxicity to identify genes that when overexpressed alter cellular survival. Application of our algorithm to these data and data from mRNA profiling provided functional explanations for many of these genes and revealed novel relations between alpha-synuclein toxicity and basic cellular pathways. PMID:19234470

Prioritizing chemicals for environmental management in China based on screening of potential risks

NASA Astrophysics Data System (ADS)

Yu, Xiangyi; Mao, Yan; Sun, Jinye; Shen, Yingwa

2014-03-01

The rapid development of China's chemical industry has created increasing pressure to improve the environmental management of chemicals. To bridge the large gap between the use and safe management of chemicals, we performed a comprehensive review of the international methods used to prioritize chemicals for environmental management. By comparing domestic and foreign methods, we confirmed the presence of this gap and identified potential solutions. Based on our literature review, we developed an appropriate screening method that accounts for the unique characteristics of chemical use within China. The proposed method is based on an evaluation using nine indices of the potential hazard posed by a chemical: three environmental hazard indices (persistence, bioaccumulation, and eco-toxicity), four health hazard indices (acute toxicity, carcinogenicity, mutagenicity, and reproductive and developmental toxicity), and two environmental exposure hazard indices (chemical amount and utilization pattern). The results of our screening agree with results of previous efforts from around the world, confirming the validity of the new system. The classification method will help decisionmakers to prioritize and identify the chemicals with the highest environmental risk, thereby providing a basis for improving chemical management in China.

Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy

PubMed Central

Oberdörster, Günter; Maynard, Andrew; Donaldson, Ken; Castranova, Vincent; Fitzpatrick, Julie; Ausman, Kevin; Carter, Janet; Karn, Barbara; Kreyling, Wolfgang; Lai, David; Olin, Stephen; Monteiro-Riviere, Nancy; Warheit, David; Yang, Hong

2005-01-01

The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicity screening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays. There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity. In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability, protein interactions, complement activation, and pro-oxidant activity is also considered. Tier 1 in vivo assays are proposed for pulmonary, oral, skin and injection exposures, and Tier 2 evaluations for pulmonary exposures are also proposed. Tier 1 evaluations include markers of inflammation, oxidant stress, and cell proliferation in portal-of-entry and selected remote organs and tissues. Tier 2 evaluations for pulmonary exposures could include deposition, translocation, and toxicokinetics and biopersistence studies; effects of multiple exposures; potential effects on the reproductive system, placenta, and fetus; alternative animal models; and mechanistic studies. PMID:16209704

Three dimensional interactive display

NASA Technical Reports Server (NTRS)

Vranish, John M. (Inventor)

2005-01-01

A three-dimensional (3-D) interactive display and method of forming the same, includes a transparent capaciflector (TC) camera formed on a transparent shield layer on the screen surface. A first dielectric layer is formed on the shield layer. A first wire layer is formed on the first dielectric layer. A second dielectric layer is formed on the first wire layer. A second wire layer is formed on the second dielectric layer. Wires on the first wire layer and second wire layer are grouped into groups of parallel wires with a turnaround at one end of each group and a sensor pad at the opposite end. An operational amplifier is connected to each of the sensor pads and the shield pad biases the pads and receives a signal from connected sensor pads in response to intrusion of a probe. The signal is proportional to probe location with respect to the monitor screen.

Sulfadiazine-selective determination in aquaculture environment: selective potentiometric transduction by neutral or charged ionophores.

PubMed

Almeida, S A A; Heitor, A M; Montenegro, M C B S M; Sales, M G F

2011-09-15

Solid-contact sensors for the selective screening of sulfadiazine (SDZ) in aquaculture waters are reported. Sensor surfaces were made from PVC membranes doped with tetraphenylporphyrin-manganese(III) chloride, α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin ionophores that were dispersed in plasticizer. Some membranes also presented a positive or a negatively charged additive. Phorphyrin-based sensors relied on a charged carrier mechanism. They exhibited a near-Nernstian response with slopes of 52 mV decade(-1) and detection limits of 3.91×10(-5) mol L(-1). The addition of cationic lipophilic compounds to the membrane originated Nernstian behaviours, with slopes ranging 59.7-62.0 mV decade(-1) and wider linear ranges. Cyclodextrin-based sensors acted as neutral carriers. In general, sensors with positively charged additives showed an improved potentiometric performance when compared to those without additive. Some SDZ selective membranes displayed higher slopes and extended linear concentration ranges with an increasing amount of additive (always <100% ionophore). The sensors were independent from the pH of test solutions within 2-7. The sensors displayed fast response, always <15s. In general, a good discriminating ability was found in real sample environment. The sensors were successfully applied to the fast screening of SDZ in real waters samples from aquaculture fish farms. The method offered the advantages of simplicity, accuracy, and automation feasibility. The sensing membrane may contribute to the development of small devices allowing in locus measurements of sulfadiazine or parent-drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

