The use of multiwell culture plates in the duckweed toxicity test-a case study on Zn nanoparticles.

PubMed

Kalčíková, Gabriela; Marolt, Gregor; Kokalj, Anita Jemec; Gotvajn, Andreja Žgajnar

2018-06-11

Extensive production of nanomaterials of various properties needs to be coupled with rapid toxicity testing in order to provide information about their potential risks to the environment and human health. Miniaturization of toxicity tests may accelerate economical testing of nanomaterials, but is not a common practice. We describe a case study to miniaturize a commonly used toxicity test with plant duckweed Lemna minor. 6-well, 12-well and 24-well culture plates were used to assess their potential use for the duckweed toxicity test with potassium chloride as reference material. The results were compared to the standard test design using 100 mL glass beakers. The comparison showed that the best agreement was with the 6-well vessels. This set-up was further used for toxicity testing of zinc oxide nanoparticles (ZnO NP) and zinc chlorides. Zinc was not adsorbed onto either glass or plastic walls of the miniaturized system. We assume that in both vessels a fast agglomeration and settling of ZnO NP took place. Linear regression and statistical testing indicated a good correlation between the toxicity results obtained in the standard test and miniaturized 6-well vessels. The miniaturization of the test system for assessing the biological effect of nanomaterials on Lemna minor could become an appropriate alternative to the traditionally used high volume vessels. Copyright © 2018. Published by Elsevier B.V.

A Preliminary Study on the Toxic Combustion Products Testing of Polymers Used in High-Pressure Oxygen Systems

NASA Technical Reports Server (NTRS)

Hshieh, Fu-Yu; Beeson, Harold D.

2004-01-01

One likely cause of polymer ignition in a high-pressure oxygen system is adiabatic-compression heating of polymers caused by pneumatic impact. Oxidative _ pyrolysis or combustion of polymers in a high-pressure oxygen system could generate toxic gases. This paper reports the preliminary results of toxic combustion product testing of selected polymers in a pneumatic-impact test system. Five polymers commonly used in high-pressure oxygen systems, Nylon 6/6, polychlorotrifluoroethylene (CTFE), polytetrafluoroethylene (PTFE), fluoroelastomer (Viton(TradeMark) A), and nitrile rubber (Buna N), were tested in a pneumatic-impact test system at 2500- or 3500-psia oxygen pressure. The polymers were ignited and burned, then combustion products were collected in a stainless-steel sample bottle and analyzed by GC/MS/IRD, GC/FID, and GC/Methanizer/FID. The results of adiabatic-compression tests show that combustion of hydrocarbon polymers, nitrogen-containing polymers, and halogenated polymers in high-pressure oxygen systems are relatively complete. Toxicity of the combustion product gas is presumably much lower than the combustion product gas generated from ambient-pressure oxygen (or air) environments. The NASA-Lewis equilibrium code was used to determine the composition of combustion product gas generated from a simulated, adiabatic-compression test of nine polymers. The results are presented and discussed.

Comparison of bulk sediment and sediment elutriate toxicity testing methods

EPA Science Inventory

Elutriate bioassays are among numerous methods that exist for assessing the potential toxicity of sediments in aquatic systems. In this study, interlaboratory results were compared from 96-hour Ceriodaphnia dubia and Pimephales promelas static-renewal acute toxicity tests conduct...

Mapping the Human Toxome by Systems Toxicology

PubMed Central

Bouhifd, Mounir; Hogberg, Helena T.; Kleensang, Andre; Maertens, Alexandra; Zhao, Liang; Hartung, Thomas

2014-01-01

Toxicity testing typically involves studying adverse health outcomes in animals subjected to high doses of toxicants with subsequent extrapolation to expected human responses at lower doses. The low-throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides and drugs) has led to a backlog of more than 80,000 chemicals to which human beings are potentially exposed whose potential toxicity remains largely unknown. Employing new testing strategies that employ the use of predictive, high-throughput cell-based assays (of human origin) to evaluate perturbations in key pathways, referred as pathways of toxicity, and to conduct targeted testing against those pathways, we can begin to greatly accelerate our ability to test the vast “storehouses” of chemical compounds using a rational, risk-based approach to chemical prioritization, and provide test results that are more predictive of human toxicity than current methods. The NIH Transformative Research Grant project Mapping the Human Toxome by Systems Toxicology aims at developing the tools for pathway mapping, annotation and validation as well as the respective knowledge base to share this information. PMID:24443875

An interlaboratory comparison of sediment elutriate preparation and toxicity test methods

EPA Science Inventory

Elutriate bioassays are among numerous methods that exist for assessing the potential toxicity of sediments in aquatic systems. In this study, interlaboratory results were compared from 96-hour Ceriodaphnia dubia and Pimephales promelas static-renewal acute toxicity tests conduct...

A Microfluidic Device for Continuous Sensing of Systemic Acute Toxicants in Drinking Water

PubMed Central

Zhao, Xinyan; Dong, Tao

2013-01-01

A bioluminescent-cell-based microfluidic device for sensing toxicants in drinking water was designed and fabricated. The system employed Vibrio fischeri cells as broad-spectrum sensors to monitor potential systemic cell toxicants in water, such as heavy metal ions and phenol. Specifically, the chip was designed for continuous detection. The chip design included two counter-flow micromixers, a T-junction droplet generator and six spiral microchannels. The cell suspension and water sample were introduced into the micromixers and dispersed into droplets in the air flow. This guaranteed sufficient oxygen supply for the cell sensors. Copper (Cu2+), zinc (Zn2+), potassium dichromate and 3,5-dichlorophenol were selected as typical toxicants to validate the sensing system. Preliminary tests verified that the system was an effective screening tool for acute toxicants although it could not recognize or quantify specific toxicants. A distinct non-linear relationship was observed between the zinc ion concentration and the Relative Luminescence Units (RLU) obtained during testing. Thus, the concentration of simple toxic chemicals in water can be roughly estimated by this system. The proposed device shows great promise for an early warning system for water safety. PMID:24300075

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

Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems.

PubMed

Chatterjee, Nivedita; Yang, Ji Su; Park, Kwangsik; Oh, Seung Min; Park, Jeonggue; Choi, Jinhee

2015-01-01

The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs) in alternative in vitro and in vivo toxicity testing models. The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [NH2]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

Environmental Sentinel Biomonitor (ESB) System Technology Assessment

DTIC Science & Technology

2007-02-01

Andersson M, Barile FA, et al. 1996. MEIC evaluation of acute systemic toxicity Part I. Methodology of 68 in vitro toxicity assays used to test the first...30 reference chemicals. ATLA 24:251-272. Clemedson C, Andersson M, Aoki Y, Barile FA, et al. 1998. MEIC evaluation of acute systemic toxicity Part IV

A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing

EPA Science Inventory

Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new prod...

Evaluation of a novel automated water analyzer for continuous monitoring of toxicity and chemical parameters in municipal water supply.

PubMed

Bodini, Sergio F; Malizia, Marzio; Tortelli, Annalisa; Sanfilippo, Luca; Zhou, Xingpeng; Arosio, Roberta; Bernasconi, Marzia; Di Lucia, Stefano; Manenti, Angela; Moscetta, Pompeo

2018-08-15

A novel tool, the DAMTA analyzer (Device for Analytical Monitoring and Toxicity Assessment), designed for fully automated toxicity measurements based on luminescent bacteria as well as for concomitant determination of chemical parameters, was developed and field-tested. The instrument is a robotic water analyzer equipped with a luminometer and a spectrophotometer, integrated on a thermostated reaction plate which contains a movable carousel with 80 cuvettes. Acute toxicity is measured on-line using a wild type Photobacterium phosphoreum strain with measurable bioluminescence and unaltered sensitivity to toxicants lasting up to ten days. The EC50 values of reference compounds tested were consistent with A. fischeri and P. phosphoreum international standards and comparable to previously published data. Concurrently, a laboratory trial demonstrated the feasibility of use of the analyzer for the determination of nutrients and metals in parallel to the toxicity measurements. In a prolonged test, the system was installed only in toxicity mode at the premises of the World Fair "Expo Milano-2015″, a high security site to ensure the quality of the supplied drinking water. The monitoring program lasted for six months during which ca. 2400 toxicity tests were carried out; the results indicated a mean non-toxic outcome of -5.5 ± 6.2%. In order to warrant the system's robustness in detecting toxic substances, Zn was measured daily with highly reproducible inhibition results, 70.8 ± 13.6%. These results assure that this novel toxicity monitor can be used as an early warning system for protection of drinking water sources from emergencies involving low probability/high impact contamination events in source water or treated water. Copyright © 2018 Elsevier Inc. All rights reserved.

Computational Systems Biology and Dose Response Modeling Workshop, September 22-26, 2008

EPA Science Inventory

The recently published National Academy of Sciences (NAS) report “Toxicity Testing in the 21st Century” recommends a new approach to toxicity testing, based on evaluating cellular responses in a suite of toxicity pathway assays in human cells or cells lines in vitro. Such a parad...

HIGH-THROUGHPUT CELLULAR ASSAYS FOR MODELING TOXICITY IN THE FISH REPRODUCTIVE SYSTEM

EPA Science Inventory

The most important benefit of this project is the experimental evaluation of all essential steps in the development and testing of adverse outcome pathways (AOP) for a diverse set of reproductive and non-reproductive toxicants. In contrast to human testing and the toxicity pat...

Toward toxicity testing of nanomaterials in the 21st century: a paradigm for moving forward.

PubMed

Lai, David Y

2012-01-01

A challenge-facing hazard identification and safety evaluation of engineered nanomaterials being introduced to market is the diversity and complexity of the types of materials with varying physicochemical properties, many of which can affect their toxicity by different mechanisms. In general, in vitro test systems have limited usefulness for hazard identification of nanoparticles due to various issues. Meanwhile, conducting chronic toxicity/carcinogenicity studies in rodents for every new nanomaterial introduced into the commerce is impractical if not impossible. New toxicity testing systems which rely on predictive, high-throughput technologies may be the ultimate goal of evaluating the potential hazard of nanomaterials. However, at present, this approach alone is unlikely to succeed in evaluating the toxicity of the wide array of nanomaterials and requires validation from in vivo studies. This article proposes a paradigm for toxicity testing and elucidation of the molecular mechanisms of reference materials for specific nanomaterial classes/subclasses using short-term in vivo animal studies in conjunction with high-throughput screenings and mechanism-based short-term in vitro assays. The hazard potential of a particular nanomaterial can be evaluated by conducting only in vitro high-throughput assays and mechanistic studies and comparing the data with those of the reference materials in the specific class/subclass-an approach in line with the vision for 'Toxicity Testing in the 21st Century' of chemicals. With well-designed experiments, testing nanomaterials of varying/selected physicochemical parameters may be able to identify the physicochemical parameters contributing to toxicity. The data so derived could be used for the development of computer model systems to predict the hazard potential of specific nanoparticles based on property-activity relationships. Copyright © 2011 John Wiley & Sons, Inc.

Embryonic stem cells and the next generation of developmental toxicity testing.

PubMed

Kugler, Josephine; Huhse, Bettina; Tralau, Tewes; Luch, Andreas

2017-08-01

The advent of stem cell technology has seen the establishment of embryonic stem cells (ESCs) as molecular model systems and screening tools. Although ESCs are nowadays widely used in research, regulatory implementation for developmental toxicity testing is pending. Areas Covered: This review evaluates the performance of current ESC, including human (h)ESC testing systems, trying to elucidate their potential for developmental toxicity testing. It shall discuss defining parameters and mechanisms, their relevance and contemplate what can realistically be expected. Crucially this includes the question of how to ascertain the quality of currently employed cell lines and tests based thereon. Finally, the use of hESCs will raise ethical concerns which should be addressed early on. Expert Opinion: While the suitability of (h)ESCs as tools for research and development goes undisputed, any routine use for developmental toxicity testing currently still seems premature. The reasons for this comprise inherent biological deficiencies as well as cell line quality and system validation. Overcoming these issues will require collaboration of scientists, test developers and regulators. Also, validation needs to be made worthwhile for academia. Finally we have to continuously rethink existing strategies, making room for improved testing and innovative approaches.

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.

20180311 - Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development (SOT)

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Air toxics evaluation of ABB Combustion Engineering Low-Emission Boiler Systems

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

Wesnor, J.D.

1993-10-26

The specific goals of the program are to identify air toxic compounds that might be emmitted from the new boiler with its various Air Pollution Control device for APCD alternatives in levels of regulatory concern. For the compounds thought to be of concern, potential air toxic control methodologies will be suggested and a Test Protocol will be written to be used in the Proof of Concept and full scale tests. The following task was defined: Define Replations and Standards; Identify Air Toxic Pollutants of Interest to Interest to Utility Boilers; Assesment of Air Toxic By-Products; State of the Art Assessmentmore » of Toxic By-Product Control Technologies; and Test Protocol Definition.« less

Acute aquatic toxicity and biodegradation potential of biodiesel fuels

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

Haws, R.A.; Zhang, X.; Marshall, E.A.

1995-12-31

Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO{sub 2} and by observing the disappearance of test substance with gas chromatography. Additional BOD{sub 5} and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicitymore » tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population.« less

RELATIONSHIPS OF QUANTITATIVE STRUCTURE-ACTIVITY TO COMPARATIVE TOXICITY OF SELECTED PHENOLS IN THE 'PIMEPHALES PROMELAS' AND 'TETRAHYMENA PYRIFORMIS' TEST SYSTEMS

EPA Science Inventory

The relative toxic response of 27 selected phenols in the 96-hr acute flowthrough Pimephales promelas (fathead minnow) and the 48- to 60-hr chronic static Tetrahymena pyriformis (ciliate protozoan) test systems was evaluated. Log Kow-dependent linear regression analyses revealed ...

TOXICITY TESTING IN THE 21ST CENTURY: A VISION AND A STRATEGY

PubMed Central

Krewski, Daniel; Acosta, Daniel; Andersen, Melvin; Anderson, Henry; Bailar, John C.; Boekelheide, Kim; Brent, Robert; Charnley, Gail; Cheung, Vivian G.; Green, Sidney; Kelsey, Karl T.; Kerkvliet, Nancy I.; Li, Abby A.; McCray, Lawrence; Meyer, Otto; Patterson, Reid D.; Pennie, William; Scala, Robert A.; Solomon, Gina M.; Stephens, Martin; Yager, James; Zeise, Lauren

2015-01-01

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology. PMID:20574894

AN EVALUATION OF THE 7-DAY TOXICITY TEST WITH AMERICAMYSIS BAHIA (FORMERLY MYSIDOPSIS BAHIA)

EPA Science Inventory

The 7-d test measuring survival, growth, and fecundity of Americamysis bahia formerly Mysidopsis bahia) was developed for estimating the chronic toxicity of effluents and associated receiving waters for National Pollutant Discharge Elimination System permits. Currently, this test...

Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

PubMed

Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR predictions.

Meta-analysis of fish early life stage tests-Association of toxic ratios and acute-to-chronic ratios with modes of action.

PubMed

Scholz, Stefan; Schreiber, Rene; Armitage, James; Mayer, Philipp; Escher, Beate I; Lidzba, Annegret; Léonard, Marc; Altenburger, Rolf

2018-04-01

Fish early life stage (ELS) tests (Organisation for Economic Co-operation and Development test guideline 210) are widely conducted to estimate chronic fish toxicity. In these tests, fish are exposed from the embryonic to the juvenile life stages. To analyze whether certain modes of action are related to high toxic ratios (i.e., ratios between baseline toxicity and experimental effect) and/or acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs) for 183 compounds were extracted from the US Environmental Protection Agency's ecotoxicity database. Analysis of ECs of narcotic compounds indicated that baseline toxicity could be observed in the fish ELS test at similar concentrations as in the acute fish toxicity test. All nonnarcotic modes of action were associated with higher toxic ratios, with median values ranging from 4 to 9.3 × 10 4 (uncoupling < reactivity < neuromuscular toxicity < methemoglobin formation < endocrine disruption < extracellular matrix formation inhibition). Four modes of action were also found to be associated with high ACRs: 1) lysyl oxidase inhibition leading to notochord distortion, 2) putative methemoglobin formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with neuromuscular toxicity. For the prediction of ECs in the fish ELS test with alternative test systems, endpoints targeted to the modes of action of compounds with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or even replace these tests. Environ Toxicol Chem 2018;37:955-969. © 2018 SETAC. © 2018 SETAC.

A Brief Study on Toxic Combustion Products of the Polymers Used in High-Pressure Oxygen Systems

NASA Technical Reports Server (NTRS)

Hshieh, Fu-Yu; Beeson, Harold D.

2005-01-01

One likely cause of polymer ignition in a high-pressure oxygen system is the adiabatic-compression heating of polymers caused by pneumatic impact. Oxidative pyrolysis or combustion of polymers in a high-pressure oxygen system could generate toxic gases. This paper investigates the feasibility of using the NASA pneumatic-impact system to conduct adiabatic-compression combustion tests and determines the toxic combustion products produced from the burning of five selected polymers. Five polymers commonly used in high-pressure oxygen systems, Zytel(Registered TradeMark) 42 (Nylon 6/6), Buna N (nitrile rubber), Witon(Registered TradeMark) A (copolymer of vinylidene fluoride and hexafluoropropylene), Neoflon(Registered TradeMark) (polychlorotrifluoroethylene), and Teflon(Registered TradeMark) (polytetrafluoroethylene), were tested in the NASA pneumatic-impact test system at 17.2-MPa oxygen pressure. The polymers were ignited and burned; combustion products were collected in a stainless-steel sample bottle and analyzed using various methods. The results show that the NASA pneumatic-impact system is an appropriate test system to conduct adiabatic-compression combustion tests and to collect combustion products for further chemical analysis. The composition of the combustion product gas generated from burning the five selected polymers are presented and discussed.

GHS additivity formula: A true replacement method for acute systemic toxicity testing of agrochemical formulations.

PubMed

Corvaro, M; Gehen, S; Andrews, K; Chatfield, R; Arasti, C; Mehta, J

2016-12-01

Acute systemic (oral, dermal, inhalation) toxicity testing of agrochemical formulations (end-use products) is mainly needed for Classification and Labelling (C&L) and definition of personal protection equipment (PPE). A retrospective analysis of 225 formulations with available in vivo data showed that: A) LD 50 /LC 50 values were above limit doses in <20.2% via oral route but only in <1% and <2.4% of cases via dermal and inhalation route, respectively; B) for each formulation the acute oral toxicity is always equal or greater than the Acute Toxicity Estimate (ATE) via the other two routes; C) the GHS (Global Harmonised System) computational method based on ATE, currently of limited acceptance, has very high accuracy and specificity for prediction of agrochemical mixture toxicity according to the internationally established classification thresholds. By integrating this evidence, an exposure- and data-based waiving strategy is proposed to determine classification and adequate PPE and to ensure only triggered animal testing is used. Safety characterisation above 2000 mg/kg body weight or 1.0 mg/L air should not be recommended, based on the agrochemical exposure scenarios. The global implementation of these tools would allow a remarkable reduction (up to 95%) in in vivo testing, often inducing lethality and/or severe toxicity, for agrochemical formulations. Copyright © 2016. Published by Elsevier Inc.

Establishment of quality assurance procedures for aquatic toxicity testing with the nematode Caenorhabditis elegans

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

Freeman, M.N.; Marse, T.J.; Williams, P.L.

1998-12-31

In this study initial data were generated to develop laboratory control charts for aquatic toxicity testing using the nematode Caenorhabditis elegans. Tests were performed using two reference toxicants: CdCl{sub 2} and CuCl{sub 2}. All tests were performed for 24 h without a food source and of 48 h with a food source in a commonly used nematode aquatic medium. Each test was replicated 6 times with each replicate having 6 wells per concentration with 10 {+-} 1 worms per well. Probit analysis was used to estimate LC{sub 50} values for each test. The data were used to construct a meanmore » ({bar x}) laboratory control chart for each reference toxicant. The coefficient of variation (CV) for three of the four reference toxicant tests was less than 20%, which demonstrates an excellent degree of reproducibility. These CV values are well within suggested standards for determination of organism sensitivity and overall test system credibility. A standardized procedure for performing 24 h and 48 h aquatic toxicity studies with C. elegans is proposed.« less

Deriving Points of Departure and Performance Baselines for Predictive Modeling of Systemic Toxicity using ToxRefDB (SOT)

EPA Science Inventory

A primary goal of computational toxicology is to generate predictive models of toxicity. An elusive target of alternative test methods and models has been the accurate prediction of systemic toxicity points of departure (PoD). We aim not only to provide a large and valuable resou...

Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

PubMed

Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

2015-06-17

Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

Sediment toxicity testing with the amphipod Ampelisca abdita in Calcasieu Estuary, Louisiana

USGS Publications Warehouse

Redmond, M.S.; Crocker, P.A.; McKenna, K.M.; Petrocelli, E.A.; Scott, K.J.; Demas, C.R.

1996-01-01

Discharges from chemical and petrochemical manufacturing facilities have contaminated portions of Louisiana's Calcasieu River estuary with a variety of organic and inorganic contaminants. As part of a special study, sediment toxicity testing was conducted to assess potential impact to the benthic community. Ten-day flow-through sediment toxicity tests with the amphipod Ampelisca abdita revealed significant toxicity at 68% (26 of 38) of the stations tested. A. abdita mortality was highest in the effluent-dominated bayous, which are tributaries to the Calcasieu River. Mortality was correlated with total heavy metal and total organic compound concentrations in the sediments. Ancillary experiments showed that sediment interstitial water salinity as low as 2.5 o/o-o did not significantly affect A. abdita's, response in the flow-through system; sediment storage for 7 weeks at 4??C did not significantly affect toxicity. Sediment toxicity to A. abdita was more prevalent than receiving water toxicity using three short-term chronic bioassays. Results suggest that toxicity testing using this amphipod is a valuable tool when assessing sediments containing complex contaminant mixtures and for assessing effects of pollutant loading over time. In conjunction with chemical analyses, the testing indicated that the effluent-dominated, brackish bayous (Bayou d'Inde and Bayou Verdine) were the portions of the estuary most impacted by toxicity.

In vitro toxicities of experimental jet fuel system ice-inhibiting agents.

PubMed

Geiss, K T; Frazier, J M

2001-07-02

One research emphasis within the Department of Defense has been to seek the replacement of operational compounds with alternatives that pose less potential risk to human and ecological systems. Alternatives to glycol ethers, such as diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel system ice-inhibiting agents (FSIIs). This group of chemicals includes three derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M-27). In addition, M-DE was evaluated as a reference compound. Our approach was to implement an in vitro test battery based on primary rat hepatocyte cultures to perform initial toxicity evaluations. Hepatocytes were exposed to experimental chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity, glutathione level, and rate of protein synthesis as indicators of toxicity. Of the compounds tested, M-1, especially at the 10-mM dose, appeared to be more potent than the other chemicals, as measured by these toxicity assays. M-DE, the current FSII, elicited little response in the toxicity assays. Although some variations in toxicity were observed at the 10-mM dose, the in vitro toxicities of the chemicals tested (except for M-1) were not considerably greater than that of M-DE.

Computational systems biology and dose-response modeling in relation to new directions in toxicity testing.

PubMed

Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B

2010-02-01

The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell biology has advanced rapidly with increasing availability of new data and powerful simulation techniques, a quantitative orientation is still lacking in life sciences education to make efficient use of these new tools to implement the new toxicity testing paradigm. A revamped undergraduate curriculum in the biological sciences including compulsory courses in mathematics and analysis of dynamical systems is required to address this gap. In parallel, dissemination of computational systems biology techniques and other analytical tools among practicing toxicologists and risk assessment professionals will help accelerate implementation of the new toxicity testing vision.

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

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

Selkirk, J.K.

The National Toxicology Program (NTP) was organized to support national public health programs by initiating research designed to understand the physiological, metabolic, and genetic basis for chemical toxicity. The primary mandated responsibilities of NTP were in vivo and vitro toxicity testing of potentially hazardous chemicals; broadening the spectrum of toxicological information on known hazardous chemicals; validating current toxicological assay systems as well as developing new and innovative toxicity testing technology; and rapidly communicating test results to government agencies with regulatory responsibilities and to the medical and scientific communities. 2 figs.

COMPUTER INTERFACED TOXICITY TESTING SYSTEM FOR SIMULATING VARIABLE EFFLUENT LOADING

EPA Science Inventory

Water quality criteria and standards are based primarily on toxicity tests carried out with single chemicals whose concentration is as nearly constant as possible. In the 'real world', however, organisms are exposed to mixtures of chemicals which usually have markedly fluctuating...

Non-Toxic Orbiter Maneuvering System (OMS) and Reaction Control System

NASA Technical Reports Server (NTRS)

Hurlbert, Eric A.; Nicholson, Leonard S. (Technical Monitor)

1999-01-01

NASA is pursuing the technology and advanced development of a non-toxic (NT) orbital maneuvering system (OMS) and reaction control system (RCS) for shuttle upgrades, RLV, and reusable first stages. The primary objectives of the shuttle upgrades program are improved safety, improved reliability, reduced operations time and cost, improved performance or capabilities, and commonality with future space exploration needs. Non-Toxic OMS/RCS offers advantages in each of these categories. A non-toxic OMS/RCS eliminates the ground hazards and the flight safety hazards of the toxic and corrosive propellants. The cost savings for ground operations are over $24M per year for 7 flights, and the savings increase with increasing flight rate up to $44M per year. The OMS/RCS serial processing time is reduced from 65 days to 13 days. The payload capability can be increased up to 5100 Ibms. The non-toxic OMS/RCS also provides improved space station reboost capability up to 20 nautical miles over the current toxic system of 14 nautical miles. A NT OMS/RCS represents a clear advancement in the SOA over MMH/NTO. Liquid oxygen and ethanol are clean burning, high-density propellants that provide a high degree of commonality with other spacecraft subsystems including life support, power, and thermal control, and with future human exploration and development of space missions. The simple and reliable pressure-fed design uses sub-cooled liquid oxygen at 250 to 350 psia, which allows a propellant to remain cryogenic for longer periods of time. The key technologies are thermal insulation and conditioning techniques are used to maintain the sub-cooling. Phase I successfully defined the system architecture, designed an integrated OMS/RCS propellant tank, analyzed the feed system, built and tested the 870 lbf RCS thrusters, and tested the 6000 lbf OMS engine. Phase 11 is currently being planned for the development and test of full-scale prototype of the system in 1999 and 2000

Test systems in drug discovery for hazard identification and risk assessment of human drug-induced liver injury.

PubMed

Weaver, Richard J; Betts, Catherine; Blomme, Eric A G; Gerets, Helga H J; Gjervig Jensen, Klaus; Hewitt, Philip G; Juhila, Satu; Labbe, Gilles; Liguori, Michael J; Mesens, Natalie; Ogese, Monday O; Persson, Mikael; Snoeys, Jan; Stevens, James L; Walker, Tracy; Park, B Kevin

2017-07-01

The liver is an important target for drug-induced toxicities. Early detection of hepatotoxic drugs requires use of well-characterized test systems, yet current knowledge, gaps and limitations of tests employed remains an important issue for drug development. Areas Covered: The current state of the science, understanding and application of test systems in use for the detection of drug-induced cytotoxicity, mitochondrial toxicity, cholestasis and inflammation is summarized. The test systems highlighted herein cover mostly in vitro and some in vivo models and endpoint measurements used in the assessment of small molecule toxic liabilities. Opportunities for research efforts in areas necessitating the development of specific tests and improved mechanistic understanding are highlighted. Expert Opinion: Use of in vitro test systems for safety optimization will remain a core activity in drug discovery. Substantial inroads have been made with a number of assays established for human Drug-induced Liver Injury. There nevertheless remain significant gaps with a need for improved in vitro tools and novel tests to address specific mechanisms of human Drug-Induced Liver Injury. Progress in these areas will necessitate not only models fit for application, but also mechanistic understanding of how chemical insult on the liver occurs in order to identify translational and quantifiable readouts for decision-making.

Microphysiological modeling of the reproductive tract: a fertile endeavor.

PubMed

Eddie, Sharon L; Kim, J Julie; Woodruff, Teresa K; Burdette, Joanna E

2014-09-01

Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs have led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling often referred to as 'organ-on-a-chip' or 'human-on-a-chip' places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology. © 2014 by the Society for Experimental Biology and Medicine.

Profiling Animal Toxicants by Automatically Mining Public Bioassay Data: A Big Data Approach for Computational Toxicology

PubMed Central

Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

2014-01-01

In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities. PMID:24950175

Profiling animal toxicants by automatically mining public bioassay data: a big data approach for computational toxicology.

PubMed

Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

2014-01-01

In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities.

Survival and growth of newly transformed Lampsilis cardium and Lampsilis siliquoidea in a flow-through, continuous feeding test system

USGS Publications Warehouse

Meinertz, Jeffery R.; Schreier, Theresa M.; Hess, Karina R.; Bartsch, Michelle

2011-01-01

A test system was evaluated for assessing chronic toxicity of waterborne chemicals with early life stage mussels. To determine if the test system could result in ≥80% survival in a control (unexposed) group, fat mucket mussels (Lampsilis siliquoidea Barnes, 1823) and plain pocketbook mussels (L. cardium Rafinesque, 1820) 1 day post transformation were stocked into test chambers (250 mL beakers, water volume, 200 mL, 21 °C, 40 mussels of 1 species per chamber) within a test system constructed for conducting chronic, continuous exposure, flow-through toxicity tests. The test system contained 60 chambers containing silica sand, 30 chambers with L. siliquoidea, and 30 with L. cardium. Each chamber in the continuous feeding system received 1 of 6 food types prepared with concentrated algal products. After 28 days, mussels were harvested from chambers to assess survival and growth. For L. siliquoidea, mean survival ranged from 34 to 80% and mean shell length ranged from 464 to 643 µm. For L. cardium, mean survival ranged from 12 to 66% and mean shell length ranged from 437 to 612 µm. The maximum mean growth rate for L. siliquoidea was 12.7 µm/d and for L. cardium was 11.8 µm/d. When offered a continuous diet of Nannochloropsis, Tetraselmis, and Chlorella for 28 days in the test system, the survival of 1 day post transformation L. siliquoidea was 80%. The test system can be easily enhanced with a pumping system continuously delivering test chemical to the test system's flow stream allowing for chronic toxicity tests with 1 day post transformation mussels.

Analyzing cytotoxic effects of selected isothiazol-3-one biocides using the toxic ratio concept and structure-activity relationship considerations.

PubMed

Arning, Jürgen; Matzke, Marianne; Stolte, Stefan; Nehen, Frauke; Bottin-Weber, Ulrike; Böschen, Andrea; Abdulkarim, Salha; Jastorff, Bernd; Ranke, Johannes

2009-12-01

To demonstrate how baseline toxicity can be separated from other more specific modes of toxic action and to address possible pitfals when dealing with hydrophobic substances, the four isothiazol-3-one biocides N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT), and 4,5-dichloro-N-octylisothiazol-3-one (DCOIT) as an example for reactive electrophilic xenobiotics were tested for their cytotoxic effects on the human hepatoblastoma cell line Hep G2, on the marine bacterium Vibrio fischeri, and on the limnic green alga Scenedesmus vacuolatus. In each of the three test systems, toxic effects were observed in a consistent pattern. The two chlorinated compounds and OIT were found to be significantly more toxic than MIT. As compared to baseline toxicants, the small and polar MIT and CIT exhibited pronounced excess toxicity in each of the three test systems that is presumably triggered by their intrinsic reactivity toward cellular thiols. In contrast, OIT and DCOIT showed mainly toxicities that could be explained by their hydrophobicity. Analyzing and comparing these results using the toxic ratio concept and with data that indicate a dramatic depletion of cellular glutathione levels after incubation with DCOIT reveals that for highly hydrophobic substances, baseline level toxicity in an assay for acute toxicity can lead to an oversight of other more specific modes of toxic action that may cause significant effects that might be less reversible than those caused by unreactive baseline toxicants. This possibility should be taken into account in the hazard assessment of chemicals that are both hydrophobic and reactive.

Toxicity hazard of organophosphate insecticide malathion identified by in vitro methods.

PubMed

Jira, David; Janousek, Stanislav; Pikula, Jiri; Vitula, Frantisek; Kejlova, Kristina

2012-01-01

Malathion is generally not classified as toxic. However, the toxicity seems to be species-dependent. Local and systemic toxicity data for birds are rare, but a decrease of wild bird densities in areas where malathion was applied was reported. Aim of the study was to extend knowledge on malathion toxicity on cellular and organ level and to evaluate embryotoxicity and genotoxicity for birds using the chick embryo model HET-CAM. Skin and eye irritation was determined using reconstructed skin and eye cornea tissues and the chorioallantoic membrane of chick embryo to simulate conjunctiva. Cytotoxicity in 3T3 Balb/c fibroblast culture was determined to estimate acute systemic toxicity. Chick embryo model was further employed to evaluate acute embryotoxicity for birds (mortality and genotoxicity). Data were analysed by means of general linear models. Malathion is not a skin and eye irritant. Cytotoxicity in vitro test provided LD50 value of 616 mg/kg suggesting higher toxic potential than is generally published based on in vivo tests on laboratory rodents. Embryotoxicity studies revealed dose and age dependent mortality of chick embryos. Genotoxicity was identified by means of micronucleus test in erythroid cells isolated from chorioallantois vascular system of chick embryos. Using in vitro alternative toxicological methods, a higher toxic potential of malathion was demonstrated than is generally declared. An increased health and environmental hazard may occur in areas with intensive agricultural production. The environmental consequences of delayed effects and embryotoxicity for bird populations in areas exposed to organophosphate insecticides, such as malathion, are obvious.

Applicability of ambient toxicity testing to national or regional water-quality assessment

USGS Publications Warehouse

Elder, John F.

1990-01-01

Comprehensive assessment of the quality of natural waters requires a multifaceted approach. Descriptions of existing conditions may be achieved by various kinds of chemical and hydrologic analyses, whereas information about the effects of such conditions on living organisms depends on biological monitoring. Toxicity testing is one type of biological monitoring that can be used to identify possible effects of toxic contaminants. Based on experimentation designed to monitor responses of organisms to environmental stresses, toxicity testing may have diverse purposes in water-quality assessments. These purposes may include identification of areas that warrant further study because of poor water quality or unusual ecological features, verification of other types of monitoring, or assessment of contaminant effects on aquatic communities. Toxicity-test results are most effective when used as a complement to chemical analyses, hydrologic measurements, and other biological monitoring. However, all toxicity-testing procedures have certain limitations that must be considered in developing the methodology and applications of toxicity testing in any large-scale water-quality-assessment program. A wide variety of toxicity-test methods have been developed to fulfill the needs of diverse applications. The methods differ primarily in the selections made relative to four characteristics: (1) test species, (2) endpoint (acute or chronic), (3) test-enclosure type, and (4) test substance (toxicant) that functions as the environmental stress. Toxicity-test approaches vary in their capacity to meet the needs of large-scale assessments of existing water quality. Ambient testing, whereby the test organism is exposed to naturally occurring substances that contain toxicant mixtures in an organic or inorganic matrix, is more likely to meet these needs than are procedures that call for exposure of the test organisms to known concentrations of a single toxicant. However, meaningful interpretation of ambient test results depends on the existence of accompanying chemical analysis of the ambient media. The ambient test substance may be water or sediments. Sediment tests have had limited application, but they are useful because most toxicants tend to accumulate in sediments and many test species either inhabit the sediments or are in frequent contact with them. Biochemical testing methods, which have been developing rapidly in recent years, are likely to be among the most useful procedures for large-scale water-quality assessments. They are relatively rapid and simple, and more. importantly, they focus on biochemical changes that are the initial responses of virtually all organisms to environmental stimuli. Most species are sensitive to relatively few toxicants, and their sensitivities vary as conditions change. Therefore, each test method has particular uses and limitations, and no single test has universal applicability. One of the most informative approaches to toxicity testing is to combine biochemical tests with other test methods in a 'battery of tests' that is diversified enough to characterize different types of toxicants and different trophic levels. However, such an approach can be costly, and if not carefully designed, it may not yield enough additional information to warrant the additional cost. The application of toxicity tests to large-scale water-quality assessments is hampered by a number of difficulties. Toxicity tests often are not sensitive enough to enable detection of most contaminant problems in the natural environment. Furthermore, because sensitivities among different species and test conditions can be highly variable, conclusions about the toxicant problems of an ecosystem are strongly dependent on the test procedure used. In addition, the experimental systems used in toxicity tests cannot replicate the complexity or variability of natural conditions, and positive test results cannot identify the source or nature of

Modeling Aquatic Toxicity through Chromatographic Systems.

PubMed

Fernández-Pumarega, Alejandro; Amézqueta, Susana; Farré, Sandra; Muñoz-Pascual, Laura; Abraham, Michael H; Fuguet, Elisabet; Rosés, Martí

2017-08-01

Environmental risk assessment requires information about the toxicity of the growing number of chemical products coming from different origins that can contaminate water and become toxicants to aquatic species or other living beings via the trophic chain. Direct toxicity measurements using sensitive aquatic species can be carried out but they may become expensive and ethically questionable. Literature refers to the use of chromatographic measurements that correlate to the toxic effect of a compound over a specific aquatic species as an alternative to get toxicity information. In this work, we have studied the similarity in the response of the toxicity to different species and we have selected eight representative aquatic species (including tadpoles, fish, water fleas, protozoan, and bacteria) with known nonspecific toxicity to chemical substances. Next, we have selected four chromatographic systems offering good perspectives for surrogation of the eight selected aquatic systems, and thus prediction of toxicity from the chromatographic measurement. Then toxicity has been correlated to the chromatographic retention factor. Satisfactory correlation results have been obtained to emulate toxicity in five of the selected aquatic species through some of the chromatographic systems. Other aquatic species with similar characteristics to these five representative ones could also be emulated by using the same chromatographic systems. The final aim of this study is to model chemical products toxicity to aquatic species by means of chromatographic systems to reduce in vivo testing.

Developing an Experimental Model of Vascular Toxicity in Embryonic Zebrafish

EPA Science Inventory

Developing an Experimental Model of Vascular Toxicity in Embryonic Zebrafish Tamara Tal, Integrated Systems Toxicology Division, U.S. EPA Background: There are tens of thousands of chemicals that have yet to be fully evaluated for their toxicity by validated in vivo testing ...

Influence of ozonation and biodegradation on toxicity of industrial textile wastewater.

PubMed

Paździor, Katarzyna; Wrębiak, Julita; Klepacz-Smółka, Anna; Gmurek, Marta; Bilińska, Lucyna; Kos, Lech; Sójka-Ledakowicz, Jadwiga; Ledakowicz, Stanisław

2017-06-15

The textile industry demands huge volumes of high quality water which converts into wastewater contaminated by wide spectrum of chemicals. Estimation of textile wastewater influence on the aquatic systems is a very important issue. Therefore, closing of the water cycle within the factories is a promising method of decreasing its environmental impact as well as operational costs. Taking both reasons into account, the aim of this work was to establish the acute toxicity of the textile wastewater before and after separate chemical, biological as well as combined chemical-biological treatment. For the first time the effects of three different combinations of chemical and biological methods were investigated. The acute toxicity analysis were evaluated using the Microtox ® toxicity test. Ozonation in two reactors of working volume 1 dm 3 (stirred cell) and 20 dm 3 (bubble column) were tested as chemical process, while biodegradation was conducted in two, different systems - Sequence Batch Reactors (SBR; working volume 1.5 dm 3 ) and Horizontal Continuous Flow Bioreactor (HCFB; working volume 12 dm 3 ). The untreated wastewater had the highest toxicity (EC50 value in range: 3-6%). Ozonation caused lower reduction of the toxicity than biodegradation. In the system with SBR the best results were obtained for the biodegradation followed by the ozonation and additional biodegradation - 96% of the toxicity removal. In the second system (with HCFB) two-stage treatment (biodegradation followed by the ozonation) led to the highest toxicity reduction (98%). Copyright © 2016 Elsevier Ltd. All rights reserved.

Aquatic toxicity information retrieval data base (AQUIRE). Data file

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

NONE

The purpose of AQUIRE is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for AQUIRE. Independently compiled data files that meet AQUIRE parameter and quality assurance criteria are also included. Relevant toxicity test results and related test information for any individual chemicals analyzed using freshwater and marine organisms in laboratory and field conditions, are included in the database. During 1992 and early 1993, nine data updates were made to themore » AQUIRE system. AQUIRE now contains 109,338 individual aquatic toxicity test results for 5,159 chemicals, 2,429 organisms, and over 160 endpoints reviewed from 7,517 publications.« less

Functional toxicology: tools to advance the future of toxicity testing

PubMed Central

Gaytán, Brandon D.; Vulpe, Chris D.

2014-01-01

The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

A Novel Water Delivery System for Administering Volatile Chemicals while Minimizing Chemical Waste in Rodent Toxicity Studies

EPA Science Inventory

Rodent toxicity studies typically use water bottles to administer test chemicals via drinking water. However, water bottles provide inconsistent exposure of volatile chemicals due to varying headspace, as well as lead to excessive waste of test material. In order to refine drin...

A novel water delivery system for administering volatile chemicals while minimizing chemical waste in rodent toxicity sutdies

EPA Science Inventory

Rodent toxicity studies typically use water bottles to administer test chemicals via drinking water. However, water bottles provide inconsistent exposure of volatile chemicals due to varying headspace, as well as lead to excessive waste of test material. In order to refine drinki...

Is there a relationship between soil and groundwater toxicity?

PubMed

Sheehan, P; Dewhurst, R E; James, S; Callaghan, A; Connon, R; Crane, M

2003-03-01

Part IIA of the Environmental Protection Act 1990 requires environmental regulators to assess the risk of contaminants leaching from soils into groundwater (DETR, 1999). This newly introduced legislation assumes a link between soil and groundwater chemistry, in which rainwater leaches contaminants from soil into the saturated zone. As the toxicity of both groundwater and overlying soils is dependent upon the chemicals present, their partitioning and their bioavailability, similar patterns of soil, leachates and groundwater toxicity should be observed at contaminated sites. Soil and groundwater samples were collected from different contaminated land sites in an urban area, and used to determine relationships between soil chemistry and toxicity, mobility of contaminants, and groundwater chemistry and toxicity. Soils were leached using water to mimic rainfall, and both the soils and leachates tested using bioassays. Soil bioassays were carried out using Eisenia fetida, whilst groundwater and leachates were tested using the Microtox test system and Daphnia magna 48 h acute tests. Analysis of the bioassay responses demonstrated that a number of the samples were toxic to test organisms, however, there were no significant statistical relationships between soil, groundwater and leachate toxicity. Nor were there significant correlations between soil, leachates and groundwater chemistry.

Initial Technology Assessment for the Environmental Sentinel Biomonitor (ESB) System

DTIC Science & Technology

2006-08-01

McFarlane-Abdulla E, Andersson M, Barile FA, et al. 1996. MEIC evaluation of acute systemic toxicity Part II. In vitro results from 68 toxicity assays used...to test the first 30 reference chemicals and a comparative cytotoxicity analysis. A TLA 24:273-311. Clemedson C, Andersson M, Aoki Y, Barile FA, et al...Clemedson C, McFarlane-Abdulla E, Andersson M, Barile FA, et al. 1996. MEIC evaluation of acute systemic toxicity Part I. Methodology of 68 in vitro

Developmental toxicity testing in the 21st century: the sword of Damocles shattered by embryonic stem cell assays?

PubMed

Seiler, Andrea; Oelgeschläger, Michael; Liebsch, Manfred; Pirow, Ralph; Riebeling, Christian; Tralau, Tewes; Luch, Andreas

2011-11-01

Modern society faces an inherent dilemma. In our globalized society, we are spoilt for choice by an ever-increasing number of products, many of which are made of new materials and compound mixtures. At the same time, as consumers we got accustomed to the idea of a life minimized for risk, including our own exposure to chemicals from the environment or to compounds present in and released from everyday products. Chemical safety testing bridges these obviously diverging interests, and the corresponding legislation has hence been tremendously extended (e.g., introduction of the European legislation REACH in 2007). However, the underlying regulatory toxicology still relies mainly on animal testing, which is relatively slow, expensive, and ethically arguable. Meanwhile, recent years have seen a surge in efforts to develop alternative testing systems and strategies. Expectations are particularly high for the applicability of stem cells as test systems especially for developmental toxicity testing in vitro. For the first time in history, test systems can be based on differentiating cells and tissue progenitors in culture, thus bringing the 'vision of toxicity testing in the 21st century' a step closer.

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

EPA Science Inventory

: The U.S. EPA is responsible for evaluating the effects of approximately 80,000 chemicals registered for use. The challenge is that limited toxicity data exists for many of these chemicals; traditional toxicity testing methods are slow, costly, involve animal studies, and canno...

Leachates draining from controlled municipal solid waste landfill: Detailed geochemical characterization and toxicity tests.

PubMed

Mavakala, Bienvenu K; Le Faucheur, Séverine; Mulaji, Crispin K; Laffite, Amandine; Devarajan, Naresh; Biey, Emmanuel M; Giuliani, Gregory; Otamonga, Jean-Paul; Kabatusuila, Prosper; Mpiana, Pius T; Poté, John

2016-09-01

Management of municipal solid wastes in many countries consists of waste disposal into landfill without treatment or selective collection of solid waste fractions including plastics, paper, glass, metals, electronic waste, and organic fraction leading to the unsolved problem of contamination of numerous ecosystems such as air, soil, surface, and ground water. Knowledge of leachate composition is critical in risk assessment of long-term impact of landfills on human health and the environment as well as for prevention of negative outcomes. The research presented in this paper investigates the seasonal variation of draining leachate composition and resulting toxicity as well as the contamination status of soil/sediment from lagoon basins receiving leachates from landfill in Mpasa, a suburb of Kinshasa in the Democratic Republic of the Congo. Samples were collected during the dry and rainy seasons and analyzed for pH, electrical conductivity, dissolved oxygen, soluble ions, toxic metals, and were then subjected to toxicity tests. Results highlight the significant seasonal difference in leachate physicochemical composition. Affected soil/sediment showed higher values for toxic metals than leachates, indicating the possibility of using lagoon system for the purification of landfill leachates, especially for organic matter and heavy metal sedimentation. However, the ecotoxicity tests demonstrated that leachates are still a significant source of toxicity for terrestrial and benthic organisms. Therefore, landfill leachates should not be discarded into the environment (soil or surface water) without prior treatment. Interest in the use of macrophytes in lagoon system is growing and toxic metal retention in lagoon basin receiving systems needs to be fully investigated in the future. This study presents useful tools for evaluating landfill leachate quality and risk in lagoon systems which can be applied to similar environmental compartments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulatory toxicology in the twenty-first century: challenges, perspectives and possible solutions.

PubMed

Tralau, Tewes; Oelgeschläger, Michael; Gürtler, Rainer; Heinemeyer, Gerhard; Herzler, Matthias; Höfer, Thomas; Itter, Heike; Kuhl, Thomas; Lange, Nikola; Lorenz, Nicole; Müller-Graf, Christine; Pabel, Ulrike; Pirow, Ralph; Ritz, Vera; Schafft, Helmut; Schneider, Heiko; Schulz, Thomas; Schumacher, David; Zellmer, Sebastian; Fleur-Böl, Gaby; Greiner, Matthias; Lahrssen-Wiederholt, Monika; Lampen, Alfonso; Luch, Andreas; Schönfelder, Gilbert; Solecki, Roland; Wittkowski, Reiner; Hensel, Andreas

2015-06-01

The advent of new testing systems and "omics"-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European "regulatory status quo", while elucidating new perspectives for regulatory toxicity testing.

Initial evaluation of developmental malformation as an end point in mixture toxicity hazard assessment for aquatic vertebrates

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

Dawson, D.A.; Wilke, T.S.

1991-04-01

The joint toxic action of three binary mixtures was determined for the embryo malformation endpoint of the aquatic FETAX (frog embryo teratogenesis assay: Xenopus) test system. Osteolathyrogenic compounds and short-chain carboxylic acids, representing separate, distinct modes of action for induction of malformation, were selected for testing in 96-hr, static-renewal tests. Three mixtures were tested for each combination, with each combination being tested on three separate occasions. Using toxic unit analysis, the combination of osteolathyrogens and the combination of carboxylic acids produced strictly additive (concentration addition) rates of malformation, while the combination of an osteolathyrogen and a carboxylic acid was less-than-additivemore » (response addition) for induction of malformation. Therefore, developmental malformation may have value as an endpoint in mixture toxicity hazard assessment.« less

Biometrical evaluation of the performance of the revised OECD Test Guideline 402 for assessing acute dermal toxicity.

PubMed

Mielke, H; Strickland, J; Jacobs, M N; Mehta, J M

2017-10-01

A comprehensive biometrical assessment was conducted to compare the performance of multiple test designs for acute dermal systemic toxicity to support the animal welfare update to the original OECD Test Guideline (TG) 402 for acute dermal toxicity. The test designs evaluated included: (1) two, three, or five animals per dose group (2) evident toxicity or lethality endpoints and (3) absence or presence of a one-animal sighting study. The revision of TG 402 respected the 3R principles (replace, reduce, refine) of animal testing. The results demonstrate that the TG 402 test design can be optimised with reduced animal numbers per test group, such that a scenario of two animals per group following a sighting study at a starting dose of 200 mg/kg bw (unless further information is available to better define the starting dose) would provide a classification which in most cases is conservative, without compromising both the statistical ability of the study to assess dermal toxicity, or the relevant classification outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

"Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

PubMed

Schütte, Julia; Hagmeyer, Britta; Holzner, Felix; Kubon, Massimo; Werner, Simon; Freudigmann, Christian; Benz, Karin; Böttger, Jan; Gebhardt, Rolf; Becker, Holger; Stelzle, Martin

2011-06-01

In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity. This test system is based on an organ-like liver 3D co-culture of hepatocytes and endothelial cells. We devised a microfluidic chip featuring cell culture chambers with integrated electrodes for the assembly of liver sinusoids by dielectrophoresis. Fluid channels enable an organ-like perfusion with culture media and test compounds. Different chamber designs were studied and optimized with regard to dielectrophoretic force distribution, hydrodynamic flow profile, and cell trapping rate using numeric simulations. Based on simulation results a microchip was injection-moulded from COP. This chip allowed the assembly of viable hepatocytes and endothelial cells in a sinusoid-like fashion.

Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

PubMed

Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

2014-12-01

A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies. Copyright © 2014 Elsevier Inc. All rights reserved.

SHORT-EXPOSURE, SUBLETHAL, SEDIMENT TOXICITY TEST USING THE MARINE BIVALVE MULINIA LATERALIS: STATISTICAL DESIGN AND COMPARATIVE SENSITIVITY

EPA Science Inventory

Over the last 10 years a great deal of research effort has concentrated on determining the effects of contaminated sediments on aquatic organisms. or marine systems, this effort has emphasized acute sediment toxicity tests using amphipods, although a variety of other end points a...

Novel in vitro and mathematical models for the prediction of chemical toxicity.

PubMed

Williams, Dominic P; Shipley, Rebecca; Ellis, Marianne J; Webb, Steve; Ward, John; Gardner, Iain; Creton, Stuart

2013-01-01

The focus of much scientific and medical research is directed towards understanding the disease process and defining therapeutic intervention strategies. The scientific basis of drug safety is very complex and currently remains poorly understood, despite the fact that adverse drug reactions (ADRs) are a major health concern and a serious impediment to development of new medicines. Toxicity issues account for ∼21% drug attrition during drug development and safety testing strategies require considerable animal use. Mechanistic relationships between drug plasma levels and molecular/cellular events that culminate in whole organ toxicity underpins development of novel safety assessment strategies. Current in vitro test systems are poorly predictive of toxicity of chemicals entering the systemic circulation, particularly to the liver. Such systems fall short because of (1) the physiological gap between cells currently used and human hepatocytes existing in their native state, (2) the lack of physiological integration with other cells/systems within organs, required to amplify the initial toxicological lesion into overt toxicity, (3) the inability to assess how low level cell damage induced by chemicals may develop into overt organ toxicity in a minority of patients, (4) lack of consideration of systemic effects. Reproduction of centrilobular and periportal hepatocyte phenotypes in in vitro culture is crucial for sensitive detection of cellular stress. Hepatocyte metabolism/phenotype is dependent on cell position along the liver lobule, with corresponding differences in exposure to substrate, oxygen and hormone gradients. Application of bioartificial liver (BAL) technology can encompass in vitro predictive toxicity testing with enhanced sensitivity and improved mechanistic understanding. Combining this technology with mechanistic mathematical models describing intracellular metabolism, fluid-flow, substrate, hormone and nutrient distribution provides the opportunity to design the BAL specifically to mimic the in vivo scenario. Such mathematical models enable theoretical hypothesis testing, will inform the design of in vitro experiments, and will enable both refinement and reduction of in vivo animal trials. In this way, development of novel mathematical modelling tools will help to focus and direct in vitro and in vivo research, and can be used as a framework for other areas of drug safety science.

Novel in vitro and mathematical models for the prediction of chemical toxicity

PubMed Central

Shipley, Rebecca; Ellis, Marianne J.; Webb, Steve; Ward, John; Gardner, Iain; Creton, Stuart

2013-01-01

The focus of much scientific and medical research is directed towards understanding the disease process and defining therapeutic intervention strategies. The scientific basis of drug safety is very complex and currently remains poorly understood, despite the fact that adverse drug reactions (ADRs) are a major health concern and a serious impediment to development of new medicines. Toxicity issues account for ∼21% drug attrition during drug development and safety testing strategies require considerable animal use. Mechanistic relationships between drug plasma levels and molecular/cellular events that culminate in whole organ toxicity underpins development of novel safety assessment strategies. Current in vitro test systems are poorly predictive of toxicity of chemicals entering the systemic circulation, particularly to the liver. Such systems fall short because of (1) the physiological gap between cells currently used and human hepatocytes existing in their native state, (2) the lack of physiological integration with other cells/systems within organs, required to amplify the initial toxicological lesion into overt toxicity, (3) the inability to assess how low level cell damage induced by chemicals may develop into overt organ toxicity in a minority of patients, (4) lack of consideration of systemic effects. Reproduction of centrilobular and periportal hepatocyte phenotypes in in vitro culture is crucial for sensitive detection of cellular stress. Hepatocyte metabolism/phenotype is dependent on cell position along the liver lobule, with corresponding differences in exposure to substrate, oxygen and hormone gradients. Application of bioartificial liver (BAL) technology can encompass in vitro predictive toxicity testing with enhanced sensitivity and improved mechanistic understanding. Combining this technology with mechanistic mathematical models describing intracellular metabolism, fluid-flow, substrate, hormone and nutrient distribution provides the opportunity to design the BAL specifically to mimic the in vivo scenario. Such mathematical models enable theoretical hypothesis testing, will inform the design of in vitro experiments, and will enable both refinement and reduction of in vivo animal trials. In this way, development of novel mathematical modelling tools will help to focus and direct in vitro and in vivo research, and can be used as a framework for other areas of drug safety science. PMID:26966512

A novel system for embryo-larval toxicity testing of pelagic fish: Applications for impact assessment of Deepwater Horizon crude oil.