SeqAPASS to evaluate conservation of high-throughput screening targets across non-mammalian species

EPA Science Inventory

Cell-based high-throughput screening (HTS) and computational technologies are being applied as tools for toxicity testing in the 21st century. The U.S. Environmental Protection Agency (EPA) embraced these technologies and created the ToxCast Program in 2007, which has served as a...

DEVELOPMENT OF TOXICITY REFERENCE VALUES FOR ECOLOGICAL SOIL SCREENING LEVELS (ECO-SSLS) FOR TERRESTRIAL WILDLIFE

EPA Science Inventory

Ecological Soil Screening Levels (Eco-SSLs) protective of terrestrial wildlife were developed by the USEPA Superfund. The wildlife Eco-SSL is the soil contaminant concentration where the Effect Dose (TRV) and Exposure Dose are equal (amount of contaminant in the diet that is take...

COMPARISON OF CHEMICAL SCREENING AND RANKING APPROACHES: THE WASTE MINIMIZATION PRIORITIZATION TOOL VERSUS TOXIC EQUIVALENCY POTENTIALS

EPA Science Inventory

Chemical screening in the United States is often conducted using scoring and ranking methodologies. Linked models accounting for chemical fate, exposure, and toxicological effects are generally preferred in Europe and in product Life Cycle Assessment. For the first time, a compar...

Comparison of Chemical-induced Changes in Proliferation and Apoptosis in Human and Mouse Neuroprogenitor Cells.***

EPA Science Inventory

There is a need to develop rapid and efficient models to screen chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present study...

COMPARISON OF NEUROSCREEN-1 AND CEREBELLAR GRANULE CELL CULTURES FOR EVALUATING NEURITE OUTGROWTH USING THE ARRAYSCAN HIGH CONTENT ANALYSIS SYSTEM

EPA Science Inventory

A major challenge facing the Environmental Protection Agency is the development of high-throughput screening assays amendable to resource-efficient developmental neurotoxicity for chemical screening and toxicity prioritization. One approach uses in vitro, cell-based assays which...

Extrapolating toxicity data across species using U.S. EPA SeqAPASS tool

EPA Science Inventory

In vitro high-throughput screening (HTS) and in silico technologies have emerged as 21st century tools for chemical hazard identification. In 2007 the U.S. Environmental Protection Agency (EPA) launched the ToxCast Program, which has screened thousands of chemicals in hundreds of...

Life-Stage Physiologically-Based Pharmacokinetic (PBPK) Model Applications to Screen Environmental Hazards.

EPA Science Inventory

This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. A...

COMPARISON OF CHEMICAL-INDUCED CHANGES IN PROLIFERATION AND APOPTOSIS IN HUMAN AND MOUSE NEUROPROGENITOR CELLS.

EPA Science Inventory

There is a need to develop rapid and efficient models for screening chemicals for their potential to cause developmental neurotoxicity. Use of in vitro neuronal models, including human cells, is one approach that allows for timely, cost-effective toxicity screening. The present s...

A high-throughput three-dimensional cell migration assay for toxicity screening with mobile device-based macroscopic image analysis

PubMed Central

Timm, David M.; Chen, Jianbo; Sing, David; Gage, Jacob A.; Haisler, William L.; Neeley, Shane K.; Raphael, Robert M.; Dehghani, Mehdi; Rosenblatt, Kevin P.; Killian, T. C.; Tseng, Hubert; Souza, Glauco R.