PubMed

Stieglitz, John D; Mager, Edward M; Hoenig, Ronald H; Alloy, Matthew; Esbaugh, Andrew J; Bodinier, Charlotte; Benetti, Daniel D; Roberts, Aaron P; Grosell, Martin

2016-11-01

Key differences in the developmental process of pelagic fish embryos, in comparison to embryos of standard test fish species, present challenges to obtaining sufficient control survival needed to successfully perform traditional toxicity testing bioassays. Many of these challenges relate to the change in buoyancy, from positive to negative, of pelagic fish embryos that occurs just prior to hatch. A novel exposure system, the pelagic embryo-larval exposure chamber (PELEC), has been developed to conduct successful bioassays on the early life stages (ELSs; embryos/larvae) of pelagic fish. Using this unique recirculating upwelling system, it was possible to significantly improve control survival in pelagic fish ELS bioassays compared to commonly used static exposure methods. Results demonstrate that control performance of mahi-mahi (Coryphaena hippurus) embryos in the PELEC system, measured as percent survival after 96-hrs, significantly outperformed agitated static exposure and static exposure systems. Similar significant improvements in 72-hr control survival were obtained with yellowfin tuna (Thunnus albacares). The PELEC system was subsequently used to test the effects of photo-induced toxicity of crude oil to mahi-mahi ELSs over the course of 96-hrs. Results indicate a greater than 9-fold increase in toxicity of Deepwater Horizon (DWH) crude oil during co-exposure to ambient sunlight compared to filtered ambient sunlight, revealing the importance of including natural sunlight in 96-hr DWH crude oil bioassays as well as the PELEC system's potential application in ecotoxicological assessments. Copyright © 2016 Elsevier Ltd. All rights reserved.

40 CFR 792.43 - Test system care facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Test system care facilities. 792.43 Section 792.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) GOOD LABORATORY PRACTICE STANDARDS Facilities § 792.43 Test system care facilities...

Biological treatment and toxicity of low concentrations of oily wastewater (bilgewater).

PubMed

Stamper, David M; Montgomery, Michael T

2008-08-01

The biodegradability and toxicity of low concentrations of oily wastewater (bilgewater) were tested under simulated sanitary wastewater treatment conditions. This was done to establish the feasibility of a combined shipboard oily and nonoily wastewater treatment system. The biodegradability of oily wastewater was determined by proxy; 14C-labeled dodecane, toluene, and phenanthrene (representing alkane, aromatic, and polyaromatic compounds, respectively) were mineralized in petroleum fuels and lubricants. We found that low concentrations of oily wastewater components were mineralized, even in the presence of more abundant substrates (such as synthetic graywater, containing vegetable oil, detergent, gelatin, and starch). The toxic effects of diesel fuel and several other components of oily wastewater (such as surfactants and a synthetic lubricant) on a naïve wastewater assemblage was also tested. In concentrations much higher than would be expected under normal shipboard conditions, we found no evidence of toxic effects of the bilgewater compounds tested. Thus, a combined shipboard bilgewater and sanitary wastewater system might be feasible.

Quantitative systems toxicology

PubMed Central

Bloomingdale, Peter; Housand, Conrad; Apgar, Joshua F.; Millard, Bjorn L.; Mager, Donald E.; Burke, John M.; Shah, Dhaval K.

2017-01-01

The overarching goal of modern drug development is to optimize therapeutic benefits while minimizing adverse effects. However, inadequate efficacy and safety concerns remain to be the major causes of drug attrition in clinical development. For the past 80 years, toxicity testing has consisted of evaluating the adverse effects of drugs in animals to predict human health risks. The U.S. Environmental Protection Agency recognized the need to develop innovative toxicity testing strategies and asked the National Research Council to develop a long-range vision and strategy for toxicity testing in the 21st century. The vision aims to reduce the use of animals and drug development costs through the integration of computational modeling and in vitro experimental methods that evaluates the perturbation of toxicity-related pathways. Towards this vision, collaborative quantitative systems pharmacology and toxicology modeling endeavors (QSP/QST) have been initiated amongst numerous organizations worldwide. In this article, we discuss how quantitative structure-activity relationship (QSAR), network-based, and pharmacokinetic/pharmacodynamic modeling approaches can be integrated into the framework of QST models. Additionally, we review the application of QST models to predict cardiotoxicity and hepatotoxicity of drugs throughout their development. Cell and organ specific QST models are likely to become an essential component of modern toxicity testing, and provides a solid foundation towards determining individualized therapeutic windows to improve patient safety. PMID:29308440

Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

PubMed

Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of two screening bioassays, based on the frog sciatic nerve and yeast cells, for the assessment of herbicide toxicity.

PubMed

Papaefthimiou, Chrisovalantis; Cabral, Maria de Guadalupe; Mixailidou, Christina; Viegas, Cristina A; Sá-Correia, Isabel; Theophilidis, George

2004-05-01

Two different test systems, one based on the isolated sciatic nerve of an amphibian and the other on a microbial eukaryote, were used for the assessment of herbicide toxicity. More specifically, we determined the deleterious effects of increasing concentrations of herbicides of different chemical classes (phenoxyacetic acids, triazines, and acetamides), and of 2,4-dichlorophenol (2,4-DCP), a degradation product of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), on electrophysiological parameters and the vitality of the axons of the isolated sciatic nerve of the frog (Rana ridibunda) and on the growth curve of the yeast Saccharomyces cerevisiae based on microtiter plate susceptibility assays. The no-observed-effect-concentration (NOEC), defined as the maximum concentration of the tested compound that has no effect on these biological parameters, was estimated. In spite of the different methodological approaches and biological systems compared, the NOEC values were identical and correlated with the lipophilicity of the tested compounds. The relative toxicity established here, 2,4-DCP > alachlor, metolachlor > metribuzin > 2,4-D, 2-methyl-4-chlorophenoxyacetic acid (MCPA), correlates with the toxicity indexes reported in the literature for freshwater organisms. Based on these results, we suggest that the relatively simple, rapid, and low-cost test systems examined here may be of interest as alternative or complementary tests for toxicological assessment of herbicides.

Toxicity assessment of industrial chemicals and airborne contaminants: transition from in vivo to in vitro test methods: a review.

PubMed

Bakand, S; Winder, C; Khalil, C; Hayes, A

2005-12-01

Exposure to occupational and environmental contaminants is a major contributor to human health problems. Inhalation of gases, vapors, aerosols, and mixtures of these can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there are approximately 80,000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from both economical and practical perspectives. While in vitro methods are capable of rapidly providing toxicity information, regulatory agencies in general are still cautious about the replacement of whole-animal methods with new in vitro techniques. Although studying the toxic effects of inhaled chemicals is a complex subject, recent studies demonstrate that in vitro methods may have significant potential for assessing the toxicity of airborne contaminants. In this review, current toxicity test methods for risk evaluation of industrial chemicals and airborne contaminants are presented. To evaluate the potential applications of in vitro methods for studying respiratory toxicity, more recent models developed for toxicity testing of airborne contaminants are discussed.

The biotic ligand model approach for addressing effects of exposure water chemistry on aquatic toxicity of metals: Genesis and challenges

EPA Science Inventory

A major uncertainty in many aquatic risk assessments for toxic chemicals is the aggregate effect of the physicochemical characteristics of exposure media on toxicity, and how this affects extrapolation of laboratory test results to natural systems. A notable example of this is h...

An ecotoxicological approach for hazard identification of energy ash.

PubMed

Stiernström, S; Hemström, K; Wik, O; Carlsson, G; Bengtsson, B-E; Breitholtz, M

2011-02-01

Within the EU, ash should be classified by its inherent hazardous effects under criterion H-14 (ecotoxic) in the Directive on waste (2008/98/EC). Today, however, there are no harmonized quantitative criterions for such a classification, but it is stated that biological test systems can be used. In this study seven ash materials were leached and characterized, both biologically and chemically. The objectives were to evaluate if (a) clear concentration-response relationships could be achieved for the selected toxicity tests (bacteria, algae, crustacean and fish), (b) some test(s) are generally more sensitive and (c) the toxic responses were consistent with the chemical analyzes. Interestingly, our results indicate that high concentrations of non-hazardous components (Ca, K) influenced the toxicity of almost all ash eluates, whereas hazardous components (e.g. Zn, Pb) only influenced the toxicity of the eluates ranked as most hazardous. If considering both hazardous and non-hazardous substances, the observed toxic responses were relatively consistent with the chemical analyzes. Our results further showed that the (sub)chronic tests were much more sensitive than the acute tests. However, the use of extrapolation factors to compensate for using the less sensitive acute tests will likely lead to either over- or underestimations of toxicity. Our recommendation is therefore that classification of waste according to H-14 should be based on (sub)chronic test data. Finally, given that treatment of the eluates prior to toxicity testing has a major significance on the concentration and speciation of released substances, further studies are needed in order to propose a relevant testing scheme. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of Environmental Toxicants on Metabolic Activity of Natural Microbial Communities

PubMed Central

Barnhart, Carole L. H.; Vestal, J. Robie

1983-01-01

Two methods of measuring microbial activity were used to study the effects of toxicants on natural microbial communities. The methods were compared for suitability for toxicity testing, sensitivity, and adaptability to field applications. This study included measurements of the incorporation of 14C-labeled acetate into microbial lipids and microbial glucosidase activity. Activities were measured per unit biomass, determined as lipid phosphate. The effects of various organic and inorganic toxicants on various natural microbial communities were studied. Both methods were useful in detecting toxicity, and their comparative sensitivities varied with the system studied. In one system, the methods showed approximately the same sensitivities in testing the effects of metals, but the acetate incorporation method was more sensitive in detecting the toxicity of organic compounds. The incorporation method was used to study the effects of a point source of pollution on the microbiota of a receiving stream. Toxic doses were found to be two orders of magnitude higher in sediments than in water taken from the same site, indicating chelation or adsorption of the toxicant by the sediment. The microbiota taken from below a point source outfall was 2 to 100 times more resistant to the toxicants tested than was that taken from above the outfall. Downstream filtrates in most cases had an inhibitory effect on the natural microbiota taken from above the pollution source. The microbial methods were compared with commonly used bioassay methods, using higher organisms, and were found to be similar in ability to detect comparative toxicities of compounds, but were less sensitive than methods which use standard media because of the influences of environmental factors. PMID:16346432

Survival and growth of freshwater pulmonate and nonpulmonate snails in 28-day exposures to copper, ammonia, and pentachlorophenol

USGS Publications Warehouse

Besser, John M.; Dorman, Rebecca A.; Hardesty, Douglas K.; Ingersoll, Christopher G.

2016-01-01

We performed toxicity tests with two species of pulmonate snails (Lymnaea stagnalis and Physa gyrina) and four taxa of nonpulmonate snails in the family Hydrobiidae (Pyrgulopsis robusta,Taylorconcha serpenticola, Fluminicola sp., and Fontigens aldrichi). Snails were maintained in static-renewal or recirculating culture systems with adults removed periodically to isolate cohorts of offspring for toxicity testing. This method successfully produced offspring for both species of pulmonate snails and for two hydrobiid species, P. robusta and Fluminicola sp. Toxicity tests were performed for 28 days with copper, ammonia, and pentachlorophenol in hard reconstituted water with endpoints of survival and growth. Tests were started with 1-week-old L. stagnalis, 2-week-old P. gyrina, 5- to 13-week-old P. robusta and Fluminicola sp., and older juveniles and adults of several hydrobiid species. For all three chemicals, chronic toxicity values for pulmonate snails were consistently greater than those for hydrobiid snails, and hydrobiids were among the most sensitive taxa in species sensitivity distributions for all three chemicals. These results suggest that the toxicant sensitivity of nonpulmonate snails in the family Hydrobiidae would not be adequately represented by results of toxicity testing with pulmonate snails.

Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

PubMed

Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

2015-05-01

Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

Evaluation of dredged material proposed for ocean disposal from Arthur Kill Project Area, New York

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

Gruendell, B.D.; Barrows, E.S.; Borde, A.B.

1997-01-01

The objective of the bioassay reevaluation of Arthur Kill Federal Project was to reperform toxicity testing on proposed dredged material following current ammonia reduction protocols. Arthur Kill was one of four waterways sampled and evaluated for dredging and disposal in April 1993. Sediment samples were recollected from the Arthur Kill Project areas in August 1995. Tests and analyses were conducted according to the manual developed by the USACE and the U.S. Environmental Protection Agency (EPA), Evaluation of Dredged Material Proposed for Ocean Disposal (Testing Manual), commonly referred to as the {open_quotes}Green Book,{close_quotes} and the regional manual developed by the USACE-NYDmore » and EPA Region II, Guidance for Performing Tests on Dredged Material to be Disposed of in Ocean Waters. The reevaluation of proposed dredged material from the Arthur Kill project areas consisted of benthic acute toxicity tests. Thirty-three individual sediment core samples were collected from the Arthur Kill project area. Three composite sediments, representing each reach of the area proposed for dredging, was used in benthic acute toxicity testing. Benthic acute toxicity tests were performed with the amphipod Ampelisca abdita and the mysid Mysidopsis bahia. The amphipod and mysid benthic toxicity test procedures followed EPA guidance for reduction of total ammonia concentrations in test systems prior to test initiation. Statistically significant acute toxicity was found in all Arthur Kill composites in the static renewal tests with A. abdita, but not in the static tests with M. bahia. Statistically significant acute toxicity and a greater than 20% increase in mortality over the reference sediment was found in the static renewal tests with A. abdita. M. bahia did not show statistically significant acute toxicity or a greater than 10% increase in mortality over reference sediment in static tests. 5 refs., 2 figs., 2 tabs.« less

3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing.

PubMed

Takayama, Kazuo; Kawabata, Kenji; Nagamoto, Yasuhito; Kishimoto, Keisuke; Tashiro, Katsuhisa; Sakurai, Fuminori; Tachibana, Masashi; Kanda, Katsuhiro; Hayakawa, Takao; Furue, Miho Kusuda; Mizuguchi, Hiroyuki

2013-02-01

Although it is expected that hepatocyte-like cells differentiated from human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells will be utilized in drug toxicity testing, the actual applicability of hepatocyte-like cells in this context has not been well examined so far. To generate mature hepatocyte-like cells that would be applicable for drug toxicity testing, we established a hepatocyte differentiation method that employs not only stage-specific transient overexpression of hepatocyte-related transcription factors but also a three-dimensional spheroid culture system using a Nanopillar Plate. We succeeded in establishing protocol that could generate more matured hepatocyte-like cells than our previous protocol. In addition, our hepatocyte-like cells could sensitively predict drug-induced hepatotoxicity, including reactive metabolite-mediated toxicity. In conclusion, our hepatocyte-like cells differentiated from human ES cells or iPS cells have potential to be applied in drug toxicity testing. Copyright © 2012 Elsevier Ltd. All rights reserved.

Demonstration of a Non-Toxic Reaction Control Engine

NASA Technical Reports Server (NTRS)

Robinson, Philip J.; Turpin, Alicia A.; Veith, Eric M.

2007-01-01

T:hree non-toxic demonstration reaction control engines (RCE) were successfully tested at the Aerojet Sacramento facility under a technology contract sponsored by the National Aeronautics and Space Administration's (NASA) Marshall Space Flight Center (MSFC). The goals of the NASA MSFC contract (NAS8-01109) were to develop and expand the technical maturity of a non-toxic, on-orbit auxiliary propulsion system (APS) thruster under the auspices of the Exploration Systems Mission Directorate. The demonstration engine utilized Liquid Oxygen (LOX) and Ethanol as propellants to produce 870 lbf thrust. The Aerojet RCE's were successfully acceptance tested over a broad range of operating conditions. Steady state tests evaluated engine response to varying chamber pressures and mixture ratios. In addition to the steady state tests, a variety of pulsing tests were conducted over a wide range of electrical pulse widths (EPW). Each EPW condition was also tested over a range of percent duty cycles (DC), and bit impulse and pulsing specific impulse were determined for each of these conditions. Subsequent to acceptance testing at Aerojet, these three engines were delivered to the NASA White Sands Test Facility (WSTF) in April 2005 for incorporation into a cryogenic Auxiliary Propulsion System Test Bed (APSTB). The APSTB is a test article that will be utilized in an altitude test cell to simulate anticipated mission applications. The objectives of this APSTB testing included evaluation of engine performance over an extended duty cycle map of propellant pressure and temperature, as well as engine and system performance at typical mission duty cycles over extended periods of time. This paper provides acceptance test results and a status of the engine performance as part of the system level testing.

Demonstration of a Non-Toxic Reaction Control Engine

NASA Technical Reports Server (NTRS)

Robinson, Philip J.; Veith, Eric M.; Turpin, Alicia A.

2006-01-01

Three non-toxic demonstration reaction control engines (RCE) were successfully tested at the Aerojet Sacramento facility under a technology contract sponsored by the National Aeronautics and Space Administration s (NASA) Marshall Space Flight Center (MSFC). The goals of the NASA MSFC contract (NAS8-01109) were to develop and expand the technical maturity of a non-toxic, on-orbit auxiliary propulsion system (APS) thruster under the auspices of the Exploration Systems Mission Directorate. The demonstration engine utilized Liquid Oxygen (LOX) and Ethanol as propellants to produce 870 lbf thrust. The Aerojet RCE s were successfully acceptance tested over a broad range of operating conditions. Steady state tests evaluated engine response to varying chamber pressures and mixture ratios. In addition to the steady state tests, a variety of pulsing tests were conducted over a wide range of electrical pulse widths (EPW). Each EPW condition was also tested over a range of percent duty cycles (DC), and bit impulse and pulsing specific impulse were determined for each of these conditions. White Sands Test Facility (WSTF) in April 2005 for incorporation into a cryogenic Auxiliary Propulsion System Test Bed (APSTB). The APSTB is a test article that will be utilized in an altitude test cell to simulate anticipated mission applications. The objectives of this APSTB testing included evaluation of engine performance over an extended duty cycle map of propellant pressure and temperature, as well as engine and system performance at typical mission duty cycles over extended periods of time. This paper provides acceptance test results and a status of the engine performance as part of the system level testing. Subsequent to acceptance testing at Aerojet, these three engines were delivered to the NASA

Comprehensive In Vitro Toxicity Testing of a Panel of Representative Oxide Nanomaterials: First Steps towards an Intelligent Testing Strategy

PubMed Central

Farcal, Lucian; Torres Andón, Fernando; Di Cristo, Luisana; Rotoli, Bianca Maria; Bussolati, Ovidio; Bergamaschi, Enrico; Mech, Agnieszka; Hartmann, Nanna B.; Rasmussen, Kirsten; Riego-Sintes, Juan; Ponti, Jessica; Kinsner-Ovaskainen, Agnieszka; Rossi, François; Oomen, Agnes; Bos, Peter; Chen, Rui; Bai, Ru; Chen, Chunying; Rocks, Louise; Fulton, Norma; Ross, Bryony; Hutchison, Gary; Tran, Lang; Mues, Sarah; Ossig, Rainer; Schnekenburger, Jürgen; Campagnolo, Luisa; Vecchione, Lucia; Pietroiusti, Antonio; Fadeel, Bengt

2015-01-01

Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO2 NMs with different surface chemistry – hydrophilic (NM-103) and hydrophobic (NM-104), two forms of ZnO – uncoated (NM-110) and coated with triethoxycapryl silane (NM-111) and two SiO2 NMs produced by two different manufacturing techniques – precipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO2>TiO2). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO2 and SiO2, while the embryonic stem cell test (EST) classified the TiO2 NMs as potentially ‘weak-embryotoxic’ and ZnO and SiO2 NMs as ‘non-embryotoxic’. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO2 NM-203 > SiO2 NM-200 > TiO2 NM-104 > TiO2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO2 displayed higher toxicity compared with ZnO and SiO2. Importantly, the in vitro methodology applied could identify cell- and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects. PMID:25996496

Status of acute systemic toxicity testing requirements and data uses by U.S. regulatory agencies.

PubMed

Strickland, Judy; Clippinger, Amy J; Brown, Jeffrey; Allen, David; Jacobs, Abigail; Matheson, Joanna; Lowit, Anna; Reinke, Emily N; Johnson, Mark S; Quinn, Michael J; Mattie, David; Fitzpatrick, Suzanne C; Ahir, Surender; Kleinstreuer, Nicole; Casey, Warren

2018-04-01

Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these data, the regulatory needs and uses for acute systemic toxicity information must first be clarified. Thus, we reviewed acute systemic toxicity testing requirements for six U.S. agencies (Consumer Product Safety Commission, Department of Defense, Department of Transportation, Environmental Protection Agency, Food and Drug Administration, Occupational Safety and Health Administration) and noted whether there is flexibility in satisfying data needs with methods that replace or reduce animal use. Understanding the current regulatory use and acceptance of non-animal data is a necessary starting point for future method development, optimization, and validation efforts. The current review will inform the development of a national strategy and roadmap for implementing non-animal approaches to assess potential hazards associated with acute exposures to industrial chemicals and medical products. The Acute Toxicity Workgroup of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), U.S. agencies, non-governmental organizations, and other stakeholders will work to execute this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

U-937 Toxicity Testing of Lunar Dust Stimulant (JSC-1A-vf)

NASA Technical Reports Server (NTRS)

Bales, Kristyn; Hammond, Dianne; Wallace, William; Jeevarajan, Antony

2007-01-01

With NASA planning to extend the human presence to the moon by 2020, the dangers of the lunar environment must be assessed and appropriate countermeasures must be developed. Possible toxic effects of the lunar dust are of particular importance to human health because of the dust's chemical composition, reactivity, and small size. This project focuses on the toxicity of lunar dust stimulant (JSC-1A-vf), in both its active and passive forms, using U-937 human monocyte cells. Simulant was mechanically activated from its passive form by grinding, and its ability to produce hydroxyl radicals was determined. To test for toxicity, active and passivated simulant was diluted in media and applied to the cells for various time periods. Toxicity was then estimated using flow cytometry on the Guava Personal Cell Analysis system. Preliminary results suggest that passivated stimulant is slightly toxic, with an increase in toxicity for activated stimulant. Toxicity results may be affected by cell lysing behavior and quenching of hydroxyl radical production by the cell media.

Aquatic toxicity information retrieval data base (aquire for non-vms) (on magnetic tape). Data file

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

NONE

The AQUIRE-AQUatic toxicity information REtrieval-data base was established in 1981 by the United States Environmental Protection Agency (US EPA), Office of Pesticide and Toxic Substances. AQUIRE continues to be updated and maintained at the US EPA Environmental Research Laboratory-Duluth. The purpose of AQUIRE is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxic effects data for freshwater and marine organisms. The AQUIRE system is one of the foremost resources for the location of aquatic toxicity information and is commonly used to evaluate and prioritize the hazards of industrial chemicals and pesticides in themore » USA and abroad. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for AQUIRE. Independently compiled data files that meet AQUIRE parameter and quality assurance criteria are also included. Relevant toxicity test results and related test information for any individual chemicals analyzed using freshwater and marine organisms in laboratory and field conditions, are included in the database. Since 1994, nine data updates were made to the AQUIRE system. AQUIRE now contains 129,740 individual aquatic toxicity test results for 5,679 chemicals, 2,827 organisms, and over 160 endpoints reviewed from 7,517 publications. Over 16,000 of the AQUIRE records represent aquatic toxicity data reported in the literature for the publication years 1989-1991. AQUIRE offers data contributed through an international data exchange clearinghouse with the Organization for Economic Cooperation and Development (OECD) and the Borok Institute in Russia. The current release of AQUIRE delivers data submitted from Germany, The Netherlands, and Russia.« less

Evaluation of cytotoxic effects of six self-etching adhesives with direct and indirect contact tests.

PubMed

Kusdemir, Mahmut; Gunal, Solen; Ozer, Fusun; Imazato, Satoshi; Izutani, Naomi; Ebisu, Shigeyuki; Blatz, Markus B

2011-01-01

This study evaluated the cytotoxicity of self-etching primers/adhesives by direct contact and dentin barrier tests. The three two-step self-etching systems Clearfil SE Bond (CSE), Clearfil Protect Bond (CPB), Prime&Bond NT/NRC (PB) and one-step self-etching systems Reactmer Bond (RB), Clearfil Tri-S Bond (CTS), and Adper Prompt L-Pop (AP) were examined. In direct contact tests, L929 cells were cultured in the presence of diluted solutions (50, 20, 10, and 1%) of primer/conditioner of adhesive systems. For dentin barrier tests, each system was applied onto 0.5 or 1.5 mm thick human dentin assembled in a simple pulp chamber device and incubated for 24 h at 37°C to make the diffusive components contact the L929 cells placed at the bottom of the chamber. The cytotoxic effects were assessed by MTT assay. Cell culture without application of any primers/adhesives served as the control for both tests. One-way ANOVA and Tukey HSD tests were used for statistical analyses. The direct contact tests demonstrated that CSE and CPB were less toxic than the other materials at all dilutions. In the dentin barrier tests, toxic effects of materials were reduced with an increase in thickness of intervening dentin. CSE and CPB showed less cytotoxicity than the other adhesives (p<0.05) when applied to 0.5 mm-thick dentin, and CSE was the least toxic in the 1.5 mm-dentin group (p<0.05). Dentin thickness positively affected biocompatibility of the tested bonding systems. Two-step self-etching systems with HEMA-based primers were more biocompatible than other self-etching adhesives.

Specifically Designed Constructed Wetlands: A Novel Treatment Approach for Scrubber Wastewater

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

John H. Rodgers Jr; James W. Castle; Chris Arrington: Derek Eggert

2005-09-01

A pilot-scale wetland treatment system was specifically designed and constructed at Clemson University to evaluate removal of mercury, selenium, and other constituents from flue gas desulfurization (FGD) wastewater. Specific objectives of this research were: (1) to measure performance of a pilot-scale constructed wetland treatment system in terms of decreases in targeted constituents (Hg, Se and As) in the FGD wastewater from inflow to outflow; (2) to determine how the observed performance is achieved (both reactions and rates); and (3) to measure performance in terms of decreased bioavailability of these elements (i.e. toxicity of sediments in constructed wetlands and toxicity ofmore » outflow waters from the treatment system). Performance of the pilot-scale constructed wetland treatment systems was assessed using two criteria: anticipated NPDES permit levels and toxicity evaluations using two sentinel toxicity-testing organisms (Ceriodaphnia dubia and Pimephales promelas). These systems performed efficiently with varied inflow simulations of FGD wastewaters removing As, Hg, and Se concentrations below NPDES permit levels and reducing the toxicity of simulated FGD wastewater after treatment with the constructed wetland treatment systems. Sequential extraction procedures indicated that these elements (As, Hg, and Se) were bound to residual phases within sediments of these systems, which should limit their bioavailability to aquatic biota. Sediments collected from constructed wetland treatment systems were tested to observe toxicity to Hyalella azteca or Chironomus tetans. Complete survival (100%) was observed for H. azteca in all cells of the constructed wetland treatment system and C. tentans had an average of 91% survival over the three treatment cells containing sediments. Survival and growth of H. azteca and C. tentans did not differ significantly between sediments from the constructed wetland treatment system and controls. Since the sediments of the constructed wetland treatment system are repositories for As, Hg, and Se and the bioavailability of these elements decreased after deposition, the pilot-scale constructed wetland treatment system contributed significantly to mitigation of risks to aquatic life from these elements.« less

Coupling of OECD standardized test and immunomarkers to select the most environmentally benign ionic liquids option--towards an innovative "safety by design" approach.

PubMed

Bado-Nilles, Anne; Diallo, Alpha-Oumar; Marlair, Guy; Pandard, Pascal; Chabot, Laure; Geffard, Alain; Len, Christophe; Porcher, Jean-Marc; Sanchez, Wilfried

2015-01-01

This paper proposed a potential industrial accompaniment to reduce ionic liquid harmfulness by a novel combination of OECD Daphnia magna standardized test and fish immunomarkers. The combination of these two tests allowed multicriteria examination of ILs impacts in different organisms and trophic levels. The work provided new data for legislation and opened a door towards an integrative environmental evaluation due to direct implications of immune system in fish and ecosystem health. Whatever the species, each IL tested induced deleterious effects suggesting that toxic impact was especially due to IL lipophilicity properties. Nevertheless, cation moieties of ILs seemed to draw overall toxicity of ILs to significant extent as supported by lower cell mortality shown with imidazolium-based ILs compared to phosphonium-based ILs. However, the anions moieties have some additional effect, as revealed by quite dissimilar toxicity within same IL family. Concerning the more integrative biomarkers, the cationic-based ILs tested possessed also dissimilar effect on immune system of fish, especially on leucocyte distribution, lysosomal membrane integrity and phagocytosis activity. These results confirm that ILs toxicity could be influenced by design and that chemical engineering processes can integrate ecological footprint reduction strategies for successful IL utilization in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Temporal and modal characterization of DoD source air toxic ...

EPA Pesticide Factsheets

This project tested three, real-/near real-time monitoring techniques to develop air toxic emission factors for Department of Defense (DoD) platform sources. These techniques included: resonance enhanced multi photon ionization time of flight mass spectrometry (REMPI-TOFMS) for organic air toxics, laser induced breakdown spectroscopy (LIBS) for metallic air toxics, and optical remote sensing (ORS) methods for measurement of criteria pollutants and other hazardous air pollutants (HAPs). Conventional emission measurements were used for verification of the real-time monitoring results. The REMPI-TOFMS system was demonstrated on the following: --a United States U.S. Marine Corps (USMC) diesel generator, --a U.S. Air Force auxiliary power unit (APU), --the waste combustor at the Portsmouth Naval Shipyard, during a multi-monitor environmental technology verification (ETV) test for dioxin monitoring systems, --two dynamometer-driven high mobility multi-purpose wheeled vehicles (HMMWVs), --an idling Abrams battle tank, --a Bradley infantry fighting vehicle (IFV), and --an F-15 and multiple F-22 U.S. Air Force aircraft engines. LIBS was tested and applied solely to the U.S. Marine Corps diesel generator. The high detection limits of LIBS for toxic metals limited its usefulness as a real time analyzer for most DoD sources. ORS was tested only on the APU with satisfactory results for non-condensable combustion products (carbon monoxide [CO], carbon dioxide

A tropical sediment toxicity test using the dipteran Chironomus crassiforceps to test metal bioavailability with sediment pH change in tropical acid-sulfate sediments.

PubMed

Peck, Mika R; Klessa, David A; Baird, Donald J

2002-04-01

The wetlands of the Magela floodplain of northern Australia, which is the major sink for dissolved metals transported in the Magela Creek system, contain acid-sulfate sediments. The rewetting of oxidized acid-sulfate soil each wet season produces acidic pulses that have the potential to alter the bioavailability of sediment-associated metal contaminants. Acute toxicity tests (72-h mean lethal concentration [LC50]) using the tropical chironomid Chironomus crassiforceps Kieffer showed that copper toxicity decreased from 0.64 mg/L at pH 6 to 2.30 mg/L at pH 4. Uranium toxicity showed a similar trend (36 mg/L at pH 6 and 58 mg/L at pH 4). Sediment toxicity tests developed using C. crassiforceps also showed that both metals were less toxic at the lower sediment pH with pore-water copper toxicity having a lowest-observed-effect concentration of 4.73 mg/L at pH 4 compared to 1.72 mg/L at pH 6. However, a lower pH increased pore-water metal concentrations and overlying water concentrations in bioassays. Hydrogen ion competition on metal receptor sites in C. crassiforceps was proposed to explain the decrease in toxicity in response to increased H+ activity. This study highlights the need to consider site-specific physicochemical conditions before applying generic risk assessment methods.

The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

PubMed

Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

2013-01-01

The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

PubMed

Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

2006-10-01

An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC(50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

Development of an in-line filter to prevent intrusion of NO2 toxic vapors into A/C systems

NASA Technical Reports Server (NTRS)

Meneghelli, Barry; Mcnulty, R. J.; Springer, Mike; Lueck, Dale E.

1995-01-01

The hypergolic propellant nitrogen tetroxide (N2O4 or NTO) is routinely used in spacecraft launched at Kennedy Space Center (KSC) and Cape Canaveral Air Station (CCAS). In the case of a catastrophic failure of the spacecraft, there would be a release of the unspent propellant in the form of a toxic cloud. Inhalation of this material at downwind concentrations which may be as high as 20 parts per million (ppm) for 30 minutes in duration, may produce irritation to the eyes, nose and respiratory tract. Studies at both KSC and CCAS have shown that the indoor concentrations of N2O4 during a toxic release may range from 1 to 15 ppm and depend on the air change rate (ACR) for a particular building and whether or not the air conditioning (A/C) system has been shut down or left in an operating mode. This project was initiated in order to assess how current A/C systems could be easily modified to prevent personnel from being exposed to toxic vapors. A sample system has been constructed to test the ability of several types of filter material to capture the N2O4 vapors prior to their infiltration into the A/C system. Test results will be presented which compare the efficiencies of standard A/C filters, water wash systems, and chemically impregnated filter material in taking toxic vapors out of the incoming air stream.

Cytogenomics of hexavalent chromium (Cr6+) exposed cells: A comprehensive review

PubMed Central

Nigam, Akanksha; Priya, Shivam; Bajpai, Preeti; Kumar, Sushil

2014-01-01

The altered cellular gene expression profile is being hypothesized as the possible molecular basis navigating the onset or progress of various morbidities. This hypothesis has been evaluated here in respect of Cr6+ induced toxicity. Several studies using gene microarray show selective and strategic dysregulations of cellular genes and pathways induced by Cr6+. Relevant literature has been reviewed to unravel these changes in different test systems after exposure to Cr6+ and also to elucidate association if any, of the altered cytogenomics with Cr6+ induced toxicity or carcinogenicity. The aim was to verify the hypothesis for critical role of altered cytogenomics in onset of Cr6+ induced biological / clinical effects by identifying genes modulated commonly by the toxicant irrespective of test system or test concentrations / doses, and by scrutinizing their importance in regulation of the flow of mechanistically linked events crucial for resultant morbidities. Their probability as biomarkers to monitor the toxicant induced biological changes is speculative. The modulated genes have been found to cluster under the pathways that manage onset of oxidative stress, DNA damage, apoptosis, cell-cycle regulation, cytoskeleton, morphological changes, energy metabolism, biosynthesis, oncogenes, bioenergetics, and immune system critical for toxicity. In these studies, the identity of genes has been found to differ remarkably; albeit the trend of pathways’ dysregulation has been found to remain similar. We conclude that the intensity of dysregulation of genes or pathways involved in mechanistic events forms a sub-threshold or threshold level depending upon the dose and type (including speciation) of the toxicant, duration of exposure, type of target cells, and niche microenvironment of cells, and the intensity of sub-threshold or threshold level of the altered cytogenomics paves way in toxicant exposed cells eventually either to opt for reversal to differentiation and growth, or to result in toxicity like dedifferentiation and apoptosis, respectively. PMID:24820829

Automated Lab-on-a-Chip Technology for Fish Embryo Toxicity Tests Performed under Continuous Microperfusion (μFET).

PubMed

Zhu, Feng; Wigh, Adriana; Friedrich, Timo; Devaux, Alain; Bony, Sylvie; Nugegoda, Dayanthi; Kaslin, Jan; Wlodkowic, Donald

2015-12-15

The fish embryo toxicity (FET) biotest has gained popularity as one of the alternative approaches to acute fish toxicity tests in chemical hazard and risk assessment. Despite the importance and common acceptance of FET, it is still performed in multiwell plates and requires laborious and time-consuming manual manipulation of specimens and solutions. This work describes the design and validation of a microfluidic Lab-on-a-Chip technology for automation of the zebrafish embryo toxicity test common in aquatic ecotoxicology. The innovative device supports rapid loading and immobilization of large numbers of zebrafish embryos suspended in a continuous microfluidic perfusion as a means of toxicant delivery. Furthermore, we also present development of a customized mechatronic automation interface that includes a high-resolution USB microscope, LED cold light illumination, and miniaturized 3D printed pumping manifolds that were integrated to enable time-resolved in situ analysis of developing fish embryos. To investigate the applicability of the microfluidic FET (μFET) in toxicity testing, copper sulfate, phenol, ethanol, caffeine, nicotine, and dimethyl sulfoxide were tested as model chemical stressors. Results obtained on a chip-based system were compared with static protocols performed in microtiter plates. This work provides evidence that FET analysis performed under microperfusion opens a brand new alternative for inexpensive automation in aquatic ecotoxicology.

Inhibitory effects of 1alpha, 25dihydroxyvitamin D3 and Ajuga iva extract on oxidative stress, toxicity and hypo-fertility in diabetic rat testes.

PubMed

Hamden, K; Carreau, S; Jamoussi, K; Ayadi, F; Garmazi, F; Mezgenni, N; Elfeki, A

2008-09-01

The aim of the current study is to investigate the therapeutic and preventive effects of 1alpha, 25dihydroxyvitaminD3 (1,25 (OH)2 D3) and Afuga iva (AI) extract on diabetes toxicity in rats testes. Thus diabetic rats were treated with 1alpha, 25dihydroxyvitaminD3 or Ajuga iva extract as both therapeutic and preventive treatments on diabetes toxicity in rats testes. Our results showed that diabetes induced a decrease in testosterone and 17beta-estradiol levels in testes and plasma. Besides, a fall in testicular antioxidant capacity appeared by a decrease in both antioxidant (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities) and nonenzymatic antioxidant (copper (Cu), magnesium (Mg) and iron (Fe) levels). All theses changes enhanced testicular toxicity (increase in testicular aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH) activities and the lipid peroxidation and triglyceride (TG) levels). In addition, a decrease in testicular total cholesterol (TCh) level was observed in diabetic rats testes. All the changes lead to a decrease in the total number and mobility of epididymal spermatozoa. The administration of 1alpha,25dihydroxyvitaminD3 and Ajuga iva extract three weeks before and after diabetes induction interfered and prevented diabetes toxicity in the reproductive system. 1,25 (OH)2 D3 and Ajuga iva extract blunted all changes observed in diabetic rats. To sum up, the data suggested that 1,25 (OH)2 D3 and Ajuga iva extract have a protective effect on alloxan-induced damage in reproductive system by enhancing the testosterone and 17beta-estradiol levels, consequently protecting from oxidative stress, cellular toxicity and maintaining the number and motility of spermatozoids.

Disinfection by-products and ecotoxicity of ballast water after oxidative treatment--results and experiences from seven years of full-scale testing of ballast water management systems.

PubMed

Delacroix, Stephanie; Vogelsang, Christian; Tobiesen, August; Liltved, Helge

2013-08-15

Since 2005, five different ballast water management systems (BWMSs) based on chlorination treatment have been tested by Norwegian Institute for Water Research (NIVA) according to guidelines from the International Maritime Organization (IMO). 25% and >50% of all the tested discharge samples exhibited acute and chronic toxic effects on algae, respectively. In most cases this toxicity was plausibly caused by a high free residual oxidant (FRO) level (>0.08 mg Cl/l). Of the 22 disinfection by-products (DBPs) that were identified in treated water at discharge, four compounds were at times found at concentrations that may pose a risk to the local aquatic environment. However, there seemed to be no clear indication that the measured DBP concentrations contributed to the observed algal toxicity. The addition of methylcellulose instead of lignin in the test water to comply with IMO requirements seemed to limit the formation of DBP. Copyright © 2013 Elsevier Ltd. All rights reserved.

Developmental immunotoxicity of chemicals in rodents and its possible regulatory impact.

PubMed

Hessel, Ellen V S; Tonk, Elisa C M; Bos, Peter M J; van Loveren, Henk; Piersma, Aldert H

2015-01-01

Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted.

Field Validation of Toxicity Tests to Evaluate the Potential for Beneficial Use of Produced Water

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

Joseph Bidwell; Jonathan Fisher; Naomi Cooper

2008-03-31

This study investigated potential biological effects of produced water contamination derived from occasional surface overflow and possible subsurface intrusion at an oil production site along the shore of Skiatook Lake, Oklahoma. We monitored basic chemistry and acute toxicity to a suite of standard aquatic test species (fathead minnow-Pimephales promelas, Daphnia pulex, Daphnia magna, and Ceriodaphnia dubia) in produced water and in samples taken from shallow groundwater wells on the site. Toxicity identification evaluations and ion toxicity modeling were used to identify toxic constituents in the samples. Lake sediment at the oil production site and at a reference site were alsomore » analyzed for brine intrusion chemically and by testing sediment toxicity using the benthic invertebrates, Chironomus dilutus, and Hyallela azteca. Sediment quality was also assessed with in situ survival and growth studies with H. azteca and the Asian clam, Corbicula fluminea, and by benthic macroinvertebrate community sampling. The produced water was acutely toxic to the aquatic test organisms at concentrations ranging from 1% to 10% of the whole produced water sample. Toxicity identification evaluation and ion toxicity modeling indicated major ion salts and hydrocarbons were the primary mixture toxicants. The standardized test species used in the laboratory bioassays exhibited differences in sensitivity to these two general classes of contaminants, which underscores the importance of using multiple species when evaluating produced water toxicity. Toxicity of groundwater was greater in samples from wells near a produced water injection well and an evaporation pond. Principle component analyses (PCA) of chemical data derived from the groundwater wells indicated dilution by lake water and possible biogeochemical reactions as factors that ameliorated groundwater toxicity. Elevated concentrations of major ions were found in pore water from lake sediments, but toxicity from these ions was limited to sediment depths of 10 cm or greater, which is outside of the primary zone of biological activity. Further, exposure to site sediments did not have any effects on test organisms, and macroinvertebrate communities did not indicate impairment at the oil production site as compared to a reference site. In situ experiments with H. azteca and C. fluminea, indicated a sublethal site effect (on growth of both species), but these could not be definitively linked with produced water infiltration. Severe weather conditions (drought followed by flooding) negatively influenced the intensity of lake sampling aimed at delineating produced water infiltration. Due to the lack of clear evidence of produced water infiltration into the sub-littoral zone of the lake, it was not possible to assess whether the laboratory bioassays of produced water effectively indicate risk in the receiving system. However, the acutely toxic nature of the produced water and general lack of biological effects in the lake at the oil production site suggest minimal to no produced water infiltration into surficial lake sediments and the near-shore water column. This study was able to demonstrate the utility of ion toxicity modeling to support data from toxicity identification evaluations aimed at identifying key toxic constituents in produced water. This information could be used to prioritize options for treating produced water in order to reduce toxic constituents and enhance options for reuse. The study also demonstrated how geographic information systems, toxicity modeling, and toxicity assessment could be used to facilitate future site assessments.« less

Blood Lead Toxicity Analysis of Multipurpose Canines and Military Working Dogs.

PubMed

Reid, Paul; George, Clinton; Byrd, Christopher M; Miller, Laura; Lee, Stephen J; Motsinger-Reif, Alison; Breen, Matthew; Hayduk, Daniel W

Special Operations Forces and their accompanying tactical multipurpose canines (MPCs) who are involved in repeated live-fire exercises and military operations have the potential for increased blood lead levels and toxicity due to aerosolized and environmental lead debris. Clinical lead-toxicity symptoms can mimic other medical disorders, rendering accurate diagnosis more challenging. The objective of this study was to examine baseline lead levels of MPCs exposed to indoor firing ranges compared with those of nontactical military working dogs (MWDs) with limited or no exposure to the same environment. In the second part of the study, results of a commercially available, human-blood lead testing system were compared with those of a benchtop inductively coupled plasma-mass spectrometry (ICP-MS) analysis technique. Blood samples from 18 MPCs were tested during routine clinical blood draws, and six samples from a canine group with limited exposure to environmental lead (nontactical MWDs) were tested for comparison. There was a high correlation between results of the commercial blood-testing system compared with ICP-MS when blood lead levels were higher than 4.0µg/dL. Both testing methods recorded higher blood lead levels in the MPC blood samples than in those of the nontactical MWDs, although none of the MPC samples tested contained lead levels approaching those at which symptoms of lead toxicity have previously been reported in animals (i.e., 35µg/dL). 2018.

Evaluation of dredged material proposed for ocean disposal from Hackensack River Project Area, New York

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

Gruendell, B.D.; Barrows, E.S.; Borde, A.B.

1997-01-01

The objective of the bioassay reevaluation of the Hackensack River Federal Project was to reperform toxicity testing on proposed dredged material with current ammonia reduction protocols. Hackensack River was one of four waterways sampled and evaluated for dredging and disposal in April 1993. Sediment samples were re-collected from the Hackensack River Project area in August 1995. Tests and analyses were conducted according to the manual developed by the USACE and the U.S. Environmental Protection Agency (EPA), Evaluation of Dredged Material Proposed for Ocean Disposal (Testing Manual), commonly referred to as the {open_quotes}Green Book,{close_quotes} and the regional manual developed by themore » USACE-NYD and EPA Region II, Guidance for Performing Tests on Dredged Material to be Disposed of in Ocean Waters. The reevaluation of proposed dredged material from the Hackensack River project area consisted of benthic acute toxicity tests. Thirty-three individual sediment core samples were collected from the Hackensack River project area. Three composite sediments, representing each reach of the area proposed for dredging, were used in benthic acute toxicity testing. Benthic acute toxicity tests were performed with the amphipod Ampelisca abdita and the mysid Mysidopsis bahia. The amphipod and mysid benthic toxicity test procedures followed EPA guidance for reduction of total ammonia concentrations in test systems prior to test initiation. Statistically significant acute toxicity was found in all three Hackensack River composites in the static renewal tests with A. abdita, but not in the static tests with M. bahia. Statistically significant acute toxicity and a greater than 20% increase in mortality over the reference sediment was found in the static renewal tests with A. abdita. Statistically significant mortality 10% over reference sediment was observed in the M. bahia static tests. 5 refs., 2 figs., 2 tabs.« less

Development of a biopolymer nanoparticle-based method of oral toxicity testing in aquatic invertebrates.

PubMed

Gott, Ryan C; Luo, Yangchao; Wang, Qin; Lamp, William O

2014-06-01

Aquatic toxicity testing generally focuses on the water absorption/dermal route of exposure to potential toxic chemicals, while much less work has been done on the oral route of exposure. This is due in part to the difficulties of applying traditional oral toxicity testing to aquatic environments, including the tendency for test chemicals to dissolve into water. The use of biopolymer nanoparticles to encapsulate test chemicals onto food to prevent dissolution is one solution presented herein. The biopolymers zein and chitosan were explored for their previously known nanoparticle-forming abilities. Nanoparticles containing the test chemical rhodamine B were formed, applied as films to coat food, and then fed to the test organism, the freshwater amphipod Hyalella azteca. In feeding trials both zein and chitosan nanoparticles showed a significantly lower release rate of rhodamine B into water than food dyed with rhodamine B without biopolymer nanoparticles. Zein nanoparticles also showed better retention ability than chitosan nanoparticles. Both kinds of nanoparticles showed no significant effect on the survival, growth, or feeding behavior of H. azteca. Thus these biopolymers may be an effective system to encapsulate and deliver chemicals to aquatic invertebrates without interfering with common toxicity assessment endpoints like survival and growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Ecotoxic effect of photocatalytic active nanoparticles (TiO2) on algae and daphnids.

PubMed

Hund-Rinke, Kerstin; Simon, Markus

2006-07-01

Due to their large potential for manifold applications, the use of nanoparticles is of increasing importance. As large amounts of nanoparticles may reach the environment voluntarily or by accident, attention should be paid on the potential impacts on the environment. First studies on potential environmental effects of photocatalytic TiO2 nanoparticles have been performed on the basis of widely accepted, standardized test systems which originally had been developed for the characterization of chemicals. The methods were adapted to the special requirements of testing photocatalytic nanoparticles. Suspensions of two different nanoparticles were illuminated to induce their photocatalytic activity. For testing, the growth inhibition test with the green alga Desmodesmus subspicatus and the immobilization test with the daphnid Daphnia magna were selected and performed following the relevant guidelines (algae: ISO 8692, OECD 201, DIN 38412-33; daphnids: ISO 6341, OECD 202, DIN 38412-30). The guidelines were adapted to meet the special requirements for testing photocatalytic nanoparticles. The results indicate that it is principally possible to determine the ecotoxicity of nanoparticles. It was shown that nanoparticles may have ecotoxicological effects which depend on the nature of the particles. Both products tested differ in their toxicity. Product 1 shows a clear concentration-effect curve in the test with algae (EC50: 44 mg/L). It could be proven that the observed toxicity was not caused by accompanying contaminants, since the toxic effect was comparable for the cleaned and the commercially available product. For product 2, no toxic effects were determined (maximum concentration: 50 mg/L). In the tests with daphnids, toxicity was observed for both products, although the concentration effect-curves were less pronounced. The two products differed in their toxicity; moreover, there was a difference in the toxicity of illuminated and non-illuminated products. Both products differ in size and crystalline form, so that these parameters are assumed to contribute to the different toxicities. The concentration-effect curves for daphnids, which are less-pronounced than the curves obtained for algae, may be due to the different test organisms and/or the differing test designs. The increased toxicity of pre-illuminated particles in the tests with daphnids demonstrates that the photocatalytic activity of nanoparticles lasts for a period of time. The following conclusions can be drawn from the test results: (I) It is principally possible to determine the ecotoxicity of (photocatalytic) nanoparticles. Therefore, they can be assessed using methods comparable to the procedures applied for assessing soluble chemicals. (II) Nanoparticles may exert ecotoxicological effects, which depend on the specific nanoparticle. (III) Comparable to traditional chemicals, the ecotoxicity depends on the test organisms and their physiology. (IV) The photocatalytic activity of nanoparticles lasts for a relevant period of time. Therefore, pre-illumination may be sufficient to detect a photocatalytic activity even by using test organisms which are not suitable for application in the pre-illumination-phase. First results are presented which indicate that the topic 'ecotoxicity and environmental effects of nanoparticles' should not be neglected. In testing photocatalytic nanoparticles, there are still many topics that need clarification or improvement, such as the cause for an observed toxicity, the improvement of the test design, the elaboration of a test battery and an assessment strategy. On the basis of optimized test systems, it will be possible to test nanoparticles systematically. If a potential risk by specific photocatalytic particles is known, a risk-benefit analysis can be performed and, if required, risk reducing measures can be taken.

Effects of three related amides on microecosystem stability

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

Flum, T.F.; Shannon, L.J.

1987-04-01

Three related amides (diuron, 2-(octyloxy) acetanilide, and salicylanilide) were evaluated for toxicity to aquatic microcosm communities. Effects were measured at the ecosystem level using changes in pH, Eh (redox potential), and dissolved oxygen as indicators of toxicity. These values were used to calculate the resistance, resilience, and relative instability of the microecosystems to each compound at comparable dose levels of approximately 2500 micrograms/liter. Such measures have often been used in a theoretical context, but have not received wide practical application. The systems showed low resistance and no resilience to diuron, high resistance and low resilience to 2-(octyloxy) acetanilide, and nomore » response to salicylanilide. At a higher exposure level (9800 micrograms/liter salicylanilide), the systems showed low resistance and high resilience. Both this approach and more traditional dose-response measures of toxicity indicated that diuron was clearly the most toxic compound, followed by 2-(octyloxy) acetanilide and salicylanilide. While microcosm toxicity tests were slightly less sensitive than some single species tests, they provided important additional information on the extent of perturbations and the rate of ecosystem recovery.« less

The use of the zebrafish (Danio rerio) embryo for the acute toxicity testing of surfactants, as a possible alternative to the acute fish test.

PubMed

Vaughan, Martin; van Egmond, Roger

2010-06-01

At present, the acute toxicity of chemicals to fish is most commonly estimated by means of a short-term test on juvenile or adult animals (OECD TG 203). Although, over the last few years, the numbers used have been reduced due to the implementation of the Three Rs (Reduction, Refinement and Replacement), significant numbers of fish are still used in acute toxicity tests. With the introduction of the new European Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) system, this number is likely to increase dramatically. The aim of this work was to test the acute toxicity of a number of anionic, cationic and non-ionic surfactants to embryos of the zebrafish (Danio rerio), over 48 hours, as a possible alternative to the standard 96-hour fish acute test. We measured the toxicities of 15 surfactants, and compared the results to previously generated adult D. rerio LC50 data (or other fish species, if these data were not available). Comparison of the LC50 data showed that embryos appear to be as sensitive to cationic and non-ionic surfactants as the adult fish, but possibly are more sensitive to anionic surfactants. Toxicity testing with the embryo test can be carried out more quickly than with the adult test, uses much less space and media, requires less effort, and therefore can be performed at a reduced cost. The embryo test may also uncover additional sub-lethal effects, although these were not observed for surfactants. The data presented here show that the 48-hour embryo test can be considered as a suitable alternative to the adult acute fish test for surfactants.

Retinal and visual system: occupational and environmental toxicology.