2013-01-01

There is a growing demand for in vitro assays for toxicity screening in three-dimensional (3D) environments. In this study, 3D cell culture using magnetic levitation was used to create an assay in which cells were patterned into 3D rings that close over time. The rate of closure was determined from time-lapse images taken with a mobile device and related to drug concentration. Rings of human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs) were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure correlated with the viability and migration of cells in two dimensions (2D). Images taken using a mobile device were similar in analysis to images taken with a microscope. Ring closure may serve as a promising label-free and quantitative assay for high-throughput in vivo toxicity in 3D cultures. PMID:24141454

Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

PubMed Central

Keating, James E.; Zorn, Bryan T.; Kochar, Tavleen K.; Wolfgang, Matthew C.; Glish, Gary L.; Tarran, Robert

2018-01-01

The e-liquids used in electronic cigarettes (E-cigs) consist of propylene glycol (PG), vegetable glycerin (VG), nicotine, and chemical additives for flavoring. There are currently over 7,700 e-liquid flavors available, and while some have been tested for toxicity in the laboratory, most have not. Here, we developed a 3-phase, 384-well, plate-based, high-throughput screening (HTS) assay to rapidly triage and validate the toxicity of multiple e-liquids. Our data demonstrated that the PG/VG vehicle adversely affected cell viability and that a large number of e-liquids were more toxic than PG/VG. We also performed gas chromatography–mass spectrometry (GC-MS) analysis on all tested e-liquids. Subsequent nonmetric multidimensional scaling (NMDS) analysis revealed that e-liquids are an extremely heterogeneous group. Furthermore, these data indicated that (i) the more chemicals contained in an e-liquid, the more toxic it was likely to be and (ii) the presence of vanillin was associated with higher toxicity values. Further analysis of common constituents by electron ionization revealed that the concentration of cinnamaldehyde and vanillin, but not triacetin, correlated with toxicity. We have also developed a publicly available searchable website (www.eliquidinfo.org). Given the large numbers of available e-liquids, this website will serve as a resource to facilitate dissemination of this information. Our data suggest that an HTS approach to evaluate the toxicity of multiple e-liquids is feasible. Such an approach may serve as a roadmap to enable bodies such as the Food and Drug Administration (FDA) to better regulate e-liquid composition. PMID:29584716

Analysing Harmonic Motions with an iPhone's Magnetometer

ERIC Educational Resources Information Center

Yavuz, Ahmet; Temiz, Burak Kagan

2016-01-01

In this paper, we propose an experiment for analysing harmonic motion using an iPhone's (or iPad's) magnetometer. This experiment consists of the detection of magnetic field variations obtained from an iPhone's magnetometer sensor. A graph of harmonic motion is directly displayed on the iPhone's screen using the "Sensor Kinetics"…

Comparison of the Insecticidal Characteristics of Commercially Available Plant Essential Oils Against Aedes aegypti and Anopheles gambiae (Diptera: Culicidae).

PubMed

Norris, Edmund J; Gross, Aaron D; Dunphy, Brendan M; Bessette, Steven; Bartholomay, Lyric; Coats, Joel R

2015-09-01

Aedes aegypti and Anopheles gambiae are two mosquito species that represent significant threats to global public health as vectors of Dengue virus and malaria parasites, respectively. Although mosquito populations have been effectively controlled through the use of synthetic insecticides, the emergence of widespread insecticide-resistance in wild mosquito populations is a strong motivation to explore new insecticidal chemistries. For these studies, Ae. aegypti and An. gambiae were treated with commercially available plant essential oils via topical application. The relative toxicity of each essential oil was determined, as measured by the 24-h LD(50) and percentage knockdown at 1 h, as compared with a variety of synthetic pyrethroids. For Ae. aegypti, the most toxic essential oil (patchouli oil) was ∼1,700-times less toxic than the least toxic synthetic pyrethroid, bifenthrin. For An. gambiae, the most toxic essential oil (patchouli oil) was ∼685-times less toxic than the least toxic synthetic pyrethroid. A wide variety of toxicities were observed among the essential oils screened. Also, plant essential oils were analyzed via gas chromatography/mass spectrometry (GC/MS) to identify the major components in each of the samples screened in this study. While the toxicities of these plant essential oils were demonstrated to be lower than those of the synthetic pyrethroids tested, the large amount of GC/MS data and bioactivity data for each essential oil presented in this study will serve as a valuable resource for future studies exploring the insecticidal quality of plant essential oils. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Teratological Effects of a Panel of Sixty Water-Soluble Toxicants on Zebrafish Development

PubMed Central

Ali, Shaukat; Aalders, Jeffrey

2014-01-01

Abstract The zebrafish larva is a promising whole-animal model for safety pharmacology, environmental risk assessment, and developmental toxicity. This model has been used for the high-throughput toxicity screening of various compounds. Our aim here is to identify possible phenotypic markers of teratogenicity in zebrafish embryos that could be used for the assaying compounds for reproductive toxicity. We have screened a panel of 60 water-soluble toxicants to examine their effects on zebrafish development. A total of 22,080 wild-type zebrafish larvae were raised in 250 μL defined buffer in 96-well plates at a plating density of one embryo per well. They were exposed for a 96-h period starting at 24 h post-fertilization. A logarithmic concentration series was used for range-finding, followed by a narrower geometric series for developmental toxicity assessment. A total of 9017 survivors were analyzed at 5 days post-fertilization for nine phenotypes, namely, (1) normal, (2) pericardial oedema, (3) yolk sac oedema, (4) melanophores dispersed, (5) bent tail tip, (6) bent body axis, (7) abnormal Meckel's cartilage, (8) abnormal branchial arches, and (9) uninflated swim bladder. For each toxicant, the EC50 (concentration required to produce one or more of these abnormalities in 50% of embryos) was also calculated. For the majority of toxicants (55/60) there was, at the population level, a statistically significant, concentration-dependent increase in the incidence of abnormal phenotypes among survivors. The commonest abnormalities were pericardial oedema, yolk sac oedema, dispersed melanophores, and uninflated swim bladder. It is possible therefore that these could prove to be general indicators of reproductive toxicity in the zebrafish embryo assay. PMID:24650241

STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies

EPA Science Inventory

The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central and peripheral nervous systems in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be trimmed ...

Improving ecological risk assessment of persistent, bioaccumulative, and toxic (PBT) chemicals by using an integrated modeling system - An example assessing chloroparaffins in riverine environments.

EPA Science Inventory

Chemical risk assessment (CRA) is primarily carried out at the screening level relying on empirical relationships between chemical properties and tested toxicity effects. Ultimately, risk to aquatic ecosystems is strongly dependent on actual exposure, which depends on chemical pr...

Optimization of DNA barcode method to assess altered chemical toxicity due to CYP-mediated metabolism

EPA Science Inventory

A drawback of current in vitro chemical testing is that many commonly used cell lines lack chemical metabolism. This hinders the use and relevance of cell culture in high throughput chemical toxicity screening. To address this challenge, we engineered HEK293T cells to overexpress...

Identifying Functionally Linked Gene Modules Within Biological Pathways Assessed by ToxCast In Vitro Assays

EPA Science Inventory

The US EPA ToxCast program is using in vitro high-throughput screening assays to profile the bioactivity of environmental chemicals, with the ultimate goal of predicting in vivo toxicity. We hypothesize that in modeling toxicity it will be more constructive to understand the pert...

Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

EPA Science Inventory

EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

A Novel Two-Step Hierarchial Quantitative Structure-Activity Relationship Modeling Workflow for Predicting Acute Toxicity of Chemicals in Rodents

EPA Science Inventory

Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database co...

Differentiating high priority pathway-based toxicity from non-specific effects in high throughput toxicity data: A foundation for prioritizing AOP development.

EPA Science Inventory

The ToxCast chemical screening approach enables the rapid assessment of large numbers of chemicals for biological effects, primarily at the molecular level. Adverse outcome pathways (AOPs) offer a means to link biomolecular effects with potential adverse outcomes at the level of...

Economic benefits of using adaptive predictive models of reproductive toxicity in the context of a tiered testing program

EPA Science Inventory

A predictive model of reproductive toxicity, as observed in rat multigeneration reproductive (MGR) studies, was previously developed using high throughput screening (HTS) data from 36 in vitro assays mapped to 8 genes or gene-sets from Phase I of USEPA ToxCast research program, t...

Human Pluripotent Stem Cell-Based Assay Predicts Developmental Toxicity Potential of ToxCast Chemicals (ACT meeting)

EPA Science Inventory

Worldwide initiatives to screen for toxicity potential among the thousands of chemicals currently in use require inexpensive and high-throughput in vitro models to meet their goals. The devTOX quickPredict platform is an in vitro human pluripotent stem cell-based assay used to as...

Evaluation of 1066 ToxCast Chemicals in a human stem cell assay for developmental toxicity (SOT)

EPA Science Inventory

To increase the diversity of assays used to assess potential developmental toxicity, the ToxCast chemical library was screened in the Stemina devTOX quickPREDICT assay using human embryonic stem (hES) cells. A model for predicting teratogenicity was based on a training set of 23 ...