PubMed

Fox, Donald A

2015-01-01

Occupational chemical exposure often results in sensory systems alterations that occur without other clinical signs or symptoms. Approximately 3000 chemicals are toxic to the retina and central visual system. Their dysfunction can have immediate, long-term, and delayed effects on mental health, physical health, and performance and lead to increased occupational injuries. The aims of this chapter are fourfold. First, provide references on retinal/visual system structure, function, and assessment techniques. Second, discuss the retinal features that make it especially vulnerable to toxic chemicals. Third, review the clinical and corresponding experimental data regarding retinal/visual system deficits produced by occupational toxicants: organic solvents (carbon disulfide, trichloroethylene, tetrachloroethylene, styrene, toluene, and mixtures) and metals (inorganic lead, methyl mercury, and mercury vapor). Fourth, discuss occupational and environmental toxicants as risk factors for late-onset retinal diseases and degeneration. Overall, the toxicants altered color vision, rod- and/or cone-mediated electroretinograms, visual fields, spatial contrast sensitivity, and/or retinal thickness. The findings elucidate the importance of conducting multimodal noninvasive clinical, electrophysiologic, imaging and vision testing to monitor toxicant-exposed workers for possible retinal/visual system alterations. Finally, since the retina is a window into the brain, an increased awareness and understanding of retinal/visual system dysfunction should provide additional insight into acquired neurodegenerative disorders. © 2015 Elsevier B.V. All rights reserved.

Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing--an integrated approach without additional animal use.

PubMed

Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S

2012-07-01

Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

Deriving allowable daily intakes for systemic toxicants lacking chronic toxicity data

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

Layton, D.W.; Mallon, B.J.; Rosenblatt, D.H.

1987-03-01

The lack of human toxicological data for most chemical compounds makes it difficult to quickly assess health risks associated with exposure to contaminants at hazardous waste sites. It would therefore be advantageous to have a technique for estimating acceptable daily intakes (ADIs) of potentially toxic substances based on more widely available animal toxicity data. This article focuses on the use of LD50 data to derive provisional ADIs, and it suggests multiplying oral LD50 values (expressed in mg/kg of body wt) by a factor in the range of 5 X 10(-6) to 1 X 10(-5) day-1 to convert them to suchmore » ADIs. It is emphasized that these interim ADI values are no substitute for toxicity testing, but that such testing would most likely result in higher ADI estimates.« less

Toxicity assessment of untreated/treated electroplating sludge using human and plant bioassay.

PubMed

Orescanin, Visnja; Durgo, Ksenija; Mikelic, Ivanka Lovrencic; Halkijevic, Ivan; Kuspilic, Marin

2018-04-30

The purpose of this work was to assess the risk to the environment arising from the electroplating sludge from both chemical and toxicological point of view. Both approaches were used for the assessment of the treatment efficiency which consisted of CaO based solidification followed by thermal treatment at 400°C. The elemental composition was determined in the bulk samples and the leachates of untreated sludge. The toxicity of the leachate was determined using two human colorectal adenocarcinoma cell lines (Caco-2 and SW 480) and Hordeum vulgare L. based plant bioassay. The same toxicity tests were employed to the leachate of the treated sludge. Untreated sludge showed extremely high cytotoxic effect to both human and plant bio-system in dose-dependent manner. The percentages higher than 0.5% and 0.05% of the leachate caused significant cytotoxic effect on Caco-2 and SW 480 cells, respectively. The percentages of the leachate higher than 0.05% also showed significant toxic effect to H. vulgare L. bio-system with complete arrest of seed germination following the treatment with 100% to 5% of the leachate. The leachate of the treated sludge showed no toxicity to any of the test systems confirming the efficiency and justification of the employed procedures for the detoxification of electroplating sludge.

Acute and Subchronic Toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from Chloroform Bay Leaf Extract (Eugenia Polyantha W.) with Palm Kernel Oil as A Carrier

NASA Astrophysics Data System (ADS)

Prihapsara, F.; Mufidah; Artanti, A. N.; Harini, M.

2018-03-01

The present study was aimed to study the acute and subchronic toxicity of Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with Palm Kernel Oil as carrier. In acute toxicity test, five groups of rat (n=5/groups) were orally treated with Self Nanoemulsifying Drug Delivery Systems (SNEDDS) from chloroform bay leaf extract with doses at 48, 240, 1200 and 6000 mg/kg/day respectively, then the median lethal dose LD50, advers effect and mortality were recorded up to 14 days. Meanwhile, in subchronic toxicity study, 4 groups of rats (n=6/group) received by orally treatment of SNEDDS from chloroform bay leaf extract with doses at 91.75; 183.5; 367 mg/kg/day respectively for 28 days, and biochemical, hematological and histopatological change in tissue such as liver, kidney, and pancreatic were determined. The result show that LD50 is 1045.44 mg/kg. Although histopathological examination of most of the organs exhibited no structural changes, some moderate damage was observed in high‑ dose group animals (367 mg/kg/day). The high dose of SNEDDS extract has shown mild signs of toxicity on organ function test.

Toxicological Evaluation of Lactase Derived from Recombinant Pichia pastoris

PubMed Central

Liu, Yifei; Chen, Delong; Luo, Yunbo; Huang, Kunlun; Zhang, Wei; Xu, Wentao

2014-01-01

A recombinant lactase was expressed in Pichia pastoris, resulting in enzymatic activity of 3600 U/mL in a 5 L fermenter. The lactase product was subjected to a series of toxicological tests to determine its safety for use as an enzyme preparation in the dairy industry. This recombinant lactase had the highest activity of all recombinant strains reported thus far. Acute oral toxicity, mutagenicity, genotoxic, and subchronic toxicity tests performed in rats and mice showed no death in any groups. The lethal dose 50% (LD50) based on the acute oral toxicity study is greater than 30 mL/kg body weight, which is in accordance with the 1500 L milk consumption of a 50 kg human daily. The lactase showed no mutagenic activity in the Ames test or a mouse sperm abnormality test at levels of up to 5 mg/plate and 1250 mg/kg body weight, respectively. It also showed no genetic toxicology in a bone marrow cell micronucleus test at levels of up to 1250 mg/kg body weight. A 90-day subchronic repeated toxicity study via the diet with lactase levels up to 1646 mg/kg (1000-fold greater than the mean human exposure) did not show any treatment-related significant toxicological effects on body weight, food consumption, organ weights, hematological and clinical chemistry, or histopathology compared to the control groups. This toxicological evaluation system is comprehensive and can be used in the safety evaluation of other enzyme preparations. The lactase showed no acute, mutagenic, genetic, or subchronic toxicity under our evaluation system. PMID:25184300

Ecotoxicological assessment of grey water treatment systems with Daphnia magna and Chironomus riparius.

PubMed

Hernández Leal, L; Soeter, A M; Kools, S A E; Kraak, M H S; Parsons, J R; Temmink, H; Zeeman, G; Buisman, C J N

2012-03-15

In order to meet environmental quality criteria, grey water was treated in four different ways: 1) aerobic 2) anaerobic+aerobic 3) aerobic+activated carbon 4) aerobic+ozone. Since each treatment has its own specific advantages and disadvantages, the aim of this study was to compare the ecotoxicity of differently treated grey water using Chironomus riparius (96 h test) and Daphnia magna (48 h and 21d test) as test organisms. Grey water exhibited acute toxicity to both test organisms. The aerobic and combined anaerobic+aerobic treatment eliminated mortality in the acute tests, but growth of C. riparius was still affected by these two effluents. Post-treatment by ozone and activated carbon completely removed the acute toxicity from grey water. In the chronic toxicity test the combined anaerobic+aerobic treatment strongly affected D. magna population growth rate (47%), while the aerobic treatment had a small (9%) but significant effect. Hence, aerobic treatment is the best option for biological treatment of grey water, removing most of the toxic effects of grey water. If advanced treatment is required, the treatment with either ozone or GAC were shown to be very effective in complete removal of toxicity from grey water. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mechanical-chemical analyses and sub-chronic systemic toxicity of chemical treated organic bovine bone.

PubMed

Lee, Kwang-il; Lee, Jung-soo; Lee, Keun-soo; Jung, Hong-hee; Ahn, Chan-min; Kim, Young-sik; Shim, Young-bock; Jang, Ju-woong

2015-12-01

Sequentially chemical-treated bovine bone was not only evaluated by mechanical and chemical analyses but also implanted into the gluteal muscles of rats for 12 weeks to investigate potential local pathological effects and systemic toxicities. The test (chemical treated bone) and control (heat treated bone) materials were compared using scanning electron microscope (SEM), x-ray diffraction pattern, inductively coupled plasma analysis, and bending strength test. In the SEM images, the micro-porous structure of heat-treated bone was changed to sintered ceramic-like structure. The structure of bone mineral from test and control materials was analyzed as100% hydroxyapatite. The ratio of calcium (Ca) to potassium (P), the main inorganic elements, was same even though the Ca and P percentages of the control material was relatively higher than the test material. No death or critical symptoms arose from implantation of the test (chemical treated bone) and control (physiological saline) materials during 12 weeks. The implanted sites were macroscopically examined, with all the groups showing non-irritant results. Our results indicate that chemical processed bovine bone has a better mechanical property than the heat treated bone and the implantation of this material does not produce systemic or pathological toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Immediate and long-term consequences of vascular toxicity during zebrafish development

EPA Science Inventory

Proper formation of the vascular system is necessary for embryogenesis, and chemical disruption of vascular development may be a key event driving developmental toxicity. In order to test the effect of environmental chemicals on this critical process, we developed a quantitative ...

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...

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...

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...

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...

Methylmercury exposure for 14 days (short-term) produces behavioral and biochemical changes in mouse cerebellum, liver, and serum.

PubMed

Macedo-Júnior, Sérgio José; Luiz-Cerutti, Murilo; Nascimento, Denise B; Farina, Marcelo; Soares Santos, Adair Roberto; de Azevedo Maia, Alcíbia Helena

2017-01-01

Various studies on methylmercury (MeHg)-induced toxicity focused on the central nervous system (CNS) as a primary target. However, MeHg-mediated toxicity is related to metallic interaction with electrophilic groups, which are not solely restricted to the CNS, but these reactive groups are present ubiquitously in several systems/organs. The aim of this study was thus to examine MeHg-induced systemic toxicity in mice using a standardized neurotoxicology testing exposure model to measure cerebellar neurotoxicity by determining biochemical and behavioral parameters in the cerebellum. After 2 weeks exposure to MeHg (40 µg/ml; diluted in drinking water; ad libitum), adult male Swiss mice showed a marked motor impairment characteristic of cerebellar toxicity as noted in the following tests: rotarod, beam walking, pole, and hind limb clasping. MeHg treatment resulted in Hg deposition in the cerebellum as well as reduction in cerebellar weight, glutathione peroxidase (GPx) activity, and interleukin (IL)-6 levels. MeHg ingestion increased cerebellar glutathione reductase (GR) activity and brain-derived neurotrophic factor (BDNF) levels. In addition to cerebellar toxicity, MeHg treatment also elevated total and non-high density lipoprotein (non-HDL) cholesterol levels, as well as serum aspartate transaminase (AST) and alanine transaminase (ALT) enzymatic activities, systemic parameters. Increased liver weight and reduced serum urea levels were also noted in MeHg-exposed mice. Taken together, our findings demonstrated that a well-standardized exposure protocol to examine MeHg-induced neurotoxicity also produced systemic toxicity in mice, which was characterized by changes in markers of hepatic function as well as serum lipid homeostasis.

Effects-based spatial assessment of contaminated estuarine sediments from Bear Creek, Baltimore Harbor, MD, USA.

PubMed

Hartzell, Sharon E; Unger, Michael A; McGee, Beth L; Wilson, Sacoby M; Yonkos, Lance T

2017-10-01

Estuarine sediments in regions with prolonged histories of industrial activity are often laden to significant depths with complex contaminant mixtures, including trace metals and persistent organic pollutants. Given the complexity of assessing risks from multi-contaminant exposures, the direct measurement of impacts to biological receptors is central to characterizing contaminated sediment sites. Though biological consequences are less commonly assessed at depth, laboratory-based toxicity testing of subsurface sediments can be used to delineate the scope of contamination at impacted sites. The extent and depth of sediment toxicity in Bear Creek, near Baltimore, Maryland, USA, was delineated using 10-day acute toxicity tests with the estuarine amphipod Leptocheirus plumulosus, and chemical analysis of trace metals and persistent organic pollutants. A gradient of toxicity was demonstrated in surface sediments with 21 of 22 tested sites differing significantly from controls. Effects were most pronounced (100% lethality) at sites proximate to a historic industrial complex. Sediments from eight of nine core samples to depths of 80 cm were particularly impacted (i.e., caused significant lethality to L. plumulosus) even in locations overlain with relatively non-toxic surface sediments, supporting a conclusion that toxicity observed at the surface (top 2 cm) does not adequately predict toxicity at depth. In seven of nine sites, toxicity of surface sediments differed from toxicity at levels beneath by 28 to 69%, in five instances underestimating toxicity (28 to 69%), and in two instances overestimating toxicity (44 to 56%). Multiple contaminants exceeded sediment quality guidelines and correlated positively with toxic responses within surface sediments (e.g., chromium, nickel, polycyclic aromatic hydrocarbon (PAH), total petroleum hydrocarbon). Use of an antibody-based PAH biosensor revealed that porewater PAH concentrations also increased with depth at most sites. This study informs future management decisions concerning the extent of impact to Bear Creek sediments, and demonstrates the benefits of a spatial approach, relying primarily on toxicity testing to assess sediment quality in a system with complex contaminant mixtures.

[Safety evaluation and risk control measures of Cassiae Semen].

PubMed

Zhao, Yi-Meng; Wu, Li; Zhang, Shuo; Zhang, Li; Gao, Xue-Min; Sun, Xiao-Bo; Wang, Chun

2017-11-01

In this study, the authors reviewed domestic and foreign literatures, conducted the textual research on origin and development of Cassia Semen, studied records in ancient books and ancient and modern literatures, clinical adverse reactions and relevant experimental studies in recent years, and summarized the clinical features and influencing factors related to the safety of Cassiae Semen. According to the findings,Cassia Semen's safety risks are mainly liver and kidney system damages, with the main clinical features of fatigue, anorexia, disgusting of oil, yellow urine and gray stool; digestive system injury, with the main clinical features of diarrhea, abdominal distension, nausea and loose stool; reproductive system damage, with the main clinical features of vaginal bleeding. Allergic reactions and clinical adverse events, with the main clinical features for numb mouth, itching skin, nausea and vomiting, diarrhea, wheezing and lip cyanosis were also reported. The toxicological studies on toxic components of Cassiae Semen obtusifolia were carried out through acute toxicity test, subacute toxicity test, subchronic toxicity test and chronic toxicity test. Risk factors might include patients, compatibility and physicians. Physicians should strictly abide by the medication requirements in the Pharmacopoeia, pay attention to rational compatibility, appropriate dosage,correct usage and appropriate processing, control the dosage below 15 g to avoid excessive intake, strictly control the course of treatment to avoid accumulated poisoning caused by long-term administration. At the same time, clinicians should pay attention to the latest research progress, update the knowledge structure, quickly find the latest and useful materials from clinical practice, scientific research and drug information and other literatures, make evaluation and judgment for the materials, establish a traditional Chinese medicine intelligence information library, and strengthen the control over adverse effects with a pre-warning consciousness. The authors suggested standardizing clinical medication of Cassiae Semen, and avoiding misuse or excessive use; clinicians should prescribe it in strict accordance with there commended usage and dosage in the Pharmacopoeia, and focus on the safety signal accumulation in clinic, while strengthening studies for toxic substance basis and toxicity mechanism, in order to give full play to Cassiae Semen's clinical efficacy and reduce its adverse reactions. Copyright© by the Chinese Pharmaceutical Association.

A Portable Environment Test System: A Field Assessment of Organotin Leachates--Test and Evaluation.

DTIC Science & Technology

1987-11-01

Environmental Test System (PETS) was evaluated with tributyltin ( TBT ) anti oling leachates in Sin Diego Bay over a 7-month period. Overall mean test...EXECUTIVE SUMMARY A Portable Environmental Test System (PETS) was evaluated with tributyltin ( TBT ) antifouling leachates in San Diego Bay for 7...of organotin-based antifouling (AF) coatings, NOSC researchers used this facility to study the effects of tributyltin ( TBT ), the primary toxic

The reactive bed plasma system for contamination control

NASA Technical Reports Server (NTRS)

Birmingham, Joseph G.; Moore, Robert R.; Perry, Tony R.

1990-01-01

The contamination control capabilities of the Reactive Bed Plasma (RBP) system is described by delineating the results of toxic chemical composition studies, aerosol filtration work, and other testing. The RBP system has demonstrated its capabilities to decompose toxic materials and process hazardous aerosols. The post-treatment requirements for the reaction products have possible solutions. Although additional work is required to meet NASA requirements, the RBP may be able to meet contamination control problems aboard the Space Station.

Optofluidic technology for monitoring rotifer Brachionus calyciflorus responses to regular light pulses

NASA Astrophysics Data System (ADS)

Cartlidge, Rhys; Campana, Olivia; Nugegoda, Dayanthi; Wlodkowic, Donald

2016-12-01

Behavioural alterations can occur as a result of a toxicant exposure at concentrations significantly lower than lethal effects that are commonly measured in acute toxicity testing. The use of alternating light and dark photoperiods to test phototactic responses of aquatic invertebrates in the presence of environmental contaminants provides an attractive analytical avenue. Quantification of phototactic responses represents a sublethal endpoint that can be employed as an early warning signal. Despite the benefits associated with the assessment of these endpoints, there is currently a lack of automated and miniaturized bioanalytical technologies to implement the development of toxicity testing with small aquatic species. In this study we present a proof-of-concept microfluidic Lab-on-a-Chip (LOC) platform for the assessment of rotifer swimming behavior in the presence of the toxicant copper sulfate. The device was designed to assess impact of toxicants at sub-lethal concentrations on freshwater crustacean Brachionus calyciflorus, testing behavioral endpoints such as animal swimming distance, speed and acceleration. The LOC device presented in this work enabled straightforward caging of microscopic crustaceans as well as non-invasive analysis of rapidly swimming animals in a focal plane of a video-microscopy system. The chip-based technology was fabricated using a new photolithography method that enabled formation of thick photoresist layers with minimal distortion. Photoresist molds were then employed for replica molding of LOC devices with poly(dimethylsiloxane) (PDMS) elastomer. The complete bioanalytical system consisted of: (i) microfluidic PDMS chip-based device; (ii) peristaltic microperfusion pumping manifold; (iii) miniaturized CMOS camera for video data acquisition; and (iv) video analysis software algorithms for quantification of changes in swimming behaviour of B. calyciflorus in response to reference toxicants.

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...

Development of a toxicity identification evaluation procedure for characterizing metal toxicity in marine sediments

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

Burgess, R.M.; Cantwell, M.G.; Pelletier, M.C.

2000-04-01

A multiagency effort is underway to develop whole sediment toxicity identification evaluation (TIE) methods. Whole sediment TIE methods will be critical tools for characterizing toxicity at hazardous waste sites and in the conduct of environmental risk assessments. The research approach is based on the predominance of three classes of toxicants in sediments: ammonia, nonpolar organic chemicals, and metals. Here the authors describe a procedure for characterizing acute toxicity caused by metals in whole marine sediments. The procedure involves adding a chelating resin to sediments, resulting in the sequestration of bioavailable metal while not stressing testing organisms. Within the testing chambers,more » the presence of resin resulted in statistically significant reductions in the overlying and interstitial water concentrations of five metals (cadmium, copper, nickel, lead, and zinc) generally by factors of 40 and 200. Toxicity to both the amphipod Ampelisca abdita and mysid Americamysis bahia (formerly Mysidopsis bahia) of sediments spiked with the five metals was decreased by approximately a factor of four when resin was present. While very effective at reducing the concentrations and toxicity of metals, the resin has only minor ameliorative effects on the toxicity of ammonia and a representative nonpolar toxicant (Endosulfan). Resin and accumulated metal were easily isolated from the testing system following exposures allowing for the initiation of phase II TIE (identification) procedures. This procedure using the addition of a chelating resin provides an approach for determining the importance of metals to the toxicity of marine sediments. Work is continuing to validate the method with environmentally contaminated sediments.« less

Long-term (30 days) toxicity of NiO nanoparticles for adult zebrafish Danio rerio

PubMed Central

Kovrižnych, Jevgenij A.; Zeljenková, Dagmar; Rollerová, Eva; Szabová, Elena

2014-01-01

Nickel oxide in the form of nanoparticles (NiO NPs) is extensively used in different industrial branches. In a test on adult zebrafish, the acute toxicity of NiO NPs was shown to be low, however longlasting contact with this compound can lead to its accumulation in the tissues and to increased toxicity. In this work we determined the 30-day toxicity of NiO NPs using a static test for zebrafish Danio rerio. We found the 30-day LC50 value to be 45.0 mg/L, LC100 (minimum concentration causing 100% mortality) was 100.0 mg/L, and LC0 (maximum concentration causing no mortality) was 6.25 mg/L for adult individuals of zebrafish. Considering a broad use of Ni in the industry, NiO NPs chronic toxicity may have a negative impact on the population of aquatic organisms and on food web dynamics in aquatic systems. PMID:26038672

Long-term (30 days) toxicity of NiO nanoparticles for adult zebrafish Danio rerio.

PubMed

Kovrižnych, Jevgenij A; Sotníková, Ružena; Zeljenková, Dagmar; Rollerová, Eva; Szabová, Elena

2014-03-01

Nickel oxide in the form of nanoparticles (NiO NPs) is extensively used in different industrial branches. In a test on adult zebrafish, the acute toxicity of NiO NPs was shown to be low, however longlasting contact with this compound can lead to its accumulation in the tissues and to increased toxicity. In this work we determined the 30-day toxicity of NiO NPs using a static test for zebrafish Danio rerio. We found the 30-day LC50 value to be 45.0 mg/L, LC100 (minimum concentration causing 100% mortality) was 100.0 mg/L, and LC0 (maximum concentration causing no mortality) was 6.25 mg/L for adult individuals of zebrafish. Considering a broad use of Ni in the industry, NiO NPs chronic toxicity may have a negative impact on the population of aquatic organisms and on food web dynamics in aquatic systems.

The history and development of FETAX (ASTM standard guide, E-1439 on conducting the frog embryo teratogenesis Assay-Xenopus)

USGS Publications Warehouse

Dumont, J.N.; Bantle, J.A.; Linder, G.; ,

2003-01-01

The energy crisis of the 1970's and 1980's prompted the search for alternative sources of fuel. With development of alternate sources of energy, concerns for biological resources potentially adversely impacted by these alternative technologies also heightened. For example, few biological tests were available at the time to study toxic effects of effluents on surface waters likely to serve as receiving streams for energy-production facilities; hence, we began to use Xenopus laevis embryos as test organisms to examine potential toxic effects associated with these effluents upon entering aquatic systems. As studies focused on potential adverse effects on aquatic systems continued, a test procedure was developed that led to the initial standardization of FETAX. Other .than a limited number of aquatic toxicity tests that used fathead minnows and cold-water fishes such as rainbow trout, X. laevis represented the only other aquatic vertebrate test system readily available to evaluate complex effluents. With numerous laboratories collaborating, the test with X. laevis was refined, improved, and developed as ASTM E-1439, Standard Guide for the Conducting Frog Embryo Teratogenesis Assay-Xenopus (FETAX). Collabrative work in the 1990s yielded procedural enhancements, for example, development of standard test solutions and exposure methods to handle volatile organics and hydrophobic compounds. As part of the ASTM process, a collaborative interlaboratory study was performed to determine the repeatability and reliability of FETAX. Parallel to these efforts, methods were also developed to test sediments and soils, and in situ test methods were developed to address "lab-to-field extrapolation errors" that could influence the method's use in ecological risk assessments. Additionally, a metabolic activation system composed of rat liver microsomes was developed which made FETAX more relevant to mammalian studies.

Generation of GHS Scores from TEST and online sources ...

EPA Pesticide Factsheets

Alternatives assessment frameworks such as DfE (Design for the Environment) evaluate chemical alternatives in terms of human health effects, ecotoxicity, and fate. T.E.S.T. (Toxicity Estimation Software Tool) can be utilized to evaluate human health in terms of acute oral rat toxicity, developmental toxicity, endocrine activity, and mutagenicity. It can be used to evaluate ecotoxicity (in terms of acute fathead minnow toxicity) and fate (in terms of bioconcentration factor). It also be used to estimate a variety of key physicochemical properties such as melting point, boiling point, vapor pressure, water solubility, and bioconcentration factor. A web-based version of T.E.S.T. is currently being developed to allow predictions to be made from other web tools. Online data sources such as from NCCT’s Chemistry Dashboard, REACH dossiers, or from ChemHat.org can also be utilized to obtain GHS (Global Harmonization System) scores for comparing alternatives. The purpose of this talk is to show how GHS (Global Harmonization Score) data can be obtained from literature sources and from T.E.S.T. (Toxicity Estimation Software Tool). This data will be used to compare chemical alternatives in the alternatives assessment dashboard (a 2018 CSS product).

Effect of zink oxyde nanoparticles on the test function of water organisms of different trophic levels

NASA Astrophysics Data System (ADS)

Morgalev, Yu; Morgaleva, T.; Gosteva, I.; Morgalev, S.; Kulizhskiy, S.; Astafurova, T.

2015-11-01

The toxicity of zinc oxide nanoparticles (nZnO) with particle size Δ50 = 20 nm was evaluated according to the degree of toxicity of the aqueous disperse system (DS) with biological testing methods using a set of test organisms representing the major trophic levels.We observed the influence of the concentration degree of nZnO on toxic effects level on the fluorescence of the bacterial biosensor "Ekolyum-13", the chemotactic response of ciliates Paramecium caudatum, the rate of growth of unicellular algae Chlorella vulgaris Bayer, mortality of entomostracans Daphnia magna Straus and fish Danio rerio. The detected values of L(E)C50 are: for biosensor "Ekolyum-13" - 0.30 mg/L, for ciliates Paramecium caudatum - 0.14 mg/L, for Chlorella vulgaris Bayer - 0.17 mg/L and for Daphnia magna Straus - 0.52 mg/L. No toxicity of nZnO was detected in relation to fish Danio rerio, L(E)C50 > 100 mg/L. In assessing the maximum effect of nZnO according to GHS and EU Directive 93/67/ EEC, it is assigned to dangerous substances with a high degree of toxicity "Acute toxicity 1".

Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System.

PubMed

Holzhütter, H G; Genschow, E; Diener, W; Schlede, E

2003-05-01

The acute toxic class (ATC) methods were developed for determining LD(50)/LC(50) estimates of chemical substances with significantly fewer animals than needed when applying conventional LD(50)/LC(50) tests. The ATC methods are sequential stepwise procedures with fixed starting doses/concentrations and a maximum of six animals used per dose/concentration. The numbers of dead/moribund animals determine whether further testing is necessary or whether the test is terminated. In recent years we have developed classification procedures for the oral, dermal and inhalation routes of administration by using biometric methods. The biometric approach assumes a probit model for the mortality probability of a single animal and assigns the chemical to that toxicity class for which the best concordance is achieved between the statistically expected and the observed numbers of dead/moribund animals at the various steps of the test procedure. In previous publications we have demonstrated the validity of the biometric ATC methods on the basis of data obtained for the oral ATC method in two-animal ring studies with 15 participants from six countries. Although the test procedures and biometric evaluations for the dermal and inhalation ATC methods have already been published, there was a need for an adaptation of the classification schemes to the starting doses/concentrations of the Globally Harmonized Classification System (GHS) recently adopted by the Organization for Economic Co-operation and Development (OECD). Here we present the biometric evaluation of the dermal and inhalation ATC methods for the starting doses/concentrations of the GHS and of some other international classification systems still in use. We have developed new test procedures and decision rules for the dermal and inhalation ATC methods, which require significantly fewer animals to provide predictions of toxicity classes, that are equally good or even better than those achieved by using the conventional LD(50)/LC(50) methods. In order to cope with rather narrow dose/concentration classes of the GHS we have, as in our previous publications, combined the outcome of all results that can be obtained during testing for the allocation to one of the defined toxicity classes of the GHS. Our results strongly recommend the deletion of the dermal LD(50) and the inhalation LC(50) test as regulatory tests and the adoption of the dermal and inhalation ATC methods as internationally accepted alternatives.

[Use of dinoflagellates as a metal toxicity assessment tool in aquatic system].

PubMed

Yuan, Li-juan; He, Meng-chang

2009-10-15

Although dinoflagellates have been used to assess biological toxicity of contaminants, this method still lacks of corresponding toxicity assessment standard. This study appraised the toxicity of selected heavy metals to dinoflagellates based on the dinoflagellates bioluminescence with QwikLite developed by the United States Navy. The results show that single heavy metal biological toxicity is in the order: Hg2+ > Cu2+ > Cd2+ > As5+ > Pb2+ > Cr6+; Two, three and four heavy metal mixture experiments show synergism primarily, antagonism is in minority. pH has not remarkable effect on dinoflagellates, they can be applied directly in natural water, but pH influence Hg2+ and Cu2+ toxicity greatly, eliminating the influence of pH is essential when doing these two kind of ions measurements. The nutrients has little influence on dinoflagellates, change in COD has obvious effect on the response relationships between dinoflagellates and Hg2+ or CU2+. Metal toxicity assessment using dinoflagellates shows great sensitivity, narrow response scope and high stability. Dinoflagellates are good species for heavy metal biological toxicity test in aquatic system.

[Chemicals toxic to the olfactory system. Analysis and description].

PubMed

Norès, J M; Biacabe, B; Bonfils, P

2000-10-28

AN IMPORTANT PROBLEM: Occupational exposure to chemical products can have toxic effects on the olfactory system. An important number of patients have experienced olfactory disorders subsequent to the development of the chemical industry and atmospheric pollution. EPIDEMIOLOGY DATA: Straightforward data are difficult to collect because several cofactors other than the toxic product are involved. Two lists of toxic products can be made. The first list includes products for which scientific data is available and the second products for which data is lacking. Olfactory tests also differ between authors and countries. TWO TYPES OF TOXICITY: Acute, accidental toxicity is evidenced by the lesions caused by inhalation of high-doses of strongly toxic agents. Chronic intoxication caused by lower concentrations of these inhaled agents does not produce a trigeminal reflex leading to a modified respiratory rate reducing the airborne aggression. APPROXIMATIONS: Clinical data describing the olfactory toxicity of certain industrial and chemical compounds are very significant but often cannot prove a cause and effect relationship. Data obtained with experimental models in rodents are difficult to extrapolate to humans.

Interactive toxicity of major ion salts: Comparisons among species and between acute and chronic endpoints

EPA Science Inventory

Increased concentrations of major ions (Na, K, Ca, Mg, Cl, SO4, HCO3) in freshwater systems can result from a variety of anthropogenic activities, and can adversely affect aquatic organisms if the increase is sufficiently severe. Laboratory tests have indicated that the toxicity...

Acute and early life stage toxicity of industrial effluent on Japanese medaka (Oryzias latipes).

PubMed

Zha, Jinmiao; Wang, Zijian

2006-03-15

To develop the whole effluent toxicity testing methods (WET), embryo larval stage toxicity test using Japanese medaka (Oryzias latipes) was conducted to evaluate an effluent from a banknote printing plant (BPP). The method is based on acute toxicity using endpoint of 96-h larval morality and on chronic toxicity using endpoints such as the time to hatch, hatching success, deformity, growth rate, swim-up failure, accumulative mortality and sexual ratio. In test for 96-h larval mortality, LC50 (the concentration was lethal to 50% of newly hatching medaka larvae) was 72.9%. In chronic toxicity test, newly fertilized embryos (<5-h old) were exposed to 1%, 6.25%, 12.5%, 25%, 50% effluent concentrations and to 200 mug/l BPA in a 24-h static renewal system at 25+/-1 degrees C until 15 day post-hatch. The results showed that all chronic endpoints were significantly different from the control at 50% dilution (p < 0.01). Embryos began to show lesions on 4th day at higher concentrations (12.5%, 25%, 50% BPP effluent concentrations). Treatment group of 25% dilution showed delayed time to hatch. A reduction in body weight was observed at 25% dilutions for males and females, respectively. Deformities were observed in newly hatched larvae at 25% and 50% BPP effluent concentrations. At 25% dilution, sex ratio of larvae was alternated and there was feminization phenomenon. We conclude that embryo larval stage test using medaka is feasible to evaluate both acute and chronic toxicities and potential endocrine disrupting activity of industrial effluents.

An evaluation of the seven-day toxicity test with Americamysis bahia (formerly Mysidopsis bahia)

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

Lussier, S.M.; Kuhn, A.; Comeleo, R.

The 7-d test measuring survival, growth, and fecundity of Americamysis bahia (formerly Mysidopsis bahia) was developed for estimating the chronic toxicity of effluents and associated receiving waters for National Pollutant Discharge Elimination System permits. Currently, this test and its derivatives are also used in toxicity identification evaluation (TIE), risk assessment, and other applications. To evaluate the relative sensitivity of three measurement endpoints (survival, growth, and fecundity), the authors analyzed results from 115 tests with effluents, organic or inorganic chemicals, and receiving waters suspected of being toxic. Controls for 78 of these achieved acceptable survival and growth. Fifty of these 78more » tests also achieved acceptable control fecundity. In the 47 tests with significant effects, survival was the most sensitive response in 57%, fecundity in 30%, and growth in 30%. There was little duplication in responses. Improving pretest holding conditions by decreasing the maximum density from {approximately}20 to 10 animals/L and increasing the temperature from {approximately}26 C to a range of 26 to 27 C improved the growth and fecundity in controls. Although the percentage of tests achieving acceptable control survival and growth decreased from 93 to 86%, the percentage achieving acceptable fecundity in controls increased from 60 to 97%. Seasonal differences in fecundity were detected among control groups. Although variable, fecundity is often the most sensitive measure of response. The 7-d mysid test estimates the chronic toxicity of effluents most effectively when all three endpoints are used.« less

Comparison of the mouse Embryonic Stem cell Test, the rat Whole Embryo Culture and the Zebrafish Embryotoxicity Test as alternative methods for developmental toxicity testing of six 1,2,4-triazoles

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

Jong, Esther de, E-mail: Esther.de.Jong@rivm.nl; Laboratory for Health Protection Research, National Institute for Public Health and the Environment; Barenys, Marta

2011-06-01

The relatively high experimental animal use in developmental toxicity testing has stimulated the search for alternatives that are less animal intensive. Three widely studied alternative assays are the mouse Embryonic Stem cell Test (EST), the Zebrafish Embryotoxicity Test (ZET) and the rat postimplantation Whole Embryo Culture (WEC). The goal of this study was to determine their efficacy in assessing the relative developmental toxicity of six 1,2,4-triazole compounds, flusilazole, hexaconazole, cyproconazole, triadimefon, myclobutanil and triticonazole. For this purpose, we analyzed effects and relative potencies of the compounds in and among the alternative assays and compared the findings to their known inmore » vivo developmental toxicity. Triazoles are antifungal agents used in agriculture and medicine, some of which are known to induce craniofacial and limb abnormalities in rodents. The WEC showed a general pattern of teratogenic effects, typical of exposure to triazoles, mainly consisting of reduction and fusion of the first and second branchial arches, which are in accordance with the craniofacial malformations reported after in vivo exposure. In the EST all triazole compounds inhibited cardiomyocyte differentiation concentration-dependently. Overall, the ZET gave the best correlation with the relative in vivo developmental toxicities of the tested compounds, closely followed by the EST. The relative potencies observed in the WEC showed the lowest correlation with the in vivo developmental toxicity data. These differences in the efficacy between the test systems might be due to differences in compound kinetics, in developmental stages represented and in the relative complexity of the alternative assays.« less

Comparison of the mouse Embryonic Stem cell Test, the rat Whole Embryo Culture and the Zebrafish Embryotoxicity Test as alternative methods for developmental toxicity testing of six 1,2,4-triazoles.

PubMed

de Jong, Esther; Barenys, Marta; Hermsen, Sanne A B; Verhoef, Aart; Ossendorp, Bernadette C; Bessems, Jos G M; Piersma, Aldert H

2011-06-01

The relatively high experimental animal use in developmental toxicity testing has stimulated the search for alternatives that are less animal intensive. Three widely studied alternative assays are the mouse Embryonic Stem cell Test (EST), the Zebrafish Embryotoxicity Test (ZET) and the rat postimplantation Whole Embryo Culture (WEC). The goal of this study was to determine their efficacy in assessing the relative developmental toxicity of six 1,2,4-triazole compounds,(1) flusilazole, hexaconazole, cyproconazole, triadimefon, myclobutanil and triticonazole. For this purpose, we analyzed effects and relative potencies of the compounds in and among the alternative assays and compared the findings to their known in vivo developmental toxicity. Triazoles are antifungal agents used in agriculture and medicine, some of which are known to induce craniofacial and limb abnormalities in rodents. The WEC showed a general pattern of teratogenic effects, typical of exposure to triazoles, mainly consisting of reduction and fusion of the first and second branchial arches, which are in accordance with the craniofacial malformations reported after in vivo exposure. In the EST all triazole compounds inhibited cardiomyocyte differentiation concentration-dependently. Overall, the ZET gave the best correlation with the relative in vivo developmental toxicities of the tested compounds, closely followed by the EST. The relative potencies observed in the WEC showed the lowest correlation with the in vivo developmental toxicity data. These differences in the efficacy between the test systems might be due to differences in compound kinetics, in developmental stages represented and in the relative complexity of the alternative assays. Copyright © 2011 Elsevier Inc. All rights reserved.

DSSTOX WEBSITE LAUNCH: IMPROVING PUBLIC ACCESS ...

EPA Pesticide Factsheets

DSSTox Website Launch: Improving Public Access to Databases for Building Structure-Toxicity Prediction ModelsAnn M. RichardUS Environmental Protection Agency, Research Triangle Park, NC, USADistributed: Decentralized set of standardized, field-delimited databases, each separatelyauthored and maintained, that are able to accommodate diverse toxicity data content;Structure-Searchable: Standard format (SDF) structure-data files that can be readily imported into available chemical relational databases and structure-searched;Tox: Toxicity data as it exists in widely disparate forms in current public databases, spanning diverse toxicity endpoints, test systems, levels of biological content, degrees of summarization, and information content.INTRODUCTIONThe economic and social pressures to reduce the need for animal testing and to better anticipate the potential for human and eco-toxicity of environmental, industrial, or pharmaceutical chemicals are as pressing today as at any time prior. However, the goal of predicting chemical toxicity in its many manifestations, the `T' in 'ADMET' (adsorption, distribution, metabolism, elimination, toxicity), remains one of the most difficult and largely unmet challenges in a chemical screening paradigm [1]. It is widely acknowledged that the single greatest hurdle to improving structure-activity relationship (SAR) toxicity prediction capabilities, in both the pharmaceutical and environmental regulation arenas, is the lack of suffici

Ecotoxicological assessment of biosolids by microcosms.

PubMed

Groth, Vitor Avelar; Carvalho-Pereira, Ticiana; da Silva, Eduardo Mendes; Niemeyer, Júlia Carina

2016-10-01

Biosolids have been applied as soil amendments to improve and maintain the soil fertility and faster plant growth. In spite of its beneficial use, the potential risks of land disposal should be analyzed, considering potential ecological receptors in soil and water. This work describes the use of an early warning laboratory microcosm system to evaluate the integrated ecotoxicological potential of two biosolids: BIO-1 and BIO-2 (18 and 28 months after landfarming, respectively), from an effluent treatment station in a petrochemical and industrial district. The endpoints related to habitat function were: a) germination, growth and biomass of Phaseolus vulgaris; b) survival, biomass and number of cocoons of Eisenia andrei (Oligochaeta) and; c) reproduction of Folsomia candida (Collembola). The retention function was evaluated by testing the leachates using the tropical cladoceran Latonopsis australis (Cladocera) in a 48-h acute toxicity test, and growth of the aquatic plant Lemna minor in a 7-d chronic test. Tropical artificial soil (TAS) and a natural soil (NS) from the region were used as control soils. Results showed no chronic toxicity of BIO-1 and BIO-2 to the soil organisms tested, but acute toxicity of BIO-1 in the leachate for 50% of L. australis, and chronic toxicity of both biosolid leachates to L. minor (inhibition of growth rate), indicating potential risks to aquatic ecosystems. The results confirmed the ability of this microcosm system as a rapid tool to assess biosolid toxicity over time and its potential for hazardous waste characterization in environmental risk assessment, in a screening phase. Copyright © 2016 Elsevier Ltd. All rights reserved.

40 CFR 792.45 - Test system supply facilities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Test system supply facilities. 792.45 Section 792.45 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... facilities. (a) There shall be storage areas, as needed, for feed, nutrients, soils, bedding, supplies, and...

Ceriodaphnia dubia as a Potential Bio-Indicator for Assessing Acute Aluminum Oxide Nanoparticle Toxicity in Fresh Water Environment

PubMed Central

Pakrashi, Sunandan; Dalai, Swayamprava; Humayun, Ahmed; Chakravarty, Sujay; Chandrasekaran, Natarajan; Mukherjee, Amitava

2013-01-01

Growing nanomaterials based consumer applications have raised concerns about their potential release into the aquatic ecosystems and the consequent toxicological impacts. So environmental monitoring of the nanomaterials in aqueous systems becomes imperative. The current study reveals the potential of Ceriodaphnia dubia (C. dubia) as a bio-indicator for aluminum oxide nanoparticles in a fresh water aquatic ecosystem where it occupies an important ecological niche as a primary consumer. This study aims to investigate the aluminium oxide nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system. The bioavailability of the aluminum oxide nanoparticles has been studied with respect to their aggregation behavior in the system and correlated with the toxicity endpoints. The oxidative stress generated by the particles contributed greatly toward their toxicity. The crucial role of leached aluminium ion mediated toxicity in the later phases (48 h and 72 h) in conjunction with the effects from the nano-sized particles in the initial phases (24 h) puts forth the dynamics of nanotoxicity in the test system. The internalization of nanoparticles (both gross and systemic uptake) as substantiated through the transmission electron microscopy (TEM) and inductively coupled plasma optical emission spectral (ICP-OES) analysis was another major contributor toward acute toxicity. Concluding the present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring the aluminium oxide nanoparticles in a fresh water system. PMID:24040143

Ceriodaphnia dubia as a potential bio-indicator for assessing acute aluminum oxide nanoparticle toxicity in fresh water environment.

PubMed

Pakrashi, Sunandan; Dalai, Swayamprava; Humayun, Ahmed; Chakravarty, Sujay; Chandrasekaran, Natarajan; Mukherjee, Amitava

2013-01-01

Growing nanomaterials based consumer applications have raised concerns about their potential release into the aquatic ecosystems and the consequent toxicological impacts. So environmental monitoring of the nanomaterials in aqueous systems becomes imperative. The current study reveals the potential of Ceriodaphnia dubia (C. dubia) as a bio-indicator for aluminum oxide nanoparticles in a fresh water aquatic ecosystem where it occupies an important ecological niche as a primary consumer. This study aims to investigate the aluminium oxide nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system. The bioavailability of the aluminum oxide nanoparticles has been studied with respect to their aggregation behavior in the system and correlated with the toxicity endpoints. The oxidative stress generated by the particles contributed greatly toward their toxicity. The crucial role of leached aluminium ion mediated toxicity in the later phases (48 h and 72 h) in conjunction with the effects from the nano-sized particles in the initial phases (24 h) puts forth the dynamics of nanotoxicity in the test system. The internalization of nanoparticles (both gross and systemic uptake) as substantiated through the transmission electron microscopy (TEM) and inductively coupled plasma optical emission spectral (ICP-OES) analysis was another major contributor toward acute toxicity. Concluding the present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring the aluminium oxide nanoparticles in a fresh water system.

Non-Toxic Orbital Maneuvering System Engine Development

NASA Technical Reports Server (NTRS)

Green, Christopher; Claflin, Scott; Maeding, Chris; Butas, John

1999-01-01

Recent results using the Aestus engine operated with LOx/ethanol propellant are presented. An experimental program at Rocketdyne Propulsion and Power is underway to adapt this engine for the Boeing Reusable Space Systems Division non-toxic Orbital Maneuvering System/Reaction control System (OMS/RCS) system. Daimler-Chrysler Aerospace designed the Aestus as an nitrogen tetroxide/monomethyl hydrazine (NTO/MMH) upper-stage engine for the Ariane 5. The non-toxic OMS/RCS system's preliminary design requires a LOx/ethanol (O2/C2H5OH) engine that operates with a mixture ratio of 1.8, a specific impulse of 323 seconds, and fits within the original OMS design envelope. This paper describes current efforts to meet these requirements including, investigating engine performance using LOx/ethanol, developing the en-ine system sizing package, and meeting the vehicle operation parameters. Data from hot-fire testing are also presented and discussed.

AN ENVIRONMENTAL TECHNOLOGY VERIFICATION (ETV) OF EIGHT RAPID TOXICITY TESTING SYSTEMS: STRATEGIC DIAGNOSTICS INC'S DELTATOX (R) AND MICTOTOX (R), SEVERN TRENT SERVICES ECLOX, HACH COMPANY TOXTRAK INTERLAB SUPPLY, LTD. POLYTOX (TM), CHECKLLIGHT, LTD TOXSCREEN, AQUA SURVEY, INC. IQ TOXICITY TEST (TM), HIDEX OY BIOTOX (TM)

EPA Science Inventory

The Environmental Technology Verification (ETV) Program, beginning as an initiative of the U.S. Environmental Protection Agency (EPA) in 1995, verifies the performance of commercially available, innovative technologies that can be used to measure environmental quality. The ETV p...

Functional Assays for Neurotoxicity Testing

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

Functional Assays for Neurotoxicity Testing*

EPA Science Inventory

Neurobehavioral and pathological evaluations of the nervous system are complementary components of basic research and toxicity testing of pharmaceutical and environmental chemicals. While neuropathological assessments provide insight as to cellular changes in neurons, behavioral ...

Food for Thought ... Mechanistic Validation

PubMed Central

Hartung, Thomas; Hoffmann, Sebastian; Stephens, Martin

2013-01-01

Summary Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st Century, either by high-throughput testing in the ToxCast/ Tox21 project or omics-based testing in the Human Toxome Project. This article explores the mostly neglected assessment of a test's scientific basis, which moves mechanism and causality to the foreground when validating/qualifying tests. Such mechanistic validation faces the problem of establishing causality in complex systems. However, pragmatic adaptations of the Bradford Hill criteria, as well as bioinformatic tools, are emerging. As critical infrastructures of the organism are perturbed by a toxic mechanism we argue that by focusing on the target of toxicity and its vulnerability, in addition to the way it is perturbed, we can anchor the identification of the mechanism and its verification. PMID:23665802

Toxicological perspectives of inhaled therapeutics and nanoparticles.

PubMed

Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Evaluation of silica nanoparticle toxicity after topical exposure for 90 days

PubMed Central

Ryu, Hwa Jung; Seong, Nak-won; So, Byoung Joon; Seo, Heung-sik; Kim, Jun-ho; Hong, Jeong-Sup; Park, Myeong-kyu; Kim, Min-Seok; Kim, Yu-Ri; Cho, Kyu-Bong; Seo, Mu Yeb; Kim, Meyoung-Kon; Maeng, Eun Ho; Son, Sang Wook

2014-01-01

Silica is a very common material that can be found in both crystalline and amorphous forms. Well-known toxicities of the lung can occur after exposure to the crystalline form of silica. However, the toxicities of the amorphous form of silica have not been thoroughly studied. The majority of in vivo studies of amorphous silica nanoparticles (NPs) were performed using an inhalation exposure method. Since silica NPs can be commonly administered through the skin, a study of dermal silica toxicity was necessary to determine any harmful effects from dermal exposures. The present study focused on the results of systemic toxicity after applying 20 nm colloidal silica NPs on rat skin for 90 days, in accordance with the Organization for Economic Cooperation and Development test guideline 411 with a good laboratory practice system. Unlike the inhalation route or gastrointestinal route, the contact of silica NPs through skin did not result in any toxicity or any change in internal organs up to a dose of 2,000 mg/kg in rats. PMID:25565831

A critical evaluation of the 2011 ECHA reports on compliance with the REACH and CLP regulations and on the use of alternatives to testing on animals for compliance with the REACH regulation.

PubMed

Spielmann, Horst; Sauer, Ursula G; Mekenyan, Ovanes

2011-10-01

On 30 June 2011, the European Chemicals Agency published two reports, one on the functioning of the REACH system, the other on the use of alternatives to animal testing in compliance with that system. The data presented are based on information gained during the first registration period under the REACH system, which included high production volume chemicals and substances of very high concern, which have the most extensive information requirements. A total of 25,460 registration dossiers were received, covering 3,400 existing, so-called 'phase-in', substances, and 900 new, so-called 'non-phase-in', substances. Data sharing and the joint submission of data are reported to have worked successfully. In the registration dossiers for these substances, results from new animal tests were included for less than 1% of all the endpoints; testing proposals (required for 'higher-tier' information requirements) were submitted for 711 in vivo tests involving vertebrate animals. The registrants mainly used old, existing experimental data, or options for the adaptation (waiving) of information requirements, before collecting new information. For predicting substance toxicity, 'read-across' was the second most-used approach, followed by 'weight-of-evidence'. In vitro toxicity tests played a minor role, and were only used when the respective test methods had gained the status of regulatory acceptance. All in all, a successful start to the REACH programme was reported, particularly since, in contrast to most predictions, it did not contribute to a significant increase in toxicity testing in animals. 2011 FRAME.

In vitro Alternative Methodologies for Central Nervous System Assessment: A Critique using Nanoscale Materials as an Example.

EPA Science Inventory

Identifying the potential health hazards to the central nervous system of a new family of materials presents many challenges. Whole-animal toxicity testing has been the tradition, but in vitro methods have been steadily gaining popularity. There are numerous challenges in testing...

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...

*Evaluating the toxicity of airborne particulate matter and nanoparticles by measuring oxidative strett potential - A workshop report and consensus statement

EPA Science Inventory

BACKGROUND: There is a strong need for laboratory in vitro test systems for the toxicity of airborne particulate matter and nanoparticles. The measurement of oxidative stress potential offers a promising way forward. OBJECTIVES: A workshop was convened involving leading workers f...

Ecotoxicity hazard assessment of styrene.

PubMed

Cushman, J R; Rausina, G A; Cruzan, G; Gilbert, J; Williams, E; Harrass, M C; Sousa, J V; Putt, A E; Garvey, N A; St Laurent, J P; Hoberg, J R; Machado, M W

1997-07-01

The ecotoxicity of styrene was evaluated in acute toxicity studies of fathead minnows (Pimephales promelas), daphnids (Daphnia magna), amphipods (Hyalella azteca), and freshwater green algae (Selenastrum capricornutum), and a subacute toxicity study of earthworms (Eisenia fostida). Stable exposure levels were maintained in the studies with fathead minnows, daphnids, and amphipods using sealed, flowthrough, serial dilution systems and test vessels. The algae were evaluated in a sealed, static system. The earthworms were exposed in artificial soil which was renewed after 7 days. Styrene concentrations in water and soil were analyzed by gas chromatography with flame ionization detection following extraction into hexane. Test results are based on measured concentrations. Styrene was moderately toxic to fathead minnows, daphnids, and amphipods: fathead minnow: LC50 (96 hr), 10 mg/liter, and NOEC, 4.0 mg/liter; daphnids: EC50 (48 hr), 4.7 mg/liter, and NOEC, 1.9 mg/liter; amphipods: LC50 (96 hr), 9.5 mg/liter, and NOEC, 4.1 mg/liter. Styrene was highly toxic to green algae: EC50 (96 hr), 0.72 mg/liter, and NOEC, 0.063 mg/liter; these effects were found to be algistatic rather than algicidal. Styrene was slightly toxic to earthworms: LC50 (14 days), 120 mg/kg, and NOEC, 44 mg/kg. There was no indication of a concern for chronic toxicity based on these studies. Styrene's potential impact on aquatic and soil environments is significantly mitigated by its volatility and biodegradability.

Pollutant sensitivity of the endangered Tar River Spinymussel as assessed by single chemical and effluent toxicity tests

USGS Publications Warehouse

Augspurger, Thomas P.; Wang, Ning; Kunz, James L.; Ingersoll, Christopher G.

2014-01-01

The federally endangered Tar River spinymussel (Elliptio steinstansana) is endemic to the Tar River and Neuse River systems in North Carolina. The extent to which water quality limits Tar River spinymussels’ recovery is important to establish, and one aspect of that is understanding the species’ pollutant sensitivity. The primary objectives of this study were to 1) develop captive propagation and culture methods for Tar River spinymussels; 2) determine the pollutant sensitivity of captively propagated Tar River spinymussels; 3) examine the utility of the non-endangered yellow lance (Elliptio lanceolata), yellow lampmussel (Lampsilis cariosa) and notched rainbow (Villosa constricta) as surrogates for the Tar River spinymussels’ chemical sensitivity; 4) develop a 7-d method for conducting effluent toxicity tests starting with newly transformed mussels; 5) assess the toxicity of municipal wastewater effluents discharged into the Tar River spinymussels’ current and historic habitat; and, 6) evaluate the protection afforded by existing effluent toxicity test requirements.

Development of a flow-through system for the fish embryo toxicity test (FET) with the zebrafish (Danio rerio).

PubMed

Lammer, E; Kamp, H G; Hisgen, V; Koch, M; Reinhard, D; Salinas, E R; Wendler, K; Zok, S; Braunbeck, Th

2009-10-01

The acute fish test is still a mandatory component in chemical hazard and risk assessment. However, one of the objectives of the new European chemicals policy (REACH - Registration, Evaluation, Authorization and Restriction of Chemicals) is to promote non-animal testing. For whole effluent testing in Germany, the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) has been an accepted and mandatory replacement of the fish test since January 2005. For chemical testing, however, further optimization of the FET is required to improve the correlation between the acute fish test and the alternative FET. Since adsorption of the test chemical to surfaces may reduce available exposure concentrations, a flow-through system for the FET using modified commercially available polystyrene 24-well microtiter plates was developed, thus combining the advantages of the standard FET with those of continuous delivery of test substances. The advantages of the design presented include: small test footprint, availability of adequate volumes of test solution for subsequent chemical analysis, and sufficient flow to compensate for effects of non-specific adsorption within 24h. The flow-through test system can also be utilized to conduct longer-term embryo larval fish tests, thus offering the possibility for teratogenicity testing.

The biological effects and possible modes of action of nanosilver.

PubMed

Völker, Carolin; Oetken, Matthias; Oehlmann, Jörg

2013-01-01

Novel physicochemical and biological properties have led to a versatile spectrum of applications for nanosized silver particles. Silver nanoparticles are applied primarily for their antimicrobial effects, and may variety of commercially available products have emerged. To better predict and prevent possible environmental impacts from silver nanoparticles that are derived from increasing production volumes and environmental release, more data on the biological effects are needed on appropriate model organisms. We examined the literature that addressed the adverse effects of silver nanoparticles on different levels of biological integration, including in vitro and in vivo test systems. Results of in vitro studies indicate a dose-dependent programmed cell death included by oxidative stress as main possible pathway of toxicity. Furthermore, silver nanoparticles may affect cellular enzymes by interference with free thiol groups and mimicry of endogenous ions. Similar mechanisms may apply for antibacterial effects produced by nonasilver. These effects are primary from the interference nanosilver has with bacterial cell membranes. Few in vivo studies have been performed to evaluated the toxic mode of action of nanosilver or to provide evidence for oxidative stress as an important mechanism of nanosilver toxicity. Organisms that are most acutely sensitive to nanosilver toxicity are the freshwater filter-freeding organisms. Both in vitro and in vivo studies have demonstrated tha silver ions released from nanoparticle surface contribute to the toxicity, and, indeed, some findings indicated a unique nanoparticles effect. For an adequate evaluation of the environmental impact of nanosilver, greater emphasis should be placed on combining mechanistic investigations that are performed in vitro, with results obtained in in vivo test systems. Future in vivo test system studies should emphasize long-term exposure scenarios. Moreover, the dietary uptake of silver nanoparticles and the potential to bioaccumulate through the food web should be examined in detail.

Zebrafish on a chip: a novel platform for real-time monitoring of drug-induced developmental toxicity.

PubMed

Li, Yinbao; Yang, Fan; Chen, Zuanguang; Shi, Lijuan; Zhang, Beibei; Pan, Jianbin; Li, Xinchun; Sun, Duanping; Yang, Hongzhi

2014-01-01

Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

Water toxicity monitoring using Vibrio fischeri: a method free of interferences from colour and turbidity.

PubMed

Faria, Elsa Correia; Treves Brown, Bernard J; Snook, Richard D

2004-02-01

In this paper the kinetic method for the determination of toxicity using Vibrio fischeri is described and suggested as a potential method for the continuous screening of wastewater toxicity. The kinetic method was demonstrated to be free from interferences due to colour and turbidity normally observed when testing wastewater samples with this organism. This is of great importance for the application of the method to remote toxicity screening of wastewaters. The effect of colour, investigated using 50 ppm Zn(2+) solutions containing the food-dye tropaeolin O, and the effect of turbidity, investigated using 50 ppm Zn(2+) solutions containing white optically reflective and coloured optically absorbing polystyrene beads, is reported. It was also found that the design of the light detection system of the instrument ensures efficient collection of the light scattered by particles in the sample, which enables a greater range of turbid samples to be tested. In addition the natural light decay was found to be negligible during the duration of a 10 min test and thus one channel would be enough to carry out the tests. This would mean halving the quantity of bacterial reagent used and reducing the cost of the tests.

Development of an in vitro toxicological test system based on zebrafish (Danio rerio) sperm analysis.

PubMed

Kollár, Tímea; Kása, Eszter; Ferincz, Árpád; Urbányi, Béla; Csenki-Bakos, Zsolt; Horváth, Ákos

2018-05-01

The effect of seven heavy metals on the motility parameter of zebrafish sperm was tested in order to develop an in vitro toxicological test system as an alternative to live animal testing. In vitro test systems are currently preferred in ecotoxicology due to their practical and ethical advantages and fish sperm can be a suitable model. A number of studies had been carried out previously on this topic, but the described methods had not been standardized in numerous aspects (donor species, measured endpoint, etc.). In this study, heavy metals (mercury, arsenic, chromium, zinc, nickel, copper, cadmium) were used as reference toxicants with known toxicity to develop a standardized fish sperm in vitro assay. The tested concentrations were determined based on preliminary range finding tests. The endpoints were progressive motility (PMOT, %), curvilinear velocity (VCL, μm/s), and linearity (LIN, %) measured by a computer-assisted sperm analysis (CASA) system. According to our results, PMOT was the most sensitive of the three investigated parameters: dose-response curves were observed for each metal at relatively low concentrations. VCL values were less sensitive: higher concentrations were needed to observe changes. Of the three parameters, LIN was the least affected: dose-response relationship was observed only in the case of mercury (e.g., lowest observed effect concentration (LOEC) of Hg at 120 min: 1 mg/L for PMOT, 2.5 mg/L for VCL, 5 mg/L for LIN; LOEC of Cu at 120 min: 1 mg/L for PMOT, 5 mg/L for VCL, any for LIN). The order of toxicity as determined by PMOT was as follows: Hg 2+  > As 3+  > Cd 2+  > Cu 2+  > Zn 2+  > Cr 3+  > Ni 2+ . In conclusion, we found that PMOT of zebrafish sperm was an accurate and fast bioindicator of heavy metal load. Sperm analysis can be adopted to estimate the possible toxic effects of various chemicals in vitro. Future investigations should concentrate on the applicability of this assay to other contaminants (e.g., organic pollutants).

Modeling for influenza vaccines and adjuvants profile for safety prediction system using gene expression profiling and statistical tools

PubMed Central

Sasaki, Eita; Momose, Haruka; Hiradate, Yuki; Furuhata, Keiko; Takai, Mamiko; Asanuma, Hideki; Ishii, Ken J.

2018-01-01

Historically, vaccine safety assessments have been conducted by animal testing (e.g., quality control tests and adjuvant development). However, classical evaluation methods do not provide sufficient information to make treatment decisions. We previously identified biomarker genes as novel safety markers. Here, we developed a practical safety assessment system used to evaluate the intramuscular, intraperitoneal, and nasal inoculation routes to provide robust and comprehensive safety data. Influenza vaccines were used as model vaccines. A toxicity reference vaccine (RE) and poly I:C-adjuvanted hemagglutinin split vaccine were used as toxicity controls, while a non-adjuvanted hemagglutinin split vaccine and AddaVax (squalene-based oil-in-water nano-emulsion with a formulation similar to MF59)-adjuvanted hemagglutinin split vaccine were used as safety controls. Body weight changes, number of white blood cells, and lung biomarker gene expression profiles were determined in mice. In addition, vaccines were inoculated into mice by three different administration routes. Logistic regression analyses were carried out to determine the expression changes of each biomarker. The results showed that the regression equations clearly classified each vaccine according to its toxic potential and inoculation amount by biomarker expression levels. Interestingly, lung biomarker expression was nearly equivalent for the various inoculation routes. The results of the present safety evaluation were confirmed by the approximation rate for the toxicity control. This method may contribute to toxicity evaluation such as quality control tests and adjuvant development. PMID:29408882

A short-term swimming speed alteration test with nauplii of Artemia franciscana.

PubMed

Morgana, Silvia; Estévez-Calvar, Noelia; Gambardella, Chiara; Faimali, Marco; Garaventa, Francesca

2018-01-01

The presence of toxicant needs to be assessed within short time in order to effectively protect the aquatic environment from serious threat. Based on the observation that at high temperatures aquatic organisms become more vulnerable to stressors than those maintained at room temperature, a new test was developed. The proposed bioassay consisted in the evaluation of the swimming speed alteration (SSA) of nauplii of Artemia franciscana incubated at 39°C (± 1) for 6h, using a Swimming Behavior Recorder system (SBR). A comparative ecotoxicological study between the 6h SSA test and the 24h mortality test was carried out in order to validate the new method in terms of sensitivity by means of EC 50 values. The bioassay was applied to screen different toxicants: K 2 Cr 2 O 7 , Cu(SO 4 ) 2 , NaClO, SDS and Sertraline hydrochloride. The EC 50s calculated for the short-term SSA test and those of the mortality test showed comparable values. For all toxicants, the 6h SSA test was proved to be as sensitive as the 24h mortality test. The method developed in this study is the first temperature-based toxicity test with nauplii of Artemia franciscana and it represents an attractive assay in ecotoxicology because of its convenience in terms of time and costs, feasibility and sensitivity. Copyright © 2017 Elsevier Inc. All rights reserved.

A flowthrough fecundity test with Nitocra spinipes (Harpacticoidea Crustacea) for aquatic toxicity.

PubMed

Bengtsson, B E; Bergström, B

1987-12-01

A sublethal flowthrough fecundity test with the euryhaline harpacticoid copepod Nitocra spinipes has been developed as a complement to the acute toxicity test (for 48 or 96 hr LC50) with the same species (B-E. Bengtsson, 1981, Mar. Pollut. Biol. 9,238-241). Bacterial suspension as feed and test water are continuously fed by a peristaltic pump to the system. Newly fertilized females with ovigerous bands are harvested from laboratory cultures and put into the test vessels at the start of the experiment. They are then exposed to a series of concentrations of chemicals or industrial effluents for 13 days. The amount of live offspring (metanauplia and copepodids) are recorded and an EC50 for fecundity is calculated. The report gives a detailed technical description of the test system and presents the results from 11 tests with pure chemicals (Zn, Cd, As, and pentachlorophenate) and six industrial effluents (pulp industry, textile industry, and refinery) in salinities ranging from 3 to 25%.

Toxicity Testing in the 21st Century Beyond Environmental Chemicals

PubMed Central

Rovida, Costanza; Asakura, Shoji; Daneshian, Mardas; Hofman-Huether, Hana; Leist, Marcel; Meunier, Leo; Reif, David; Rossi, Anna; Schmutz, Markus; Valentin, Jean-Pierre; Zurlo, Joanne; Hartung, Thomas

2018-01-01

Summary After the publication of the report titled Toxicity Testing in the 21st Century – A Vision and a Strategy, many initiatives started to foster a major paradigm shift for toxicity testing – from apical endpoints in animal-based tests to mechanistic endpoints through delineation of pathways of toxicity (PoT) in human cell based systems. The US EPA has funded an important project to develop new high throughput technologies based on human cell based in vitro technologies. These methods are currently being incorporated into the chemical risk assessment process. In the pharmaceutical industry, the efficacy and toxicity of new drugs are evaluated during preclinical investigations that include drug metabolism, pharmacokinetics, pharmacodynamics and safety toxicology studies. The results of these studies are analyzed and extrapolated to predict efficacy and potential adverse effects in humans. However, due to the high failure rate of drugs during the clinical phases, a new approach for a more predictive assessment of drugs both in terms of efficacy and adverse effects is getting urgent. The food industry faces the challenge of assessing novel foods and food ingredients for the general population, while using animal safety testing for extrapolation purposes is often of limited relevance. The question is whether the latest paradigm shift proposed by the Tox21c report for chemicals may provide a useful tool to improve the risk assessment approach also for drugs and food ingredients. PMID:26168280

Effect of AL2O3 and TiO2 nanoparticles on aquatic organisms

NASA Astrophysics Data System (ADS)

Gosteva, I.; Morgalev, Yu; Morgaleva, T.; Morgalev, S.

2015-11-01

Environmental toxicity of aqueous disperse systems of nanoparticles of binary compounds of titanium dioxides (with particle size Δ50=5 nm, Δ50=50 nm, Δ50=90 nm), aluminum oxide alpha-forms (Δ50=7 nm and Δ50=70 nm) and macro forms (TiO2 Δ50=350 nm, Al2O3 A50=4000 nm) were studied using biological testing methods. The bioassay was performed using a set of test organisms representing the major trophic levels. We found the dependence of the toxic effect concentration degree of nTiO2 and nAl2O3 on the fluorescence of the bacterial biosensor "Ekolyum", the chemotactic response of ciliates Paramecium caudatum, the growth of unicellular algae Chlorella vulgaris Beijer and mortality of entomostracans Daphnia magna Straus. We revealed the selective dependence of nTiO2 and nAl2O3 toxicity on the size, concentration and chemical nature of nanoparticles. The minimal concentration causing an organism's response on nTiO2 and nAl2O3 effect depends on the type of the test- organism and the test reaction under study. We specified L(E)C50 and acute toxicity categories for all the studied nanoparticles. We determined that nTiO2 (Δ50=5 nm) belong to the category «Acute toxicity 1», nTiO2 (A50=90 nm) and nAl2O3 (Δ50=70 nm) - to the category «Acute toxicity 2», nAl2O3 (Δ50=7 nm) - to the category «Acute toxicity 3». No acute toxicity was registered for nTiO2 (Δ50=50 nm) and macro form TiO2.

Conspicuousness, color resemblance, and toxicity in geographically diverging mimicry: The pan-Amazonian frog Allobates femoralis.

PubMed

Amézquita, Adolfo; Ramos, Óscar; González, Mabel Cristina; Rodríguez, Camilo; Medina, Iliana; Simões, Pedro Ivo; Lima, Albertina Pimentel

2017-04-01

Predation risk is allegedly reduced in Batesian and Müllerian mimics, because their coloration resembles the conspicuous coloration of unpalatable prey. The efficacy of mimicry is thought to be affected by variation in the unpalatability of prey, the conspicuousness of the signals, and the visual system of predators that see them. Many frog species exhibit small colorful patches contrasting against an otherwise dark body. By measuring toxicity and color reflectance in a geographically variable frog species and the syntopic toxic species, we tested whether unpalatability was correlated with between-species color resemblance and whether resemblance was highest for the most conspicuous components of coloration pattern. Heterospecific resemblance in colorful patches was highest between species at the same locality, but unrelated to concomitant variation in toxicity. Surprisingly, resemblance was lower for the conspicuous femoral patches compared to the inconspicuous dorsum. By building visual models, we further tested whether resemblance was affected by the visual system of model predators. As predicted, mimic-model resemblance was higher under the visual system of simulated predators compared to no visual system at all. Our results indicate that femoral patches are aposematic signals and support a role of mimicry in driving phenotypic divergence or mimetic radiation between localities. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Effect of olive mill wastewaters on the oxygen consumption by activated sludge microorganisms: an acute toxicity test method.

PubMed

Paixão, S M; Anselmo, A M

2002-01-01

The test for inhibition of oxygen consumption by activated sludge (ISO 8192-1986 (E)) was evaluated as a tool for assessing, the acute toxicity of olive mill wastewaters (OMW). According to the ISO test, information generated by this method may be helpful in estimating the effect of a test material on bacterial communities in the aquatic environment, especially in aerobic biological treatment systems. However, the lack of standardized bioassay methodology for effluents imposed that the test conditions were modified and adapted. The experiments were conducted in the presence or absence of an easily biodegradable carbon source (glucose) with different contact times (20 min and 24 h). The results obtained showed a remarkable stimulatory effect of this effluent to the activated sludge microorganisms. In fact, the oxygen uptake rate values increase with increasing effluent concentrations and contact times up to 0.98 microl O(2) h(-1) mg(-1) dry weight for a 100% OMW sample, 24 h contact time, with blanks exhibiting an oxygen uptake rate of ca. 1/10 of this value (0.07-0.10). It seems that the application of the ISO test as an acute toxicity test for effluents should be reconsidered, with convenient adaptation for its utilization as a method of estimating the effect on bacterial communities present in aerobic biological treatment systems. Copyright 2002 John Wiley & Sons, Ltd.

Acute toxicities of toxaphene and endrin to larvae of seven species of amphibians

USGS Publications Warehouse

Hall, R.J.; Swineford, D.M.

1981-01-01

Seven species of amphibian larvae were exposed to toxaphene and endrin in a continuous-flow dosing system to determine differences in sensitivity to the two compounds, EC50 and LC50 estimates varied from those for Rana sphenocephala by no more than one order of magnitude when calculated on the basis of intended concentrations. Removal of pesticides from water by the test animals was significant and it makes interpretation of results difficult. Continuous-flow toxicity tests conflict with the adaptations of amphibian larvae for static water; use of such tests for amphibians requires further evaluation.

Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

USGS Publications Warehouse

Johnson, W. Waynon; Finley, Mack T.

1980-01-01

Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data from the Columbia Laboratory and its field laboratories. It presents definitive acute toxicity data on 271 chemicals tested against a variety of freshwater invertebrates and fishes. The chemicals represent all major groups of pesticides, as well as numerous industrial chemicals. This compilation should serve as a useful database for the many agencies and organizations dealing with research and management programs concerned with the impact of chemicals on aquatic resources.The Columbia Laboratory has played a major role in developing currently used standard methodology for static acute toxicity testing. The use of standardized methodology greatly reduces variation in results. The data presented here have been carefully scrutinized to eliminate tests that failed to follow acceptable procedures. Handling of test organisms and procedures for static toxicity tests followed those described by Lennon and Walker (1964) and Macek and McAllister (1970), and conform well with those recommended by Brauhn and Schoettger (1975) and the Committee on Methods for Toxicity Tests with Aquatic Organisms (1975).The species of fish and invertebrates that were tested are listed in phylogenetic order in Tables 1 and 2. Fish were obtained from Federal and State hatcheries as either eggs or fry. Original stocks of invertebrates were collected and cultured from wild populations with no known source of contamination; these populations were replenished regularly. The invertebrates were cultured in the Laboratory by methods similar to those described by Sanders and Cope (1966).Test chemicals usually consisted of technical or analytical grade samples of known purity. Formulations of the chemicals were also tested when available. When purity of test chemicals was known, all calculated concentrations were based on percent active ingredients. Stock solutions were prepared immediately before each test, with commercial grade acetone as the carrier solvent. Occasionally, ethanol or dimethyl-formamide was substituted. Solvent concentrations did not exceed 0.5 mL/L in final dilution water.Test water (dilution water) was reconstituted from deionized water of at least 106 ohms resistivity by the addition of appropriate reagent grade chemicals (Marking 1969). Water was buffered to maintain a pH of 7.2 to 7.5, an alkalinity of 30 to 35 mg/L, and a hardness of 40 to 50 mg/L as CaCO3. Test water was mixed thoroughly and aerated before transfer into test chambers. Fish were acclimated to dilution water by gradually changing the water in acclimated tanks from 100% well water to 100% reconstituted water over a 1- to 3-day period at the desired testing temperature. Invertebrates were acclimated from well water to dilution water over a 4- to 6-h period. Toxicity tests were conducted under static conditions without aeration, and the organisms were not fed during acclimation or testing. Temperature of test solutions was maintained within ± 1°C of that required for a given test.Toxicity tests with fish were conducted in 18.9-liter (5-gal) wide-mouthed jars containing 15 liters of test solution. Fingerling fish weighing 0.2 to 1.5 g were tested at each concentration. Caution was taken not to exceed 0.8 g of test organisms per liter of solution. Duplicate test chambers were used to accommodate larger fish. Test chambers varied in size for invertebrates, depending on the species used; volume of test solution ranged from 0.25 to 4 liters. At least 10 organisms were exposed to each concentration for all definitive tests. At least six concentrations were used per toxicity test.The tests began upon initial exposure to the toxicant and continued for 96 h. Immobilization tests with invertebrates were conducted for only 48 h. The number of dead or affected organisms in each test chamber were recorded and the dead organisms were removed every 24 h; general observations on the condition of test organisms were also recorded at these times.Toxicity data were analyzed by a statistical method described by Litchfield and Wilcoxon (1949) to determine LC50 (theoretical estimate of the concentration lethal to 50% of the test animals) and 95% confidence intervals. This method is recommended by the American Public Health Association (1971) and by Sprague (1969) for determining median lethal concentrations. The procedure is easily modified for computing a single LC50 when replicate tests are performed.

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

Shallow Habitat Air Dive Series (SHAD I and II): The Effects on Visual Performance and Physiology

DTIC Science & Technology

1974-10-02

APPLICATION Since the tests employed cover all the major, known visual symptoms of oxygen toxicity , the data indicate that man can live under...included a number of measures of visual physiology and visual performance, since many of the symptoms of oxygen toxicity involve the visual system. The...oxygen toxic - ity. Nitrogen narcosis, which normally occurs at 200 to 300 ft, is the lesser of the two problems for shaUow habitat divers, since

Organotypic liver culture models: Meeting current challenges in toxicity testing

PubMed Central

LeCluyse, Edward L.; Witek, Rafal P.; Andersen, Melvin E.; Powers, Mark J.

2012-01-01

Prediction of chemical-induced hepatotoxicity in humans from in vitro data continues to be a significant challenge for the pharmaceutical and chemical industries. Generally, conventional in vitro hepatic model systems (i.e. 2-D static monocultures of primary or immortalized hepatocytes) are limited by their inability to maintain histotypic and phenotypic characteristics over time in culture, including stable expression of clearance and bioactivation pathways, as well as complex adaptive responses to chemical exposure. These systems are less than ideal for longer-term toxicity evaluations and elucidation of key cellular and molecular events involved in primary and secondary adaptation to chemical exposure, or for identification of important mediators of inflammation, proliferation and apoptosis. Progress in implementing a more effective strategy for in vitro-in vivo extrapolation and human risk assessment depends on significant advances in tissue culture technology and increasing their level of biological complexity. This article describes the current and ongoing need for more relevant, organotypic in vitro surrogate systems of human liver and recent efforts to recreate the multicellular architecture and hemodynamic properties of the liver using novel culture platforms. As these systems become more widely used for chemical and drug toxicity testing, there will be a corresponding need to establish standardized testing conditions, endpoint analyses and acceptance criteria. In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment. PMID:22582993

Bioretention storm water control measures decrease the toxicity of copper roof runoff.

PubMed

LaBarre, William J; Ownby, David R; Rader, Kevin J; Lev, Steven M; Casey, Ryan E

2017-06-01

The present study evaluated the ability of 2 different bioretention storm water control measures (SCMs), planter boxes and swales, to decrease the toxicity of sheet copper (Cu) roofing runoff to Daphnia magna. The present study quantified changes in storm water chemistry as it passed through the bioretention systems and utilized the biotic ligand model (BLM) to assess whether the observed D. magna toxicity could be predicted by variations found in water chemistry. Laboratory toxicity tests were performed using select storm samples with D. magna cultured under low ionic strength conditions that were appropriate for the low ionic strength of the storm water samples being tested. The SCMs decreased toxicity of Cu roof runoff in both the BLM results and the storm water bioassays. Water exiting the SCMs was substantially higher than influent runoff in pH, ions, alkalinity, and dissolved organic carbon and substantially lower in total and dissolved Cu. Daphnids experienced complete mortality in untreated runoff from the Cu roof (the SCM influent); however, for planter and swale effluents, survival averaged 86% and 95%, respectively. The present study demonstrated that conventional bioretention practices, including planter boxes and swales, are capable of decreasing the risk of adverse effects from sheet Cu roof runoff to receiving systems, even before considering dilution of effluents in those receiving systems and associated further reductions in copper bioavailability. Environ Toxicol Chem 2017;36:1680-1688. © 2016 SETAC. © 2016 SETAC.

Mixtures of Chemical Pollutants at European Legislation Safety Concentrations: How Safe Are They?

PubMed Central

Carvalho, Raquel N.; Arukwe, Augustine; Ait-Aissa, Selim; Bado-Nilles, Anne; Balzamo, Stefania; Baun, Anders; Belkin, Shimshon; Blaha, Ludek; Brion, François; Conti, Daniela; Creusot, Nicolas; Essig, Yona; Ferrero, Valentina E. V.; Flander-Putrle, Vesna; Fürhacker, Maria; Grillari-Voglauer, Regina; Hogstrand, Christer; Jonáš, Adam; Kharlyngdoh, Joubert B.; Loos, Robert; Lundebye, Anne-Katrine; Modig, Carina; Olsson, Per-Erik; Pillai, Smitha; Polak, Natasa; Potalivo, Monica; Sanchez, Wilfried; Schifferli, Andrea; Schirmer, Kristin; Sforzini, Susanna; Stürzenbaum, Stephen R.; Søfteland, Liv; Turk, Valentina; Viarengo, Aldo; Werner, Inge; Yagur-Kroll, Sharon; Zounková, Radka; Lettieri, Teresa

2014-01-01

The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations. PMID:24958932

Methods For Collecting , Culturing And Performing Toxicity Tests With Daphnia ambigua

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

Specht, Winona L.

2005-07-01

Toxicity tests conducted on water collected from impacted locations in SRS streams often failed chronic toxicity tests and sometimes failed acute toxicity tests (Specht 1995). These findings prompted SRS to determine the cause of the failures. Some SRS NPDES outfalls were also failing chronic toxicity tests, even though no toxicant could be identified and when TIEs were performed, none of the TIE treatments removed the toxicity. Ultimately, it was determined that the failures were due to the low hardness of SRS surface waters, rather than to the presence of a toxicant. The species of cladoceran that the EPA recommends formore » toxicity testing, Ceriodaphnia dubia, is stressed by the very low hardness of SRS waters. SRS developed an alternate species toxicity test that is similar to the EPA test, but uses an indigenous cladoceran, Daphnia ambigua (Specht and Harmon, 1997; Harmon et al., 2003). In 2001, SCDHEC approved the use of D. ambigua for toxicity testing at SRS, contingent upon approval by EPA Region 4. In 2002, EPA Region 4 approved the use of this species for compliance toxicity testing at SRS. Ultimately, the use of this species demonstrated that SRS effluents were not toxic, and most toxicity testing requirements were removed from the NPDES permit that was issued in December 2003, with the exception of one round of chronic definitive testing on outfalls A-01, A-11, and G-10 just before the next NPDES permit application is submitted to SCDHEC. Although the alternate species test was developed at SRS (1996-1998), the culture was transferred to a contract toxicity testing lab (ETT Environmental) located in Greer, SC in 1998. ETT Environmental became certified by SCDHEC to perform toxicity tests using D. ambigua in 2002, and at this time is the only laboratory certified by SCDHEC to perform tests with this species. Because of the expense associated with maintaining the D. ambigua culture for several years when no toxicity testing is required, SRS decided to suspend financial support associated with maintaining the cultures until testing is needed. The purpose of this document is to provide guidance on how to establish a laboratory culture of D. ambigua so that a culture can be restarted when needed.« less

40 CFR 799.9537 - TSCA in vitro mammalian chromosome aberration test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... demonstrates the sensitivity of the test system. Positive control concentrations should be chosen so that the... aberration test. 799.9537 Section 799.9537 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND...

40 CFR 799.9537 - TSCA in vitro mammalian chromosome aberration test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... demonstrates the sensitivity of the test system. Positive control concentrations should be chosen so that the... aberration test. 799.9537 Section 799.9537 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND...

Toxicity of nonylphenol diethoxylate in lab-scale anaerobic digesters.

PubMed

Bozkurt, Hande; Sanin, F Dilek

2014-06-01

Nonylphenol compounds have high commercial, industrial and domestic uses owing to their surface active properties. In addition to their toxic, carcinogenic and persistent characteristics; they have drawn the attention of scientists lately due to their endocrine disrupting properties. Their widespread use and disposal cause them to enter wastewater treatment systems at high concentrations. Since they are highly persistent and hydrophobic, they accumulate mostly on sludge. In this study using Anaerobic Toxicity Assay (ATA) tests, the toxicity of a model nonylphenol compound, nonylphenol diethoxylate (NP2EO), for anaerobic digestion of sludge was determined. The test bottles were dosed with NP2EO in acetone, with concentrations ranging from 1 mg L(-1) to 30 mg L(-1). During the tests, gas productions and compositions in terms of methane and carbon dioxide were monitored. To be able to judge about the fate, the target compounds were extracted from water and sludge and analyzed using GC/MS. The sludge samples used for assembling the reactors were found to contain NP and NP1EO but no NP2EO. After the assay was completed, all the NP2EO spiked into the live reactors was found to disappear. The increase seen in NP1EO and NP and further accumulation of NP in the system, indicated the conversion of NP2EO to these metabolites. On the other hand, no conversion was observed in abiotic reactors. Inhibition of NP2EO for anaerobic microorganisms was not observed throughout the tests considering the biogas production of the test reactors in comparison to the control reactors. Copyright © 2013 Elsevier Ltd. All rights reserved.

An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells

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

Noor, Fozia; Niklas, Jens; Mueller-Vieira, Ursula

2009-06-01

Efficient and accurate safety assessment of compounds is extremely important in the preclinical development of drugs especially when hepatotoxicty is in question. Multiparameter and time resolved assays are expected to greatly improve the prediction of toxicity by assessing complex mechanisms of toxicity. An integrated approach is presented in which Hep G2 cells and primary rat hepatocytes are compared in frequently used cytotoxicity assays for parent compound toxicity. The interassay variability was determined. The cytotoxicity assays were also compared with a reliable alternative time resolved respirometric assay. The set of training compounds consisted of well known hepatotoxins; amiodarone, carbamazepine, clozapine, diclofenac,more » tacrine, troglitazone and verapamil. The sensitivity of both cell systems in each tested assay was determined. Results show that careful selection of assay parameters and inclusion of a kinetic time resolved assay improves prediction for non-metabolism mediated toxicity using Hep G2 cells as indicated by a sensitivity ratio of 1. The drugs with EC{sub 50} values 100 {mu}M or lower were considered toxic. The difference in the sensitivity of the two cell systems to carbamazepine which causes toxicity via reactive metabolites emphasizes the importance of human cell based in-vitro assays. Using the described system, primary rat hepatocytes do not offer advantage over the Hep G2 cells in parent compound toxicity evaluation. Moreover, respiration method is non invasive, highly sensitive and allows following the time course of toxicity. Respiration assay could serve as early indicator of changes that subsequently lead to toxicity.« less

Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use.

PubMed

Aschner, Michael; Ceccatelli, Sandra; Daneshian, Mardas; Fritsche, Ellen; Hasiwa, Nina; Hartung, Thomas; Hogberg, Helena T; Leist, Marcel; Li, Abby; Mundi, William R; Padilla, Stephanie; Piersma, Aldert H; Bal-Price, Anna; Seiler, Andrea; Westerink, Remco H; Zimmer, Bastian; Lein, Pamela J

2017-01-01

There is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the modulation of fundamental neurodevelopmental processes (such as neuronal differentiation, precursor cell migration or neuronal network formation) by chemicals, the first generation of alternative DNT tests target these processes. The advantage of such types of assays is that they capture toxicants with multiple targets and modes-of-action. Moreover, the processes modelled by the assays can be linked to toxicity endophenotypes, i.e., alterations in neural connectivity that form the basis for neurofunctional deficits in man. The authors of this review convened in a workshop to define criteria for the selection of positive/negative controls, to prepare recommendations on their use, and to initiate the setup of a directory of reference chemicals. For initial technical optimization of tests, a set of > 50 endpoint-specific control compounds was identified. For further test development, an additional "test" set of 33 chemicals considered to act directly as bona fide DNT toxicants is proposed, and each chemical is annotated to the extent it fulfills these criteria. A tabular compilation of the original literature used to select the test set chemicals provides information on statistical procedures, and toxic/non-toxic doses (both for pups and dams). Suggestions are provided on how to use the > 100 compounds (including negative controls) compiled here to address specificity, adversity and use of alternative test systems.

Gaseous VOCs rapidly modify particulate matter and its biological effects - Part 2: Complex urban VOCs and model PM

NASA Astrophysics Data System (ADS)

Ebersviller, S.; Lichtveld, K.; Sexton, K. G.; Zavala, J.; Lin, Y.-H.; Jaspers, I.; Jeffries, H. E.

2012-03-01

This is the second study in a three-part study designed to demonstrate dynamic entanglements among gaseous organic compounds (VOCs), particulate matter (PM), and their subsequent potential biological effects. We study these entanglements in increasingly complex VOC and PM mixtures in urban-like conditions in a large outdoor chamber, both in the dark and in sunlight. To the traditional chemical and physical characterizations of gas and PM, we added new measurements of gas-only- and PM-only-biological effects, using cultured human lung cells as model living receptors. These biological effects are assessed here as increases in cellular damage or expressed irritation (i.e., cellular toxic effects) from cells exposed to chamber air relative to cells exposed to clean air. Our exposure systems permit side-by-side, gas-only- and PM-only-exposures from the same air stream containing both gases and PM in equilibria, i.e., there are no extractive operations prior to cell exposure for either gases or PM. In Part 1 (Ebersviller et al., 2012a), we demonstrated the existence of PM "effect modification" (NAS, 2004) for the case of a single gas-phase toxicant and an inherently non-toxic PM (mineral oil aerosol, MOA). That is, in the presence of the single gas-phase toxicant in the dark, the initially non-toxic PM became toxic to lung cells in the PM-only-biological exposure system. In this Part 2 study, we used sunlit-reactive systems to create a large variety of gas-phase toxicants from a complex mixture of oxides of nitrogen and 54 VOCs representative of those measured in US city air. In these mostly day-long experiments, we have designated the period in the dark just after injection (but before sunrise) as the "Fresh" condition and the period in the dark after sunset as the "Aged" condition. These two conditions were used to expose cells and to collect chemical characterization samples. We used the same inherently non-toxic PM from the Part 1 study as the target PM for "effect modification". Fortunately, in the absence of "seed particles", the complex highly-reactive VOC system used does not create any secondary aerosol in situ. All PM present in these tests were, therefore, introduced by injection of MOA to serve as PM-to-be-modified by the gaseous environment. PM addition was only done during dark periods, either before or after the daylight period. The purpose of this design is to test if a non-toxic PM becomes toxic in initially unreacted ("Fresh"), or in reacted ("Aged") complex VOC conditions. To have a complete design, we also tested the effects of clean air and the same VOC conditions, but without introducing any PM. Thus, there were six exposure treatment conditions that were evaluated with the side-by-side, gas-only- and PM-only-effects exposure systems; five separate chamber experiments were performed: two with clean air and three with the complex VOC/NOx mixture. For all of these experiments and exposures, chemical composition data and matching biological effects results for two end-points were compared. Chemical measurements demonstrate the temporal evolution of oxidized species, with a corresponding increase in toxicity observed from exposed cells. The largest increase in gas-phase toxicity was observed in the two "Aged" VOC exposures. The largest increase in particle-phase toxicity was observed in the "Aged" VOC exposure with the addition of PM after sunset. These results are a clear demonstration that the findings from Part 1 can be extended to the complex urban oxidized environment. This further demonstrates that the atmosphere itself cannot be ignored as a source of toxic species when establishing the risks associated with exposure to PM. Because gases and PM are transported and deposited differently within the atmosphere and lungs, these results have significant consequences. In the next (and final) part of the study, testing is further applied to systems with real diesel exhaust, including primary PM from a vehicle operated with different types of diesel fuel.

Gaseous VOCs rapidly modify particulate matter and its biological effects - Part 2: Complex urban VOCs and model PM

NASA Astrophysics Data System (ADS)

Ebersviller, S.; Lichtveld, K.; Sexton, K. G.; Zavala, J.; Lin, Y.-H.; Jaspers, I.; Jeffries, H. E.

2012-12-01

This is the second study in a three-part study designed to demonstrate dynamic entanglements among gaseous organic compounds (VOCs), particulate matter (PM), and their subsequent potential biological effects. We study these entanglements in increasingly complex VOC and PM mixtures in urban-like conditions in a large outdoor chamber, both in the dark and in sunlight. To the traditional chemical and physical characterizations of gas and PM, we added new measurements of gas-only- and PM-only-biological effects, using cultured human lung cells as model living receptors. These biological effects are assessed here as increases in cellular damage or expressed irritation (i.e., cellular toxic effects) from cells exposed to chamber air relative to cells exposed to clean air. Our exposure systems permit side-by-side, gas-only- and PM-only-exposures from the same air stream containing both gases and PM in equilibria, i.e., there are no extractive operations prior to cell exposure for either gases or PM. In Part 1 (Ebersviller et al., 2012a), we demonstrated the existence of PM "effect modification" (NAS, 2004) for the case of a single gas-phase toxicant and an inherently non-toxic PM (mineral oil aerosol, MOA). That is, in the presence of the single gas-phase toxicant in the dark, the initially non-toxic PM became toxic to lung cells in the PM-only-biological exposure system. In this Part 2 study, we used sunlit-reactive systems to create a large variety of gas-phase toxicants from a complex mixture of oxides of nitrogen and 54 VOCs representative of those measured in US city air. In these mostly day-long experiments, we have designated the period in the dark just after injection (but before sunrise) as the "Fresh" condition and the period in the dark after sunset as the "Aged" condition. These two conditions were used to expose cells and to collect chemical characterization samples. We used the same inherently non-toxic PM from the Part 1 study as the target PM for "effect modification". Fortunately, in the absence of "seed particles", the complex highly-reactive VOC system used does not create any secondary aerosol in situ. All PM present in these tests were, therefore, introduced by injection of MOA to serve as PM-to-be-modified by the gaseous environment. PM addition was only done during dark periods, either before or after the daylight period. The purpose of this design is to test if a non-toxic PM becomes toxic in initially unreacted ("Fresh"), or in reacted ("Aged") complex VOC conditions. To have a complete design, we also tested the effects of clean air and the same VOC conditions, but without introducing any PM. Thus, there were six exposure treatment conditions that were evaluated with the side-by-side, gas-only- and PM-only-effects exposure systems; five separate chamber experiments were performed: two with clean air and three with the complex VOC/NOx mixture. For all of these experiments and exposures, chemical composition data and matching biological effects results for two end-points were compared. Chemical measurements demonstrate the temporal evolution of oxidized species, with a corresponding increase in toxicity observed from exposed cells. The largest increase in gas-phase toxicity was observed in the two "Aged" VOC exposures. The largest increase in particle-phase toxicity was observed in the "Aged" VOC exposure with the addition of PM after sunset. These results are a clear demonstration that the findings from Part 1 can be extended to the complex urban oxidized environment. This further demonstrates that the atmosphere itself cannot be ignored as a source of toxic species when establishing the risks associated with exposure to PM. Because gases and PM are transported and deposited differently within the atmosphere and lungs, these results have significant consequences. In the next (and final) part of the study, testing is further applied to systems with real diesel exhaust, including primary PM from a vehicle operated with different types of diesel fuel.

Is the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) a potential alternative for the fish acute toxicity test?

PubMed

Lammer, E; Carr, G J; Wendler, K; Rawlings, J M; Belanger, S E; Braunbeck, Th

2009-03-01

The fish acute toxicity test is a mandatory component in the base set of data requirements for ecotoxicity testing. The fish acute toxicity test is not compatible with most current animal welfare legislation because mortality is the primary endpoint and it is often hypothesized that fish suffer distress and perhaps pain. Animal alternative considerations have also been incorporated into new European REACH regulations through strong advocacy for the reduction of testing with live animals. One of the most promising alternative approaches to classical acute fish toxicity testing with live fish is the fish embryo toxicity (FET) test. The FET has been a mandatory component in routine whole effluent testing in Germany since 2005 and has already been standardized at the international level. In order to analyze the applicability of the FET also in chemical testing, a comparative re-evaluation of both fish and fish embryo toxicity data was carried out for a total of 143 substances, and statistical approaches were developed to evaluate the correlation between fish and fish embryo toxicity data. Results confirm that fish embryo tests are neither better nor worse than acute fish toxicity tests and provide strong scientific support for the FET as a surrogate for the acute fish toxicity test.

A Study on the D. magna and V. fischeri Toxicity Relationship of Industrial Wastewater from Korea

NASA Astrophysics Data System (ADS)

Pyo, S.; Lee, S.; Chun Sang, H.; Park, T. J.; Kim, M. S.

2015-12-01

It is well known that high concentration of TDS (total dissolved solid) in industrial effluent gives rise to the toxicity to the Daphnia magna toxicity test. D. magna is vulnerable to relatively low TDS concentration showing the 24-hr EC50 of Salinity 0.6% (as the sea salt concentration). Recently, standard mandatory toxicity testing using Daphnia magna has been used to monitor industrial effluent toxicity according to Korea standard method (Acute Toxicity Test Method of the Daphnia magna Straus (Cladocera, Crustacea), ES 04704. 1a) under regulation. Since only one acute toxicity testing is applied in the present, we are trying to introduce microbial battery for more complete toxicity assessment. In this study, the acute toxicities between daphnids and microbes were compared. The results of D. magna and Vibrio fischeri toxicity test from 165 industrial wastewater effluents showed high positive correlation. In addition, the possibility of predicting daphnia toxicity from the bacterial toxicity data amounts to 92.6% if we consider salinity effect (>5ppt) together. From this study, we found that the V. fischeri toxicity test is a powerful battery tool to assess the industrial wastewater toxicity. Here, we suggest that luminescent bacteria toxicity test be useful not only for complete toxicity assessment which can't be obtained by daphnia toxicity testing only but also for the reduction cost, time, and labor in the Korean society. Keywords : D. magna, V. fischeri, Industrial waste water, battery test Acknowledgement This research was supported by a grant (15IFIP-B089908-02) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government

Application of recombinant fluorescent mammalian cells as a toxicity biosensor.

PubMed

Kim, E J; Lee, Y; Lee, J E; Gu, M B

2002-01-01

With respect to developing a more sensitive biosensor, a recombinant fluorescent Chinese Hamster Ovary cell line was used for the monitoring of various toxicants. Both cell lines, EFC-500 and KFC-A10, were able to detect toxicants sensitively. They were characterized with mitomycin C and gamma-ray as genotoxicants and bisphenol A, nonylphenol, ziram and methyl bromide as possible and known EDCs. When compared to each other, the response of KFC-A10 was generally more informative and sensitive. Compared to typical bacterial biosensor systems, these cell lines offered a sensitivity of 2- to 50-fold greater for the tested chemicals. Based on these results, the use of mammalian cells offers a sensitive biosensor system that is not only fast, cheap and reproducible but also capable of monitoring the endocrine-like characteristics of environmental toxicants.

A toxicity test in artificial soil based on the life-history strategy of the nematode Plectus acuminatus

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

Kammenga, J.E.; Van Koert, P.H.G.; Riksen, J.A.G.

1996-05-01

The ecological risk assessment of toxicants in soil requires reproducible and relevant test systems using a wide range of species. To supplement present test methods from the Organisation of Economic Cooperation and Development (OECD) in artificial soil with earthworms and springtails, a toxicity test in OECD artificial soil has been developed using the bacterivorous nematode Plectus acuminatus (Bastian, 1865) (Nematoda; Plectidae). The juvenile to adult ratio was used as a test parameter since previous life-cycle studies pointed out that fitness of P. acuminatus was strongly determined by changes in both reproduction and juvenile survival. Optimal conditions for the performance ofmore » nematodes in OECD artificial soil were determined (pH{sub KCl} = 5.5, temperature = 20C, and a moisture content of 70% dry wt. artificial soil), and tests were conducted with cadmium, copper, and pentachlorophenol. After an exposure period of 3 weeks the EC50 for cadmium was 321.0 {+-} 1.7 mg/kg dry wt., and the no-observed-effect concentration (NOEC) was 32 mg/kg dry wt. The EC50 for pentachlorophenol was 47.9 {+-} 1.2 mg/kg dry wt., and the NOEC was <10 mg/kg dry wt. For copper the EC50 was 162 {+-} 0.2 mg/kg dry wt., and the NOEC was 32 mg/kg dry wt. It is concluded that the nematode test may well supplement current coil test systems using earthworms and springtails.« less

20170312 - Computer Simulation of Developmental ...

EPA Pesticide Factsheets

Rationale: Recent progress in systems toxicology and synthetic biology have paved the way to new thinking about in vitro/in silico modeling of developmental processes and toxicities, both for embryological and reproductive impacts. Novel in vitro platforms such as 3D organotypic culture models, engineered microscale tissues and complex microphysiological systems (MPS), together with computational models and computer simulation of tissue dynamics, lend themselves to a integrated testing strategies for predictive toxicology. As these emergent methodologies continue to evolve, they must be integrally tied to maternal/fetal physiology and toxicity of the developing individual across early lifestage transitions, from fertilization to birth, through puberty and beyond. Scope: This symposium will focus on how the novel technology platforms can help now and in the future, with in vitro/in silico modeling of complex biological systems for developmental and reproductive toxicity issues, and translating systems models into integrative testing strategies. The symposium is based on three main organizing principles: (1) that novel in vitro platforms with human cells configured in nascent tissue architectures with a native microphysiological environments yield mechanistic understanding of developmental and reproductive impacts of drug/chemical exposures; (2) that novel in silico platforms with high-throughput screening (HTS) data, biologically-inspired computational models of

Computer Simulation of Developmental Processes and ...

EPA Pesticide Factsheets

Rationale: Recent progress in systems toxicology and synthetic biology have paved the way to new thinking about in vitro/in silico modeling of developmental processes and toxicities, both for embryological and reproductive impacts. Novel in vitro platforms such as 3D organotypic culture models, engineered microscale tissues and complex microphysiological systems (MPS), together with computational models and computer simulation of tissue dynamics, lend themselves to a integrated testing strategies for predictive toxicology. As these emergent methodologies continue to evolve, they must be integrally tied to maternal/fetal physiology and toxicity of the developing individual across early lifestage transitions, from fertilization to birth, through puberty and beyond. Scope: This symposium will focus on how the novel technology platforms can help now and in the future, with in vitro/in silico modeling of complex biological systems for developmental and reproductive toxicity issues, and translating systems models into integrative testing strategies. The symposium is based on three main organizing principles: (1) that novel in vitro platforms with human cells configured in nascent tissue architectures with a native microphysiological environments yield mechanistic understanding of developmental and reproductive impacts of drug/chemical exposures; (2) that novel in silico platforms with high-throughput screening (HTS) data, biologically-inspired computational models of

Prediction of in vivo developmental toxicity by combination of Hand1-Luc embryonic stem cell test and metabolic stability test with clarification of metabolically inapplicable candidates.

PubMed

Nagahori, Hirohisa; Suzuki, Noriyuki; Le Coz, Florian; Omori, Takashi; Saito, Koichi

2016-09-30

Hand1-Luc Embryonic Stem Cell Test (Hand1-Luc EST) is a promising alternative method for evaluation of developmental toxicity. However, the problems of predictivity have remained due to appropriateness of the solubility, metabolic system, and prediction model. Therefore, we assessed the usefulness of rat liver S9 metabolic stability test using LC-MS/MS to develop new prediction model. A total of 71 chemicals were analyzed by measuring cytotoxicity and differentiation toxicity, and highly reproducible (CV=20%) results were obtained. The first prediction model was developed by discriminant analysis performed on a full dataset using Hand1-Luc EST, and 66.2% of the chemicals were correctly classified by the cross-validated classification. A second model was developed with additional descriptors obtained from the metabolic stability test to calculate hepatic availability, and an accuracy of 83.3% was obtained with applicability domain of 50.7% (=36/71) after exclusion of 22 metabolically inapplicable candidates, which potentially have a metabolic activation property. A step-wise prediction scheme with combination of Hand1-Luc EST and metabolic stability test was therefore proposed. The current results provide a promising in vitro test method for accurately predicting in vivo developmental toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

40 CFR 799.9110 - TSCA acute oral toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... number. A system to assign animals to test groups and control groups randomly is required. (E) Housing... randomization in assigning animals to test and control groups. (3) Rationale for selection of species, if other... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9110 - TSCA acute oral toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... number. A system to assign animals to test groups and control groups randomly is required. (E) Housing... randomization in assigning animals to test and control groups. (3) Rationale for selection of species, if other... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9110 - TSCA acute oral toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... number. A system to assign animals to test groups and control groups randomly is required. (E) Housing... randomization in assigning animals to test and control groups. (3) Rationale for selection of species, if other... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9110 - TSCA acute oral toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... number. A system to assign animals to test groups and control groups randomly is required. (E) Housing... randomization in assigning animals to test and control groups. (3) Rationale for selection of species, if other... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9110 - TSCA acute oral toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... number. A system to assign animals to test groups and control groups randomly is required. (E) Housing... randomization in assigning animals to test and control groups. (3) Rationale for selection of species, if other... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

The application of the micronucleus test in Chinese hamster V79 cells to detect drug-induced photogenotoxicity.

PubMed

Kersten, B; Zhang, J; Brendler-Schwaab, S Y; Kasper, P; Müller, L

1999-09-15

Recent reports on the photochemical carcinogenicity and photochemical genotoxicity of fluoroquinolone antibacterials led to an increasing awareness for the need of a standard approach to test for photochemical genotoxicity. In this study the micronucleus test using V79 cells was adapted to photogenotoxicity testing. Results of using different UVA/UVB relationships enabled us to identify a suitable irradiation regimen for the activation of different kinds of photosensitizers. Using this regimen, 8-methoxypsoralen and the fluoroquinolones lomefloxacin, grepafloxacin and Bay Y 3118 were identified to cause micronuclei and toxicity upon photochemical activation. Among the phenothiazines tested, chlorpromazine and 2-chlorophenothiazine, were positive for both endpoints, whereas triflupromazine was only slightly photoclastogenic in the presence of strong phototoxicity. Among the other potential human photosensitizers tested (oxytetracycline, doxycycline, metronidazole, emodin, hypericin, griseofulvin), only hypericin was slightly photogenotoxic. Photochemical toxicity in the absence of photochemical genotoxicity was noted for doxycycline and emodin. With the assay system described, it is possible to determine photochemical toxicity and photochemical genotoxicity concomitantly with sufficient reliability.

Allium-test as a tool for toxicity testing of environmental radioactive-chemical mixtures

NASA Astrophysics Data System (ADS)

Oudalova, A. A.; Geras'kin, S. A.; Dikareva, N. S.; Pyatkova, S. V.

2017-01-01

Bioassay-based approaches have been propagated to assess toxicity of unknown mixtures of environmental contaminants, but it was rarely applied in cases of chemicals with radionuclides combinations. Two Allium-test studies were performed to assess environmental impact from potential sources of combined radioactive-chemical pollution. Study sites were located at nuclear waste storage facilities in European and in Far-Eastern parts of Russia. As environmental media under impact, waters from monitor wells and nearby water bodies were tested. Concentrations of some chemicals and radionuclides in the samples collected enhanced the permitted limits. Cytogenetic and cytotoxic effects were used as biological endpoints, namely, frequency and spectrum of chromosome aberrations and mitotic abnormalities in anatelophase cells as well as mitotic activity in Allium root tips. Sample points were revealed where waters have an enhanced mutagenic potential. The findings obtained could be used to optimize monitoring system and advance decision making on management and rehabilitation of industrial sites. The Allium-test could be recommended and applied as an effective tool for toxicity testing in case of combined contamination of environmental compartments with radionuclides and chemical compounds.

Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: example lists and criteria for their selection and use

PubMed Central

Aschner, Michael; Ceccatelli, Sandra; Daneshian, Mardas; Fritsche, Ellen; Hasiwa, Nina; Hartung, Thomas; Hogberg, Helena T.; Leist, Marcel; Li, Abby; Mundy, William R.; Padilla, Stephanie; Piersma, Aldert H.; Bal-Price, Anna; Seiler, Andrea; Westerink, Remco H.; Zimmer, Bastian; Lein, Pamela J.

2016-01-01

Summary There is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the modulation of fundamental neurodevelopmental processes (such as neuronal differentiation, precursor cell migration or neuronal network formation) by chemicals, the first generation of alternative DNT tests target these processes. The advantage of such types of assays is that they capture toxicants with multiple targets and modes-of-action. Moreover, the processes modelled by the assays can be linked to toxicity endophenotypes, i.e. alterations in neural connectivity that form the basis for neurofunctional deficits in man. The authors of this review convened in a workshop to define criteria for the selection of positive/negative controls, to prepare recommendations on their use, and to initiate the setup of a directory of reference chemicals. For initial technical optimization of tests, a set of >50 endpoint-specific control compounds was identified. For further test development, an additional “test” set of 33 chemicals considered to act directly as bona fide DNT toxicants is proposed, and each chemical is annotated to the extent it fulfills these criteria. A tabular compilation of the original literature used to select the test set chemicals provides information on statistical procedures, and toxic/non-toxic doses (both for pups and dams). Suggestions are provided on how to use the >100 compounds (including negative controls) compiled here to address specificity, adversity and use of alternative test systems. PMID:27452664

Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

PubMed

Segal, L; Penman, M G; Piriou, Y

2018-01-01

The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

The Development of Carriers and Adjuvants for use with Peptides to Induce Mucosal and Systemic Immunity against Biologic Toxins

DTIC Science & Technology

1991-06-30

not toxic in vitro and is toxic at low doses only in man and monkey . In order to test the SEB vaccines made, new ideas for a mouse model for SEB...Secretory immunity experiments using shigella LPS with protaosones to evaluate oral and intranasal immunization using antigens of known military importance

Body-on-a-chip systems for animal-free toxicity testing.

PubMed

Mahler, Gretchen J; Esch, Mandy B; Stokol, Tracy; Hickman, James J; Shuler, Michael L

2016-10-01

Body-on-a-chip systems replicate the size relationships of organs, blood distribution and blood flow, in accordance with human physiology. When operated with tissues derived from human cell sources, these systems are capable of simulating human metabolism, including the conversion of a prodrug to its effective metabolite, as well as its subsequent therapeutic actions and toxic side-effects. The system also permits the measurement of human tissue electrical and mechanical reactions, which provide a measure of functional response. Since these devices can be operated with human tissue samples or with in vitro tissues derived from induced pluripotent stem cells (iPS), they can play a significant role in determining the success of new pharmaceuticals, without resorting to the use of animals. By providing a platform for testing in the context of human metabolism, as opposed to animal models, the systems have the potential to eliminate the use of animals in preclinical trials. This article will review progress made and work achieved as a direct result of the 2015 Lush Science Prize in support of animal-free testing. 2016 FRAME.

Sediment quality triad assessment survey of the Galveston Bay, Texas system

USGS Publications Warehouse

Carr, R. Scott; Chapman, Duane C.; Howard, Cynthia L.; Biedenbach, James M.

1996-01-01

To characterize the quality of sediments at key sites in the Galveston Bay Estuary, sediment samples were collected concurrently for chemical and physical analyses, toxicity testing and an assessment of benthic community structure. Significant toxicity, as determined by the sea urchin (Arbacia punetulata) pore water embryological development assay, was observed at 12 of the 24 sites investigated in this study. No toxicity was observed at any of the sites with the amphipod (Grandidierella japonica) solid-phase test. There were a number of sites with elevated levels of trace metals and petroleum hydrocarbons. The chemistry, toxicity and benthic data were ranked by station and a scaled rank sum was calculated to facilitate comparisons among the stations. Five sites exhibited strong evidence of contaminant-induced degradation, while 15 stations showed no evidence of contaminant-induced degradation. At eight additional sites the sediment quality triad (SQT) data indicated that unmeasured chemicals or conditions were stressing the system. Contaminant impacts could be reduced or eliminated by alternative regulatory and management practices, including the restriction of produced water discharges into coastal estuaries and the use of dredge material disposal practices that minimize the reintroduction of sediment-associated contaminants to the bays.