75 FR 22234 - Phosphate Ester, Tallowamine, Ethoxylated; Exemption from the Requirement of a Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

.../Developmental Toxicity Screening Test, clinical signs of toxicity (abnormal respiratory sounds, dyspnea... the AAPs are carcinogenic. The Agency used a qualitative structure activity relationship (QSAR... = 10x MOE = 300 in rats (MRID FQPA SF = 3x 47600707) (10% Dermal absorption; LOAEL = 200 mg/kg/day 100...

USE OF WHOLE BODY CHEMICAL RESIDUE ANALYSIS AND LASER SCREENING CONFOCAL MICROSCOPY TO DESCRIBE DISTRIBUTION OF PBTS IN FISH EARLY LIFE STAGES

EPA Science Inventory

Fish early life stages (ELS) are more sensitive than juveniles or adults to many persistent bioaccumulative toxicants (PBTs). To better understand the mechanisms by which these chemicals produce toxicity during fish ELS, dose-response relationships need to be determined in relat...

High Throughput Prioritization for Integrated Toxicity Testing Based on ToxCast Chemical Profiling

EPA Science Inventory

The rational prioritization of chemicals for integrated toxicity testing is a central goal of the U.S. EPA’s ToxCast™ program (http://epa.gov/ncct/toxcast/). ToxCast includes a wide-ranging battery of over 500 in vitro high-throughput screening assays which in Phase I was used to...

Quantitative Model of Systemic Toxicity Using ToxCast and ToxRefDB (SOT)

EPA Science Inventory

EPA’s ToxCast program profiles the bioactivity of chemicals in a diverse set of ~700 high throughput screening (HTS) assays. In collaboration with L’Oreal, a quantitative model of systemic toxicity was developed using no effect levels (NEL) from ToxRefDB for 633 chemicals with HT...

Reproducibility of polycarbonate reference material in toxicity evaluation

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Huttlinger, P. A.

1981-01-01

A specific lot of bisphenol A polycarbonate has been used for almost four years as the reference material for the NASA-USF-PSC toxicity screening test method. The reproducibility of the test results over this period of time indicate that certain plastics may be more suitable reference materials than the more traditional cellulosic materials.

Tutorial Video Series: Using Stakeholder Outreach to Increase Usage of ToxCast Data (SETAC EU)

EPA Science Inventory

The limited amount of toxicity data on thousands of chemicals found in consumer products has led to the development of research endeavors such as the U.S. EPA’s Toxicity Forecaster (ToxCast). ToxCast uses high-throughput screening technology to evaluate thousands of chemicals for...

Introduction to Toxicity and Risk Assessment for Project Chemists

DTIC Science & Technology

2012-03-27

Toxicity of Hexavalent Chromium  External review complete  EPA will wait until studies underway on carcinogenic mode of action are complete to...finalize the assessment  NJ and Cal values for hex chrome 16 Risk-Based Screening Levels Resident Soil (mg/kg) Resident Water Use (µg/L) DRAFT 0.04

Species-specific predictive models of developmental toxicity using the ToxCast chemical library

EPA Science Inventory

EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive models that correlate with observed in vivo toxicity. In vitro profiling methods are based on ToxCast data, consisting of over 600 high-throughput screening (HTS) and high-content sc...

Ultrasonic material hardness depth measurement

DOEpatents

Good, M.S.; Schuster, G.J.; Skorpik, J.R.

1997-07-08

The invention is an ultrasonic surface hardness depth measurement apparatus and method permitting rapid determination of hardness depth of shafts, rods, tubes and other cylindrical parts. The apparatus of the invention has a part handler, sensor, ultrasonic electronics component, computer, computer instruction sets, and may include a display screen. The part handler has a vessel filled with a couplant, and a part rotator for rotating a cylindrical metal part with respect to the sensor. The part handler further has a surface follower upon which the sensor is mounted, thereby maintaining a constant distance between the sensor and the exterior surface of the cylindrical metal part. The sensor is mounted so that a front surface of the sensor is within the vessel with couplant between the front surface of the sensor and the part. 12 figs.

Bioluminescent bioreporter pad biosensor for monitoring water toxicity.

PubMed

Axelrod, Tim; Eltzov, Evgeni; Marks, Robert S

2016-01-01

Toxicants in water sources are of concern. We developed a tool that is affordable and easy-to-use for monitoring toxicity in water. It is a biosensor composed of disposable bioreporter pads (calcium alginate matrix with immobilized bacteria) and a non-disposable CMOS photodetector. Various parameters to enhance the sensor's signal have been tested, including the effect of alginate and bacterium concentrations. The effect of various toxicants, as well as, environmental samples were tested by evaluating their effect on bacterial luminescence. This is the first step in the creation of a sensitive and simple operative tool that may be used in different environments. Copyright © 2015 Elsevier B.V. All rights reserved.