An Environmental Sentinel Biomonitor System for Drinking Water Protection

DTIC Science & Technology

2008-12-01

threat chemicals. Potential interferences include chemicals commonly used for drinking water disinfection (chlorine and chloramine ), byproducts of...range. Of the potential interferences tested, the ECIS test was affected only by the disinfectants chlorine and chloramine ; chlorine is typically...Industrial and Potential Interfering Chemicals Used to Evaluate ESB System Toxicity Sensors TICs Potential Interferences Acrylonitrile Chloramine

Inhalation toxicology. I., Design of a small-animal test system, II. Determination of the relative toxic hazards of 75 aircraft cabin materials.

DOT National Transportation Integrated Search

1977-01-01

In an effort to further the cause of increased safety for those who ride in commercial aircraft, this paper presents a detailed description of the genesis of a small-scale, laboratory test system that utilizes small animals to evaluate the relative t...

Predicting the future: opportunities and challenges for the chemical industry to apply 21st-century toxicity testing.

PubMed

Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

2015-03-01

Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process.

Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

PubMed Central

2011-01-01

The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a “red list” pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish. PMID:21410251

The unicellular fungal tool RhoTox for risk assessments in groundwater systems.

PubMed

Lategan, Maria Josie; Klare, William; Kidd, Sarah; Hose, Grant C; Nevalainen, Helena

2016-10-01

The recent inclusion of yeasts in environmental monitoring recognizes their ecological significance and sensitivity to toxicants. Here we present a robust and simple two-step toxicity assay and demonstrate the sensitivity of an ubiquitous groundwater yeast, Rhodotorula minuta, to a range of metals and metalloids. The test species was sensitive to copper with a 24h EC50 of 35µg Cu/L, followed in order of decreasing sensitivity by zinc, chromium (VI) and arsenic (EC50 4.40mg As (III)/L). The strain demonstrated an unexpected tolerance to chromium (VI), having an EC50 value (3.45mg Cr (VI)/L) similar to that of arsenic. The inclusion of a unicellular, microbial test-species into the suite of existing multicellular test species for toxicity evaluation is a key step towards strengthening the assessment of risk for groundwater ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Aquatic toxicity information retrieval data base (AQUIRE for non-vms) (1600 bpi). Data file

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

NONE

The purpose of AQUIRE is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. During 1992 and early 1993, nine data updates were made to the AQUIRE system. AQUIRE now contains 109,338 individual aquatic toxicity test results for 5,159 chemicals, 2,429 organisms, and over 160 endpoints reviewed from 7,517 publications. New features include a data selection option that permits searches that are restricted to data added or modified through any of the eight most recent updates, and a report generation (Full Record Detail) that displays the entire AQUIRE record for each testmore » identified in a search. Selection of the Full Record Detail feature allows the user to peruse all AQUIRE fields for a given test, including the information stored in the remarks section, while the standard AQUIRE output format presents selected data fields in a concise table. The standard report remains an available option for rapid viewing of system output.« less

Aquatic toxicity information retrieval data base (AQUIRE for non-vms) (6250 bpi). Data file

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

NONE

The purpose of AQUIRE is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. During 1992 and early 1993, nine data updates were made to the AQUIRE system. AQUIRE now contains 109,338 individual aquatic toxicity test results for 5,159 chemicals, 2,429 organisms, and over 160 endpoints reviewed from 7,517 publications. New features include a data selection option that permits searches that are restricted to data added or modified through any of the eight most recent updates, and a report generation (Full Record Detail) that displays the entire AQUIRE record for each testmore » identified in a search. Selection of the Full Record Detail feature allows the user to peruse all AQUIRE fields for a given test, including the information stored in the remarks section, while the standard AQUIRE output format presents selected data fields in a concise table. The standard report remains an available option for rapid viewing of system output.« less

Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

PubMed

Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

2010-05-15

The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Evaluation of ability of reference toxicity tests to identify stress in laboratory populations of the amphipod Hyalella azteca

USGS Publications Warehouse

McNulty, E.W.; Dwyer, F.J.; Ellersieck, Mark R.; Greer, E.I.; Ingersoll, C.G.; Rabeni, C.F.

1999-01-01

Standard methods for conducting toxicity tests imply that the condition of test organisms can be established using reference toxicity tests. However, only a limited number of studies have evaluated whether reference toxicity tests can actually be used to determine if organisms are in good condition at the start of a test. We evaluated the ability of reference toxicants to identify stress associated with starvation in laboratory populations of the amphipod Hyalella azteca using acute toxicity tests and four reference toxicants: KCl, CdCl2, sodium pentachlorophenate (NaPCP), and carbaryl. Stress associated with severe starvation was observed with exposure of amphipods to carbaryl or NaPCP but not with exposure to KCl or CdCl2 (i.e., lower LC50 with severe starvation). Although the LC50s for NaPCP and carbaryl were statistically different between starved and fed amphipods, this difference may not be biologically significant given the variability expected in acute lethality tests. Stress associated with sieving, heat shock, or cold shock of amphipods before the start of a test was not evident with exposure to carbaryl or KCl as reference toxicants. The chemicals evaluated in this study provided minimal information about the condition of the organisms used to start a toxicity test. Laboratories should periodically perform reference toxicity tests to assess the sensitivity of life stages or strains of test organisms. However, use of other test acceptability criteria required in standard methods such as minimum survival, growth, or reproduction of organisms in the control treatment at the end of a test, provides more useful information about the condition of organisms used to start a test compared to data generated from reference toxicity tests.

40 CFR 797.1300 - Daphnid acute toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... continuous exposure over a specified period of time. In this guideline, the effect measured is immobilization... at a point in time, or passing through the test chamber during a specific interval. (7) Static system..., daphnids which have been cultured and acclimated in accordance with the test design are randomly placed...

40 CFR 797.1300 - Daphnid acute toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... continuous exposure over a specified period of time. In this guideline, the effect measured is immobilization... at a point in time, or passing through the test chamber during a specific interval. (7) Static system..., daphnids which have been cultured and acclimated in accordance with the test design are randomly placed...

40 CFR 797.1300 - Daphnid acute toxicity test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... continuous exposure over a specified period of time. In this guideline, the effect measured is immobilization... at a point in time, or passing through the test chamber during a specific interval. (7) Static system..., daphnids which have been cultured and acclimated in accordance with the test design are randomly placed...

40 CFR 797.1300 - Daphnid acute toxicity test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... continuous exposure over a specified period of time. In this guideline, the effect measured is immobilization... at a point in time, or passing through the test chamber during a specific interval. (7) Static system..., daphnids which have been cultured and acclimated in accordance with the test design are randomly placed...

40 CFR 797.1300 - Daphnid acute toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... continuous exposure over a specified period of time. In this guideline, the effect measured is immobilization... at a point in time, or passing through the test chamber during a specific interval. (7) Static system..., daphnids which have been cultured and acclimated in accordance with the test design are randomly placed...

40 CFR 160.43 - Test system care facilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (1) In tests with plants or aquatic animals, proper separation of species can be accomplished within..., aquarium, or housing unit. (2) Aquatic toxicity tests for individual projects shall be isolated to the... protocol. (h) For plants, an adequate supply of soil of the appropriate composition, as specified in the...

Principles and Procedures for Evaluating the Toxicity of Household Substances. Revised.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC. Assembly of Life Sciences.

This report was prepared for use by the professional toxicologist. It contains chapters on ingestion exposure, dermal and dye toxicity tests, inhalation exposure, chronic toxicity and carcinogenicity tests, mutagenicity tests, reproduction and teratogenicity tests, and behavioral toxicity tests. In addition, regulations under the Federal Hazardous…

An ecotoxicological study on tin- and bismuth-catalysed PDMS based coatings containing a surface-active polymer.

PubMed

Pretti, Carlo; Oliva, Matteo; Mennillo, Elvira; Barbaglia, Martina; Funel, Marco; Reddy Yasani, Bhaskar; Martinelli, Elisa; Galli, Giancarlo

2013-12-01

Novel films were prepared by condensation curing reaction of a poly(dimethyl siloxane) (PDMS) matrix with bismuth neodecanoate and dibutyltin diacetate catalysts. An ecotoxicological study was performed on the leachates of the coatings using the bacterium Vibrio fischeri, the unicellular alga Dunaliella tertiolecta, the crustacean Artemia salina and the fish Sparus aurata (larvae) as testing organisms. A copper-based self-polishing commercial paint was also tested as reference. The results showed that the tin-catalysed coatings and the copper paint were highly toxic against at least two of the four test organisms, whereas bismuth-catalysed coatings did not show any toxic effect. Moreover, the same biological assessment was also carried out on PDMS coatings containing a surface-active fluorinated polymer. The toxicity of the entire polymeric system resulted only from the tin catalyst used for the condensation curing reaction, as the bismuth catalysed coatings incorporating the surface-active polymer remained atoxic toward all the tested organisms. © 2013 Elsevier Inc. All rights reserved.

Remote sensing and field test capabilities at U.S. Army Dugway Proving Ground

NASA Astrophysics Data System (ADS)

Pearson, James T.; Herron, Joshua P.; Marshall, Martin S.

2011-11-01

U.S. Army Dugway Proving Ground (DPG) is a Major Range and Test Facility Base (MRTFB) with the mission of testing chemical and biological defense systems and materials. DPG facilities include state-of-the-art laboratories, extensive test grids, controlled environment calibration facilities, and a variety of referee instruments for required test measurements. Among these referee instruments, DPG has built up a significant remote sensing capability for both chemical and biological detection. Technologies employed for remote sensing include FTIR spectroscopy, UV spectroscopy, Raman-shifted eye-safe lidar, and other elastic backscatter lidar systems. These systems provide referee data for bio-simulants, chemical simulants, toxic industrial chemicals (TICs), and toxic industrial materials (TIMs). In order to realize a successful large scale open-air test, each type of system requires calibration and characterization. DPG has developed specific calibration facilities to meet this need. These facilities are the Joint Ambient Breeze Tunnel (JABT), and the Active Standoff Chamber (ASC). The JABT and ASC are open ended controlled environment tunnels. Each includes validation instrumentation to characterize simulants that are disseminated. Standoff systems are positioned at typical field test distances to measure characterized simulants within the tunnel. Data from different types of systems can be easily correlated using this method, making later open air test results more meaningful. DPG has a variety of large scale test grids available for field tests. After and during testing, data from the various referee instruments is provided in a visual format to more easily draw conclusions on the results. This presentation provides an overview of DPG's standoff testing facilities and capabilities, as well as example data from different test scenarios.

Remote sensing and field test capabilities at U.S. Army Dugway Proving Ground

NASA Astrophysics Data System (ADS)

Pearson, James T.; Herron, Joshua P.; Marshall, Martin S.

2012-05-01

U.S. Army Dugway Proving Ground (DPG) is a Major Range and Test Facility Base (MRTFB) with the mission of testing chemical and biological defense systems and materials. DPG facilities include state-of-the-art laboratories, extensive test grids, controlled environment calibration facilities, and a variety of referee instruments for required test measurements. Among these referee instruments, DPG has built up a significant remote sensing capability for both chemical and biological detection. Technologies employed for remote sensing include FTIR spectroscopy, UV spectroscopy, Raman-shifted eye-safe lidar, and other elastic backscatter lidar systems. These systems provide referee data for bio-simulants, chemical simulants, toxic industrial chemicals (TICs), and toxic industrial materials (TIMs). In order to realize a successful large scale open-air test, each type of system requires calibration and characterization. DPG has developed specific calibration facilities to meet this need. These facilities are the Joint Ambient Breeze Tunnel (JABT), and the Active Standoff Chamber (ASC). The JABT and ASC are open ended controlled environment tunnels. Each includes validation instrumentation to characterize simulants that are disseminated. Standoff systems are positioned at typical field test distances to measure characterized simulants within the tunnel. Data from different types of systems can be easily correlated using this method, making later open air test results more meaningful. DPG has a variety of large scale test grids available for field tests. After and during testing, data from the various referee instruments is provided in a visual format to more easily draw conclusions on the results. This presentation provides an overview of DPG's standoff testing facilities and capabilities, as well as example data from different test scenarios.

Immunotoxicant screening and prioritization in the 21st century

EPA Science Inventory

Current immunotoxicity testing guidance for drugs, high production volume chemicals and pesticides specifies the use of animal models that measure immune function or evaluation of general indicators of immune system health generated in routine toxicity testing. The assays are ...

Immunotoxicant screening and prioritization in the 21st century*

EPA Science Inventory

Current immunotoxicity testing guidance for drugs, high production volume chemicals and pesticides specifies the use of animal models that measure immune function or evaluation of general indicators of immune system health generated in routine toxicity testing. The assays are r...

Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina) Hospital Wastewater

PubMed Central

Juárez, Ángela Beatriz; Dragani, Valeria; Saenz, Magalí Elizabeth; Moretton, Juan

2014-01-01

Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was performed using the green algae Pseudokirchneriella subcapitata and the Allium cepa test, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8). The A. cepa test showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA) and micronucleus (MN) showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic to A. cepa but toxic to the algae (%I = 41%), showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system. PMID:25214834

Residual organic matter and microbial respiration in bottom ash: Effects on metal leaching and eco-toxicity.

PubMed

Ilyas, A; Persson, K M; Persson, M

2015-09-01

A common assumption regarding the residual organic matter, in bottom ash, is that it does not represent a significant pool of organic carbon and, beyond metal-ion complexation process, it is of little consequence to evolution of ash/leachate chemistry. This article evaluates the effect of residual organic matter and associated microbial respiratory processes on leaching of toxic metals (i.e. arsenic, copper, chromium, molybdenum, nickel, lead, antimony and zinc), eco-toxicity of ash leachates. Microbial respiration was quantified with help of a respirometric test equipment OXITOP control system. The effect of microbial respiration on metal/residual organic matter leaching and eco-toxicity was quantified with the help of batch leaching tests and an eco-toxicity assay - Daphnia magna. In general, the microbial respiration process decreased the leachate pH and eco-toxicity, indicating modification of bioavailability of metal species. Furthermore, the leaching of critical metals, such as copper and chromium, decreased after the respiration in both ash types (fresh and weathered). It was concluded that microbial respiration, if harnessed properly, could enhance the stability of fresh bottom ash and may promote its reuse. © The Author(s) 2015.

Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

PubMed

Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

2015-04-01

Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

Effect of hardness on acute toxicity of metal mixtures using Daphnia magna: prediction of acid mine drainage toxicity.

PubMed

Yim, Jin Hee; Kim, Kyoung W; Kim, Sang D

2006-11-02

In this study, the effect of hardness on the combined outcome of metal mixtures was investigated using Daphnia magna. The toxic unit (TU) was calculated using modified LC(50) values based on the hardness (i.e., LC(50-soft) and LC(50-hard)). From a bioassay test, the degree of sensitivity to hardness on the toxicity changes was in the order: Cd

Towards sensible toxicity testing for nanomaterials: proposal for the specification of test design

NASA Astrophysics Data System (ADS)

Potthoff, Annegret; Weil, Mirco; Meißner, Tobias; Kühnel, Dana

2015-12-01

During the last decade, nanomaterials (NM) were extensively tested for potential harmful effects towards humans and environmental organisms. However, a sound hazard assessment was so far hampered by uncertainties and a low comparability of test results. The reason for the low comparability is a high variation in the (1) type of NM tested with regard to raw material, size and shape and (2) procedures before and during the toxicity testing. This calls for tailored, nanomaterial-specific protocols. Here, a structured approach is proposed, intended to lead to test protocols not only tailored to specific types of nanomaterials, but also to respective test system for toxicity testing. There are existing standards on single procedures involving nanomaterials, however, not all relevant procedures are covered by standards. Hence, our approach offers a detailed way of weighting several plausible alternatives for e.g. sample preparation, in order to decide on the procedure most meaningful for a specific nanomaterial and toxicity test. A framework of several decision trees (DT) and flow charts to support testing of NM is proposed as a basis for further refinement and in-depth elaboration. DT and flow charts were drafted for (1) general procedure—physicochemical characterisation, (2) choice of test media, (3) decision on test scenario and application of NM to liquid media, (4) application of NM to the gas phase, (5) application of NM to soil and sediments, (6) dose metrics, (S1) definition of a nanomaterial, and (S2) dissolution. The applicability of the proposed approach was surveyed by using experimental data retrieved from studies on nanoscale CuO. This survey demonstrated the DT and flow charts to be a convenient tool to systematically decide upon test procedures and processes, and hence pose an important step towards harmonisation of NM testing.

Towards sensible toxicity testing for nanomaterials: proposal for the specification of test design.

PubMed

Potthoff, Annegret; Weil, Mirco; Meißner, Tobias; Kühnel, Dana

2015-12-01

During the last decade, nanomaterials (NM) were extensively tested for potential harmful effects towards humans and environmental organisms. However, a sound hazard assessment was so far hampered by uncertainties and a low comparability of test results. The reason for the low comparability is a high variation in the (1) type of NM tested with regard to raw material, size and shape and (2) procedures before and during the toxicity testing. This calls for tailored, nanomaterial-specific protocols. Here, a structured approach is proposed, intended to lead to test protocols not only tailored to specific types of nanomaterials, but also to respective test system for toxicity testing. There are existing standards on single procedures involving nanomaterials, however, not all relevant procedures are covered by standards. Hence, our approach offers a detailed way of weighting several plausible alternatives for e.g. sample preparation, in order to decide on the procedure most meaningful for a specific nanomaterial and toxicity test. A framework of several decision trees (DT) and flow charts to support testing of NM is proposed as a basis for further refinement and in-depth elaboration. DT and flow charts were drafted for (1) general procedure-physicochemical characterisation, (2) choice of test media, (3) decision on test scenario and application of NM to liquid media, (4) application of NM to the gas phase, (5) application of NM to soil and sediments, (6) dose metrics, (S1) definition of a nanomaterial, and (S2) dissolution. The applicability of the proposed approach was surveyed by using experimental data retrieved from studies on nanoscale CuO. This survey demonstrated the DT and flow charts to be a convenient tool to systematically decide upon test procedures and processes, and hence pose an important step towards harmonisation of NM testing.

Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats.

PubMed

Abdel-Bar, Hend Mohamed; Osman, Rihab; Abdel-Reheem, Amal Youssef; Mortada, Nahed; Awad, Gehanne A S

2016-02-08

This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.

An F1-extended one-generation reproductive toxicity study in Crl:CD(SD) rats with 2,4-dichlorophenoxyacetic acid.

PubMed

Marty, Mary Sue; Neal, Barbara H; Zablotny, Carol L; Yano, Barry L; Andrus, Amanda K; Woolhiser, Michael R; Boverhof, Darrell R; Saghir, Shakil A; Perala, Adam W; Passage, Julie K; Lawson, Marie A; Bus, James S; Lamb, James C; Hammond, Larry

2013-12-01

2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10-12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The "No Observed Adverse Effect Level" for systemic toxicity was 300 ppm in both males (16.6 mg/kg/day) and females (20.6 mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies.

An F1-Extended One-Generation Reproductive Toxicity Study in Crl:CD(SD) Rats With 2,4-Dichlorophenoxyacetic Acid

PubMed Central

Marty, Mary Sue

2013-01-01

2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10–12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The “No Observed Adverse Effect Level” for systemic toxicity was 300 ppm in both males (16.6mg/kg/day) and females (20.6mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies. PMID:24072463

Development of Low-Toxicity Wastewater Stabilization for Spacecraft Water Recovery Systems

NASA Technical Reports Server (NTRS)

Mitchell, Julie L.; Adam, Niklas; Pickering, Karen D.; Alvarez, Giraldo N.

2015-01-01

Wastewater stabilization was an essential component of the spacecraft water cycle. The purpose of stabilizing wastewater was two-fold. First, stabilization prevents the breakdown of urea into ammonia, a toxic gas at high concentrations. Second, it prevents the growth of microorganisms, thereby mitigating hardware and water quality issues due to due biofilm and planktonic growth. Current stabilization techniques involve oxidizers and strong acids (pH=2) such as chromic and sulfuric acid, which are highly toxic and pose a risk to crew health. The purpose of this effort was to explore less toxic stabilization techniques, such as food-grade and commercial care preservatives. Additionally, certain preservatives were tested in the presence of a low-toxicity organic acid. Triplicate 300-milliliter volumes of urine were dosed with a predetermined quantity of stabilizer and stored for two weeks. During that time, pH, total organic carbon (TOC), ammonia, and turbidity were monitored. Those preservatives that showed the lowest visible microbial growth and stable pH were further tested in a six-month stability study. The results of the six-month study are also included in this paper.

Development of Low-Toxicity Urine Stabilization for Spacecraft Water Recovery Systems

NASA Technical Reports Server (NTRS)

Adam, Niklas; Mitchell, Julie L.; Pickering, Karen D.

2012-01-01

Wastewater stabilization is an essential component of the spacecraft water cycle. The purpose of stabilizing wastewater is two-fold. First, stabilization prevents the breakdown of urea into ammonia, a toxic gas at high concentrations. Second, it prevents the growth of microorganisms, thereby mitigating hardware and water quality issues due to due biofilm and planktonic growth. Current stabilization techniques involve oxidizers and strong acids (pH=2) such as chromic and sulfuric acid, which are highly toxic and pose a risk to crew health. The purpose of this effort is to explore less toxic stabilization techniques, such as food-grade and commercial care preservatives. Additionally, certain preservatives were tested in the presence of a low-toxicity organic acid. Triplicate 300-mL volumes of urine were dosed with a predetermined quantity of stabilizer and stored for two weeks. During that time, pH, total organic carbon (TOC), ammonia, and turbidity were monitored. Those preservatives that showed the lowest visible microbial growth and stable pH were further tested in a six-month stability study. The results of the six-month study are also included in this paper.

Development of Low-Toxicity Wastewater Stabilization for Spacecraft Water Recovery Systems

NASA Technical Reports Server (NTRS)

Adam, Niklas; Mitchell, Julie; Pickering, Karen; Carrier, Chris; Vega, Letty; Muirhead, Dean

2014-01-01

Wastewater stabilization was an essential component of the spacecraft water cycle. The purpose of stabilizing wastewater was two-fold. First, stabilization prevents the breakdown of urea into ammonia, a toxic gas at high concentrations. Second, it prevents the growth of microorganisms, thereby mitigating hardware and water quality issues due to due biofilm and planktonic growth. Current stabilization techniques involve oxidizers and strong acids (pH=2) such as chromic and sulfuric acid, which are highly toxic and pose a risk to crew health. The purpose of this effort was to explore less toxic stabilization techniques, such as food-grade and commercial care preservatives. Additionally, certain preservatives were tested in the presence of a low-toxicity organic acid. Triplicate 300-mL volumes of urine were dosed with a predetermined quantity of stabilizer and stored for two weeks. During that time, pH, total organic carbon (TOC), ammonia, and turbidity were monitored. Those preservatives that showed the lowest visible microbial growth and stable pH were further tested in a six-month stability study. The results of the six-month study are also included in this paper.

Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach.

PubMed

Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

2016-07-15

Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials.

Hydra as a model organism to decipher the toxic effects of copper oxide nanorod: Eco-toxicogenomics approach

PubMed Central

Murugadas, Anbazhagan; Zeeshan, Mohammed; Thamaraiselvi, Kaliannan; Ghaskadbi, Surendra; Akbarsha, Mohammad Abdulkader

2016-01-01

Nanotechnology has emerged as a powerful field of applied research. However, the potential toxicity of nano-materials is a cause of concern. A thorough toxicological investigation is required before a nanomaterial is evaluated for application of any kind. In this context, there is concerted effort to find appropriate test systems to assess the toxicity of nanomaterials. Toxicity of a nanomaterial greatly depends on its physicochemical properties and the biological system with which it interacts. The present research was carried out with a view to generate data on eco-toxicological impacts of copper oxide nanorod (CuO NR) in Hydra magnipapillata 105 at organismal, cellular and molecular levels. Exposure of hydra to CuO NR resulted in severe morphological alterations in a concentration- as well as duration-dependent manner. Impairment of feeding, population growth, and regeneration was also observed. In vivo and in vitro analyses revealed induction of oxidative stress, genotoxicity, and molecular machinery of apoptotic cell death, accompanied by disruption of cell cycle progression. Taken together, CuO nanorod is potentially toxic to the biological systems. Also, hydra offers potential to be used as a convenient model organism for aquatic ecotoxicological risk assessment of nanomaterials. PMID:27417574

Optimization of Hyalella azteca IQ Toxicity Test{trademark} for prediction of 28-day sediment toxicity tests

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

Novotny, A.N.; Ezzard, C.L.; Douglas, W.S.

1995-12-31

The IQ Toxicity Test, which is a rapid screening toxicity test consisting of the observation of in-vivo inhibition of an enzymatic process using a fluorescent substrate, has proven successful for the determination of 24 and 48-hour EC50`s of D. magna, C. dubia, D. pulex and M. bahia. The application of this concept to utilize the freshwater amphipod Hyalella azteca may be an excellent way in which to reduce the standard 28-day chronic sediment toxicity test to possibly one hour`s time. This study incorporates an additive experimental design to explore the effects of and interactions between five specific variables: size ofmore » the amphipod, exposure time to the toxicant, concentration of substrate, exposure time to the substrate, and length of time starved prior to testing. The results of the IQ toxicity test were compared to those of a 28-day chronic sediment toxicity test. Preliminary data indicate that there is an optimal combination of these variables which results in a concise, reproducible toxicity test for use with Hyalella azteca, and would potentially be applicable to other freshwater amphipods in the future.« less

A Testing Service for Industry

NASA Technical Reports Server (NTRS)

1994-01-01

A small isolated NASA facility provides assistance to industry in the design, testing, and operation of oxygen systems. White Sands Test Facility (WSTF) was originally established to test rocket propulsion systems for the Apollo program. The facility's role was later expanded into testing characterization, flammability and toxicity characteristics of materials. Its materials and components test methods were adopted by the American society for Testing and Materials. When research and testing results became known, industry requested assistance, and in 1980, NASA authorized WSTF to open its facility to private firms, a valuable service, as oxygen systems testing is often too expensive and too hazardous for many companies. Today, some of the best known American industries utilize White Sands testing capabilities.

A fluorescence-based bioassay for aquatic macrophytes and its suitability for effect analysis of non-photosystem II inhibitors.

PubMed

Küster, Anette; Pohl, Korinna; Altenburger, Rolf

2007-09-01

BACKGROUND, GOALS AND SCOPE: During the last years the miniaturization of toxicity test systems for rapid and parallel measurements of large quantities of samples has often been discussed. For unicellular algae as well as for aquatic macrophytes, fluorescence-based miniaturized test systems have been introduced to analyze photosystem II (PSII) inhibitors. Nevertheless, high-throughput screening should also guarantee the effect detection of a broad range of toxicants in order to ensure routinely applicable, high-throughput measuring device experiments which can cover a broad range of toxicants and modes of action others than PSII inhibition. Thus, the aim of this study was to establish a fast and reproducible measuring system for non-PSII inhibitors for aquatic macrophyte species to overcome major limitations for use. A newly developed imaging pulse-amplitude-modulated chlorophyll fluorometer (I-PAM) was applied as an effect detector in short-term bioassays with the aquatic macrophyte species Lemna minor. This multiwell-plate based measuring device enabled the incubation and measurement of up to 24 samples in parallel. The chemicals paraquat-dichloride, alizarine and triclosan were chosen as representatives for the toxicant groups of non-PSII herbicides, polycyclic aromatic hydrocarbons (PAHs) and pharmaceuticals and personal care products (PPCPs), which are often detected in the aquatic environment. The I-PAM was used (i) to establish and validate the sensitivity of the test system to the three non-PSII inhibitors, (ii) to compare the test systems with standardized and established biotests for aquatic macrophytes, and (iii) to define necessary time scales in aquatic macrophyte testing. For validation of the fluorescence-based assay, the standard growth test with L. minor (ISO/DIS 20079) was performed in parallel for each chemical. The results revealed that fluorescence-based measurements with the I-PAM allow rapid and parallel analysis of large amounts of aquatic macrophyte samples. The I-PAM enabled the recording of concentration-effect-curves with L. minor samples on a 24-well plate with single measurements. Fluorescence-based concentration-effect-curves could be detected for all three chemicals after only 1 h of incubation. After 4-5 h incubation time, the maximum inhibition of fluorescence showed an 80-100% effect for the chemicals tested. The EC50 after 24 h incubation were estimated to be 0.06 mg/L, 0.84 mg/L and 1.69 mg/L for paraquat-dichloride, alizarine and triclosan, respectively. The results obtained with the I-PAM after 24 h for the herbicide paraquat-dichloride and the polycyclic aromatic hydrocarbon alizarine were in good accordance with median effective concentrations (EC50s) obtained by the standardized growth test for L. minor after 7 d incubation (0.09 mg/L and 0.79 mg/L for paraquat-dichloride and alizarine, respectively). Those results were in accordance with literature findings for the two chemicals. In contrast, fluorescence-based EC50 of the antimicrobial agent triclosan proved to be two orders of magnitude greater when compared to the standard growth test with 7 d incubation time (0.026 mg/L) as well as with literature findings. Typically, aquatic macrophyte testing is very time consuming and relies on laborious experimental set-ups. The I-PAM measuring device enabled fast effect screening for the three chemicals tested. While established test systems for aquatic macrophytes need incubation times of > or = 7 d, the I-PAM can detect inhibitory effects much earlier (24 h), even if inhibition of chemicals is not specifically associated with PSII. Thus, the fluorescence-based bioassay with the I-PAM offers a promising approach for the miniaturization and high-throughput testing of chemicals with aquatic macrophytes. For the chemical triclosan, however, the short-term effect prediction with the I-PAM has been shown to be less sensitive than with long-term bioassays, which might be due to physicochemical substance properties such as lipophilicity. The results of this study show that the I-PAM represents a promising tool for decreasing the incubation times of aquatic macrophyte toxicity testing to about 24 h as a supplement to existing test batteries. The applicability of this I-PAM bioassay on emergent and submerged aquatic macrophyte species should be investigated in further studies. Regarding considerations that physicochemical properties of the tested substances might play an important role in microplate bioassays, the I-PAM bioassay should either be accompanied by evaluating physicochemical properties modeled from structural information prior to an experimental investigation, or by intensified chemical analyses to identify and determine nominal concentrations of the toxicants tested. The chemicals paraquat-dichloride, alizarine and triclosan were chosen as representatives for the toxicant groups of non-PSII herbicides, PAHs and PPCPs which are often detected in the aquatic environment. Nevertheless, in order to ensure a routinely applicable measuring device, experiments with a broader range of toxicants and samples of surface and/or waste waters are necessary.

Genetic toxicity studies of organic chemicals found as contaminants in spacecraft cabin atmospheres

NASA Technical Reports Server (NTRS)

Torres, Joseph, Jr.

1987-01-01

Astronauts can be exposed during spaceflight to organic chemical contaminants in the spacecraft cabin atmosphere. Toxic exposures may cause lesions in the cellular DNA which are subsequently expressed as sister-chromatid exchanges (SCE). Analysis of SCE is a sensitive short term assay techinque to detect and quantitate exposures to DNA damaging (mutagenic) substances. The increase in SCE incidence over baseline (control) levels is generally proportional to the concentration of the mutagen and to the duration of exposure. The BHK-21 baby hamster kidney cell line was the in vitro test system used. Test organics were added to the culture media for 18 hrs, in concentrations ranging from one to 20 ppm. Acetaldehyde and carbon disulfide were chosen for this study since they have occurred as atmospheric contaminants in many of the STS flights, and have been reported to have toxic and mutagenic effects in various test systems. Glutaraldehyde was chosen because few data are available on the mutagenicity of this common fixative, which is carried on STS flights for use in biological experiments. Acetaldehyde was a very strong inducer of SCE at concentrations of 2 ppm and above. Glutaraldehyde and carbon disulfide failed to induce SCE.

In vitro cytogenetic studies of organic chemicals found as contaminants in spacecraft cabin atmospheres

NASA Technical Reports Server (NTRS)

Torres, J.

1986-01-01

Astronauts can be exposed during spaceflight to organic chemical contaminants in the spacecraft cabin atmosphere. Toxic exposures may cause lesions in the cellular DNA which are subsequently expressed as sister-chromatid exchanges (SCE). Analysis of SCE is a sensitive short-term assay technique to detect and quantitate exposures to DNA-damaging (mutagenic) substances. The increase in SCE incidence over baseline (control) levels is generally proportional to the concentration of the mutagen and to the duration of exposure. Dichloromethane (methylene chloride) was chosen for this study since it occurred as an atmospheric contaminant in ten of the first 12 STS flights, and has been reported to have toxic and mutagenic effects in various test systems. Glutaraldehyde was chosen because relatively few data are available on the toxicity or mutagenicity of this common biological fixative, which is carried on STS flights for use in biological experiments. The BHK-21 baby hamster kidney cell line was the in vitro test system used in this study. Neither dichloromethane (10 ppm to 500 ppm) nor glutaraldehyde (1 ppm to 10 ppm) increased SCE levels following 20-hour exposure of BHK-21 cells to the test chemicals.

Metabolic response of environmentally isolated microorganisms to industrial effluents: Use of a newly described cell culture assay

NASA Technical Reports Server (NTRS)

Ferebee, Robert N.

1992-01-01

An environmental application using a microtiter culture assay to measure the metabolic sensitivity of microorganisms to petrochemical effluents will be tested. The Biomedical Operations and Research Branch at NASA JSC has recently developed a rapid and nondestructive method to measure cell growth and metabolism. Using a colorimetric procedure the uniquely modified assay allows the metabolic kinetics of prokaryotic and eukaryotic cells to be measured. Use of such an assay if adapted for the routine monitoring of waste products, process effluents, and environmentally hazardous substances may prove to be invaluable to the industrial community. The microtiter method as described will be tested using microorganisms isolated from the Galveston Bay aquatic habitat. The microbial isolates will be identified prior to testing using the automated systems available at JSC. Sodium dodecyl sulfate (SDS), cadmium, and lead will provide control toxic chemicals. The toxicity of industrial effluent from two industrial sites will be tested. An effort will be made to test the efficacy of this assay for measuring toxicity in a mixed culture community.

SEDIMENT TOXICITY ASSESSMENT: COMPARISON OF STANDARD AND NEW TESTING DESIGNS

EPA Science Inventory

Standard methods of sediment toxicity testing are fairly well accepted; however, as with all else, evolution of these methods is inevitable. We compared a standard ASTM 10-day amphipod toxicity testing method with smaller, 48- and 96-h test methods using very toxic and reference ...

Toxicity of polymeric nanoparticles in vivo and in vitro

NASA Astrophysics Data System (ADS)

Voigt, Nadine; Henrich-Noack, Petra; Kockentiedt, Sarah; Hintz, Werner; Tomas, Jürgen; Sabel, Bernhard A.

2014-06-01

Polybutylcyanoacrylate nanoparticles (PBCA NPs) are candidates for a drug delivery system, which can cross the blood-brain barrier (BBB). Because little is known about their toxicity, we exposed cells to PBCA NPs in vitro and in vivo and monitored their life and death assays. PBCA NPs were fabricated with different surfactants according to the mini-emulsion technique. Viabilities of HeLa and HEK293 cells after NP incubation were quantified by analysing cellular metabolic activity (MTT-test). We then repetitively injected i.v. rhodamine-labelled PBCA NP variations into rats and monitored the survival and morphology of retrogradely labelled neurons by in vivo confocal neuroimaging (ICON) for five weeks. To test for carrier-efficacy and safety, PBCA NPs loaded with Kyotorphin were injected in rats, and a hot plate test was used to quantify analgesic effects. In vitro, we found dose-dependent cell death which was, however, only detectable at very high doses and mainly seen in the cultures incubated with NPs fabricated with the tensids SDS and Tween. However, the in vivo experiments did not show any NP-induced neuronal death, even with particles which were toxic at high dose in vitro, i.e. NPs with Tween and SDS. The increased pain threshold at the hot plate test demonstrated that PBCA NPs are able to cross the BBB and thus comprise a useful tool for drug delivery into the central nervous system (CNS). Our findings showing that different nanoparticle formulations are non-toxic have important implications for the value of NP engineering approaches in medicine.

40 CFR 158.2230 - Toxicology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... systems (collectively referred to as HVAC&R). Instead, two 90-day toxicity tests, one by the dermal route... causes treatment-related neurological effects in developing animals, following pre- or post-natal... individual test, including specific conditions, qualifications, or exceptions are listed in paragraph (h) of...

40 CFR 792.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED... following terms shall have the meanings specified: Batch means a specific quantity or lot of a test, control... substance is combined for administration to a test system. Control substance means any chemical substance or...

40 CFR 792.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED... following terms shall have the meanings specified: Batch means a specific quantity or lot of a test, control... substance is combined for administration to a test system. Control substance means any chemical substance or...

40 CFR 792.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED... following terms shall have the meanings specified: Batch means a specific quantity or lot of a test, control... substance is combined for administration to a test system. Control substance means any chemical substance or...

40 CFR 792.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED... following terms shall have the meanings specified: Batch means a specific quantity or lot of a test, control... substance is combined for administration to a test system. Control substance means any chemical substance or...

40 CFR 792.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED... following terms shall have the meanings specified: Batch means a specific quantity or lot of a test, control... substance is combined for administration to a test system. Control substance means any chemical substance or...

Behavioral toxicity of selected radioprotectors

NASA Astrophysics Data System (ADS)

Landauer, M. R.; Davis, H. D.; Kumar, K. S.; Weiss, J. F.

1992-10-01

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

16 CFR 1500.40 - Method of testing toxic substances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... bleeding. (c) Procedures for testing. The sleeve is slipped onto the animal which is then placed in a... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Method of testing toxic substances. 1500.40... testing toxic substances. The method of testing the toxic substances referred to in § 1500.3(c) (1)(ii)(C...

16 CFR 1500.40 - Method of testing toxic substances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... bleeding. (c) Procedures for testing. The sleeve is slipped onto the animal which is then placed in a... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Method of testing toxic substances. 1500.40... testing toxic substances. The method of testing the toxic substances referred to in § 1500.3(c) (1)(ii)(C...

16 CFR 1500.40 - Method of testing toxic substances.

Code of Federal Regulations, 2011 CFR

2011-01-01

... bleeding. (c) Procedures for testing. The sleeve is slipped onto the animal which is then placed in a... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Method of testing toxic substances. 1500.40... testing toxic substances. The method of testing the toxic substances referred to in § 1500.3(c) (1)(ii)(C...

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress

PubMed Central

Kilic, Gozde; Kilic, Volkan; Ucarcan, Seyda; Atli, Ozlem

2017-01-01

Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. Sperm DNA damage was determined by comet assay and histopathological examination of the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and oxidative stress are potential contributors to reproductive toxicity. PMID:28419133

Reproductive toxicity after levetiracetam administration in male rats: Evidence for role of hormonal status and oxidative stress.

PubMed

Baysal, Merve; Ilgin, Sinem; Kilic, Gozde; Kilic, Volkan; Ucarcan, Seyda; Atli, Ozlem

2017-01-01

Levetiracetam (LEV) is an antiepileptic drug commonly used in the treatment of epilepsy because of its excellent safety profile in all age groups. It is remarkable that there are no studies evaluating the toxic effects of this drug on the male reproductive system, as it is commonly used in male patients of reproductive age. From this point of view, our aim was to evaluate the possible toxic effects of LEV on the male reproductive system. Therefore, LEV was administered to male rats orally at 50, 150, and 300 mg/kg for 70 consecutive days. At the end of this period, alterations to body and organ weights were calculated, and sperm concentration, motility, and morphology were investigated by a computer-assisted sperm analysis system. Sperm DNA damage was determined by comet assay and histopathological examination of the testes was carried out. Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were measured by ELISAs to determine the effects of hormonal status, while glutathione, superoxide dismutase, catalase, and malondialdehyde levels in the testes were measured by colorimetric assay kits to determine the role of oxidative status in potential toxicity. According to the results, sperm quality was decreased by LEV treatment in a dose-dependent manner. LEV induced significant DNA damage in the 150 and 300 mg/kg LEV-administered groups. Histopathology of the testes showed that LEV resulted in testicular injury in the 300 mg/kg LEV-administered group. Serum testosterone, FSH, and LH levels were significantly decreased in the 300 mg/kg LEV-administered group. Glutathione, superoxide dismutase, and catalase levels were significantly decreased in all experimental groups while malondialdehyde levels were significantly increased in 150 and 300 mg/kg LEV-administered groups. According to these results, it was determined that LEV administration decreased sperm quality and it was alleged that hormonal alteration and oxidative stress are potential contributors to reproductive toxicity.

A SURROGATE SUBCHRONIC TOXICITY TEST METHOD FOR WATERS WITH HIGH TOTAL DISSOLVED SOLIDS

EPA Science Inventory

Total dissolved solids (TDS) are often identified as a toxicant in whole-effluent toxicity (WET) testing. The primary test organism used in WET testing, Ceriodaphnia dubia, is very sensitive to TDS ions, which can be problematic when differentiating the toxicity of TDS from those...

Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

PubMed

Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

2015-07-01

The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests. © 2015 SETAC.

THERMOREGULATION AND ITS INFLUENCE ON TOXICITY ASSESSMENT

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

Gordon, Christopher J.; Spencer, Pamela J.; Hotchkiss, Jon

2008-02-28

The thermoregulatory system of laboratory rodents is susceptible to a variety of chemical toxicants. Because temperature directly affects the reaction of virtually all biological processes, it is critical to consider how changes in the thermoregulatory response to a toxicant may affect physiological, behavioral, and pathological endpoints. Researchers in industry and government laboratories are often faced with addressing how changes in body temperature of their experimental subjects may affect the outcome of a particular toxicity test and/or screening panel. However, many toxicologists are either unaware of the importance or ignore the potential impact of a toxic-induced change in body temperature. Thismore » paper endeavors to summarize the importance of thermoregulation in the study of toxicology and propose recommendations for thermometry that researchers may utilize in their toxicological studies.« less

Phytotoxicity Evaluation of Type B Trichothecenes Using a Chlamydomonas reinhardtii Model System

PubMed Central

Suzuki, Tadahiro; Iwahashi, Yumiko

2014-01-01

Type B trichothecenes, which consist of deoxynivalenol (DON) and nivalenol (NIV) as the major end products, are produced by phytotoxic fungi, such as the Fusarium species, and pollute arable fields across the world. The DON toxicity has been investigated using various types of cell systems or animal bioassays. The evaluation of NIV toxicity, however, has been relatively restricted because of its lower level compared with DON. In this study, the Chlamydomonas reinhardtii testing system, which has been reported to have adequate NIV sensitivity, was reinvestigated under different mycotoxin concentrations and light conditions. The best concentration of DON and NIV, and their derivatives, for test conditions was found to be 25 ppm (2.5 × 10−2 mg/mL). In all light test conditions, DON, NIV, and fusarenon-X (FusX) indicated significant growth inhibition regardless of whether a light source existed, or under differential wavelength conditions. FusX growth was also influenced by changes in photon flux density. These results suggest that C. reinhardtii is an appropriate evaluation system for type B trichothecenes. PMID:24476708

Development of a BALB/c 3T3 neutral red uptake cytotoxicity test using a mainstream cigarette smoke exposure system

PubMed Central

2014-01-01

Background Tobacco smoke toxicity has traditionally been assessed using the particulate fraction under submerged culture conditions which omits the vapour phase elements from any subsequent analysis. Therefore, methodologies that assess the full interactions and complexities of tobacco smoke are required. Here we describe the adaption of a modified BALB/c 3T3 neutral red uptake (NRU) cytotoxicity test methodology, which is based on the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) protocol for in vitro acute toxicity testing. The methodology described takes into account the synergies of both the particulate and vapour phase of tobacco smoke. This is of particular importance as both phases have been independently shown to induce in vitro cellular cytotoxicity. Findings The findings from this study indicate that mainstream tobacco smoke and the gas vapour phase (GVP), generated using the Vitrocell® VC 10 smoke exposure system, have distinct and significantly different toxicity profiles. Within the system tested, mainstream tobacco smoke produced a dilution IC50 (dilution (L/min) at which 50% cytotoxicity is observed) of 6.02 L/min, whereas the GVP produced a dilution IC50 of 3.20 L/min. In addition, we also demonstrated significant dose-for-dose differences between mainstream cigarette smoke and the GVP fraction (P < 0.05). This demonstrates the importance of testing the entire tobacco smoke aerosol and not just the particulate fraction, as has been the historical preference. Conclusions We have adapted the NRU methodology based on the ICCVAM protocol to capture the full interactions and complexities of tobacco smoke. This methodology could also be used to assess the performance of traditional cigarettes, blend and filter technologies, tobacco smoke fractions and individual test aerosols. PMID:24935030

Screening for eye irritancy using cultured HeLa cells.

PubMed

Selling, J; Ekwall, B

1985-01-01

To investigate whether toxicity tests on HeLa cells were predictive of eye irritancy, 18 compounds of known eye irritancy and in vitro cytotoxicity were tested on HeLa cells in the MIT-24 system. The results correlated well with eye irritancy as determined by the Draize test in rabbits for 16 of the test substances, but failed to detect the high eye irritancy of 1-heptanol and allyl alcohol, both of which were cytotoxic in other cellular systems.

Toxicity of crude oil chemically dispersed in a wave tank to embryos of Atlantic herring (Clupea harengus).

PubMed

Greer, Colleen D; Hodson, Peter V; Li, Zhengkai; King, Thomas; Lee, Kenneth

2012-06-01

Tests of crude oil toxicity to fish are often chronic, exposing embryos from fertilization to hatch to oil solutions prepared using standard mixing procedures. However, during oil spills, fish are not often exposed for long periods and the dynamic nature of the ocean is not easily replicated in the lab. Our objective was to determine if brief exposures of Atlantic herring (Clupea harengus) embryos to dispersed oil prepared by standard mixing procedures was as toxic as oil dispersed in a more realistic model system. Embryos were first exposed to chemically dispersed Alaska North Slope crude and Arabian light crude oil for 2.4 h to 14 d from fertilization to determine if exposure time affected toxicity. Toxicity increased with exposure time, but 2.4-h exposures at realistic concentrations of oil induced blue-sac disease and reduced the percentage of normal embryos at hatch; there was little difference in toxicity between the two oils. Secondly, oil was chemically dispersed in a wave tank to determine if the resultant oil solutions were as toxic to herring embryos as laboratory-derived dispersed oil using a single exposure period of 24 h. Samples taken 15 min postdispersion were more toxic than laboratory-prepared solutions, but samples taken at 5, 30, and 60 min postdispersion were less toxic. Overall, the laboratory- and wave tank-derived solutions of dispersed oil provided similar estimates of toxicity despite differences in the methods for preparing test solutions, suggesting that laboratory and wave tank data are a reliable basis for ecological risk assessments of spilled oil. Copyright © 2012 SETAC.

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...

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Acute Toxicity to Daphnia: ASTM E 729 3. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the... conditions. Test Group 1 for C2: 1. Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM...

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Acute Toxicity to Daphnia: ASTM E 729 3. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the... conditions. Test Group 1 for C2: 1. Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM...

Ecological impacts of lead mining on Ozark streams: toxicity of sediment and pore water.

PubMed

Besser, John M; Brumbaugh, William G; Allert, Ann L; Poulton, Barry C; Schmitt, Christopher J; Ingersoll, Christopher G

2009-02-01

We studied the toxicity of sediments downstream of lead-zinc mining areas in southeast Missouri, using chronic sediment toxicity tests with the amphipod, Hyalella azteca, and pore-water toxicity tests with the daphnid, Ceriodaphnia dubia. Tests conducted in 2002 documented reduced survival of amphipods in stream sediments collected near mining areas and reduced survival and reproduction of daphnids in most pore waters tested. Additional amphipod tests conducted in 2004 documented significant toxic effects of sediments from three streams downstream of mining areas: Strother Creek, West Fork Black River, and Bee Fork. Greatest toxicity occurred in sediments from a 6-km reach of upper Strother Creek, but significant toxic effects occurred in sediments collected at least 14 km downstream of mining in all three watersheds. Toxic effects were significantly correlated with metal concentrations (nickel, zinc, cadmium, and lead) in sediments and pore waters and were generally consistent with predictions of metal toxicity risks based on sediment quality guidelines, although ammonia and manganese may also have contributed to toxicity at a few sites. Responses of amphipods in sediment toxicity tests were significantly correlated with characteristics of benthic invertebrate communities in study streams. These results indicate that toxicity of metals associated with sediments contributes to adverse ecological effects in streams draining the Viburnum Trend mining district.

Ecological impacts of lead mining on Ozark streams: Toxicity of sediment and pore water

USGS Publications Warehouse

Besser, J.M.; Brumbaugh, W.G.; Allert, A.L.; Poulton, B.C.; Schmitt, C.J.; Ingersoll, C.G.

2009-01-01

We studied the toxicity of sediments downstream of lead-zinc mining areas in southeast Missouri, using chronic sediment toxicity tests with the amphipod, Hyalella azteca, and pore-water toxicity tests with the daphnid, Ceriodaphnia dubia. Tests conducted in 2002 documented reduced survival of amphipods in stream sediments collected near mining areas and reduced survival and reproduction of daphnids in most pore waters tested. Additional amphipod tests conducted in 2004 documented significant toxic effects of sediments from three streams downstream of mining areas: Strother Creek, West Fork Black River, and Bee Fork. Greatest toxicity occurred in sediments from a 6-km reach of upper Strother Creek, but significant toxic effects occurred in sediments collected at least 14 km downstream of mining in all three watersheds. Toxic effects were significantly correlated with metal concentrations (nickel, zinc, cadmium, and lead) in sediments and pore waters and were generally consistent with predictions of metal toxicity risks based on sediment quality guidelines, although ammonia and manganese may also have contributed to toxicity at a few sites. Responses of amphipods in sediment toxicity tests were significantly correlated with characteristics of benthic invertebrate communities in study streams. These results indicate that toxicity of metals associated with sediments contributes to adverse ecological effects in streams draining the Viburnum Trend mining district.

Predicting toxic effects of copper on aquatic biota in mineralized areas by using the Biotic Ligand Model

USGS Publications Warehouse

Smith, Kathleen S.; Ranville, James F.; Adams, M.; Choate, LaDonna M.; Church, Stan E.; Fey, David L.; Wanty, Richard B.; Crock, James G.

2006-01-01

The chemical speciation of metals influences their biological effects. The Biotic Ligand Model (BLM) is a computational approach to predict chemical speciation and acute toxicological effects of metals on aquatic biota. Recently, the U.S. Environmental Protection Agency incorporated the BLM into their regulatory water-quality criteria for copper. Results from three different laboratory copper toxicity tests were compared with BLM predictions for simulated test-waters. This was done to evaluate the ability of the BLM to accurately predict the effects of hardness and concentrations of dissolved organic carbon (DOC) and iron on aquatic toxicity. In addition, we evaluated whether the BLM and the three toxicity tests provide consistent results. Comparison of BLM predictions with two types of Ceriodaphnia dubia toxicity tests shows that there is fairly good agreement between predicted LC50 values computed by the BLM and LC50 values determined from the two toxicity tests. Specifically, the effect of increasing calcium concentration (and hardness) on copper toxicity appears to be minimal. Also, there is fairly good agreement between the BLM and the two toxicity tests for test solutions containing elevated DOC, for which the LC50 is 3-to-5 times greater (less toxic) than the LC50 for the lower-DOC test water. This illustrates the protective effects of DOC on copper toxicity and demonstrates the ability of the BLM to predict these protective effects. In contrast, for test solutions with added iron there is a decrease in LC50 values (increase in toxicity) in results from the two C. dubia toxicity tests, and the agreement between BLM LC50 predictions and results from these toxicity tests is poor. The inability of the BLM to account for competitive iron binding to DOC or DOC fractionation may be a significant shortcoming of the BLM for predicting site- specific water-quality criteria in streams affected by iron-rich acidic drainage in mined and mineralized areas.

Investigation of Acute and Chronic Toxicity Trends of Pesticides Using High-Throughput Bioluminescence Assay Based on the Test Organism Vibrio fischeri.

PubMed

Westlund, Paul; Nasuhoglu, Deniz; Isazadeh, Siavash; Yargeau, Viviane

2018-05-01

High-throughput acute and chronic toxicity tests using Vibrio fischeri were used to assess the toxicity of a variety of fungicides, herbicides, and neonicotinoids. The use of time points beyond the traditional 30 min of an acute test highlighted the sensitivity and applicability of the chronic toxicity test and indicated that for some compounds toxicity is underestimated using only the acute test. The comparison of EC 50 values obtained from acute and chronic tests provided insight regarding the toxicity mode of action, either being direct or indirect. Using a structure-activity relationship approach similar to the one used in hazard assessments, the relationship between toxicity and key physicochemical properties of pesticides was investigated and trends were identified. This study not only provides new information regarding acute toxicity of some pesticides but also is one of the first studies to investigate the chronic toxicity of pesticides using the test organism V. fischeri. The findings demonstrated that the initial bioluminescence has a large effect on the calculated effective concentrations for target compounds in both acute and chronic tests, providing a way to improve and standardize the test protocol. In addition, the findings emphasize the need for additional investigation regarding the relationship between a toxicant's physicochemical properties and mode of action in nontarget organisms.

Neurotoxicity of dental amalgam is mediated by zinc.

PubMed

Lobner, D; Asrari, M

2003-03-01

The use of dental amalgam is controversial largely because it contains mercury. We tested whether amalgam caused toxicity in neuronal cultures and whether that toxicity was caused by mercury. In this study, we used cortical cell cultures to show for the first time that amalgam causes nerve cell toxicity in culture. However, the toxicity was not blocked by the mercury chelator, 2,3-dimercaptopropane-1-sulphonate (DMPS), but was blocked by the metal chelator, calcium disodium ethylenediaminetetraacetate (CaEDTA). DMPS was an effective mercury chelator in this system, since it blocked mercury toxicity. Of the components that comprise amalgam (mercury, zinc, tin, copper, and silver), only zinc neurotoxicity was blocked by CaEDTA. These results indicate that amalgam is toxic to nerve cells in culture by releasing zinc. While zinc is known to be neurotoxic, ingestion of zinc is not a major concern because zinc levels in the body are tightly regulated.

Modern pesticides and bobwhite populations

USGS Publications Warehouse

Stromborg, K.L.; Schitoskey, Frank=; Schitoskey, Elizabeth C.; Talent, Larry G.

1982-01-01

Bobwhite (Colinus virginianus) are frequently used as test animals for wildlife tests of pesticides. The organophosphate and carbamate pesticides that have replaced the organochlorines have many desirable properties, but they span a wide range of acute toxicities and some of them affe,ct survival, reproduction, food consumption, behavior, and nervous system enzymes in laboratory tests. Applying these laboratory findings to the field requires assumptions about the severity of exposure in the field. Direct field measurements show that birds may be exposed to significant amounts of these pesticides or even more toxic degradation products under some conditions. Adverse population effects may also result from depression of insect populations during the seasons when bobwhites rely on insects for food.

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

Cave, D.A.; Foster, P.M.

Previous work has shown that m-dinitrobenzene is a testicular toxicant in rats in vivo, and in vitro produces comparable morphological changes in rat testicular Sertoli-germ cell cocultures. m-Dinitrobenzene is metabolized both in vivo and in the in vitro system to m-nitroaniline m-nitroaniline and m-nitroacetanilide. These metabolites do not provoke testicular toxicity in vivo or in vitro. We have therefore proposed a pathway for the metabolism of m-dinitrobenzene to m-nitroaniline and m-nitroacetanilide, which involved the intermediate m-nitrosonitrobenzene (1-nitroso-3-nitrobenzene, NNB). When tested, m-nitrosonitrobenzene, at equimolar doses to m-dinitrobenzene, produced similar morphological changes in the culture system to those exhibited by m-dinitrobenzene. However,more » m-nitrosonitrobenzene produced a greater toxicity than did m-dinitrobenzene (as measured by germ cell detachment). When the intracellular thiol levels were reduced in the cocultures pretreated with diethyl maleate, the toxicity of both m-dinitrobenzene and m-nitrosonitrobenzene was enhanced. In contrast, pretreatment of cocultures with agents known to increase cellular thiol (cysteamine) or scavenge reactive intermediates (cysteamine or ascorbate) reduced the toxicity of m-dinitrobenzene and m-nitrosonitrobenzene. We propose that m-dinitrobenzene requires metabolic activation before it can exert its toxicity to Sertoli cells, and it appears that the toxic species is m-nitrosonitrobenzene or a further metabolite of m-nitrosonitrobenzene.« less

Evaluation of the scientific underpinnings for identifying estrogenic chemicals in non-mammalian taxa using mammalian test systems

EPA Science Inventory

A major challenge in chemical risk assessment is extrapolation of toxicity data from tested to untested species. Successful cross-species extrapolation involves understanding similarities and differences in toxicokinetic and toxicodynamic processes among species. Herein we consi...

Toxic Encephalopathy

PubMed Central

Kim, Jae Woo

2012-01-01

This article schematically reviews the clinical features, diagnostic approaches to, and toxicological implications of toxic encephalopathy. The review will focus on the most significant occupational causes of toxic encephalopathy. Chronic toxic encephalopathy, cerebellar syndrome, parkinsonism, and vascular encephalopathy are commonly encountered clinical syndromes of toxic encephalopathy. Few neurotoxins cause patients to present with pathognomonic neurological syndromes. The symptoms and signs of toxic encephalopathy may be mimicked by many psychiatric, metabolic, inflammatory, neoplastic, and degenerative diseases of the nervous system. Thus, the importance of good history-taking that considers exposure and a comprehensive neurological examination cannot be overemphasized in the diagnosis of toxic encephalopathy. Neuropsychological testing and neuroimaging typically play ancillary roles. The recognition of toxic encephalopathy is important because the correct diagnosis of occupational disease can prevent others (e.g., workers at the same worksite) from further harm by reducing their exposure to the toxin, and also often provides some indication of prognosis. Physicians must therefore be aware of the typical signs and symptoms of toxic encephalopathy, and close collaborations between neurologists and occupational physicians are needed to determine whether neurological disorders are related to occupational neurotoxin exposure. PMID:23251840

A model compound study: the ecotoxicological evaluation of five organic contaminants employing a battery of marine bioassays.

PubMed

Macken, Ailbhe; Giltrap, Michelle; Foley, Barry; McGovern, Evin; McHugh, Brendan; Davoren, Maria

2008-06-01

This paper describes the ecotoxicological evaluation of five organic contaminants frequently detected in marine sediments (tributyltin, triphenyltin, benzo[a]pyrene, fluoranthene, and PCB 153) using three marine species (Vibrio fischeri, Tetraselmis suecica, and Tisbe battagliai). The sensitivity of each species varied for all compounds. The triorganotins were consistently the most toxic to all species. The applicability of each test system to assess the acute toxicity of environmental contaminants and their use in Toxicity Identification Evaluation (TIE) is discussed. Suitability of the Microtox and T. battagliai tests for employment in TIE studies were further assessed through spiking experiments with tributyltin. Results demonstrated that the most effective treatment to remove organotin toxicity from the sample was the C18 resin. The results of this study have important implications for risk assessment in estuarine and coastal waters in Ireland, where, at present the monitoring of sediment and water quality is predominantly reliant on chemical analysis alone.

Pleiotrophin prevents cocaine-induced toxicity in vitro.

PubMed

Gramage, Esther; Alguacil, Luis F; Herradon, Gonzalo

2008-10-24

Pleiotrophin is a cytokine involved in differentiation, survival and repair processes in the central nervous system. Pleiotrophin is upregulated in the brain after administration of different drugs of abuse, thus suggesting a protective role of this cytokine on drug-induced toxicity. We have tested this hypothesis in vitro using NG108-15 cells, a line widely used for neurotoxicity studies. It was found that pleiotrophin (3 and 6 microM) significantly prevents cocaine (5 mM)-induced cytotoxicity as measured by the neutral red test. Similar results were obtained in PC12 cells, which were found to endogenously express both pleiotrophin and its main target, receptor protein tyrosine phosphatase (RPTP) beta/zeta. Blockade of pleiotrophin signaling using anti-pleiotrophin antibodies (2 microg/ml) did not potentiate cocaine-induced toxicity; interestingly, incubation of PC12 cells only with anti-pleiotrophin antibodies significantly reduced cellular viability, thus suggesting an important role of endogenous pleiotrophin signaling in cell survival. The data suggest that pleiotrophin overexpression in response to drugs of abuse may be relevant to prevent drug-induced toxicity.

[Are acute toxicity testing and the three Rs rule reconcilable? Example of the lethal dose 50 determination].

PubMed

Dorandeu, Fr; Lallement, G

2003-11-01

Toxicity assessment and demonstration of innocuousness of chemical compounds have been part of the research studies conducted in the fields of pharmacy, agriculture and chemical industry for years. Acute systemic toxicity studies are an important element of the safety evaluation. They remain compulsory for regulatory purposes and important for the public opinion that does not accept the risk anymore. Evolutions of the ethics in animal experiments foster a necessary reduction of the number of animals involved in this type of experiments, following the well-known principle of the three Rs rule of Russell and Burch (1959) (Reduction, refinement and replacement). These two views seem in contradiction. Using the example of acute toxicity testing and focusing on the now very criticized parameter lethal dose 50, we will present approaches, including statistical ones, that a toxicologist can use, when free to choose, to keep on conducting the indispensable in vivo studies while abiding by ethical recommendations.

Comparison of the toxicity of aluminum oxide nanorods with different aspect ratio.

PubMed

Park, Eun-Jung; Lee, Gwang-Hee; Shim, Jae-Hun; Cho, Myung-Haing; Lee, Byoung-Seok; Kim, Yong-Bum; Kim, Jae-Ho; Kim, Younghun; Kim, Dong-Wan

2015-10-01

Aluminum oxide nanoparticles are listed among 14 high-priority nanomaterials published by the Organization for Economic Co-operation and Development, but limited information is available on their potential hazards. In this study, we compared the toxicity of two different aluminum oxide nanorods (AlNRs) commercially available in vivo and in vitro. Considering aspect ratio, one was 6.2 ± 0.6 (long-AlNRs) and the other was 2.1 ± 0.4 (short-AlNRs). In mice, long-AlNRs induced longer and stronger inflammatory responses than short-AlNRs, and the degree reached the maximum on day 7 for both types and decreased with time. In addition, in vitro tests were performed on six cell lines derived from potential target organs for AlNPs, HEK-293 (kidney), HACAT (skin), Chang (liver), BEAS-2B (lung), T98G (brain), and H9C2 (heart), using MTT assay, ATP assay, LDH release, and xCELLigence system. Long-AlNRs generally produced stronger toxicity than short-AlNRs, and HEK-293 cells were the most sensitive for both AlNRs, followed by BEAS-2B cells, although results from 4 kinds of toxicity tests conflicted among the cell lines. Based on these results, we suggest that toxicity of AlNRs may be related to aspect ratio (and resultant surface area). Furthermore, novel in vitro toxicity testing methods are needed to resolve questionable results caused by the unique properties of nanoparticles.

Overview of ToxCast™ | Science Inventory | US EPA

EPA Pesticide Factsheets

In 2007, EPA launched ToxCast™ in order to develop a cost-effective approach for prioritizing the toxicity testing of large numbers of chemicals in a short period of time. Using data from state-of-the-art high throughput screening (HTS) bioassays developed in the pharmaceutical industry, ToxCast™ is building computational models to forecast the potential human toxicity of chemicals. These hazard predictions will provide EPA regulatory programs with science-based information helpful in prioritizing chemicals for more detailed toxicological evaluations, and lead to more efficient use of animal testing. In its first phase, ToxCast™ is profiling over 300 well-characterized chemicals (primarily pesticides) in over 400 HTS endpoints. These endpoints include biochemical assays of protein function, cell-based transcriptional reporter assays, multi-cell interaction assays, transcriptomics on primary cell cultures, and developmental assays in zebrafish embryos. Almost all of the compounds being examined in Phase 1 of ToxCast™ have been tested in traditional toxicology tests, including developmental toxicity, multi-generation studies, and sub-chronic and chronic rodent bioassays. ToxRefDB, a relational database being created to house this information, will contain nearly $1B worth of toxicity studies in animals when completed. ToxRefDB is integrated into a more comprehensive data management system developed by NCCT called ACToR (Aggregated Computational Toxicology

Impact of non-constant concentration exposure on lethality of inhaled hydrogen cyanide.

PubMed

Sweeney, Lisa M; Sommerville, Douglas R; Channel, Stephen R

2014-03-01

The ten Berge model, also known as the toxic load model, is an empirical approach in hazard assessment modeling for estimating the relationship between the inhalation toxicity of a chemical and the exposure duration. The toxic load (TL) is normally expressed as a function of vapor concentration (C) and duration (t), with TL equaling C(n) × t being a typical form. Hypothetically, any combination of concentration and time that yields the same "toxic load" will give a constant biological response. These formulas have been developed and tested using controlled, constant concentration animal studies, but the validity of applying these assumptions to time-varying concentration profiles has not been tested. Experiments were designed to test the validity of the model under conditions of non-constant acute exposure. Male Sprague-Dawley rats inhaled constant or pulsed concentrations of hydrogen cyanide (HCN) generated in a nose-only exposure system for 5, 15, or 30 min. The observed lethality of HCN for the 11 different C versus t profiles was used to evaluate the ability of the model to adequately describe the lethality of HCN under the conditions of non-constant inhalation exposure. The model was found to be applicable under the tested conditions, with the exception of the median lethality of very brief, high concentration, discontinuous exposures.

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...

Alternative methods for toxicity assessments in fish: comparison of the fish embryo toxicity and the larval growth and survival tests in zebrafish and fathead minnows.

PubMed

Jeffries, Marlo K Sellin; Stultz, Amy E; Smith, Austin W; Rawlings, Jane M; Belanger, Scott E; Oris, James T

2014-11-01

An increased demand for chemical toxicity evaluations has resulted in the need for alternative testing strategies that address animal welfare concerns. The fish embryo toxicity (FET) test developed for zebrafish (Danio rerio) is one such alternative, and the application of the FET test to other species such as the fathead minnow (Pimephales promelas) has been proposed. In the present study, the performances of the FET test and the larval growth and survival (LGS; a standard toxicity testing method) test in zebrafish and fathead minnows were evaluated. This required that testing methods for the fathead minnow FET and zebrafish LGS tests be harmonized with existing test methods and that the performance of these testing strategies be evaluated by comparing the median lethal concentrations of 2 reference toxicants, 3,4-dicholoraniline and ammonia, obtained via each of the test types. The results showed that procedures for the zebrafish FET test can be adapted and applied to the fathead minnow. Differences in test sensitivity were observed for 3,4-dicholoraniline but not ammonia; therefore, conclusions regarding which test types offer the least or most sensitivity could not be made. Overall, these results show that the fathead minnow FET test has potential as an alternative toxicity testing strategy and that further analysis with other toxicants is warranted in an effort to better characterize the sensitivity and feasibility of this testing strategy. © 2014 SETAC.

In vitro techniques for the assessment of neurotoxicity.

PubMed Central

Harry, G J; Billingsley, M; Bruinink, A; Campbell, I L; Classen, W; Dorman, D C; Galli, C; Ray, D; Smith, R A; Tilson, H A

1998-01-01

Risk assessment is a process often divided into the following steps: a) hazard identification, b) dose-response assessment, c) exposure assessment, and d) risk characterization. Regulatory toxicity studies usually are aimed at providing data for the first two steps. Human case reports, environmental research, and in vitro studies may also be used to identify or to further characterize a toxic hazard. In this report the strengths and limitations of in vitro techniques are discussed in light of their usefulness to identify neurotoxic hazards, as well as for the subsequent dose-response assessment. Because of the complexity of the nervous system, multiple functions of individual cells, and our limited knowledge of biochemical processes involved in neurotoxicity, it is not known how well any in vitro system would recapitulate the in vivo system. Thus, it would be difficult to design an in vitro test battery to replace in vivo test systems. In vitro systems are well suited to the study of biological processes in a more isolated context and have been most successfully used to elucidate mechanisms of toxicity, identify target cells of neurotoxicity, and delineate the development and intricate cellular changes induced by neurotoxicants. Both biochemical and morphological end points can be used, but many of the end points used can be altered by pharmacological actions as well as toxicity. Therefore, for many of these end points it is difficult or impossible to set a criterion that allows one to differentiate between a pharmacological and a neurotoxic effect. For the process of risk assessment such a discrimination is central. Therefore, end points used to determine potential neurotoxicity of a compound have to be carefully selected and evaluated with respect to their potential to discriminate between an adverse neurotoxic effect and a pharmacologic effect. It is obvious that for in vitro neurotoxicity studies the primary end points that can be used are those affected through specific mechanisms of neurotoxicity. For example, in vitro systems may be useful for certain structurally defined compounds and mechanisms of toxicity, such as organophosphorus compounds and delayed neuropathy, for which target cells and the biochemical processes involved in the neurotoxicity are well known. For other compounds and the different types of neurotoxicity, a mechanism of toxicity needs to be identified first. Once identified, by either in vivo or in vitro methods, a system can be developed to detect and to evaluate predictive ability for the type of in vivo neurotoxicity produced. Therefore, in vitro tests have their greatest potential in providing information on basic mechanistic processes in order to refine specific experimental questions to be addressed in the whole animal. Images Figure 1 PMID:9539010

Microfluidics for Antibiotic Susceptibility and Toxicity Testing

PubMed Central

Dai, Jing; Hamon, Morgan; Jambovane, Sachin

2016-01-01

The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA) bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing. PMID:28952587

[Products toxic to reproduction used in the occupational environment: Definition, risk assessment, classification].

PubMed

Lafon, D

2006-10-01

European regulations (transcribed into French law) aimed at protecting employees from chemicals toxic to reproduction enable classification and labelling of such substances, if they are liable to cause an alteration of male or female reproductive functions or capacity, or to induce non-hereditary harmful effects on their offspring. Three categories can be used to classify these substances in two areas, namely their impairment of fertility and their effects on development. This classification is rarely based on epidemiological study results, but most often on those of experimental toxicological studies conducted by substance manufacturers. These reproduction toxicological studies are only compulsory above a certain tonnage placed on the market. The high level of this tonnage means that these tests are effectively only conducted on rare occasions. It is reckoned that there is no reproduction experimental data for over 95% of substances newly placed on the market. These products therefore appear to be reproduction non-toxic only because they have not been tested. This is a major fault in the current labelling system, which does not allow non-toxic products to be differentiated from non-tested products. The future EU regulatory framework for Registration, Evaluation and Authorisation of CHemicals (REACH) will only slightly enhance information in this area. It can be estimated that over 80% of chemical products will not be exhaustively tested for reproduction and nearly 75% will not be tested to any degree.

Predicting the Future: Opportunities and Challenges for the Chemical Industry to Apply 21st-Century Toxicity Testing

PubMed Central

Settivari, Raja S; Ball, Nicholas; Murphy, Lynea; Rasoulpour, Reza; Boverhof, Darrell R; Carney, Edward W

2015-01-01

Interest in applying 21st-century toxicity testing tools for safety assessment of industrial chemicals is growing. Whereas conventional toxicology uses mainly animal-based, descriptive methods, a paradigm shift is emerging in which computational approaches, systems biology, high-throughput in vitro toxicity assays, and high-throughput exposure assessments are beginning to be applied to mechanism-based risk assessments in a time- and resource-efficient fashion. Here we describe recent advances in predictive safety assessment, with a focus on their strategic application to meet the changing demands of the chemical industry and its stakeholders. The opportunities to apply these new approaches is extensive and include screening of new chemicals, informing the design of safer and more sustainable chemical alternatives, filling information gaps on data-poor chemicals already in commerce, strengthening read-across methodology for categories of chemicals sharing similar modes of action, and optimizing the design of reduced-risk product formulations. Finally, we discuss how these predictive approaches dovetail with in vivo integrated testing strategies within repeated-dose regulatory toxicity studies, which are in line with 3Rs principles to refine, reduce, and replace animal testing. Strategic application of these tools is the foundation for informed and efficient safety assessment testing strategies that can be applied at all stages of the product-development process. PMID:25836969

Modulation of m-dinitrobenzene and m-nitrosonitrobenzene toxicity in rat Sertoli--germ cell cocultures.

PubMed

Cave, D A; Foster, P M

1990-01-01

Previous work has shown that m-dinitrobenzene is a testicular toxicant in rats in vivo, and in vitro produces comparable morphological changes in rat testicular Sertoli-germ cell cocultures. m-Dinitrobenzene is metabolized both in vivo and in the in vitro system to m-nitroaniline m-nitroaniline and m-nitroacetanilide. These metabolites do not provoke testicular toxicity in vivo or in vitro. We have therefore proposed a pathway for the metabolism of m-dinitrobenzene to m-nitroaniline and m-nitroacetanilide, which involved the intermediate m-nitrosonitrobenzene (1-nitroso-3-nitrobenzene, NNB). When tested, m-nitrosonitrobenzene, at equimolar doses to m-dinitrobenzene, produced similar morphological changes in the culture system to those exhibited by m-dinitrobenzene. However, m-nitrosonitrobenzene produced a greater toxicity than did m-dinitrobenzene (as measured by germ cell detachment). When the intracellular thiol levels were reduced in the cocultures pretreated with diethyl maleate, the toxicity of both m-dinitrobenzene and m-nitrosonitrobenzene was enhanced. In contrast, pretreatment of cocultures with agents known to increase cellular thiol (cysteamine) or scavenge reactive intermediates (cysteamine or ascorbate) reduced the toxicity of m-dinitrobenzene and m-nitrosonitrobenzene. We propose that m-dinitrobenzene requires metabolic activation before it can exert its toxicity to Sertoli cells, and it appears that the toxic species is m-nitrosonitrobenzene or a further metabolite of m-nitrosonitrobenzene.

Predictions of sediment toxicity using consensus-based freshwater sediment quality guidelines

USGS Publications Warehouse

Ingersoll, C.G.; MacDonald, D.D.; Wang, N.; Crane, J.L.; Field, L.J.; Haverland, P.S.; Kemble, N.E.; Lindskoog, R.A.; Severn, C.; Smorong, D.E.

2001-01-01

The objectives of this study were to compare approaches for evaluating the combined effects of chemical mixtures on the toxicity in field-collected sediments and to evaluate the ability of consensus-based probable effect concentrations (PECs) to predict toxicity in a freshwater database on both a national and regional geographic basis. A database was developed from 92 published reports, which included a total of 1,657 samples with high-quality matching sediment toxicity and chemistry data from across North America. The database was comprised primarily of 10- to 14-day or 28- to 42-day toxicity tests with the amphipod Hyalella azteca (designated as the HA10 or HA28 tests) and 10- to 14-day toxicity tests with the midges Chironomus tentans or C. riparius (designated as the CS10 test). Mean PEC quotients were calculated to provide an overall measure of chemical contamination and to support an evaluation of the combined effects of multiple contaminants in sediments. There was an overall increase in the incidence of toxicity with an increase in the mean quotients in all three tests. A consistent increase in the toxicity in all three tests occurred at a mean quotient > 0.5, however, the overall incidence of toxicity was greater in the HA28 test compared to the short-term tests. The longer-term tests, in which survival and growth are measured, tend to be more sensitive than the shorter-term tests, with acute to chronic ratios on the order of six indicated for H. azteca. Different patterns were observed among the various procedures used to calculate mean quotients. For example, in the HA28 test, a relatively abrupt increase in toxicity was associated with elevated polychlorinated biphenyls (PCBs) alone or with elevated polycyclic aromatic hydrocarbons (PAHs) alone, compared to the pattern of a gradual increase in toxicity observed with quotients calculated using a combination of metals, PAHs, and PCBs. These analyses indicate that the different patterns in toxicity may be the result of unique chemical signals associated with individual contaminants in samples. Though mean quotients can be used to classify samples as toxic or nontoxic, individual quotients might be useful in helping identify substances that may be causing or substantially contributing to the observed toxicity. An increase in the incidence of toxicity was observed with increasing mean quotients within most of the regions, basins, and areas in North America for all three toxicity tests. The results of these analyses indicate that the consensus-based PECs can be used to reliably predict toxicity of sediments on both a regional and national basis.

Olive oil mill wastewaters before and after treatment: a critical review from the ecotoxicological point of view.

PubMed

Justino, Celine I L; Pereira, Ruth; Freitas, Ana C; Rocha-Santos, Teresa A P; Panteleitchouk, Teresa S L; Duarte, Armando C

2012-03-01

The olive oil mill wastewater (OMW) is a problematic and polluting effluent which may degrade the soil and water quality, with critical negative impacts on ecosystems functions and services provided. The main purpose of this review paper is presenting the state of the art of OMW treatments focusing on their efficiency to reduce OMW toxicity, and emphasizing the role of ecotoxicological tests on the evaluation of such efficiency before the up-scale of treatment methodologies being considered. In the majority of research works, the reduction of OMW toxicity is related to the degradation of phenolic compounds (considered as the main responsible for the toxic effects of OMW on seed germination, on bacteria, and on different species of soil and aquatic invertebrates) or the decrease of chemical oxygen demand content, which is not scientifically sound. Batteries of ecotoxicological tests are not applied before and after OMW treatments as they should be, thus leading to knowledge gaps in terms of accurate and real assessment of OMW toxicity. Although the toxicity of OMW is usually high, the evaluation of effects on sub-lethal endpoints, on individual and multispecies test systems, are currently lacking, and the real impacts yielded by its dilution, in freshwater trophic chains of receiving systems can not be assessed. As far as the terrestrial compartment is considered, ecotoxicological data available include tests only with plants and the evaluation of soil microbial parameters, reflecting concerns with the impacts on crops when using OMW for irrigation purposes. The evaluation of its ecotoxicity to other edaphic species were not performed giving rise to a completely lack of knowledge about the consequences of such practice on other soil functions. OMW production is a great environmental problem in Mediterranean countries; hence, engineers, chemists and ecotoxicologists should face this problem together to find an ecologically friend solution.

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.

Dermal Sensitization Potential of Triethyleneglycol Dinitrate (TEGDN) in Guinea Pigs

DTIC Science & Technology

1989-01-01

mutagenicity assay, acute oral toxicity tests in rats and mice, acute dermal toxicity in rabbits, dermal and ocular irritation studies in rabbits, and...conditions: 85E0102 had diffuse tracheitis, mild endocarditis , mild hepatitis, and diffuse pigment granules in the small intestine; 85E0103 had mild...severe ulceration progressing to necrosis. Sensitization is manifested as indirect inflammation mediated by components of the immune system in

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice.

PubMed

Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

2016-11-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute toxicity and inactivation tests of CO2 on invertebrates in drinking water treatment systems.

PubMed

Yin, Wen-Chao; Zhang, Jin-Song; Liu, Li-Jun; Zhao, Jian-Shu; Li, Tuo

2011-01-01

In addition to the esthetic problem caused by invertebrates, researchers are recently starting to be more aware of their potential importance in terms of public health. However, the inactivation methods of invertebrates which could proliferate in drinking water treatment systems are not well developed. The objective of this study is to assess the acute toxicity and inactivation effects of CO2 on familiar invertebrates in water treatment processes. The results of this study revealed that CO2 has a definite toxicity to familiar invertebrates. The values of 24-h LC50 (median lethal concentration) were calculated for each test with six groups of invertebrates. The toxicity of CO2 was higher with increasing concentrations in solution but was lower with the increase in size of the invertebrates. Above the concentration of 1,000 mg/L for the CO2 solution, the 100% inactivation time of all the invertebrates was less than 5 s, and in 15 min, the inactivation ratio showed a gradient descent with a decline in concentration. As seen for Mesocyclops thermocyclopoides, by dosing with a sodium bicarbonate solution first and adding a dilute hydrochloric acid solution 5 min later, it is possible to obtain a satisfactory inactivation effect in the GAC (granular activated carbon) filters.

A new biological test of water toxicity-yeast Saccharomyces cerevisiae conductometric test.

PubMed

Dolezalova, Jaroslava; Rumlova, Lubomira

2014-11-01

This new biological test of water toxicity is based on monitoring of specific conductivity changes of yeast Saccharomyces cerevisiae suspension as a result of yeast fermentation activity inhibition in toxic conditions. The test was verified on ten substances with various mechanisms of toxic effect and the results were compared with two standard toxicity tests based on Daphnia magna mobility inhibition (EN ISO 6341) and Vibrio fischeri bioluminescence inhibition (EN ISO 11348-2) and with the results of the S. cerevisiae lethal test (Rumlova and Dolezalova, 2012). The new biological test - S. cerevisiae conductometric test - is an express method developed primarily for field conditions. It is applicable in case of need of immediate information about water toxicity. Fast completion is an advantage of this test (time necessary for test completion is about 60min), the test is simple and the test organism - dried instant yeast - belongs among its biggest advantages because of its long-term storage life and broad availability. Copyright © 2014 Elsevier B.V. All rights reserved.

Static renewal tests using Anodonta imbecillus (freshwater mussels). Anodonta imbecillis copper sulfate reference toxicant test, Clinch River-Environmental Restoration Program (CR-ERP)

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

Simbeck, D.J.

1993-12-31

Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Toxicity testing of copper sulfate reference toxicant was conducted from May 12--21, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Results from this test showed an LC{sub 50} value of 1.12 mg Cu/L which is lower than the value of 2.02 mg Cu/L obtained inmore » a previous test. Too few tests have been conducted with copper as the toxicant to determine a normal range of values. Attachments to this report include: Toxicity test bench sheets and statistical analyses; Copper analysis request and results; and Personnel training documentation.« less

Sediment quality assessment studies of Tampa bay, Florida

USGS Publications Warehouse

Carr, Scott R.; Chapman, Duane C.; Long, Edward R.; Windom, Herbert L.; Thursby, Glen; Sloane, Gail M.; Wolfe, Douglas A.

1996-01-01

A survey of the toxicity of sediments throughout the Tampa Bay estuary was performed as part of the National Oceanic and Atmospheric Administration's National Status and Trends Program. The objectives of the survey were to determine the spatial extent and severity of toxicity and to identify relationships between chemical contamination and toxicity. Three independent toxicity tests were performed: a 10-d amphipod survival test of the whole sediments with Ampelisca abdita, a sea urchin fertilization test of sediment pore water with Arbacia punctulata, and a 5-min Microtox® bioluminescence test with solvent extracts of the sediments. Seventy-three percent of the 165 undiluted sediment pore-water samples were significantly toxic relative to reference samples with the sea urchin fertilization test. In contrast, only 2% of the 165 samples were significantly toxic in the amphipod tests. The causes of toxicity were not determined. However, concentrations of numerous trace metals, pesticides, polychlorinated biphenyl (PCB) congeners, polycyclic aromatic hydrocarbons (PAHs), and ammonia were highly correlated with pore-water toxicity. Concentrations of many substances, especially total dichlorodiphenyltrichloroethanes (DDTs), endrin, total PCBs, certain PAHs, lead, and zinc, occurred at concentrations in the toxic samples that equaled or exceeded concentrations that have been previously associated with sediment toxicity.

Toxicity of three pesticides individually and in mixture to larval grass shrimp (Palaemonetes pugio).

PubMed

Key, Peter; Chung, Katy; Siewicki, Tom; Fulton, Mike

2007-10-01

This study examined the toxicity of three pesticides, singly and in mixture, to grass shrimp (Palaemonetes pugio) larvae. The pesticides included atrazine, an herbicide used on turf grass and field crops; fipronil, a persistent insecticide used against termites and fire ants; and imidacloprid, a systemic insecticide used in agricultural and home products. Fipronil was the most toxic to shrimp larvae with a 96-h LC50 of 0.68microg/L (95% CI 0.57-0.79microg/L). Shrimp larvae were less sensitive to imidacloprid with a 96-h LC50 of 308.8microg/L (95% CI 273.6-348.6microg/L). Atrazine was non-toxic to shrimp larvae at concentrations up to 10,000microg/L. In mixtures, fipronil plus atrazine and imidacloprid plus atrazine had no change in toxicity compared to fipronil and imidacloprid tested singly. Similarly, a fipronil/imidacloprid mixture did not show greater than additive toxicity. However, when atrazine was added to the fipronil/imidacloprid mix, greater than additive toxicity occurred.

Simultaneous and iterative weighted regression analysis of toxicity tests using a microplate reader.

PubMed

Galgani, F; Cadiou, Y; Gilbert, F

1992-04-01

A system is described for determination of LC50 or IC50 by an iterative process based on data obtained from a plate reader using a marine unicellular alga as a target species. The esterase activity of Tetraselmis suesica on fluorescein diacetate as a substrate was measured using a fluorescence titerplate. Simultaneous analysis of results was performed using an iterative process adopting the sigmoid function Y = y/1 (dose of toxicant/IC50)slope for dose-response relationships. IC50 (+/- SEM) was estimated (P less than 0.05). An application with phosalone as a toxicant is presented.

Models of germ cell development and their application for toxicity studies

PubMed Central

Ferreira, Daniel W.; Allard, Patrick

2015-01-01

Germ cells are unique in their ability to transfer genetic information and traits from generation to generation. As such, the proper development of germ cells and the integrity of their genome are paramount to the health of organisms and the survival of species. Germ cells are also exquisitely sensitive to environmental influences although the testing of germ cell toxicity, especially in females, has proven particularly challenging. In this review, we first describe the remarkable odyssey of germ cells in mammals, with an emphasis on the female germline, from their initial specification during embryogenesis to the generation of mature gametes in adults. We also describe the current methods used in germ cell toxicity testing and their limitations in examining the complex features of mammalian germ cell development. To bypass these challenges, we propose the use of alternative model systems such as Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and in vitro germ cell methods that have distinct advantages over traditional toxicity models. We discuss the benefits and limitations of each approach, their application to germ cell toxicity studies, and the need for computational approaches to maximize the usefulness of these models. Together, the inclusion of these alternative germ cell toxicity models will be invaluable for the examination of stages not easily accessible in mammals as well as the large scale, high-throughput investigation of germ cell toxicity. PMID:25821157

A test strategy for the assessment of additive attributed toxicity of tobacco products.

PubMed

Kienhuis, Anne S; Staal, Yvonne C M; Soeteman-Hernández, Lya G; van de Nobelen, Suzanne; Talhout, Reinskje

2016-08-01

The new EU Tobacco Product Directive (TPD) prohibits tobacco products containing additives that are toxic in unburnt form or that increase overall toxicity of the product. This paper proposes a strategy to assess additive attributed toxicity in the context of the TPD. Literature was searched on toxicity testing strategies for regulatory purposes from tobacco industry and governmental institutes. Although mainly traditional in vivo testing strategies have been applied to assess toxicity of unburnt additives and increases in overall toxicity of tobacco products due to additives, in vitro tests combined with toxicogenomics and validated using biomarkers of exposure and disease are most promising in this respect. As such, tests are needed that are sensitive enough to assess additive attributed toxicity above the overall toxicity of tobacco products, which can associate assay outcomes to human risk and exposure. In conclusion, new, sensitive in vitro assays are needed to conclude whether comparable testing allows for assessment of small changes in overall toxicity attributed to additives. A more pragmatic approach for implementation on a short-term is mandated lowering of toxic emission components. Combined with risk assessment, this approach allows assessment of effectiveness of harm reduction strategies, including banning or reducing of additives. Copyright © 2016 Elsevier Ltd. All rights reserved.

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 ...

Bioswales reduce contaminants associated with toxicity in urban storm water.

PubMed

Anderson, Brian S; Phillips, Bryn M; Voorhees, Jennifer P; Siegler, Katie; Tjeerdema, Ronald

2016-12-01

Contamination and toxicity associated with urban storm water runoff are a growing concern because of the potential impacts on receiving systems. California water regulators are mandating implementation of green infrastructure as part of new urban development projects to treat storm water and increase infiltration. Parking lot bioswales are low impact development practices that promote filtering of runoff through plants and soil. Studies have demonstrated that bioswales reduce concentrations of suspended sediments, metals, and hydrocarbons. There have been no published studies evaluating how well these structures treat current-use pesticides, and studies have largely ignored whether bioswales reduce toxicity in surface water. Three storms were monitored at 3 commercial and residential sites, and reductions of contaminants and associated toxicity were quantified. Toxicity testing showed that the majority of untreated storm water samples were toxic to amphipods (Hyalella azteca) and midges (Chironomus dilutus), and toxicity was reduced by the bioswales. No samples were toxic to daphnids (Ceriodaphnia dubia) or fish (Pimephales promelas). Contaminants were significantly reduced by the bioswales, including suspended solids (81% reduction), metals (81% reduction), hydrocarbons (82% reduction), and pyrethroid pesticides (74% reduction). The single exception was the phenypyrazole pesticide fipronil, which showed inconsistent treatment. The results demonstrate these systems effectively treat contaminated storm water associated with surface water toxicity but suggest that modifications of their construction may be required to treat some contaminant classes. Environ Toxicol Chem 2016;35:3124-3134. © 2016 SETAC. © 2016 SETAC.

Acute toxicity of low pH to the brown darter Etheostoma edwini under flow-through conditions

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

Kase, J.; Burnett, M.; Shortelle, A.B.

1995-12-31

The Okaloosa darter, Etheostoma okaloosae, is found exclusively in the Rocky and Boggy Bayou stream systems entering Choctawhatchee Bay, Florida. Due to its limited range and habitat degradation, E. okaloosae was added to the List of Endangered Species in 1973. The Air Force controls several active test areas situated near streams known to contain Okaloosa darters. The possible release and deposition of strong acids such as hydrochloric acid and hydrofluoric acid to stream surface water during some testing activities has raised concerns that the Okaloosa darter population may be adversely affected by episodic pH depression as a result of testingmore » activities. To evaluate the sensitivity of the Okaloosa darter to pH depression, acute toxicity tests using a closely related species, E. edwini, were conducted. Ninety-six hour and 200 min acute pH depression flow-through toxicity tests were performed with surface water collected from the Rocky Bayou stream system. The 96 h test was conducted using six concentrations held at constant pH throughout the duration of the exposure. The 200 min test used an episodic exposure; pH in the exposure chambers were initially dropped and allowed to return to normal. Mortality data obtained during the studies were used to determine the pH depression necessary to cause 50% mortality (LC50) in each scenario. The 96 h and 200 min LC50 values are, respectively, 3.79 and 2.99 s.u. The 200 min LC50 calculations are based on the lowest achieved pH in each exposure during the test. The results of these tests are part of an effort by the Air Force to make risk-based management decision regarding testing activities.« less

A ten year summary of concurrent ambient water column and sediment toxicity tests in the Chesapeake Bay watershed: 1990-1999.

PubMed

Hall, Lenwood W; Anderson, Ronald D; Alden, Raymond W

2002-06-01

The goal of this study was to identify the relative toxicity of ambient areas in the Chesapeake Bay watershed by using a suite of concurrent water column and sediment toxicity tests at seventy-five ambient stations in 20 Chesapeake Bay rivers from 1990 through 1999. Spatial and temporal variability was examined at selected locations throughout the 10 yr study. Inorganic and organic contaminants were evaluated in ambient water and sediment concurrently with water column and sediment tests to assess possible causes of toxicity although absolute causality can not be established. Multivariate statistical analysis was used to develop a multiple endpoint toxicity index (TOX-INDEX) at each station for both water column and sediment toxicity data. Water column tests from the 10 yr testing period showed that 49% of the time, some degree of toxicity was reported. The most toxic sites based on water column results were located in urbanized areas such as the Anacostia River, Elizabeth River and the Middle River. Water quality criteria for copper, lead, mercury, nickel and zinc were exceeded at one or more of these sites. Water column toxicity was also reported in localized areas of the South and Chester Rivers. Both spatial and temporal variability was reported from the suite of water column toxicity tests. Some degree of sediment toxicity was reported from 62% of the tests conducted during the ten year period. The Elizabeth River and Baltimore Harbor stations were reported as the most toxic areas based on sediment results. Sediment toxicity guidelines were exceeded for one or more of the following metals at these two locations: arsenic, cadmium, chromium, copper, lead, nickel and zinc. At the Elizabeth River stations nine of sixteen semi-volatile organics and two of seven pesticides measured exceeded the ER-M values in 1990. Ambient sediment toxicity tests in the Elizabeth River in 1996 showed reduced toxicity. Various semi-volatile organics exceeded the ER-M values at a number of Baltimore Harbor sites; pyrene and dibenzo(a,h)anthracene were particularly high at one of the stations (Northwest Harbor). Localized sediment toxicity was also reported in the Chester, James, Magothy, Rappahannock, and Potomac Rivers but the link with contaminants was not determined. Both spatial and temporal variability was less for sediment toxicity data when compared with water column toxicity data. A comparison of water column and sediment toxicity data for the various stations over the 10 yr study showed that approximately half the time agreement occurred (either both suite of tests showed toxicity or neither suite of tests showed toxicity).

Nanoparticles in medicine: Current challenges facing inorganic nanoparticle toxicity assessments and standardizations.

PubMed

Hofmann-Amtenbrink, Margarethe; Grainger, David W; Hofmann, Heinrich

2015-10-01

Although nanoparticles research is ongoing since more than 30years, the development of methods and standard protocols required for their safety and efficacy testing for human use is still in development. The review covers questions on toxicity, safety, risk and legal issues over the lifecycle of inorganic nanoparticles for medical applications. The following topics were covered: (i) In vitro tests may give only a very first indication of possible toxicity as in the actual methods interactions at systemic level are mainly neglected; (ii) the science-driven and the regulation-driven approaches do not really fit for decisive strategies whether or not a nanoparticle should be further developed and may receive a kind of "safety label". (iii) Cost and time of development are the limiting factors for the drug pipeline. Knowing which property of a nanoparticle makes it toxic it may be feasible to re-engineer the particle for higher safety (safety by design). Testing the safety and efficacy of nanoparticles for human use is still in need of standardization. In this concise review, the author described and discussed the current unresolved issues over the application of inorganic nanoparticles for medical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

Transport, fate, and long-term impacts of metal oxide nanoparticles on the stability of an anaerobic methanogenic system with anaerobic granular sludge.

PubMed

Li, Huiting; Cui, Fuyi; Liu, Zhiquan; Li, Dapeng

2017-06-01

The fate and long-term effect of different metal oxide (TiO 2 , CuO and ZnO) nanoparticles (NPs) on anaerobic granular sludge (AGS) was evaluated in an anaerobic methanogenic system. Operation stability and structural characteristics of the granules were compared, the metabolism changes in the microbial community were quantified, and NPs fate were investigated. CuO NPs had greatest toxic effect on AGS after extended exposure, whereas ZnO NPs benefited methanogenesis temporarily (no more than 5d). The inhibition on AGS caused by NPs varied due to the unique structure of AGS and different toxic mechanism. Structural changes of AGS provided new evidence that tested NPs have different toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2014 CFR

2014-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2012 CFR

2012-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2013 CFR

2013-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

40 CFR 798.4100 - Dermal sensitization.

Code of Federal Regulations, 2011 CFR

2011-07-01

... system selected is recommended; (ii) Animals may act as their own controls or groups of induced animals... CONTROL ACT (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Specific Organ/Tissue Toxicity § 798.4100 Dermal... hypersensitive state is developed. (3) Induction exposure is an experimental exposure of a subject to a test...

Biohybrid Membrane Systems and Bioreactors as Tools for In Vitro Drug Testing.

PubMed

Salerno, Simona; Bartolo, Loredana De

2017-01-01

In drug development, in vitro human model systems are absolutely essential prior to the clinical trials, considering the increasing number of chemical compounds in need of testing, and, keeping in mind that animals cannot predict all the adverse human health effects and reactions, due to the species-specific differences in metabolic pathways. The liver plays a central role in the clearance and biotransformation of chemicals and xenobiotics. In vitro liver model systems by using highly differentiated human cells could have a great impact in preclinical trials. Membrane biohybrid systems constituted of human hepatocytes and micro- and nano-structured membranes, represent valuable tools for studying drug metabolism and toxicity. Membranes act as an extracellular matrix for the adhesion of hepatocytes, and compartmentalise them in a well-defined physical and chemical microenvironment with high selectivity. Advanced 3-D tissue cultures are furthermore achieved by using membrane bioreactors (MBR), which ensure the continuous perfusion of cells protecting them from shear stress. MBRs with different configurations allow the culturing of cells at high density and under closely monitored high perfusion, similarly to the natural liver. These devices that promote the long-term maintenance and differentiation of primary human hepatocytes with preserved liver specific functions can be employed in drug testing for prolonged exposure to chemical compounds and for assessing repeated-dose toxicity. The use of primary human hepatocytes in MBRs is the only system providing a faster and more cost-effective method of analysis for the prediction of in vitro human drug metabolism and enzyme induction alternative and/or complementary to the animal experimentation. In this paper, in vitro models for studying drug metabolism and toxicity as advanced biohybrid membrane systems and MBRs will be reviewed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Parallel Analyses of Alexandrium catenella Cell Concentrations and Shellfish Toxicity in the Puget Sound▿

PubMed Central

Dyhrman, Sonya T.; Haley, Sheean T.; Borchert, Jerry A.; Lona, Bob; Kollars, Nicole; Erdner, Deana L.

2010-01-01

Alexandrium catenella is widespread in western North America and produces a suite of potent neurotoxins that cause paralytic shellfish poisoning (PSP) in humans and have deleterious impacts on public health and economic resources. There are seasonal PSP-related closures of recreational and commercial shellfisheries in the Puget Sound, but the factors that influence cell distribution, abundance, and relationship to paralytic shellfish toxins (PSTs) in this system are poorly described. Here, a quantitative PCR assay was used to detect A. catenella cells in parallel with state shellfish toxicity testing during the 2006 bloom season at 41 sites from April through October. Over 500,000 A. catenella cells liter−1 were detected at several stations, with two main pulses of cells driving cell distribution, one in June and the other in August. PSTs over the closure limit of 80 μg of PST 100 per g of shellfish tissue were detected at 26 of the 41 sites. Comparison of cell numbers and PST data shows that shellfish toxicity is preceded by an increase in A. catenella cells in 71% of cases. However, cells were also observed in the absence of PSTs in shellfish, highlighting the complex relationship between A. catenella and the resulting shellfish toxicity. These data provide important information on the dynamics of A. catenella cells in the Puget Sound and are a first step toward assessing the utility of plankton monitoring to augment shellfish toxicity testing in this system. PMID:20495054

Risk assessment of an abandoned pyrite mine in Spain based on direct toxicity assays.

PubMed

García-Gómez, Concepción; Sánchez-Pardo, Beatriz; Esteban, Elvira; Peñalosa, Jesús Manuel; Fernández, María Dolores

2014-02-01

This research reports the risk assessment of an abandoned pyrite mine using direct toxicity assays of soil and groundwater samples taken at the site. The toxicity of As and heavy metals from mining soils to soil and aquatic organisms was studied using the Multispecies Soil System (MS-3) in soil columns. Ecotoxicological assessment was performed with soil samples diluted with a control soil at concentrations of 12.5, 25, 50 and 100% test soil/soil (w/w). In this way, changes in the mobility and bioavailability of soil contaminants due to changes in geochemical soil properties via soil dilution were studied. The toxicity of water samples was tested on algae and Daphnia magna. The assessment of the mining area indicated that the current presence of As and heavy metals at the site may cause injuries to soil and aquatic organisms in the entire research area. Moreover, this investigation demonstrated that changes in geochemical conditions can increase the availability of arsenic and, consequently, the environmental risk of these soils. A good correlation was not found between toxicity parameters and the concentrations of soil contaminants based on total and extracted element concentrations. This finding reinforces the usefulness of direct toxicity assays for evaluating environmental risk. © 2013.

Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

PubMed

Dent, M P

2007-08-01

The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert for possible effects on fertility (or early embryonic development), the biological significance of which can be ascertained in a littering (e.g. 2-generation) study. From the chemicals reviewed it would appear that where there are no alerts from a repeat-dose toxicity study, a pre-natal developmental toxicity study and sex steroid receptor binding assays, there exists a low priority for animal studies to address the fertility endpoint. The ability for these types of tests to provide alerts for effects on fertility is clearly dependent on the mode of action of the toxicant in question. Further work should therefore be performed to determine the 'failure rate' of this type of approach when applied to a larger group of chemicals with diverse modes of action.

Fractionation of fulvic acid by iron and aluminum oxides: influence on copper toxicity to Ceriodaphnia dubia

USGS Publications Warehouse

Smith, Kathleen S.; Ranville, James F.; Lesher, Emily K.; Diedrich, Daniel J.; McKnight, Diane M.; Sofield, Ruth M.

2014-01-01

This study examines the effect on aquatic copper toxicity of the chemical fractionation of fulvic acid (FA) that results from its association with iron and aluminum oxyhydroxide precipitates. Fractionated and unfractionated FAs obtained from streamwater and suspended sediment were utilized in acute Cu toxicity tests on ,i>Ceriodaphnia dubia. Toxicity test results with equal FA concentrations (6 mg FA/L) show that the fractionated dissolved FA was 3 times less effective at reducing Cu toxicity (EC50 13 ± 0.6 μg Cu/L) than were the unfractionated dissolved FAs (EC50 39 ± 0.4 and 41 ± 1.2 μg Cu/L). The fractionation is a consequence of preferential sorption of molecules having strong metal-binding (more aromatic) moieties to precipitating Fe- and Al-rich oxyhydroxides, causing the remaining dissolved FA to be depleted in these functional groups. As a result, there is more bioavailable dissolved Cu in the water and hence greater potential for Cu toxicity to aquatic organisms. In predicting Cu toxicity, biotic ligand models (BLMs) take into account dissolved organic carbon (DOC) concentration; however, unless DOC characteristics are accounted for, model predictions can underestimate acute Cu toxicity for water containing fractionated dissolved FA. This may have implications for water-quality criteria in systems containing Fe- and Al-rich sediment, and in mined and mineralized areas in particular. Optical measurements, such as specific ultraviolet absorbance at 254 nm (SUVA254), show promise for use as spectral indicators of DOC chemical fractionation and inferred increased Cu toxicity.

Sediment toxicity in Savannah Harbor

USGS Publications Warehouse

Winger, P.V.; Lasier, P.J.

1995-01-01

Savannah Harbor, located near the mouth of the Savannah River, Georgia and South Carolina, is impacted by industrial and municipal effluents. Potential release of contaminants stored in harbor sediments through dredging and shipping operations requires that contaminated areas be identified for proper management of the system and protection of wildlife resources. During 1991, Hyalella azteca were exposed in 10-d static-renewal toxicity tests to pore-water and solid-phase sediment samples collected from 26 sites within Savannah Harbor. Pore-water toxicity was more pronounced than that for solidphase sediment. Toxicity and reduced leaf consumption demonstrated impaired sediment quality at specific sites within Savannah Harbor and Back River. Factors responsible for the decreased sediment quality were ammonia, alkalinity, and metal concentrations (cadmium, chromium, lead, molybdenum, and nickel). Elevated concentrations of metals and toxicities in Back River sediments indicated impacts from adjacent dredge-spoil areas.

Adverse Outcome Pathways and Systems Biology as Conceptual Approaches to Support Development of 21st Century Test Methods and Extrapolation Tools

EPA Science Inventory

The proposed paradigm for “Toxicity Testing in the 21st Century” supports the development of mechanistically-based, high-throughput in vitro assays as a potential cost effective and scientifically-sound alternative to some whole animal hazard testing. To accomplish this long-term...

A New Framework for Addressing Adverse Childhood and Community Experiences: The Building Community Resilience Model.

PubMed

Ellis, Wendy R; Dietz, William H

We propose a transformative approach to foster collaboration across child health, public health, and community-based agencies to address the root causes of toxic stress and childhood adversity and to build community resilience. Physicians, members of social service agencies, and experts in toxic stress and adverse childhood experiences (ACEs) were interviewed to inform development of the Building Community Resilience (BCR) model. Through a series of key informant interviews and focus groups, we sought to understand the role of BCR for child health systems and their partners to reduce toxic stress and build community resilience to improve child health outcomes. Key informants indicated the intentional approach to ACEs and toxic stress through continuous quality improvement (data-driven decisions and program development, partners testing and adapting to changes to their needs, and iterative development and testing) which provides a mechanism by which social determinants or a population health approach could be introduced to physicians and community partners as part of a larger effort to build community resilience. Structured interviews also reveal a need for a framework that provides guidance, structure, and support for child health systems and community partners to develop collective goals, shared work plans, and a means for data-sharing to reinforce the components that will contribute to community resilience. Key informant interviews and focus group dialogues revealed a deep understanding of the factors related to toxic stress and ACEs. Respondents endorsed the BCR approach as a means to explore capacity issues, reduce fragmented health care delivery, and facilitate integrated systems across partners in efforts to build community resilience. Current financing models are seen as a potential barrier, because they often do not support restructured roles, partnership development, and the work to sustain upstream efforts to address toxic stress and community resilience. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Environmental and toxicological planning in polymer production and disposal.

PubMed Central

Levinskas, G J

1975-01-01

There is neither a prescribed format nor a rigid sequence of testing to follow for the assessment of health and environmental effects of chemicals. Conventional animal toxicity tests plus medical surveillance and monitoring of exposed human populations will provide knowledge of the biological effects of chemicals and assurance that they can be handled safely. Useful information also can be derived from other test procedures. These include extraction studies to measure the amounts of additives which can leach from polymers, toxicity tests using aquatic organisms and birds, and determination of the biodegradability of materials and their potential for accumulation and magnification in biological systems. Current concern over pyrolysis products of polymers points up the need for defining the variables involved and development of test procedures by which meaningful evaluations of potential health hazards can be made. PMID:1175554

Influence of temperature and nutrient strength on the susceptibility of Saccharomyces cerevisiae to heavy metals

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

Hsu, T.; Lee, L.W.; Chang, T.H.

1992-09-01

Saccharomyces cerevisiae is not only a key microorganism in brewing or fermentation processes, it has also been employed for monitoring aquatic pollutants. The major advantage of using Saccharomyces cerevisiae as a bioassay system is that this yeast can be easily obtained as dry pellets from commercial sources at low cost. In addition to its economical aspect, Saccharomyces cerevisiae, like other microorganisms, is easy to handle, grows rapidly, and provides a large number of homogeneous individuals for utilization in toxicity tests. Although cell growth, cell viability, electron transport and mitochondrial respiration of Saccharomyces cerevisiaes have all been selected as parameters formore » toxicity assessment, measuring cell growth by absorbance is by farm the most convenient and rapid method when large amounts of water samples are to be tested. Mochida et al. (1988), however, reported that Saccharomyces cerevisiae was five to ten times less sensitive than cell culture systems to cadmium, mercury and nickel, when cell growth of both systems was monitored. This relative insensitivity to heavy metals might handicap the practical use of this yeast strain for bioassays. Since previous studies indicated that the susceptibility of microorganisms to environmental toxicants can be influenced by incubation temperature and nutrient strength, we attempted to examine the effect of incubation temperature and nutrient strength on the susceptibility of Saccharomyces cerevisiae to heavy metals in order to obtain the optimum bioassay sensitivity. In this study, we used cadmium and mercury as model toxicants. 9 refs., 2 figs., 1 tab.« less

Research of nickel nanoparticles toxicity with use of Aquatic Organisms

NASA Astrophysics Data System (ADS)

Morgaleva, T.; Morgalev, Yu; Gosteva, I.; Morgalev, S.