Relative toxicity of pyrolysis products of some materials used in home furnishings

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Furst, A.

1976-01-01

Seventy samples of cushioning and upholstery materials used in home furnishings were evaluated for relative toxicity by means of the USF/NASA toxicity screening test. The materials were variably toxic under pyrolysis conditions, and this test appeared suitable for discriminating among them on the bases of time to incapacitation and time to death. The addition of fire retardants to these materials to comply with flammability regulations either had no significant effect on toxicity, or resulted in a reduction in relative toxicity. The modification of materials to comply with California upholstered furniture flammability regulations appears to have resulted in desirable limitations on toxicity. Fifty percent of the 70 materials tested caused incapacitation earlier than did the materials in compliance, and 30 percent caused death earlier.

Lead Toxicity in the Pediatric Patient with Sickle Cell Disease: Unique Risks and Management.

PubMed

Jung, Josephine Misun; Peddinti, Radhika

2018-01-01

Lead toxicity is the result of lead ingestion, one of the most common ingestions in the pediatric population. Nationwide and statewide efforts to recognize and curtail this epidemic have led to declining rates of toxicity. In patients with sickle cell disease (SCD), lead toxicity can be an elusive diagnosis due to overlapping symptom profiles, and inconsistent follow-up with a primary care physician can make the diagnosis even more difficult. In this article, two illustrative cases of lead toxicity in patients with SCD are described. The discussion reviews the current risk factors, screening, and inpatient management of lead toxicity, as well as describing the unique and sometimes confounding presentations of lead toxicity versus sickle cell crisis. [Pediatr Ann. 2018;47(1):e36-e40.]. Copyright 2018, SLACK Incorporated.

Electrochemical Biosensors: A Solution to Pollution Detection with Reference to Environmental Contaminants.

PubMed

Hernandez-Vargas, Gustavo; Sosa-Hernández, Juan Eduardo; Saldarriaga-Hernandez, Sara; Villalba-Rodríguez, Angel M; Parra-Saldivar, Roberto; Iqbal, Hafiz M N

2018-03-24

The increasing environmental pollution with particular reference to emerging contaminants, toxic heavy elements, and other hazardous agents is a serious concern worldwide. Considering this global issue, there is an urgent need to design and develop strategic measuring techniques with higher efficacy and precision to detect a broader spectrum of numerous contaminants. The development of precise instruments can further help in real-time and in-process monitoring of the generation and release of environmental pollutants from different industrial sectors. Moreover, real-time monitoring can also reduce the excessive consumption of several harsh chemicals and reagents with an added advantage of on-site determination of contaminant composition prior to discharge into the environment. With key scientific advances, electrochemical biosensors have gained considerable attention to solve this problem. Electrochemical biosensors can be an excellent fit as an analytical tool for monitoring programs to implement legislation. Herein, we reviewed the current trends in the use of electrochemical biosensors as novel tools to detect various contaminant types including toxic heavy elements. A particular emphasis was given to screen-printed electrodes, nanowire sensors, and paper-based biosensors and their role in the pollution detection processes. Towards the end, the work is wrapped up with concluding remarks and future perspectives. In summary, electrochemical biosensors and related areas such as bioelectronics, and (bio)-nanotechnology seem to be growing areas that will have a marked influence on the development of new bio-sensing strategies in future studies.

Chemical sensors for space applications

NASA Technical Reports Server (NTRS)

Bonting, Sjoerd L.

1992-01-01

The payload of the Space Station Freedom will include sensors for frequent monitoring of the water recycling process and for measuring the many biochemical parameters related to onboard experiments. This paper describes the sensor technologies and the types of transducers and selectors considered for these sensors. Particular attention is given to such aspects of monitoring of the water recycling process as the types of water use, the sources of water and their hazards, the sensor systems for monitoring, microbial monitoring, and monitoring toxic metals and organics. An approach for monitoring water recycling is suggested, which includes microbial testing with a potentiometric device (which should be in first line of tests), the use of an ion-selective electrode for inorganic ion determinations, and the use of optic fiber techniques for the determination of total organic carbon.