2015-11-01

The effect of nanoparticles with the particle size Δ50=5 nm on the test function of aquatic organisms was analyzed by means of biotesting methods with the use of a complex of test-organisms representing general trophic levels. The dependence of an infusoria Paramecium caudatum chemoattractant-elicited response, unicellular algae Chlorella vulgaris Beijer growth rate, Daphnia magna Straus mortality and trophic activity and Danio rerio fish kill due to nNi disperse system concentration, is estimated. It is determined that the release of chlorella into cultivated environment including nNi as a feed for daphnias raises the death rate of entomostracans. The minimal concentration, whereby an organism response to the effect of nNi is registered, depends on the type of test organism and the analysed test function. L(E)C20 is determined for all the organisms used in bioassays. L(E)C50 is estimated for Paramecium caudatum (L(E)C50 = 0.0049 mg/l), for Chlorella vulgaris Beijer (L(E)C50 = 0.529 mg/l), for Daphnia m. S (L(E)C50 > 100 mg/l) and for fish Danio rerio (L(E)C50 > 100 mg/l). According to the Globally Harmonized System hazard substance evaluation criteria and Commission Directive 93/67/EEC, nNi belongs to the “acute toxicity 1” category of toxic substances.

Ionic liquids as lubricants or lubrication additives: an ecotoxicity and biodegradability assessment.

PubMed

Stolte, Stefan; Steudte, Stephanie; Areitioaurtena, Olatz; Pagano, Francesco; Thöming, Jorg; Stepnowski, Piotr; Igartua, Amaya

2012-11-01

This paper reports on the (eco)toxicity and biodegradability of ionic liquids considered for application as lubricants or lubrication additives. Ammonium- and pyrrolidinium-based cations combined with methylsulphate, methylsulphonate and/or (CF(3)SO(2))(2)N(-) anions were investigated in tests to determine their aquatic toxicity using water fleas Daphnia magna, green algae Selenastrum capricornutum and marine bacteria (Vibrio fischeri). Additional test systems with an isolated enzyme (acetylcholinesterase) and isolated leukaemia cells from rats (IPC-81) were used to assess the biological activity of the ionic liquids. These compounds generally exhibit low acute toxicity and biological activity. Their biodegradability was screened according to OECD test procedures 301 B and 301 F. For choline and methoxy-choline ionic liquids ready biodegradability was observed within 5 or 10 d, respectively. Some of the compounds selected have a considerable potential to contribute to the development of more sustainable products and processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hydra, a model system for environmental studies.

PubMed

Quinn, Brian; Gagné, François; Blaise, Christian

2012-01-01

Hydra have been extensively used for studying the teratogenic and toxic potential of numerous toxins throughout the years and are more recently growing in popularity to assess the impacts of environmental pollutants. Hydra are an appropriate bioindicator species for use in environmental assessment owing to their easily measurable physical (morphology), biochemical (xenobiotic biotransformation; oxidative stress), behavioural (feeding) and reproductive (sexual and asexual) endpoints. Hydra also possess an unparalleled ability to regenerate, allowing the assessment of teratogenic compounds and the impact of contaminants on stem cells. Importantly, Hydra are ubiquitous throughout freshwater environments and relatively easy to culture making them appropriate for use in small scale bioassay systems. Hydra have been used to assess the environmental impacts of numerous environmental pollutants including metals, organic toxicants (including pharmaceuticals and endocrine disrupting compounds), nanomaterials and industrial and municipal effluents. They have been found to be among the most sensitive animals tested for metals and certain effluents, comparing favourably with more standardised toxicity tests. Despite their lack of use in formalised monitoring programmes, Hydra have been extensively used and are regarded as a model organism in aquatic toxicology.

Predictive Modeling of Apical Toxicity Endpoints Using Data ...

EPA Pesticide Factsheets

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 using a variety of in vitro assays and using the results to prioritize chemicals for further, more detailed testing. Phase I of ToxCast is testing 320 chemicals (mainly pesticide active ingredients) against ~400 cell-based and biochemical assays. In order to anchor these studies, we are using in vivo guideline study data for subchronic, chronic, cancer, reproductive and developmental endpoints. This data is compiled in the EPA toxicity reference database, ToxRefDB. The main goal of ToxCast is the discovery and validation of “signatures” linking in vitro assay data to in vivo toxicity endpoints. These signatures will be collections of assays that are correlated with particular endpoints. These assay collections should also help define molecular-and cellular-level mechanisms of toxicity. This talk will discuss our strategy to use a combination of statistical and machine learning methods, coupled with biochemical network or systems biology approaches. Our initial examples will focus signatures for endpoints from 2 year rodent cancer bioassays. Most of the data we have analyzed is in dose or concentration response series, so to effectively use this data we have developed novel appro

Animal use in the chemical and product manufacturing sectors - can the downtrend continue?

PubMed

Curren, Rodger

2009-12-01

During the 1990s and early 2000s, a number of manufacturing companies in the cosmetic, personal care and household product industries were able to substantially reduce their use of animals for testing (or to not use animals in the first place). These reductions were almost always the result of significant financial contributions to either direct, in-house alternatives research, or to support personnel whose duties were to understand and apply the current state-of-the-art for in vitro testing. They occurred almost exclusively in non-regulatory areas, and primarily involved acute topical toxicities. Over the last few years, the reduction in animal use has been much less dramatic, because some companies are still reluctant to change from the traditional animal studies, because systemic, repeat-dose toxicity is more difficult to model in vitro, and because many products still require animal testing for regulatory approval. Encouragingly, we are now observing an increased acceptance of non-animal methods by regulatory agencies. This is due to mounting scientific evidence from larger databases, agreement by companies to share data and testing strategies with regulatory agencies, and a focus on smaller domains of applicability. These changes, along with new emphasis and financial support for addressing systemic toxicities, promise to provide additional possibilities for industry to replace animals with in vitro methods, alone or in combination with in silico methods. However, the largest advance will not occur until more companies commit to using the non-animal test strategies that are currently available. 2009 FRAME.

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.

Environmental hazard assessment of cheese manufacturing effluent treated for hydrogen production.

PubMed

Karadima, Constantina; Theodoropoulos, Chris; Iliopoulou-Georgudaki, Joan

2009-09-01

Toxicity of effluents after treatment in an anaerobic fermentation system for hydrogen production is evaluated with three biotests: The zebrafish Danio rerio embryo test, the Thamnotoxkit F and the Daphtoxkit F(TM) magna. Samples were classified from "very" to "extremely toxic". Average toxicity values for zebrafish were 1.55% (24 h) and 0.75% (48 h), for Thamnocephalus 0.69% (24 h) and for Daphnia 2.51% (24 h) and 1.82% (48 h). Statistical analysis between physicochemical parameters and LC(50) values revealed that PO(4)(-3), SO(4)(-2), NH(3)N and NO(3)(-) have the major contribution to toxicity. Based on results, this treatment is considered an environmentally ineffective way of managing the specific wastes.

Toxicity of granular activated carbon treated coal gasification water as determined by the Microtox test and Escherichia coli.

PubMed

Makino, Y; Adams, J C; McTernan, W F

1986-01-01

The Microtox assay and various parameters (growth, ATP concentration and electrochemical detection) of Escherichia coli were used to assess the toxicity of various levels of granular activated carbon treated coal gasification process water. The generation time of E. coli was statistically significantly slower at the level of 50 percent treatment than any other level of treatment. No differences were seen for ATP concentration per cell or in the electrochemical detection methods for any level treatment. There was a very high correlation between total organic carbon removal by GAC treatment and reduction in toxicity as measured by the Microtox system. However, even the treated water which had 91 percent of the TOC removed was still highly toxic.

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...

TEST (Toxicity Estimation Software Tool) Ver 4.1

EPA Science Inventory

The Toxicity Estimation Software Tool (T.E.S.T.) has been developed to allow users to easily estimate toxicity and physical properties using a variety of QSAR methodologies. T.E.S.T allows a user to estimate toxicity without requiring any external programs. Users can input a chem...

Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

USGS Publications Warehouse

Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

1979-01-01

Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

Biodistribution and toxicity of spherical aluminum oxide nanoparticles.

PubMed

Park, Eun-Jung; Lee, Gwang-Hee; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun; Cho, Myung-Haing; Kim, Dong-Wan

2016-03-01

With the rapid development of the nano-industry, concerns about their potential adverse health effects have been raised. Thus, ranking accurately their toxicity and prioritizing for in vivo testing through in vitro toxicity test is needed. In this study, we used three types of synthesized aluminum oxide nanoparticles (AlONPs): γ-aluminum oxide hydroxide nanoparticles (γ-AlOHNPs), γ- and α-AlONPs. All three AlONPs were spherical, and the surface area was the greatest for γ-AlONPs, followed by the α-AlONPs and γ-AlOHNPs. In mice, γ-AlOHNPs accumulated the most 24 h after a single oral dose. Additionally, the decreased number of white blood cells (WBC), the increased ratio of neutrophils and the enhanced secretion of interleukin (IL)-8 were observed in the blood of mice dosed with γ-AlOHNPs (10 mg kg(-1)). We also compared their toxicity using four different in vitro test methods using six cell lines, which were derived from their potential target organs, BEAS-2B (lung), Chang (liver), HACAT (skin), H9C2 (heart), T98G (brain) and HEK-293 (kidney). The results showed γ-AlOHNPs induced the greatest toxicity. Moreover, separation of particles was observed in a transmission electron microscope (TEM) image of cells treated with γ-AlOHNPs, but not γ-AlONPs or α-AlONPs. In conclusion, our results suggest that the accumulation and toxicity of AlONPs are stronger in γ-AlOHNPs compared with γ-AlONPs and α-AlONPs owing their low stability within biological system, and the presence of hydroxyl group may be an important factor in determining the distribution and toxicity of spherical AlONPs. Copyright © 2015 John Wiley & Sons, Ltd.

Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

USGS Publications Warehouse

Vyas, Nimish B.; Rattner, Barnett A.

2012-01-01

Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

Predicting In Vivo Effect Levels for Repeat Dose Systemic Toxicity using Chemical, Biological, Kinetic and Study Covariates

EPA Science Inventory

In an effort to ensure chemical safety while reducing reliance on animal testing, USEPA and L’Oréal have collaborated to address a major challenge in chemical safety assessment using alternative approaches: the prediction of points-of-departure (POD) of systemic effects. Systemic...

TESTING OF TOXICOLOGY AND EMISSIONS SAMPLING METHODOLOGY FOR OCEAN INCINERATION OF HAZARDOUS WASTES

EPA Science Inventory

The report addresses the development and testing of a system to expose marine organisms to hazardous waste emissions in order to assess the potential toxicity of incinerator plumes at sea as they contact the marine environment through air-sea exchange and initial mixing. A sampli...

Developmental toxicity and structure/activity correlates of glycols and glycol ethers.

PubMed Central

Johnson, E M; Gabel, B E; Larson, J

1984-01-01

In recent years, the National Toxicology Program (NTP) has selected numerous glycol ethers for testing in routine laboratory mammals to ascertain the magnitude of their ability to injure the conceptus. From the lists available of ongoing and projected NTP test chemicals, a series of glycol ethers was selected for examination in vitro in the hydra assay. Also tested were additional chemicals of similar molecular configuration and/or composition. This short-term screening test placed the 14 glycols and glycol ethers tested into a rank order sequence according to their degree of hazard potential to developmental biology, i.e., their ability to interfere with the developmental events characteristic of all ontogenic systems. They were ranked according to the difference between the lowest dose or concentration overtly toxic to adults (A) and the lowest concentration interfering with development (D) of the artificial embryo of reaggregated adult hydra cells and the A/D ratio. Published data from mammalian studies were available for a few of the test chemicals, and in each instance the hydra assay was in direct agreement with the outcomes reported of the more elaborate and standard animal tests. Ethylene glycol and ethylene glycol monomethyl ether were shown by both standard evaluations in mammals, and by the hydra assay, to disrupt embryos only at or very near to their respective adult toxic doses, whereas the mono-ethyl ether perturbed development at approximately one-fifth of the lowest dose overtly toxic to adults.(ABSTRACT TRUNCATED AT 250 WORDS) Images FIGURE 1. A FIGURE 1. B FIGURE 1. C PMID:6499797

Non-animal Replacements for Acute Toxicity Testing.

PubMed

Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

2015-07-01

Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

Evaluation of acute toxicity, sedative and analgesic effects of Taverniera glabra methanolic extract on mice.

PubMed

Marvi, -; Iqbal, Javeid; Muhammad, Shafi; Ahmad, Mansoor

2016-11-01

Present study was conducted on crude methanolic extract of stem and root of Taverniera glabra. In Pakistan T. glabra is found in the region of Balochistan only. T. glabra has numerous therapeutic uses in traditional medicine and it is also used for the pain relief. Current study was carried out to evaluate acute toxicity, analgesic and CNS depressant activity of the plant. Acute toxicity was carried out by oral administration of the T. glabra extract from 250 to 2000mg/kg oral dose. Analgesic activity was carried out by acetic acid induced writhing test and formalin test. Central Nervous System (CNS) depressant activity was carried out by exploratory activities (open field activity, cage crossing activity, rearing test) and forced swimming test. Oral administration of the methanolic extract of T. glabra was nontoxic at the dose of 1500mg/kg in the acute toxicity test. Exploratory behavior of mice treated with the methanolic extract of T. glabra showed sedative effects (P<0.05) in open field, cage crossing, traction and rearing test, particularly at the dose of 500mg as compared with standard drug Diazepam. In forced swimming test, mobility time was significantly (P<0.05) increased at 500mg/kg oral dose, and results were significant as compared with control. Methanolic extract of T. glabra produced significant (P<0.05) analgesic effects at the dose of 500mg/kg in the acetic acid induced writhing test and the formalin test. In conclusion, results show that the crude methanolic extract of T. glabra possess sedative as well as potent analgesic effects. Present pharmacological studies are the first ever studies conducted on the methanolic extract of T. glabra.

Review of toxicity studies performed on an underground coal gasification condensate water

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

Barker, F.P.

1987-09-01

Three studies related to the toxicity of underground coal gasification (UCG) waters have bee conducted: (1) toxicity study of UCG water and its fractions as determined by the Microtox test, (2) toxicity study of biotreated UCG water as determined by the Microtox test, and (3) toxicity study of UCG water to macroinvertebrates. The results of these studies are summarized herein. The gas condensate water from the UCG process is extremely toxic as determined by assays with photoluminescent bacteria (Microtox), benthic (bottom-dwelling) macroinvertebrates (mayflies), and Daphnia magna (water flea). Microtox bioassays reveal that the toxic components of the water reside inmore » both the organophilic and hydrophilic fractions, although the organophilic fraction is notably more toxic. A sequential treatment process reduced the toxicity of the UCG water, as measured by the Microtox test. Solvent extraction (to remove phenols) followed by ammonia stripping yielded a less toxic water. Additional treatment by activated sludge further reduced toxicity. Finally, the addition of powdered activated carbon to the activated sludge yielded the least toxic water. A bioassay technique was developed for lotic (running water) macroinvertebrates (Drunella doddsi and Iron longimanus). The toxicity results were compared with results from the traditional test animal, Daphnia magna. Short-term exposures to the UCG waters were more toxic to Daphnia magna than to Drunella doddsi or Iron longimanus, although the toxicity values begin to merge with longer test exposure. The greater toxicity seems to be related to a thinner exoskeleton. 26 refs., 2 figs., 6 tabs.« less

Kombucha--toxicity alert.

PubMed

The Kombucha mushroom, also known as Manchurian mushroom, is a mail-order product touted to lower blood pressure and raise T-cell counts. No controlled trials have been conducted to test these claims. Aspergillus, a mold that may grow on the Kombucha mushroom, attacks the brain and may be fatal to persons with weakened immune systems. Reported toxicity reactions have included stomach problems and yeast infections. Taking Kombucha in combination with other drugs may affect the drugs potency.

Toxicity of Tolyltriazole to Gram-Positive Coccus Microorganisms

DTIC Science & Technology

2000-03-01

Bausmith and Neufield 459). The second general category is the SAE Type II ADAF, which is a Type I ADAF with the addition of synthetic polymers...Act of 1972 ( Bausmith and Neufield 459, Gallagher 1995:109). The FAA and EPA requirements concerning ADAFs are often in conflict; as the FAA...AZUR Environmental. "Microtox Rapid Toxicity Testing System". http://www.azurenv.com/mtox.htm. October 1999. 3. Bausmith , David S. and Ronald D

Evaluating porewater polycyclic aromatic hydrocarbon-related toxicity at a contaminated sediment site using a spiked field-sediment approach.

PubMed

Hartzell, Sharon E; Unger, Michael A; Vadas, George G; Yonkos, Lance T

2018-03-01

Although the complexity of contaminant mixtures in sediments can confound the identification of causative agents of adverse biological response, understanding the contaminant(s) of primary concern at impacted sites is critical to sound environmental management and remediation. In the present study, a stock mixture of 18 polycyclic aromatic hydrocarbon (PAH) compounds was prepared to reflect the variety and relative proportions of PAHs measured in surface sediment samples collected from discrete areas of a historically contaminated industrial estuary. This site-specific PAH stock mixture was spiked into nontoxic in-system and out-of-system field-collected reference sediments in dilution series spanning the range of previously measured total PAH concentrations from the region. Spiked sediments were evaluated in 10-d Leptocheirus plumulosus tests to determine whether toxicity in laboratory-created PAH concentrations was similar to the toxicity found in field-collected samples with equivalent PAH concentrations. The results show that toxicity of contaminated sediments was not explained by PAH exposure, while indicating that toxicity in spiked in-system (fine grain, high total organic carbon [TOC]) and out-of-system (course grain, low TOC) sediments was better explained by porewater PAH concentrations, measured using an antibody-based biosensor that quantified 3- to 5-ring PAHs, than total sediment PAH concentrations. The study demonstrates the application of site-specific spiking experiments to evaluate sediment toxicity at sites with complex mixtures of multiple contaminant classes and the utility of the PAH biosensor for rapid sediment-independent porewater PAH analysis. Environ Toxicol Chem 2018;37:893-902. © 2017 SETAC. © 2017 SETAC.

A REVIEW OF SINGLE SPECIES TOXICITY TESTS: ARE THE TESTS RELIABLE PREDICTORS OF AQUATIC ECOSYSTEM COMMUNITY RESPONSES?

EPA Science Inventory

This document provides a comprehensive review to evaluate the reliability of indicator species toxicity test results in predicting aquatic ecosystem impacts, also called the ecological relevance of laboratory single species toxicity tests.

Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

USGS Publications Warehouse

Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

2008-01-01

The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

Anodonta imbecillis copper sulfate reference toxicant test, Clinch River - Environmental Restoration Program (CR-ERP)

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

Simbeck, D.J.

1997-06-01

Reference toxicant testing using juvenile freshwater mussels was conducted as part of the CR-ERP biomonitoring study of Clinch River sediments to assess the sensitivity of test organisms and the overall performance of the test. Tests were conducted using moderately hard synthetic water spiked with known concentrations of copper as copper sulfate. Toxicity testing of copper sulfate reference toxicant was conducted from May 12-21, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Results from this test showed an LC{sub 50} value of 1.12 mg Cu/L which is lower than the value of 2.02 mg Cu/L obtained inmore » a previous test. Too few tests have been conducted with copper as the toxicant to determine a normal range of values.« less

Applicability of ambient toxicity testing to national or regional water-quality assessment

USGS Publications Warehouse

Elder, J.F.

1989-01-01

Comprehensive assessment of the quality of natural waters requires a multifaceted approach. Based on experimentation designed to monitor responses of organisms to environmental stresses, toxicity testing may have diverse purposes in water quality assessments. These purposes may include identification that warrant further study because of poor water quality or unusual ecological features, verification of other types of monitoring, or assessment of contaminant effects on aquatic communities. A wide variety of toxicity test methods have been developed to fulfill the needs of diverse applications. The methods differ primarily in the full selections made relative to four characteristics: (1) test species, (2) endpoints (acute or chronic), (3) test enclosure type, and (4) test substance (toxicant) that functions as the environmental stress. Toxicity test approachs vary in their capacity to meet the needs of large-scale assessments of existing water quality. Ambient testing is more likely to meet these needs than are the procedures that call for exposure of the test organisms to known concentrations of a single toxicant. However, meaningful interpretation of ambient test results depend on the existence of accompanying chemical analysis of the ambient media. The ambient test substance may be water or sediments. Sediment tests have had limited application, but they are useful because of the fact that most toxicants tend to accumulate in sediments, and many test species either inhabit the sediments or are in frequent contact with them. Biochemical testing methods, which have been developing rapidly in recent years, are likely to be among the most useful procedures for large-scale water quality assessments. They are relatively rapid and simple, and more importantly, they focus on biochemical changes that are the initial responses of virtually all organisms to environmental stimuli. Most species are sensitive to relatively few toxicants and their sensitivities vary as conditions change. One of the most informative approaches for toxicity testing is to combine biochemical tests with other test methods in a ' battery or tests ' that is diversified enough to characterize different types of toxicants and different trophic levels. (Lantz-PTT)

Influence of flow-through and renewal exposures on the toxicity of copper to rainbow trout

USGS Publications Warehouse

Welsh, P.G.; Lipton, J.; Mebane, C.A.; Marr, J.C.A.

2008-01-01

We examined changes in water chemistry and copper (Cu) toxicity in three paired renewal and flow-through acute bioassays with rainbow trout (Oncorhynchus mykiss). Test exposure methodology influenced both exposure water chemistry and measured Cu toxicity. Ammonia and organic carbon concentrations were higher and the fraction of dissolved Cu lower in renewal tests than in paired flow-through tests. Cu toxicity was also lower in renewal tests; 96 h dissolved Cu LC50 values were 7-60% higher than LC50s from matching flow-through tests. LC50 values in both types of tests were related to dissolved organic carbon (DOC) concentrations in exposure tanks. Increases in organic carbon concentrations in renewal tests were associated with reduced Cu toxicity, likely as a result of the lower bioavailability of Cu-organic carbon complexes. The biotic ligand model of acute Cu toxicity tended to underpredict toxicity in the presence of DOC. Model fits between predicted and observed toxicity were improved by assuming that only 50% of the measured DOC was reactive, and that this reactive fraction was present as fulvic acid. ?? 2007 Elsevier Inc. All rights reserved.

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.

Imaging of hepatic toxicity of systemic therapy in a tertiary cancer centre: chemotherapy, haematopoietic stem cell transplantation, molecular targeted therapies, and immune checkpoint inhibitors.

PubMed

Alessandrino, F; Tirumani, S H; Krajewski, K M; Shinagare, A B; Jagannathan, J P; Ramaiya, N H; Di Salvo, D N

2017-07-01

The purpose of this review is to familiarise radiologists with the spectrum of hepatic toxicity seen in the oncology setting, in view of the different systemic therapies used in cancer patients. Drug-induced liver injury can manifest in various forms, and anti-neoplastic agents are associated with different types of hepatotoxicity. Although chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure. The recent arrival of immune checkpoint inhibitors in oncology has introduced a new range of immune-related adverse events, with differing mechanisms of liver toxicity and varied imaging presentation of liver injury. High-dose chemotherapy regimens for haematopoietic stem cell transplantation are associated with sinusoidal obstruction syndrome. Management of hepatic toxicity depends on the clinical scenario, the drug in use, and the severity of the findings. In this article, we will (1) present the most common types of oncological drugs associated with hepatic toxicity and associated liver injuries; (2) illustrate imaging findings of hepatic toxicities and the possible differential diagnosis; and (3) provide a guide for management of these conditions. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Oxidant generation and toxicity enhancement of aged-diesel exhaust

NASA Astrophysics Data System (ADS)

Li, Qianfeng; Wyatt, Anna; Kamens, Richard M.

Diesel exhaust related airborne Particulate Matter (PM) has been linked to a myriad of adverse health outcomes, ranging from cancer to cardiopulmonary disease. The underlying toxicological mechanisms are of great scientific interest. A hypothesis under investigation is that many of the adverse health effects may derive from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within affected cells. In this study, the main objective was to determine whether aged-diesel exhaust PM has a higher oxidant generation and toxicity than fresh diesel exhaust PM. The diesel exhaust PM was generated from a 1980 Mercedes-Benz model 300SD, and a dual 270 m 3 Teflon film chamber was utilized to generate two test atmospheres. One side of the chamber is used to produce ozone-diesel exhaust PM system, and another side of the chamber was used to produce diesel exhaust PM only system. A newly optimized dithiothreitol (DTT) method was used to assess their oxidant generation and toxicity. The results of this study showed: (1) both fresh and aged-diesel exhaust PM had high oxidant generation and toxicity; (2) ozone-diesel exhaust PM had a higher toxicity response than diesel exhaust PM only; (3) the diesel exhaust PM toxicity increased with time; (4) the optimized DTT method could be used as a good quantitative chemical assay for oxidant generation and toxicity measurement.

The Preparation of Some Compounds for Testing as Insect Repellents

DTIC Science & Technology

1945-12-28

have been submitted for 90-day subacute toxicity studies « 0-7139, 0-7209 and 0-7227 have passed acute toxicity tests (0- 7227 with reservations...but have not been submitted for 90-day subacute toxicity studies , 0-7392, 0-7430 and 0-13058 have been submitted for acute toxicity tests. Forty-fivo...evaluate adequately the promising candidate insect repellents prepared under this contract. Some toxicity studies as indicated above are being made

Galleria mellonella (greater wax moth) larvae as a model for antibiotic susceptibility testing and acute toxicity trials.

PubMed

Ignasiak, Katarzyna; Maxwell, Anthony

2017-08-29

Infectivity trials and toxicity testing in rodents are important prerequisites to the use of compounds in man. However, trials in rats and mice are expensive and there are ethical considerations. Galleria mellonella (greater wax moth) larvae are a potential alternative. We have assessed the use of these insects in infectivity trials and toxicity testing. Using four bacterial species (two Gram-negative and two Gram-positive) we have assessed the efficacy of four antibiotics against infections in Galleria and compared the antibiotic susceptibility with that in humans. In general, we find a good correlation. Similarly, we have assessed 11 compounds (initially tested blind) for their toxicity in Galleria and compared this with toxicity trials in mice and rats. Again we found a good correlation between toxicity in Galleria and that in rodents. We have found, in our hands, that G. mellonella larvae can be used in infectivity trials and toxicity testing, and that these assays represent an inexpensive and readily executable alternative to testing in rodents.

Mobile lidar system for monitoring of gaseous pollutants in atmosphere over industrial and urban area

NASA Astrophysics Data System (ADS)

Moskalenko, Irina V.; Shecheglov, Djolinard A.; Rogachev, Aleksei P.; Avdonin, Aleksandr A.; Molodtsov, Nikolai A.

1999-01-01

The lidar remote sensing techniques are powerful for monitoring of gaseous toxic species in atmosphere over wide areas. The paper presented describes design, development and field testing of Mobile Lidar System (MLS) based on utilization of Differential Absorption Lidar (DIAL) technique. The activity is performed by Russian Research Center 'Kurchatov Institute' and Research Institute of Pulse Technique within the project 'Mobile Remote SEnsing System Based on Tunable Laser Transmitter for Environmental Monitoring' under funding of International Scientific and Technology Center Moscow. A brief description of MLS is presented including narrowband transmitter, receiver, system steering, data acquisition subsystem and software. MLS is housed in a mobile truck and is able to provide 3D mapping of gaseous species. Sulfur dioxide and elemental mercury were chosen as basic atmospheric pollutants for field test of MLS. The problem of anthropogenic ozone detection attracts attention due to increase traffic in Moscow. The experimental sites for field testing are located in Moscow Region. Examples of field DIAL measurements will be presented. Application of remote sensing to toxic species near-real time measurements is now under consideration. The objective is comparison of pollution level in working zone with maximum permissible concentration of hazardous pollutant.

Necessity of toxicity assessment in Turkish industrial discharges (examples from metal and textile industry effluents).

PubMed

Sponza, Delia Teresa

2002-01-01

Toxicity of some organic and inorganic chemicals to microorganisms is an important consideration in assessing their environmental impact against their economic benefits. Microorganisms play an important role in several environmental processes, both natural and engineered. Some organic and inorganics at toxic levels have been detected in industrial discharges resulting in plant upsets and discharge permit violations. In addition to this, even though in some cases the effluent wastewater does not exceed the discharge limits, the results of toxicity tests show potential toxicity. Toxicity knowledge of effluents can benefit treatment plant operators in optimising plant operation, setting pre-treatment standards, and protecting receiving water quality and in establishing sewer discharge permits to safeguard the plant. In the Turkish regulations only toxicity dilution factor (TDF) with fish is part of the toxicity monitoring program of permissible wastewater discharge. In various countries, laboratory studies involving the use of different organisms and protocol for toxicity assessment was conducted involving a number of discharges. In this study, it was aimed to investigate the acute toxicity of textile and metal industry wastewaters by traditional and enrichment toxicity tests and emphasize the importance of toxicity tests in wastewater discharge regulations. The enrichment toxicity tests are novel applications and give an idea whether there is potential toxicity or growth limiting and stimulation conditions. Different organisms were used such as bacteria (Floc and Coliform bacteria) algae (Chlorella sp.). fish (Lepistes sp.) and protozoan (Vorticella sp.) to represent four tropic levels. The textile industry results showed acute toxicity for at least one organism in 8 out of 23 effluent samples. Acute toxicity for at least two organisms in 7 out of 23 effluent sampling was observed for the metal industry. The toxicity test results were assessed with chemical analyses such as COD, BOD, color and heavy metals. It was observed that the toxicity of the effluents could not be explained by using physicochemical analyses in 5 cases for metal and 4 cases for the textile industries. The results clearly showed that the use of bioassay tests produce additional information about the toxicity potential of industrial discharges and effluents.

Towards a theory of tiered testing.

PubMed

Hansson, Sven Ove; Rudén, Christina

2007-06-01

Tiered testing is an essential part of any resource-efficient strategy for the toxicity testing of a large number of chemicals, which is required for instance in the risk management of general (industrial) chemicals, In spite of this, no general theory seems to be available for the combination of single tests into efficient tiered testing systems. A first outline of such a theory is developed. It is argued that chemical, toxicological, and decision-theoretical knowledge should be combined in the construction of such a theory. A decision-theoretical approach for the optimization of test systems is introduced. It is based on expected utility maximization with simplified assumptions covering factual and value-related information that is usually missing in the development of test systems.

Groundwater Remediation and Alternate Energy at White Sands Test Facility

NASA Technical Reports Server (NTRS)

Fischer, Holger

2008-01-01

White Sands Test Facility Core Capabilities: a) Remote Hazardous Testing of Reactive, Explosive, and Toxic Materials and Fluids; b) Hypergolic Fluids Materials and Systems Testing; c) Oxygen Materials and System Testing; d) Hypervelocity Impact Testing; e)Flight Hardware Processing; and e) Propulsion Testing. There is no impact to any drinking water well. Includes public wells and the NASA supply well. There is no public exposure. Groundwater is several hundred feet below ground. No air or surface water exposure. Plume is moving very slowly to the west. Plume Front Treatment system will stop this westward movement. NASA performs on-going monitoring. More than 200 wells and zones are routinely sampled. Approx. 850 samples are obtained monthly and analyzed for over 300 different hazardous chemicals.

Introduction to Immunotoxicity

EPA Science Inventory

Recognition that the immune system is vulnerable to adverse effects after exposure to xenobiotics led to the discipline of immunotoxicology and the subsequent addition of immunotoxicology testing to regulatory guidelines for toxicity. Immunotoxic effects can result in immunosuppr...

2003 Children's Health Protection Advisory Committee Letters

EPA Pesticide Factsheets

These letters, mostly to Administrator Christine Todd Whitman, are regarding the bioethical issues on the use of human data, the national pesticide incident reporting system, toxicity testing, and chemical contaminants in human milk.

78 FR 46267 - Trifluralin; Pesticide Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

...), trifluralin was tested up to the limit dose (1000 mg/kg/day) and caused no systemic toxicity. Handler exposure... detection (ECD)) is available to enforce the tolerance expression. The method may be requested from: Chief...

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

Gustafsson, Helena; Runesson, Johan; Lundqvist, Jessica

The objective of the EU-funded integrated project ACuteTox is to develop a strategy in which general cytotoxicity, together with organ-specific toxicity and biokinetic features, are used for the estimation of human acute systemic toxicity. Our role in the project is to characterise the effect of reference chemicals with regard to neurotoxicity. We studied cell membrane potential (CMP), noradrenalin (NA) uptake, acetylcholine esterase (AChE) activity, acetylcholine receptor (AChR) signalling and voltage-operated calcium channel (VOCC) function in human neuroblastoma SH-SY5Y cells after exposure to 23 pharmaceuticals, pesticides or industrial chemicals. Neurotoxic alert chemicals were identified by comparing the obtained data with cytotoxicitymore » data from the neutral red uptake assay in 3T3 mouse fibroblasts. Furthermore, neurotoxic concentrations were correlated with estimated human lethal blood concentrations (LC50). The CMP assay was the most sensitive assay, identifying eight chemicals as neurotoxic alerts and improving the LC50 correlation for nicotine, lindane, atropine and methadone. The NA uptake assay identified five neurotoxic alert chemicals and improved the LC50 correlation for atropine, diazepam, verapamil and methadone. The AChE, AChR and VOCC assays showed limited potential for detection of acute toxicity. The CMP assay was further evaluated by testing 36 additional reference chemicals. Five neurotoxic alert chemicals were generated and orphendrine and amitriptyline showed improved LC50 correlation. Due to the high sensitivity and the simplicity of the test protocol, the CMP assay constitutes a good candidate assay to be included in an in vitro test strategy for prediction of acute systemic toxicity.« less

Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants.

PubMed

Nyffeler, Johanna; Karreman, Christiaan; Leisner, Heidrun; Kim, Yong Jun; Lee, Gabsang; Waldmann, Tanja; Leist, Marcel

2017-01-01

Migration of neural crest cells (NCCs) is one of the pivotal processes of human fetal development. Malformations arise if NCC migration and differentiation are impaired genetically or by toxicants. In the currently available test systems for migration inhibition of NCC (MINC), the manual generation of a cell-free space results in extreme operator dependencies, and limits throughput. Here a new test format was established. The assay avoids scratching by plating cells around a commercially available circular stopper. Removal of the stopper barrier after cell attachment initiates migration. This microwell-based circular migration zone NCC function assay (cMINC) was further optimized for toxicological testing of human pluripotent stem cell (hPSC)-derived NCCs. The challenge of obtaining data on viability and migration by automated image processing was addressed by developing a freeware. Data on cell proliferation were obtained by labelling replicating cells, and by careful assessment of cell viability for each experimental sample. The role of cell proliferation as an experimental confounder was tested experimentally by performing the cMINC in the presence of the proliferation-inhibiting drug cytosine arabinoside (AraC), and by a careful evaluation of mitotic events over time. Data from these studies led to an adaptation of the test protocol, so that toxicant exposure was limited to 24 h. Under these conditions, a prediction model was developed that allows classification of toxicants as either inactive, leading to unspecific cytotoxicity, or specifically inhibiting NC migration at non-cytotoxic concentrations.

Acute Oral Toxicity Up-And-Down-Procedure

EPA Pesticide Factsheets

The Up-and-Down Procedure is an alternative acute toxicity test that provides a way to determine the toxicity of chemicals with fewer test animals by using sequential dosing steps. Find out about this test procedure.

Sediment Toxicity Testing

EPA Science Inventory

Sediment toxicity testing has become a fundamental component of regulatory frameworks for assessing the risks posed by contaminated sediments and for development of chemical sediment quality guidelines. Over the past two decades, sediment toxicity testing methods have advanced co...

Toxicity Estimation Software Tool (TEST)

EPA Science Inventory

The Toxicity Estimation Software Tool (TEST) was developed to allow users to easily estimate the toxicity of chemicals using Quantitative Structure Activity Relationships (QSARs) methodologies. QSARs are mathematical models used to predict measures of toxicity from the physical c...

Rice seed toxicity tests for organic and inorganic substances

USGS Publications Warehouse

Wang, W.

1994-01-01

Plant seed toxicity tests can be used to evaluate hazardous waste sites and to assess toxicity of complex effluents and industrial chemicals. Conventional plant seed toxicity tests are performed using culture dishes containing filter paper. Some reports indicate that filter papers might interfere with the toxicity of inorganic substances. In this study, a plastic seed tray was used. Rice was used as the test species. A comparison of results in the literature and this study revealed that variation of test species, methods, exposure duration, and other factors may affect the test results. The results of this study showed that the order of decreasing toxicity of metal ions was Cu>Ag>Ni>Cd>Cr(VI)>Pb>Zn>Mn>NaF for rice. The test results were similar to those reported in the literature for lettuce Ag>Ni>Cd,Cu>Cr (VI)>Zn>Mn, millet Cu,Ni>Cd>Cr(VI)>Zn>Mn, and ryegrass Cu>Ni>Mn>>Pb>Cd>Zn> Al>Hg>Cr>Fe. The order of decreasing toxicity of organic herbicides was paraquat, 2,4-D>>glyphosate>bromacil.

The systemic toxicity of equipotent proxymetacaine, oxybuprocaine, and bupivacaine during continuous intravenous infusion in rats.

PubMed

Hung, Ching-Hsia; Liu, Kuo-Sheng; Shao, Dong-Zi; Cheng, Kuang-I; Chen, Yu-Chung; Chen, Yu-Wen

2010-01-01

Although proxymetacaine and oxybuprocaine produce topical ocular and spinal anesthesia, they have never been tested as cutaneous anesthetics. We compared cutaneous analgesia of proxymetacaine and oxybuprocaine with bupivacaine and tested their central nervous system and cardiovascular toxicity. After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the local anesthetic effect of proxymetacaine and oxybuprocaine on cutaneous analgesia in rats. After i.v. infusions of equipotent doses of oxybuprocaine, proxymetacaine, and bupivacaine, we observed the onset time of seizure, apnea, and impending death and monitored mean arterial blood pressure and heart rate. Proxymetacaine and oxybuprocaine acted like bupivacaine and produced dose-related cutaneous analgesia. On a 50% effective dose basis, the ranks of potencies were proxymetacaine > oxybuprocaine > bupivacaine (P < 0.01). Under equipotent doses, the infusion times of proxymetacaine or oxybuprocaine required to cause seizure, apnea, and impending death were longer than that of bupivacaine (P < 0.05). The decrease in mean arterial blood pressure and heart rate was slower with oxybuprocaine and proxymetacaine compared with bupivacaine (P < 0.05 for the differences) at equipotent doses. Oxybuprocaine and proxymetacaine were more potent at producing cutaneous anesthesia but were less potent than bupivacaine at producing central nervous system and cardiovascular toxicity.

Use of porewater extracts to identify the cause of toxicity in marine and estuarine sediments

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

Douglas, W.S.

1994-12-31

Amphipod toxicity tests in the evaluation of dredged material proposed for ocean disposal has come under increased scrutiny by the regulated community in the Port of NY/NJ. In recent large-scale assessments of sediment quality in the harbor, the vast majority of locations were deemed highly contaminated when tested with Ampelisca abdita. Toxicity tests, by themselves, do not provide data regarding the cause of toxicity of these sediments. The enormous potential costs associated with most proposed alternatives to ocean disposal of dredged sediments has prompted the investigation of the causative agents of toxicity in sediments of the NY/NJ Harbor. Sediment frommore » five locations in the harbor, selected in consultation with local regulatory agencies to represent diverse potential contamination scenarios, was collected and tested for toxicity to the amphipods Ampelisca abdita, Leptocheirus plumulosus, Eohaustorius estuadus, Rhepoxynius abronius, and the mysid shrimp, Mysidopsis bahia, using 10-day static bioassays. Porewater from each of the five sediments was extracted under centrifugation and used in water-only toxicity tests with A. abdita, L. plumulosus, R. abronius, E. estuadus, M. bahia, M. beryllina, and Microtox. A Phase 1 Toxicity Identification Evaluation of the three most toxic porewater samples was conducted using several of the species tested. Results from the preliminary investigations and the ongoing TIE`s will be presented. Species selection, porewater toxicity test procedures, and Phase 1, 2, and 3 paradigms will be discussed.« less

A PEG-Based Hydrogel for Effective Wound Care Management

PubMed Central

Chen, Sen-Lu; Fu, Ru-Huei; Liao, Shih-Fei; Liu, Shih-Ping; Lin, Shinn-Zong; Wang, Yu-Chi

2018-01-01

It is extremely challenging to achieve strong adhesion in soft tissues while minimizing toxicity, tissue damage, and other side effects caused by wound sealing materials. In this study, flexible synthetic hydrogel sealants were prepared based on polyethylene glycol (PEG) materials. PEG is a synthetic material that is nontoxic and inert and, thus, suitable for use in medical products. We evaluated the in vitro biocompatibility tests of the dressings to assess cytotoxicity and irritation, sensitization, pyrogen toxicity, and systemic toxicity following the International Organization for Standardization 10993 standards and the in vivo effects of the hydrogel samples using Coloskin liquid bandages as control samples for potential in wound closure. PMID:29637814

Nitrosamine toxicity and metabolism. May 1978-October 1989 (A Bibliography from the Life Sciences Collection data base). Report for May 1978-October 1989

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

Not Available

This bibliography contains citations concerning the toxicity, metabolism, and carcinogenicity of nitrosamines. Nitrosamines occur in foods, tobacco products, industrial emissions, cosmetics, beverages, and rubber products. Articles include testing methods for nitrosamine carcinogenicity and mutagenicity, analysis and determination in various food and cosmetic products, relative toxicities of nitrosamines, metabolism of nitrosamines, and their production in foods and the human intestinal system. Animal studies of nitrosamine toxicology are not included in this publication. Nitrosamine contents of meat products are referenced in a related published bibliography. (Contains 176 citations fully indexed and including a title list.)

Toxicodynamic and toxicokinetic descriptors of combined chromium (VI) and nickel toxicity.

PubMed

Minigaliyeva, Ilzira A; Katsnelson, Boris A; Privalova, Larisa I; Gurvich, Vladimir B; Panov, Vladimir G; Varaksin, Anatoly N; Makeyev, Oleg H; Sutunkova, Marina P; Loginova, Nadezhda V; Kireyeva, Ekaterina P; Grigoryeva, Ekaterina V; Slyshkina, Tatyana V; Ganebnykh, Eugenia V; Grebenkina, Svetlana V

2014-01-01

After repeated intraperitoneal injections of nickel and chromium (VI) salts to rats, we found, and confirmed by mathematical modeling, that their combined subchronic toxicity can either be of additive type or depart from it (predominantly toward subadditivity) depending on the effect assessed. Against the background of moderate systemic toxicity, the combination under study proved to possess a marked additive genotoxicity assessed by means of the random amplification of polymorphic DNA test. We also demonstrated that chromium and nickel reciprocally influenced the retention of these metals in some organs (especially in the spleen) but not their urinary excretion in this study. © The Author(s) 2014.

Guidance on the selection of cohorts for the extended one-generation reproduction toxicity study (OECD test guideline 443).

PubMed

Moore, Nigel P; Beekhuijzen, Manon; Boogaard, Peter J; Foreman, Jennifer E; North, Colin M; Palermo, Christine; Schneider, Steffen; Strauss, Volker; van Ravenzwaay, Bennard; Poole, Alan

2016-10-01

The extended one-generation reproduction toxicity study (EOGRTS; OECD test guideline 433) is a new and technically complex design to evaluate the putative effects of chemicals on fertility and development, including effects upon the developing nervous and immune systems. In addition to offering a more comprehensive assessment of developmental toxicity, the EOGRTS offers important improvements in animal welfare through reduction and refinement in a modular study design. The challenge to the practitioner is to know how the modular aspects of the study should be triggered on the basis of prior knowledge of a particular chemical, or on earlier findings in the EOGRTS itself, requirements of specific regulatory frameworks notwithstanding. The purpose of this document is to offer guidance on science-based triggers for these extended evaluations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Planarians in toxicology. Responses of asexual Dugesia dorotocephala to selected metals

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

Kapu, M.M.; Schaeffer, D.J.

1991-08-01

The planarian Dugesia dorotocephala is a freshwater invertebrate found in unpolluted flowing surface waters. Planarians have a sensitive nervous system with synapses and true brain and evidence these in a variety of social and response behaviors. The inclusion of planarians in a screening battery would provide improved sensitivity in detecting toxicity because planarians commonly respond to lower levels of contamination than do other species. Numerous toxicity test have been conducted to determine the acute and chronic effects of toxicants to provide data necessary for the development of water quality criteria. The appropriateness of Illinois water quality standards for metals wasmore » investigated using a 1-hr behavioral test based on the responses of the planarian D. dorotocephala. One possible difficulty with water quality standards for metals is that the standard for each metal is usually established without regard to the effects of other metals present in the receiving water.« less

The toxicity of ammonia/ammonium to the vermifiltration wastewater treatment process.

PubMed

Hughes, R J; Nair, J; Ho, G

2008-01-01

This study was undertaken to assess the toxicity of ammonia/ammonium to key species within the vermifiltration process. The key species, the earthworm Eisenia fetida, was subjected to a series of tests in solid phase mesocosms and full-scale units. The solid phase tests showed a relatively low toxicity to ammonium with ammonium chloride having an LC50 for ammonium of 1.49 g/kg. Ammonium sulfate did not show an effect on mortality at 2 g/kg ammonium. The full-scale units showed that ammonia hydroxide can change the pH and concentration of ammonia in wastewater and while it caused some mortality to the worms its overall affect on system functioning was minimal with no significant difference in terms of worm survival found between treatments. The affect on nitrifying bacteria was also minimal with no linear trend shown with ammonia concentration. IWA Publishing 2008.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

Can interpreting sediment toxicity tests a mega sites benefit from novel approaches to normalization to address batching of tests?

EPA Science Inventory

Sediment toxicity tests are a key tool used in Ecological Risk Assessments for contaminated sediment sites. Interpreting test results and defining toxicity is often a challenge. This is particularly true at mega sites where the testing regime is large, and by necessity performed ...

Freshwater in situ toxicity testing: Daphnia magna, Ceriodaphnia dubia, Pimephales promelas, Hyalella azteca and Chironomus tentans

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

Burton, G.A. Jr.

The use of traditional laboratory toxicity test species in field exposures have proven to be a valuable assessment tool for monitoring effluent, water, sediment and storm water quality. Mimicking fluctuating exposures of stressors with associated interactions with differing physico-chemical variables is difficult. In situ exposures are conducted for similar time periods measuring similar response endpoints as in more traditional laboratory tests. However, organisms are transferred to the field and exposed in various types of test chambers. The author has observed responses which are similar and which are significantly different from simultaneous laboratory exposures. Temperature, dissolved oxygen, suspended solids, natural light,more » flow, and predation may affect in situ responses, but are often removed from laboratory exposures. The strengths and weaknesses observed with these test systems over the past few years will be reviewed.« less

Metabolic activation of hepatotoxic drug (benzbromarone) induced mitochondrial membrane permeability transition

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

Shirakawa, Maho; Sekine, Shuichi; Tanaka, Ayaka

The risk of drug-induced liver injury (DILI) is of great concern to the pharmaceutical industry. It is well-known that metabolic activation of drugs to form toxic metabolites (TMs) is strongly associated with DILI onset. Drug-induced mitochondrial dysfunction is also strongly associated with increased risk of DILI. However, it is difficult to determine the target of TMs associated with exacerbation of DILI because of difficulties in identifying and purifying TMs. In this study, we propose a sequential in vitro assay system to assess TM formation and their ability to induce mitochondrial permeability transition (MPT) in a one-pot process. In this assaymore » system, freshly-isolated rat liver mitochondria were incubated with reaction solutions of 44 test drugs preincubated with liver microsomes in the presence or absence of NADPH; then, NADPH-dependent MPT pore opening was assessed as mitochondrial swelling. In this assay system, several hepatotoxic drugs, including benzbromarone (BBR), significantly induced MPT in a NADPH-dependent manner. We investigated the rationality of using BBR as a model drug, since it showed the most prominent MPT in our assay system. Both the production of a candidate toxic metabolite of BBR (1′,6-(OH){sub 2} BBR) and NADPH-dependent MPT were inhibited by several cytochrome P450 (CYP) inhibitors (clotrimazole and SKF-525A, 100 μM). In summary, this assay system can be used to evaluate comprehensive metabolite-dependent MPT without identification or purification of metabolites. - Highlights: • We constructed a sequential assay system for toxic metabolite induced MPT in one pot. • 14 drugs (e.g. benzbromarone (BBR)) induced toxic metabolite dependent MPT. • Both the production of toxic metabolite and MPT could be inhibited by CYP inhibitors. • This system could evaluate the comprehensive MPT without purification of metabolites.« less

Anticancer activities against cholangiocarcinoma, toxicity and pharmacological activities of Thai medicinal plants in animal models

PubMed Central

2012-01-01

Background Chemotherapy of cholangiocarcinoma (CCA), a devastating cancer with increasing worldwide incidence and mortality rates, is largely ineffective. The discovery and development of effective chemotherapeutics is urgently needed. Methods/Design The study aimed at evaluating anticancer activities, toxicity, and pharmacological activities of the curcumin compound (CUR), the crude ethanolic extracts of rhizomes of Zingiber officinale Roscoe (Ginger: ZO) and Atractylodes lancea thung. DC (Khod-Kha-Mao: AL), fruits of Piper chaba Hunt. (De-Plee: PC), and Pra-Sa-Prao-Yhai formulation (a mixture of parts of 18 Thai medicinal plants: PPF) were investigated in animal models. Anti-cholangiocarcinoma (anti-CCA) was assessed using CCA-xenograft nude mouse model. The antihypertensive, analgesic, anti-inflammatory, antipyretic, and anti-ulcer activities and effects on motor coordination were investigated using Rota-rod test, CODA tail-cuff system, writhing and hot plate tests, carrageenan-induced paw edema test, brewer's yeast test, and alcohol-induced gastric ulcer test, respectively. Acute and subacute toxicity tests were performed according to the OECD guideline for testing of chemicals with modification. Results Promising anticancer activity against CCA in nude mouse xenograft model was shown for the ethanolic extract of AL at all oral dose levels (1000, 3000, and 5000 mg/kg body weight) as well as the extracts of ZO, PPF, and CUR compound at the highest dose level (5000, 4000, and 5000 mg/kg body weight, respectively). PC produced no significant anti-CCA activity. Results from acute and subacute toxicity tests both in mice and rats indicate safety profiles of all the test materials in a broad range of dose levels. No significant toxicity except stomach irritation and general CNS depressant signs were observed. Investigation of pharmacological activities of the test materials revealed promising anti-inflammatory (ZO, PPF, and AL), analgesic (CUR and PPF), antipyretic (CUR and AL), antihypertensive (ZO and AL), and anti-ulcer (CUR, ZO, and AL) activities. Conclusion Plants used in Thai traditional medicine for the treatment of various ailments may provide reservoirs of promising candidate chemotherapeutics for the treatment of CCA. PMID:22448640

Tracking pyrethroid toxicity in surface water samples: Exposure dynamics and toxicity identification tools for laboratory tests with Hyalella azteca (Amphipoda).

PubMed

Deanovic, Linda A; Stillway, Marie; Hammock, Bruce G; Fong, Stephanie; Werner, Inge

2018-02-01

Pyrethroid insecticides are commonly used in pest control and are present at toxic concentrations in surface waters of agricultural and urban areas worldwide. Monitoring is challenging as a result of their high hydrophobicity and low toxicity thresholds, which often fall below the analytical methods detection limits (MDLs). Standard daphnid bioassays used in surface water monitoring are not sensitive enough to protect more susceptible invertebrate species such as the amphipod Hyalella azteca and chemical loss during toxicity testing is of concern. In the present study, we quantified toxicity loss during storage and testing, using both natural and synthetic water, and presented a tool to enhance toxic signal strength for improved sensitivity of H. azteca toxicity tests. The average half-life during storage in low-density polyethylene (LDPE) cubitainers (Fisher Scientific) at 4 °C of 5 pyrethroids (permethrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, and esfenvalerate) and one organophosphate (chlorpyrifos; used as reference) was 1.4 d, and piperonyl butoxide (PBO) proved an effective tool to potentiate toxicity. We conclude that toxicity tests on ambient water samples containing these hydrophobic insecticides are likely to underestimate toxicity present in the field, and mimic short pulse rather than continuous exposures. Where these chemicals are of concern, the addition of PBO during testing can yield valuable information on their presence or absence. Environ Toxicol Chem 2018;37:462-472. © 2017 SETAC. © 2017 SETAC.

Estimation of bisphenol A-Human toxicity by 3D cell culture arrays, high throughput alternatives to animal tests.

PubMed

Lee, Dong Woo; Oh, Woo-Yeon; Yi, Sang Hyun; Ku, Bosung; Lee, Moo-Yeal; Cho, Yoon Hee; Yang, Mihi

2016-09-30

Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D) on a micropillar chip coupled to a panel of metabolic enzymes on a microwell chip. As a result, we were able to assess the toxicity of BPA under various metabolic enzyme conditions using a high-throughput and micro assay; sample volumes were nearly 2,000 times less than that required for a 96-well plate. We applied a total of 28 different enzymes to each chip, including 10 cytochrome P450s (CYP450s), 10 UDP-glycosyltransferases (UGTs), 3 sulfotransferases (SULTs), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase 2 (ALDH2). Phase I enzyme mixtures, phase II enzyme mixtures, and a combination of phase I and phase II enzymes were also applied to the chip. BPA toxicity was higher in samples containing CYP2E1 than controls, which contained no enzymes (IC50, 184±16μM and 270±25.8μM, respectively, p<0.01). However, BPA-induced toxicity was alleviated in the presence of ADH (IC50, 337±17.9μM), ALDH2 (335±13.9μM), and SULT1E1 (318±17.7μM) (p<0.05). CYP2E1-mediated cytotoxicity was confirmed by quantifying unmetabolized BPA using HPLC/FD. Therefore, we suggest the present micropillar/microwell chip platform as an effective alternative to animal testing for estimating BPA toxicity via human metabolic systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2012 CFR

2012-07-01

.... Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the special conditions for C1, C2, C3, C4, C5.... Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C2: 1...

Combined toxicity of imidacloprid and three insecticides to the earthworm, Eisenia fetida (Annelida, Oligochaeta).

PubMed

Cang, Tao; Dai, Dejiang; Yang, Guiling; Yu, Yijun; Lv, Lu; Cai, Leiming; Wang, Qiang; Wang, Yanhua

2017-03-01

Although the earthworm Eisenia fetida has been used in many ecotoxicological studies in recent years, most of these studies have only focused on assessing the effects of individual insecticides. In the present study, we aimed to compare the individual and combined toxic effects of imidacloprid and three insecticides (phoxim, chlorpyrifos, and lambda-cyhalothrin) on E. fetida. We showed that imidacloprid had the highest intrinsic toxicity to the worms in filter paper contact test, followed by phoxim and lambda-cyhalothrin, while the least toxicity was found from chlorpyrifos. Moreover, 14-day soil toxicity test revealed that the highest toxicity was still detected for imidacloprid with an LC 50 value of 2.82 (2.61∼3.17) mg a.i. kg -1 dry weight (DW), followed by chlorpyrifos with an LC 50 value of 384.9 (353.5∼440.3) mg a.i. kg -1 DW. Meanwhile, a relatively less toxicity was found for lambda-cyhalothrin with an LC 50 value of 560.3 (475.9∼718.5) mg a.i. kg -1 DW, while the lowest toxicity to E. fetida was observed for phoxim with an LC 50 value of 901.5 (821.3∼1017) mg a.i. kg -1 DW. In addition, significant synergistic responses were found from the ternary mixture of imidacloprid-phoxim-lambda-cyhalothrin and quaternary mixture of imidacloprid-phoxim-chlorpyrifos-lambda-cyhalothrin in both bioassay systems. Therefore, our findings highlighted that the simultaneous presence of several insecticides in the soil environment might lead to increased toxicity, resulting in serious damage to the nontarget organisms compared with individual insecticides.

Testing and Risk Assessment of Chemicals that Impact Highly Adaptive Biological Systems: The Case of Endocrine Systems

EPA Science Inventory

Animals have evolved a variety of mechanisms for responding to toxic chemicals of both natural and anthropogenic origin. Well-known examples include activation of cellular repair pathways and induction of metabolizing enzymes. From a governmental regulatory perspective, these a...

A comparison of sediment toxicity test methods at three Great Lake Areas of Concern

USGS Publications Warehouse

Burton, G. Allen; Ingersoll, Christopher G.; Burnett, LouAnn C.; Henry, Mary; Hinman, Mark L.; Klaine, Stephen J.; Landrum, Peter F.; Ross, Phillipe; Tuchman, Marc

1996-01-01

The significance of sediment contamination is often evaluated using sediment toxicity (bioassay) testing. There are relatively few “standardized” test methods for evaluating sediments. Popular sediment toxicity methods examine the extractable water (elutriate), interstitial water, or whole (bulk) sediment phases using test species spanning the aquatic food chain from bacteria to fish. The current study was designed to evaluate which toxicity tests were most useful in evaluations of sediment contamination at three Great Lake Areas of Concern. Responses of 24 different organisms including fish, mayflies, amphipods, midges, cladocerans, rotifers, macrophytes, algae, and bacteria were compared using whole sediment or elutriate toxicity assays. Sediments from several sites in the Buffalo River, Calumet River (Indiana Harbor), and Saginaw River were tested, as part of the U.S. Environmental Protection Agency's (USEPA) Assessment and Remediation of Contaminated Sediments (ARCS) Project. Results indicated several assays to be sensitive to sediment toxicity and able to discriminate between differing levels of toxicity. Many of the assay responses were significantly correlated to other toxicity responses and were similar based on factor analysis. For most applications, a test design consisting of two to three assays should adequately detect sediment toxicity, consisting of various groupings of the following species: Hyalella azteca, Ceriodaphnia dubia, Chironomus riparius, Chironomus tentans, Daphnia magna, Pimephales promelas, Hexagenia bilineata, Diporeia sp., Hydrilla verticillata, or Lemna minor.

Predictive Modeling of Developmental Toxicity

EPA Science Inventory

The use of alternative methods in conjunction with traditional in vivo developmental toxicity testing has the potential to (1) reduce cost and increase throughput of testing the chemical universe, (2) prioritize chemicals for further targeted toxicity testing and risk assessment,...

Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants

DTIC Science & Technology

1997-08-01

AL/EQ-TR-1997-0050 DEVELOPMENT AND EVALUATION OF REPRODUCTIVE AND DEVELOPMENT TOXICITY TESTS FOR ASSESSING THE HAZARDS OF ENVIRONMENTAL...SUBTITLE Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants 6...pd in testing toxicity in surface waters, ground waters and H- ™t™j£J^^^M hazard assessment when used in conjunction in sediments. FETAX can be usea

THE TOXICITY OF RUBBERS AND PLASTICS USED IN TRANSFUSION-GIVING SETS

PubMed Central

Cruickshank, C. N. D.; Hooper, Caroline; Lewis, H. B. M.; MacDougall, J. D. B.

1960-01-01

The toxicity of different rubbers and plastics used in transfusion-giving sets has been investigated by examining their effects on (a) cultures of chick embryo tissues, (b) the oxygen uptake of guinea-pig skin tissue cultures, and (c) the growth of Str. pyogenes. The results of the laboratory tests have been compared with the incidence of thrombophlebitis after prolonged transfusions through the various materials. It was found that where the materials inhibited the growth of Str. pyogenes they were also toxic to tissue cultures, but that some materials which were toxic to tissue cultures did not inhibit bacterial growth. The assessments of the relative toxicity of the materials tested by the two tissue culture methods were in agreement. The skin respiration studies, however, gave more information on the early effects of the toxic materials. The relative toxicity of the materials as revealed by these tests could be correlated with the differences in the incidence of thrombophlebitis following intravenous infusions administered through giving-sets assembled with the materials tested. It is suggested therefore that the toxicity revealed by these tests is of clinical importance, and that tissue culture toxicity tests will prove to be of value in selecting rubbers and plastics for clinical purposes. Images PMID:13813084

U.S. Coast Guard 1994 Oil Pollution Research Grants Publications - Part II.

DTIC Science & Technology

1996-09-01

preparations. However, toxicity testing in various salinities may be of future interest in a number of cases. We have no direct data on the effect of different...of oil toxicity. Factors such as temperature (Korn et al. 1979), salinity (Linden et al. 1979), pH and route of exposure (Lee et al. 1976) may effect ...Evidence of altered metabolic pathways provides information concerning enzyme systems sensitive to oil-dispersant expostre. Any factors effecting these

Development and application of a marine sediment pore-water toxicity test using Ulva fasciata zoospores

USGS Publications Warehouse

Hooten, Russell L.; Carr, R. Scott

1998-01-01

An acute (96 h) pore-water toxicity test protocol using germination and growth of Ulva fasciatazoospores as endpoints was developed to test the toxicity of marine and estuarine sediment pore-water samples. Tests with an organic toxicant (sodium dodecyl sulfate; SDS), three metals (Cd, Cu, and Zn), and ammonia (NH3) were conducted to determine zoospore sensitivity. Zoospore germination and gametophyte growth were as sensitive to SDS as sea urchin (Arbacia punctulata) fertilization and embryological development. Zoospore sensitivity to metals was greater than or comparable to that of adult macroalgae. Zoospores were less sensitive to NH3than were other commonly used toxicity test organisms. Test results using this algal assay with sediment pore-water samples with high NH3 concentrations were compared with results from sea urchin fertilization and embryological development tests for the same samples. Ulva fasciatazoospore germination was not affected by samples with high NH3 concentrations that were toxic in both sea urchin tests. Zoospore tolerance of NH3 and sensitivity to other contaminants indicate that their response may be useful in toxicity identification evaluation studies with pore-water samples that contain high concentrations of unionized NH3.

Toxicity of waters from the Rochester Embayment Area of Concern to the plankton species Pseudokirchneriella subcapitata and Ceriodaphnia dubia

USGS Publications Warehouse

Baldigo, Barry P.; Duffy, Brian T.; Smith, Alexander J.; George, Scott D.

2016-01-01

The lower Genesee River and Rochester Embayment of Lake Ontario are a designated Area of Concern (AOC) under the binational Great Lakes Water Quality Agreement. The “degradation of phytoplankton and zooplankton populations” or plankton Beneficial Use Impairment (BUI) was classified as unknown and in need of further assessment in this AOC because water quality data suggested plankton communities could be effected and community data were either unavailable or indicated impacts. The plankton BUI may now be obsolete because local contaminant sources have been largely eliminated. The present study was conducted between July 2013 and August 2014 to assess the BUI-removal criteria: “AOC plankton bioassays confirm that toxicity in ambient waters (i.e., no growth inhibition) is not significantly higher than comparable non-AOC controls”. Acute and chronic toxicity of waters from 13 sites were quantified seasonally using standardized bioassays with the green alga Pseudokirchneriella subcapitata and water flea Ceriodaphnia dubia to test the hypothesis that toxicity of waters from AOC sites was not higher than that of waters from comparable non-AOC reference sites. Survival and reproduction of C. dubia did not differ significantly between site types, systems, or months. The growth of P. subcapitata did not differ between site types, but differed among systems and months. All results indicate that waters from AOC sites were no more toxic to both plankton species than waters from reference sites. Assuming test species represent natural plankton assemblages, water quality should not negatively affect survival and growth of resident plankton populations in the Rochester Embayment AOC.

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice

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

Zhang, Jianhai

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150 mg/L NaF in drinking water, 5.75 g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15 weeks. The resultsmore » showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. - Highlights: • Fluoride exposure altered the growth and development, sperm count and sperm survival percentages, testicular histology • Fluoride exposure decreased NGF, Ras, and Mek mRNA and NGF and p-MEK protein expressions in testis of mice. • Choline supplementation diminishes fluoride-induced testicular toxicity.« less

Allergy and "toxic mold syndrome".

PubMed

Edmondson, David A; Nordness, Mark E; Zacharisen, Michael C; Kurup, Viswanath P; Fink, Jordan N

2005-02-01

"Toxic mold syndrome" is a controversial diagnosis associated with exposure to mold-contaminated environments. Molds are known to induce asthma and allergic rhinitis through IgE-mediated mechanisms, to cause hypersensitivity pneumonitis through other immune mechanisms, and to cause life-threatening primary and secondary infections in immunocompromised patients. Mold metabolites may be irritants and may be involved in "sick building syndrome." Patients with environmental mold exposure have presented with atypical constitutional and systemic symptoms, associating those symptoms with the contaminated environment. To characterize the clinical features and possible etiology of symptoms in patients with chief complaints related to mold exposure. Review of patients presenting to an allergy and asthma center with the chief complaint of toxic mold exposure. Symptoms were recorded, and physical examinations, skin prick/puncture tests, and intracutaneous tests were performed. A total of 65 individuals aged 1 1/2 to 52 years were studied. Symptoms included rhinitis (62%), cough (52%), headache (34%), respiratory symptoms (34%), central nervous system symptoms (25%), and fatigue (23%). Physical examination revealed pale nasal mucosa, pharyngeal "cobblestoning," and rhinorrhea. Fifty-three percent (33/62) of the patients had skin reactions to molds. Mold-exposed patients can present with a variety of IgE- and non-IgE-mediated symptoms. Mycotoxins, irritation by spores, or metabolites may be culprits in non-IgE presentations; environmental assays have not been perfected. Symptoms attributable to the toxic effects of molds and not attributable to IgE or other immune mechanisms need further evaluation as to pathogenesis. Allergic, rather than toxic, responses seemed to be the major cause of symptoms in the studied group.

Respiratory Toxicity of Lunar Highland Dust

NASA Technical Reports Server (NTRS)

James, John T.; Lam, Chiu-wing; Wallace, William T.

2009-01-01

Lunar dust exposures occurred during the Apollo missions while the crew was on the lunar surface and especially when microgravity conditions were attained during rendezvous in lunar orbit. Crews reported that the dust was irritating to the eyes and in some cases respiratory symptoms were elicited. NASA s vision for lunar exploration includes stays of 6 months on the lunar surface hence the health effects of periodic exposure to lunar dust need to be assessed. NASA has performed this assessment with a series of in vitro and in vivo tests on authentic lunar dust. Our approach is to "calibrate" the intrinsic toxicity of lunar dust by comparison to a nontoxic dust (TiO2) and a highly toxic dust (quartz) using intratrachael instillation of the dusts in mice. A battery of indices of toxicity is assessed at various time points after the instillations. Cultures of selected cells are exposed to test dusts to assess the adverse effects on the cells. Finally, chemical systems are used to assess the nature of the reactivity of various dusts and to determine the persistence of reactivity under various environmental conditions that are relevant to a space habitat. Similar systems are used to assess the dissolution of the dust. From these studies we will be able to set a defensible inhalation exposure standard for aged dust and predict whether we need a separate standard for reactive dust. Presently-available data suggest that aged lunar highland dust is slightly toxic, that it can adversely affect cultured cells, and that the surface reactivity induced by grinding the dust persists for a few hours after activation.

77 FR 47380 - Final National Pollutant Discharge Elimination System (NPDES) General Permit for Discharges From...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

... permit. Major changes also include definition of ``operator'', acute toxicity test for produced water... Category as authorized by section 402 of the Clean Water Act, (CWA). This permit renewal authorizes... considered all comments received and makes few changes to the proposed permit: pH limit for formation test...

75 FR 5405 - Sixty-Fifth Report of the TSCA Interagency Testing Committee to the Administrator of the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-02

.... SUMMARY: The Toxic Substances Control Act (TSCA) Interagency Testing Committee (ITC) transmitted its Sixty... manufacture (defined by statute to include import) and/or process TSCA-covered chemicals and you may be identified by the North American Industrial Classification System (NAICS) codes 325 and 32411. Because this...

Further Development and Validation of the Frog Embryo Teratogenesis Assay - Xenopus (Fetax)

DTIC Science & Technology

1989-05-12

other in vitro teratogenesis assays such as cell culture, planarian , fruitfly, and Hydra systems. The costs of performing the above mentioned tests are...Utilization of alternative species for toxicity testing: an overview. J. Appl. Toxicol. 5:193-219, 1985. 3. Best, J. B., and M. Morita. Planarians as a

Evaluation of repeated exposure systemic toxicity test of PVC with new plasticizer on rats via dual parenteral routes

PubMed Central

Hou, Li; Fan, Chunguang; Liu, Chenghu; Qu, Qiujin; Wang, Chunren

2018-01-01

Abstract Systemic toxicity caused by repeated exposure to both polar and nonpolar leachables of di(2-ethylhexyl)-1,2-cyclohexane plasticized polyvinyl chloride (PVC) was evaluated with dual routes of parenteral administration method on rats in the study. Experimental group and control group were designed by researchers. Tail intravenous injection with 0.9% sodium chloride injection extracts and intraperitoneal injection with corn oil extracts were conducted to the experimental rats while tail intravenous injection with 0.9% sodium chloride Injection and intraperitoneal injection with corn oil were conducted to the control rats. After 14 days, blood specimens were collected for clinical pathology (hematology and clinical chemistry) analysis. Selected organs were weighed and a histopathological examination was conducted. As a result, compared with the control animals, there were no toxicity-related changes on the parameters above. The results show that the rats do not show obvious systemic toxicity reaction caused by repeated exposure with dual routes of parenteral administration method on rats after administration with both polar and nonpolar exacts of di(2-ethylhexyl)-1,2-cyclohexane plasticized PVC simultaneously up for 14 days. PMID:29423263

Time-to-death approach to reveal chronic and cumulative toxicity of a fungicide for honeybees not revealed with the standard ten-day test.

PubMed

Simon-Delso, Noa; San Martin, Gilles; Bruneau, Etienne; Hautier, Louis

2018-05-08

Synthetic fungicides are pesticides widely used in agriculture to control phytopathogenic fungi. The systemicity, persistency and intense application of some of these fungicides, such as boscalid, leads to long periods of exposure for honeybees via contaminated water, pollen and nectar. We exposed adult honeybees in the lab to food contaminated with boscalid for 33 days instead of the standard 10-day test. Most of the toxic effects were observed after 10 days. The median time to death (LT 50 ) ranged from 24.9 days (lowest concentration) to 7.1 days (highest concentration) and was significantly shorter in all cases than with the control (32.0 days). The concentration and dietary doses of boscalid inducing 50% mortality (LC 50 and LDD 50 , respectively) decreased strongly with the time of exposure: LC 50  = 14,729 and 1,174 mg/l and LDD 50  = 0.318 and 0.0301 mg bee -1 day -1 at days 8 and 25, respectively. We found evidence of reinforced toxicity when exposure is prolonged, but with an unusual pattern: no cumulative toxicity is observed until 17-18 days, when a point of inflexion appears that suggests a reduced capacity of bees to deal with the toxicant. Our results show the importance of time-to-death experiments rather than fixed-duration studies for evaluating chronic toxicity.

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2012 CFR

2012-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products.

PubMed

Ruiz, Patricia; Begluitti, Gino; Tincher, Terry; Wheeler, John; Mumtaz, Moiz

2012-07-27

Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR), has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance's database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (LD₅₀) for determining relative toxicity of a number of substances. In general, the smaller the LD₅₀ value, the more toxic the chemical, and the larger the LD₅₀ value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s) of interest, during emergency responses, LD₅₀ values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD₅₀ models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD) are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD₅₀ values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field.

Influence of chloride on the chronic toxicity of sodium nitrate to Ceriodaphnia dubia and Hyalella azteca.

PubMed

Soucek, David J; Dickinson, Amy

2016-09-01

While it has been well established that increasing chloride concentration in water reduces the toxicity of nitrite to freshwater species, little work has been done to investigate the effect of chloride on nitrate toxicity. We conducted acute and chronic nitrate (as sodium nitrate) toxicity tests with the cladoceran Ceriodaphnia dubia and the amphipod Hyalella azteca (chronic tests only) over a range of chloride concentrations spanning natural chloride levels found in surface waters representative of watersheds of the Great Lakes Region. Chronic nitrate toxicity test results with both crustaceans were variable, with H. azteca appearing to be one of the more sensitive invertebrate species tested and C. dubia being less sensitive. While the variability in results for H. azteca were to an extent related to chloride concentration in test water that was distinctly not the case for C. dubia. We concluded that the chloride dependent toxicity of nitrate is not universal among freshwater crustaceans. An additional sodium chloride chronic toxicity test with the US Lab strain of H. azteca in the present study suggested that when present as predominantly sodium chloride and with relatively low concentrations of other ions, there is a narrow range of chloride concentrations over which this strain is most fit, and within which toxicity test data are reliable.

Early Combination of Material Characteristics and Toxicology Is Useful in the Design of Low Toxicity Carbon Nanofiber

PubMed Central

Jensen, Ellen K.; Larsen, Sten Y.; Nygaard, Unni C.; Marioara, Calin D.; Syversen, Tore

2012-01-01

This paper describes an approach for the early combination of material characterization and toxicology testing in order to design carbon nanofiber (CNF) with low toxicity. The aim was to investigate how the adjustment of production parameters and purification procedures can result in a CNF product with low toxicity. Different CNF batches from a pilot plant were characterized with respect to physical properties (chemical composition, specific surface area, morphology, surface chemistry) as well as toxicity by in vitro and in vivo tests. A description of a test battery for both material characterization and toxicity is given. The results illustrate how the adjustment of production parameters and purification, thermal treatment in particular, influence the material characterization as well as the outcome of the toxic tests. The combination of the tests early during product development is a useful and efficient approach when aiming at designing CNF with low toxicity. Early quality and safety characterization, preferably in an iterative process, is expected to be efficient and promising for this purpose. The toxicity tests applied are preliminary tests of low cost and rapid execution. For further studies, effects such as lung inflammation, fibrosis and respiratory cancer are recommended for the more in-depth studies of the mature CNF product.

The effects of plant essential oils on escape response and mortality rate of Aedes aegypti and Anopheles minimus.

PubMed

Sathantriphop, Sunaiyana; Achee, Nicole L; Sanguanpong, Unchalee; Chareonviriyaphap, Theeraphap

2015-12-01

The High Throughput Screening System (HITSS) has been applied in insecticide behavioral response studies with various mosquito species. In general, chemical or natural compounds can produce a range of insect responses: contact irritancy, spatial repellency, knock-down, and toxicity. This study characterized these actions in essential oils derived from citronella, hairy basil, catnip, and vetiver in comparison to DEET and picaridin against Aedes aegypti and Anopheles minimus mosquito populations. Results indicated the two mosquito species exhibited significantly different (P<0.05) contact irritant escape responses between treatment and control for all tested compound concentrations, except with the minimum dose of picaridin (P>0.05) against Ae. aegypti. Spatial repellency responses were elicited in both mosquito species when exposed to all compounds, but the strength of the repellent response was dependent on compound and concentration. Data show that higher test concentrations had greatest toxic effects on both mosquito populations, but vetiver had no toxic effect on Ae. aegypti and picaridin did not elicit toxicity in either Ae. aegypti or An. minimus at any test concentration. Ultimately, this study demonstrates the ability of the HITSS assay to guide selection of effective plant essential oils for repelling, irritating, and killing mosquitoes. © 2015 The Society for Vector Ecology.

Alleviating monoterpene toxicity using a two-phase extractive fermentation for the bioproduction of jet fuel mixtures in Saccharomyces cerevisiae.

PubMed

Brennan, Timothy C R; Turner, Christopher D; Krömer, Jens O; Nielsen, Lars K

2012-10-01

Monoterpenes are a diverse class of compounds with applications as flavors and fragrances, pharmaceuticals and more recently, jet fuels. Engineering biosynthetic pathways for monoterpene production in microbial hosts has received increasing attention. However, monoterpenes are highly toxic to many microorganisms including Saccharomyces cerevisiae, a widely used industrial biocatalyst. In this work, the minimum inhibitory concentration (MIC) for S. cerevisiae was determined for five monoterpenes: β-pinene, limonene, myrcene, γ-terpinene, and terpinolene (1.52, 0.44, 2.12, 0.70, 0.53 mM, respectively). Given the low MIC for all compounds tested, a liquid two-phase solvent extraction system to alleviate toxicity during fermentation was evaluated. Ten solvents were tested for biocompatibility, monoterpene distribution, phase separation, and price. The solvents dioctyl phthalate, dibutyl phthalate, isopropyl myristate, and farnesene showed greater than 100-fold increase in the MIC compared to the monoterpenes in a solvent-free system. In particular, the MIC for limonene in dibutyl phthalate showed a 702-fold (308 mM, 42.1 g L(-1) of limonene) improvement while cell viability was maintained above 90%, demonstrating that extractive fermentation is a suitable tool for the reduction of monoterpene toxicity. Finally, we estimated that a limonane to farnesane ratio of 1:9 has physicochemical properties similar to traditional Jet-A aviation fuel. Since farnesene is currently produced in S. cerevisiae, its use as a co-product and extractant for microbial terpene-based jet fuel production in a two-phase system offers an attractive bioprocessing option. Copyright © 2012 Wiley Periodicals, Inc.

Systems Toxicology: Real World Applications and Opportunities.

PubMed

Hartung, Thomas; FitzGerald, Rex E; Jennings, Paul; Mirams, Gary R; Peitsch, Manuel C; Rostami-Hodjegan, Amin; Shah, Imran; Wilks, Martin F; Sturla, Shana J

2017-04-17

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams ("big data"), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity.

Systems Toxicology: Real World Applications and Opportunities

PubMed Central

2017-01-01

Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data. Systems Toxicology involves the use of large-scale data streams (“big data”), such as those derived from omics measurements that require computational means for obtaining informative results. Thus, integrative analysis of multiple molecular measurements, particularly acquired by omics strategies, is a key approach in Systems Toxicology. In recent years, there have been significant advances centered on in vitro test systems and bioanalytical strategies, yet a frontier challenge concerns linking observed network perturbations to phenotypes, which will require understanding pathways and networks that give rise to adverse responses. This summary perspective from a 2016 Systems Toxicology meeting, an international conference held in the Alps of Switzerland, describes the limitations and opportunities of selected emerging applications in this rapidly advancing field. Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized, from empirical end points to pathways of toxicity. This requires the integration of in vitro and in vivo data with computational modeling. Test systems and bioanalytical technologies have made significant advances, but ensuring data reliability and relevance is an ongoing concern. The major challenge facing the new pathway approach is determining how to link observed network perturbations to phenotypic toxicity. PMID:28362102

Application of a multi-channel system for continuous monitoring and an early warning system.

PubMed

Lee, J H; Song, C H; Kim, B C; Gu, M B

2006-01-01

A multi-channel continuous toxicity monitoring system developed in our laboratory, based on two-stage mini-bioreactors, was successfully implemented in the form of computer-based data acquisition. The multi-channel system consists of a series of a two-stage minibioreactor systems connected by a fiber optic probe to a luminometer, and uses genetically engineered bioluminescent bacteria for the detection of the potential toxicity from the soluble chemicals. This system can be stably and continuously operated due to the separation of the culture reactor from the test reactor and accomplish easy and long-term monitoring without system shut down by abrupt inflows of severe polluting chemicals. Four different recombinant bioluminescent bacteria were used in different channels so that the modes of the samples toxicities can be reasonably identified and evaluated based upon the response signature of each channel. The bioluminescent signatures were delivered from four channels by switching one at once, while the data is automatically logged to an IBM compatible computer. We also achieved the enhancement of the system through the manipulation of the dilution rate and the use of thermo-lux fusion strains. Finally, this system is now being implemented to a drinking water reservoir and river for remote sensing as an early warning system.

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.

A Prospective Comparative Study of the Toxicity Profile of 5-Flurouracil, Adriamycin, Cyclophosphamide Regime VS Adriamycin, Paclitaxel Regime in Patients with Locally Advanced Breast Carcinoma

PubMed Central

Pillai, Pradeep Sadasivan; Jayakumar, Krishnan Nair Lalithamma

2015-01-01

Introduction A 5-flurouracil, Adriamycin, Cyclophosphamide (FAC) and Adriamycin, Paclitaxel (AT) are two popular chemotherapeutic regimens for treatment of breast carcinoma. The most time tested and popular regimen is FAC. It is extensively studied for efficacy and toxicity. But data regarding toxicity profile and efficacy of AT regimen is sparse. Aim To study the toxicity profile, severity of toxicities and clinical response rate of FAC and AT regimens in patients with locally advanced breast carcinoma. Materials and Methods A prospective observational study with 50 patients in each treatment arm. Study duration was 12 months from November 2012 to October 2013. Consecutive patients with locally advanced breast carcinoma receiving treatment with either FAC or AT regimen, satisfying inclusion criteria were enrolled into the study after getting informed written consent. Prior to initiation of treatment detailed medical history was taken from all patients. General clinical examination, examination of organ systems and local examination of breast lump were done. After each cycle of chemotherapy and after completion of treatment patients were interviewed and examined for clinical response and toxicities. Toxicities were graded with WHO toxicity grading criteria. All data were entered in a structured proforma. At least 50% reduction in tumour size was taken as adequate clinical response. Statistical Analysis Data was analysed using Chi-square test with help of Excel 2007 and SPSS-16 statistical software. Results Different pattern of toxicities were seen with FAC and AT regimens. Anaemia, thrombocytopenia, stomatitis, hyperpigmentation, photosensitivity and diarrhoea were more common with patients receiving FAC regimen. Leucopenia, peripheral neuropathy, myalgia, arthralgia, vomiting and injection site reactions were more common in AT regimen. Both FAC and AT regimens gave 100% clinical response. Conclusion FAC and AT regimens are equally efficacious but have different toxicity profiles. Patient’s predisposition to toxicities may govern the selection of a particular regime. PMID:26870703

OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

PubMed

Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

2014-08-01

The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV<30%) for most chemicals and laboratories. The reproducibility was lower (CV>30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Flow-through bioassay for measuring bioaccumulation of toxic substances from sediment

USGS Publications Warehouse

Mac, Michael J.; Edsall, Carol C.; Hesselberg, Robert J.; Sayers, Richard E.

1984-01-01

Over 10 million cubic meters of sediment are dredged annually from Great Lakes waterways. Because much of this material is taken from harbors, connecting channels, and other nearshore areas that often are contaminated with toxic substances, the sediments proposed for dredging need to be evaluated for the presence of bioavailable contaminants and the potential for toxicity to the biota. Sound decisions on the appropriate disposal of the dredged material can be made only after such an evaluation. Presently, no standardized procedure exists for evaluating dredged material in freshwater systems although current criteria for discharge of dredged material into marine water have been developed (USEPA/CE 1977). In the ocean discharge guideline, it is recommended that bioassays be conducted on liquid, solid, and suspended particulate phases of dredged material. because it appears that the solid phase has the greatest potential for environmental damage and because measurement of bioaccumulation must be made to evaluate sediments for disposal (USEPA/CE 1977, Seeyle and Mac 1983), we developed a bioassay for testing the solid phase of dredged material that measures the survival of organisms and, perhaps more important, the bioaccumulation of toxic substances by aquatic organisms from naturally contaminated sediments (Peddicord et al. 1980; Rubinstein et al. 1980, 1983; Seeyle st al. 1982), several have used testing methods that result in unacceptable mortality to control organisms (Bahnick et al. 1981, Prater et al. 1983). Our bioassay is intended to estimate the potential for bioaccumlation of contaminants from sediments that are not acutely toxic to test organisms, but are suspected of containing persistent contaminants. By using test organisms that are not highly susceptible to toxic compounds, the bioaccumulation test allows estimation of the potential food-chain accumulation of contaminants that may occur in local biota from surficial sediments. In practice, bioaccumulation observed in this bioassay by organisms exposed to test sediments (sediments to be dredged) would be compared to bioaccumulation observed from sediments collected from a reference site (e.g. a disposal site or open lake), and also from control sediments (relatively clean sediment). Decisions could then be based on a comparison of results between tests and reference sediments to determine if disposal would cause dehydration to the habitat, and between reference and control sediment to determine if even the reference material is seriously contaminated. Although the test is not intended to be a toxicity test per se, use of test, reference, and control sediments enables interpretation of any mortality of organisms that may occur during the bioassays. High mortality in bioassays with test or reference sediment would indicate acute toxicity of sediments in the project area. However if high mortality occurs in all three sediments, it can be assumed that the organisms were not in a healthy state at the time of testing. We describe the results of 10-day sediment bioassays in which both mortality and bioaccumulation were measured in four aquatic organisms. We exposed two infaunal organisms and two species of fish to test and control sediments in the laboratory.

Acute toxicity testing with the tropical marine copepod Acartia sinjiensis: optimisation and application.

PubMed

Gissi, F; Binet, M T; Adams, M S

2013-11-01

Globally there is limited toxicity data for tropical marine species, and there has been a call for further research and development in the area of tropical marine ecotoxicology. An increase in developmental pressures in northern tropical Australia is causing a higher demand for toxicity test protocols with ecologically relevant species. Copepods are a diverse group of zooplankton that are major components of marine food webs. The calanoid copepod Acartia sinjiensis is widely distributed across tropical and sub-tropical brackish to marine waters of Australia and was identified in a recent comprehensive review of marine tropical toxicity testing in Australia as a suitable test organism. Through a number of optimisation steps including feeding trials, changes to culture and test conditions; a 48-h acute toxicity test with A. sinjiensis was modified to become a highly reliable and reproducible standard test protocol. Control mobility was improved significantly, and the sensitivity of A. sinjiensis to copper (EC50 of 33µg/L), ammonia (EC50 of 10mg/L) and phenol (EC50 of 13mg/L) fell within the ranges of those reported previously, indicating that the modifications did not alter its sensitivity. In a comprehensive literature search we found that this species was the most sensitive to copper out of a range of marine copepods. The test was also successfully applied in toxicity assessments of four environmental samples: two produced formations waters (PFWs) and two mine tailing liquors (MTLs). The toxicity assessments utilised toxicity data from a suite of marine organisms (bacteria, microalgae, copepods, sea urchins, oysters, prawns, and fish). For the PFWs, which were predominantly contaminated with organic chemicals, A. sinjiensis was the most sensitive species (EC50 value 2-17 times lower than for any other test species). For the predominantly metal-contaminated mine tailing liquors, its sensitivity was similar to that of other test species used. The modified 48-h acute toxicity test with A. sinjiensis proved to be a valuable tool in these toxicity assessments, and is recommended for use in tropical marine toxicity assessments for northern Australia. Copyright © 2013 Elsevier Inc. All rights reserved.

Zebrafish as a Model System for Environmental Health Studies in the Grade 9–12 Classroom

PubMed Central

Hesselbach, Renee; Carvan, Michael John; Goldberg, Barbara; Berg, Craig A.; Petering, David H.

2014-01-01

Abstract Developing zebrafish embryos were used as a model system for high school students to conduct scientific investigations that reveal features of normal development and to test how different environmental toxicants impact the developmental process. The primary goal of the module was to engage students from a wide range of socio-economic backgrounds, with particular focus on underserved inner-city high schools, in inquiry-based learning and hands-on experimentation. In addition, the module served as a platform for both teachers and students to design additional inquiry-based experiments. In this module, students spawned adult zebrafish to generate developing embryos, exposed the embryos to various toxicants, then gathered, and analyzed data obtained from control and experimental embryos. The module provided a flexible, experimental framework for students to test the effects of numerous environmental toxicants, such as ethanol, caffeine, and nicotine, on the development of a model vertebrate organism. Students also observed the effects of dose on experimental outcomes. From observations of the effects of the chemical agents on vertebrate embryos, students drew conclusions on how these chemicals could impact human development and health. Results of pre-tests and post-tests completed by participating students indicate statistically significant changes in awareness of the impact of environmental agents on fish and human beings In addition, the program's evaluator concluded that participation in the module resulted in significant changes in the attitude of students and teachers toward science in general and environmental health in particular. PMID:24941301

Antinociceptive effects, acute toxicity and chemical composition of Vitex agnus-castus essential oil.

PubMed

Khalilzadeh, Emad; Vafaei Saiah, Gholamreza; Hasannejad, Hamideh; Ghaderi, Adel; Ghaderi, Shahla; Hamidian, Gholamreza; Mahmoudi, Razzagh; Eshgi, Davoud; Zangisheh, Mahsa

2015-01-01

Vitex agnus-castus (VAC) and its essential oil have been traditionally used to treat many conditions and symptoms such as premenstrual problems, mastalgia, inflammation, sexual dysfunction, and pain. In this study, the effects of essential oil extracted from Vitex agnus-castus (EOVAC) leaves were investigated in three behavioral models of nociception in adult male Wistar rats. Chemical composition of EOVAC was analyzed using gas chromatography - mass spectrometry (GC-MS) and also its possible toxicity was determined in mice. Analgesic effect of EOVAC was determined using tail immersion test, formalin test, and acetic acid-induced visceral pain in rats. EOVAC (s.c.) and morphine (i.p.) significantly (p<0.05) reduced pain responses in both formalin and tail immersion tests. In the study of evolved mechanisms, pretreatment with naloxone or atropine significantly (p <0.05) reversed the essential oil-induced analgesia in both formalin and tail immersion tests. Moreover, EOVAC and Piroxicam produced significant (p<0.05) inhibition in the acetic acid-induced writhing response. EOVAC did not show any mortality even at high dose (5 g/kg, p.o.) of administration in toxicity test. Moreover, according to GC-MS results, major components of the EOVAC were α-pinene (14.83%), limonene (10.29%), β-caryophyllene (6.9%), sabinene (5.27%), and β-farnesene (5.9%). These results suggest that endogenous opioidergic system as well as muscarinergic receptors of cholinergic system may be involve in the antinociceptive activity of Vitex agnus-castus essential oil in these models of pain in rats.

Antinociceptive effects, acute toxicity and chemical composition of Vitex agnus-castus essential oil

PubMed Central

Khalilzadeh, Emad; Vafaei Saiah, Gholamreza; Hasannejad, Hamideh; Ghaderi, Adel; Ghaderi, Shahla; Hamidian, Gholamreza; Mahmoudi, Razzagh; Eshgi, Davoud; Zangisheh, Mahsa

2015-01-01

Objective: Vitex agnus-castus (VAC) and its essential oil have been traditionally used to treat many conditions and symptoms such as premenstrual problems, mastalgia, inflammation, sexual dysfunction, and pain. In this study, the effects of essential oil extracted from Vitex agnus-castus (EOVAC) leaves were investigated in three behavioral models of nociception in adult male Wistar rats. Materials and methods: Chemical composition of EOVAC was analyzed using gas chromatography – mass spectrometry (GC-MS) and also its possible toxicity was determined in mice. Analgesic effect of EOVAC was determined using tail immersion test, formalin test, and acetic acid-induced visceral pain in rats. Results: EOVAC (s.c.) and morphine (i.p.) significantly (p<0.05) reduced pain responses in both formalin and tail immersion tests. In the study of evolved mechanisms, pretreatment with naloxone or atropine significantly (p <0.05) reversed the essential oil-induced analgesia in both formalin and tail immersion tests. Moreover, EOVAC and Piroxicam produced significant (p<0.05) inhibition in the acetic acid-induced writhing response. EOVAC did not show any mortality even at high dose (5 g/kg, p.o.) of administration in toxicity test. Moreover, according to GC-MS results, major components of the EOVAC were α-pinene (14.83%), limonene (10.29%), β-caryophyllene (6.9%), sabinene (5.27%), and β-farnesene (5.9%). Conclusions: These results suggest that endogenous opioidergic system as well as muscarinergic receptors of cholinergic system may be involve in the antinociceptive activity of Vitex agnus-castus essential oil in these models of pain in rats. PMID:26101755

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish).

PubMed

Watanabe, Haruna; Tamura, Ikumi; Abe, Ryoko; Takanobu, Hitomi; Nakamura, Ataru; Suzuki, Toshinari; Hirose, Akihiko; Nishimura, Tetsuji; Tatarazako, Norihisa

2016-04-01

Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no-observed-effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action were nearly identical for alga, as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action. © 2015 SETAC.

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

Stephenson, G.L.; Scroggins, R.

Environment Canada has embarked on a five year program to develop, standardize, and validate a battery of soil toxicity tests which can be used to assess the relative toxicity of contaminants in soils to terrestrial organisms. These tests must be applicable to soil conditions typically found in Canadian environments and the test species must be representative of the species of soil invertebrates or plants inhabiting soil ecosystems in Canada. One of the toxicity tests being developed is designed to assess the toxicity of contaminated soils to earthworms. Five of the potential test species belong to the Lumbricidae family and includemore » the Canadian worm (Allobophora calignosa/Aporrectodea tuberculate), the European bark worm (Dendrodtilus rubidus (rubida)), the pink soil worm (Eisenia rosea), the red marsh worm (Lumbricus rubellus), and the Canadian night crawler or dew worm (Lumbricus terrestris). The sixth species, the white pot worm (Enchytraeus albidus), belongs to the Enchytraeidae family. Further assessment reduced the number of representative species to three. Most earthworm test methods have been developed to assess the toxicity of chemically-spiked artificial soils to Eisenia fetida or E. andrei. Test methods have also been developed to assess the relative toxicity of contaminated soils from hazardous waste sites. Comparative acute toxicity data for three species of earthworm exposed to a hydrocarbon contamination will be presented. Comparative toxicity data for the same three species of earthworm will also be presented using test procedures and conditions that have been modified to accommodate biological differences among the species of earthworm. Recommendations regarding test design, methods, and conditions optimal for each test species will be summarized and discussed with respect to the precision of test results.« less

Effect of test conditions on relative toxicity rankings of fifteen materials

NASA Technical Reports Server (NTRS)

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

1977-01-01

Fifteen materials were evaluated for relative toxicity of pyrolysis effluents, using different test conditions in the USF methodology. Wool fabrics were consistently among the most toxic materials, and polystyrene and polychloroprene flexible foam were consistently among the least toxic materials.

AQUIRE: Aquatic Toxicity Information Retrieval data base. Data file

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

Anderson, E.; Pilli, A.

The purpose of Aquatic Toxicity Information Retrieval (AQUIRE) data base is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for AQUIRE. Independently compiled data files that meet AQUIRE parameter and quality assurance criteria are also included. Selected toxicity-test results and related testing information for any individual chemical from laboratory and field aquatic toxicity tests are extracted and added to AQUIRE. Acute, sublethal, and bioconcentration effects are included for tests withmore » freshwater and marine organisms. The total number of data records in AQUIRE now equals 104,500. This includes data from 6000 references, for 5200 chemicals and 2400 test species. A major data file, Acute Toxicity of Organic Chemicals (ATOC), has been incorporated into AQUIRE. The ATOC file contains laboratory acute test data on 525 organic chemicals using juvenile fathead minnows. The complete data file can be accessed by requesting review code 5 as a search parameter.« less

Removal of emerging micropollutants from water using cyclodextrin.

PubMed

Nagy, Zsuzsanna Magdolna; Molnár, Mónika; Fekete-Kertész, Ildikó; Molnár-Perl, Ibolya; Fenyvesi, Éva; Gruiz, Katalin

2014-07-01

Small scale laboratory experiment series were performed to study the suitability of a cyclodextrin-based sorbent (ß-cyclodextrin bead polymer, BCDP) for modelling the removal of micropollutants from drinking water and purified waste water using simulated inflow test solutions containing target analytes (ibuprofen, naproxen, ketoprofen, bisphenol-A, diclofenac, β-estradiol, ethinylestradiol, estriol, cholesterol at 2-6 μg/L level). This work was focused on the preliminary evaluation of BCDP as a sorbent in two different model systems (filtration and fluidization) applied for risk reduction of emerging micropollutants. For comparison different filter systems combined with various sorbents (commercial filter and activated carbon) were applied and evaluated in the filtration experiment series. The spiked test solution (inflow) and the treated outflows were characterized by an integrated methodology including chemical analytical methods gas chromatography-tandem mass spectrometry (GC-MS/MS) and various environmental toxicity tests to determine the efficiency and selectivity of the applied sorbents. Under experimental conditions the cyclodextrin-based filters used for purification of drinking water in most cases were able to absorb more than 90% of the bisphenol-A and of the estrogenic compounds. Both the analytical chemistry and toxicity results showed efficient elimination of these pollutants. Especially the toxicity of the filtrate decreased considerably. Laboratory experiment modelling post-purification of waste water was also performed applying fluidization technology by ß-cyclodextrin bead polymer. The BCDP removed efficiently from the spiked test solution most of the micropollutants, especially the bisphenol-A (94%) and the hormones (87-99%) The results confirmed that the BCDP-containing sorbents provide a good solution to water quality problems and they are able to decrease the load and risk posed by micropollutants to the water systems. Copyright © 2014 Elsevier B.V. All rights reserved.

Weakly electric fish for biomonitoring water quality.

PubMed

Clausen, Juergen; van Wijk, Roeland; Albrecht, Henning

2012-06-01

Environmental pollution is a major issue that calls for suitable monitoring systems. The number of possible pollutants of municipal and industrial water grows annually as new chemicals are developed. Technical devices for pollutant detection are constructed in a way to detect a specific and known array of pollutants. Biological systems react to lethal or non-lethal environmental changes without pre-adjustment, and a wide variety have been employed as broad-range monitors for water quality. Weakly electric fish have proven particularly useful for the purpose of biomonitoring municipal and industrial waters. The frequency of their electric organ discharges directly correlates with the quality of the surrounding water and, in this way, concentrations of toxicants down to the nanomolar range have been successfully detected by these organisms. We have reviewed the literature on biomonitoring studies to date, comparing advantages and disadvantages of this test system and summarizing the lowest concentrations of various toxicants tested. Eighteen publications were identified investigating 35 different chemical substances and using six different species of weakly electric fish.

Sensor-enabled chem/bio contamination detection system dedicated to situational awareness of water distribution security status

NASA Astrophysics Data System (ADS)

Ginsberg, Mark D.; Smith, Eddy D.; VanBlaricum, Vicki; Hock, Vincent F.; Kroll, Dan; Russell, Kevin J.

2010-04-01

Both real events and models have proven that drinking water systems are vulnerable to deliberate and/or accidental contamination. Additionally, homeland security initiatives and modeling efforts have determined that it is relatively easy to orchestrate the contamination of potable water supplies. Such contamination can be accomplished with classic and non-traditional chemical agents, toxic industrial chemicals (TICs), and/or toxic industrial materials (TIMs). Subsequent research and testing has developed a proven network for detection and response to these threats. The method uses offthe- shelf, broad-spectrum analytical instruments coupled with advanced interpretive algorithms. The system detects and characterizes any backflow events involving toxic contaminants by employing unique chemical signature (fingerprint) response data. This instrumentation has been certified by the Office of Homeland Security for detecting deliberate and/or accidental contamination of critical water infrastructure. The system involves integration of several mature technologies (sensors, SCADA, dynamic models, and the HACH HST Guardian Blue instrumentation) into a complete, real-time, management system that also can be used to address other water distribution concerns, such as corrosion. This paper summarizes the reasons and results for installing such a distribution-based detection and protection system.

Lethal and sub-lethal evaluation of Indigo Carmine dye and byproducts after TiO2 photocatalysis in the immune system of Eisenia andrei earthworms.

PubMed

Genázio Pereira, Patrícia Christina; Reimão, Roberta Valoura; Pavesi, Thelma; Saggioro, Enrico Mendes; Moreira, Josino Costa; Veríssimo Correia, Fábio

2017-09-01

The Indigo carmine (IC) dye has been widely used in textile industries, even though it has been considered toxic for rats, pigs and humans. Owing to its toxicity, wastes containing this compound should be treated to minimize or eliminate their toxic effects on the biota. As an alternative to wastewater treatment, advanced oxidative processes (AOPs) have been highlighted due to their high capacity to destruct organic molecules. In this context, this study aimed to evaluate Indigo Carmine toxicity to soil organisms using the earthworm Eisenia andrei as a model-organism and also verify the efficiency of AOP in reducing its toxicity to these organisms. To this end, lethal (mortality) and sub-lethal (loss or gain of biomass, reproduction, behavior, morphological changes and immune system cells) effects caused by this substance and its degradation products in these annelids were evaluated. Morphological changes were observed even in organisms exposed to low concentrations, while mortality was the major effect observed in individuals exposed to high levels of indigo carmine dye. The organisms exposed to the IC during the contact test showed mortality after 72h of exposure (LC 50 = 75.79mgcm - 2 ), while those exposed to photoproducts showed mortality after 48h (LC 50 = 243min). In the chronic study, the organisms displayed a mortality rate of 14%, while those exposed to the photoproduct reached up to 32.7%. A negative influence of the dye on the reproduction rate was observed, while by-products affected juvenile survival. A loss of viability and alterations in the cellular proportion was verified during the chronic test. However, the compounds did not alter the behavior of the annelids in the leak test (RL ranged from 20% to 30%). Although photocatalysis has been presented as an alternative technology for the treatment of waste containing the indigo carmine dye, this process produced byproducts even more toxic than the original compounds to E. andrei. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of sediment toxicity in the Lagoon of Venice (Italy) using a multi-species set of bioassays.

PubMed

Picone, Marco; Bergamin, Martina; Losso, Chiara; Delaney, Eugenia; Arizzi Novelli, Alessandra; Ghirardini, Annamaria Volpi

2016-01-01

Within the framework of a Weight of Evidence (WoE) approach, a set of four toxicity bioassays involving the amphipod Corophium volutator (10 d lethality test on whole sediment), the sea urchin Paracentrotus lividus (fertilization and embryo toxicity tests on elutriate) and the pacific oyster Crassostrea gigas (embryo toxicity test on elutriate) was applied to sediments from 10 sampling sites of the Venice Lagoon (Italy). Sediments were collected during three campaigns carried out in May 2004 (spring campaign), October 2004 (autumn campaign) and February 2005 (winter campaign). Toxicity tests were performed on all sediment samples. Sediment grain-size and chemistry were measured during spring and autumn campaigns. This research investigated (i) the ability of toxicity tests in discriminating among sites with different contamination level, (ii) the occurrence of a gradient of effect among sampling sites, (iii) the possible correlation among toxicity tests, sediment chemistry, grain size and organic carbon, and (iv) the possible occurrence of toxicity seasonal variability. Sediment contamination levels were from low to moderate. No acute toxicity toward amphipods was observed, while sea urchin fertilization was affected only in few sites in just a single campaign. Short-term effects on larval development of sea urchin and oyster evidenced a clear spatial trend among sites, with increasing effects along the axis connecting the sea-inlets with the industrial area. The set of bioassays allowed the identification of a spatial gradient of effect, with decreasing toxicity from the industrial area toward the sea-inlets. Multivariate data analysis showed that the malformations of oyster embryos were significantly correlated to the industrial contamination (metals, polynuclear aromatic hydrocarbons, hexachlorobenzene and polychlorinated biphenyls), while sea urchin development to sediment concentrations of As, Cr and organic carbon. Both embryo toxicity tests were significantly affected by high ammonia concentrations found in the elutriates extracted from some mudflat and industrial sediments. No significant temporal variation of the toxicity was observed within the experimental period. Amendments to the set of bioassays, with inclusion of chronic tests, can certainly provide more reliability and consistency to the characterization of the (possible) toxic effects. Copyright © 2015 Elsevier Inc. All rights reserved.

The use of a behavioral response system in the USF/NASA toxicity screening test method

NASA Technical Reports Server (NTRS)

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

1977-01-01

Relative toxicity data on the pyrolysis effluents from bisphenol A polycarbonate and wool fabric were obtained, based on visual observations of the behavior of free-moving mice and on an avoidance response behavioral paradigm of restrained rats monitored by an instrumented behavioral system. The initial experiments show an essentially 1:1 correlation between the two systems with regard to first signs of incapacitation, collapse, and death from pyrolysis effluents from polycarbonate. It is hypothesized that similarly good correlations between these two systems might exist for other materials exhibiting predominantly carbon monoxide mechanisms of intoxication. This hypothesis needs to be confirmed, however, by additional experiments. Data with wool fabric exhibited greater variability with both procedures, indicating possibly different mechanisms of intoxication for wool as compared with bisphenol A polycarbonate.

The chemical exposure toxicity space (CETS) model: Displaying exposure time, aqueous and organic concentration, activity, and onset of toxicity.

PubMed

Mackay, Donald; Celsie, Alena K D; Parnis, J Mark; McCarty, Lynn S; Arnot, Jon A; Powell, David E

2017-05-01

A 1-compartment toxicokinetic model is used to characterize the chemical exposure toxicity space (CETS), providing a novel graphic tool that can aid in the design of aquatic toxicity tests for fish and for interpreting their results. The graph depicts the solution to the differential equation describing the uptake kinetics of a chemical by a modeled fish under conventional bioassay conditions. The model relates the exposure concentration in the water to a dimensionless time and the onset of toxicity as determined by an estimated or assumed critical body residue or incipient lethal aqueous concentration. These concentration graphs are specific to each chemical and exposure and organism parameters and clearly demonstrate differences in toxicity between chemicals and how factors such as hydrophobicity influence the toxic endpoint. The CETS plots can also be used to assess bioconcentration test conditions to ensure that concentrations are well below toxic levels. Illustrative applications are presented using a recent set of high-quality toxicity data. Conversion of concentrations to chemical activities in the plots enables results for different baseline toxicants to be superimposed. For chemicals that have different modes of toxic action, the increased toxicity then becomes apparent. Implications for design and interpretation of aquatic toxicity tests are discussed. The model, and pictorial visualization of the time-course of aquatic toxicity tests, may contribute to improvements in test design, implementation, and interpretation, and to reduced animal usage. Environ Toxicol Chem 2017;36:1389-1396. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

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.

Cytotoxicity evaluation of gold nanoparticles on microalga Dunaliella salina in microplate test system

NASA Astrophysics Data System (ADS)

Chumakov, Daniil; Prilepskii, Artur; Dykman, Lev; Khlebtsov, Boris; Khlebtsov, Nikolai; Bogatyrev, Vladimir

2018-04-01

Gold nanoparticles are intensively studied in biomedicine. Assessment of their biocompatibility is highly important. Currently there is lack of evidence, concerning nanotoxicity of ultrasmall gold nanoparticles < 5 nm. Existing data are rather contradictory. The aim of that study was to evaluate the toxicity of 2 nm colloidal gold, using microalga Dunaliella salina. Cellular barriers of that microalga are very similar to animal cells so it might be considered as a valuable model for nanotoxicity testing. Chlorophyll content as a test-function was used. Spectrophotometric method for chlorophyll determination in vivo in suspensions of D.salina cultures was applied. Calculated EC50 48h value of ionic gold was 25.8 +/- 0.3 mg Au/L. EC50 value of phosphine-stabilized gold nanoclusters was 32.2 +/-1.1 mg Au/L. It was not possible to calculate EC50 for 15 nm citrate gold nanoparticles, as they were non-toxic at all concentrations tested. These results are confirmed by fluorescent -microscopic monitoring of the same probes. It was shown that 10-fold growth of phosphine-stabilized gold nanoparticles (from 2.3 +/- 0.9 nm to 21.1 +/- 7.5 nm) led to 7-fold decrease of their toxicity.

Use of higher plants as screens for toxicity assessment.

PubMed

Kristen, U

1997-01-01

This review deals with the use of entire plants, seedlings, cell suspension cultures and pollen tubes for the estimation of potential toxicity in the environment, and for risk assessment of chemicals and formulations of human relevance. It is shown that the roots of onions and various crop seedlings, as well as in vitro growing pollen tubes of some mono- and dicotyledonous plants, are most frequently used to obtain toxicity data by determination of root and tube growth inhibition. Both roots and pollen tubes are chloroplast free, non-photosynthetic systems and, therefore, with regard to their cytotoxic reactions are closer to vertebrate tissues and cells than are chloroplast-containing plant organs. Root tips and anthers of flower buds are shown to be applicable to genotoxicity screening by microscopic analysis of mitotic or meiotic aberrations during cell division or microspore development, respectively. The processes of mitosis and meiosis are similar in plants and animals. Therefore, meristematic and sporogenic tissues of plants generally show patterns of cytotoxic response similar to those of embryogenic and spermatogenic tissues of vertebrates. The suitability of root tips, cell suspensions and pollen tubes for the investigation of mechanisms of toxic action and for the analysis of structure-activity relationships is also demonstrated. Two plant-based assays, the Allium test and the pollen tube growth test, both currently being evaluated alongside with established mammalian in vivo and in vitro protocols, are emphasized with regard to their potential use as alternatives to animal in vivo toxicity tests. For both assays, preliminary results indicate that the tips of growing roots and the rapidly elongating pollen tubes of certain higher plant species are as reliable as mammalian cell lines for detecting basal cytotoxicity. It is suggested that seeds and pollen grains, in particular, provide easily storable and convenient systems for inexpensive, relatively simple but precise toxicological assays. (c) 1997 Elsevier Science Ltd.

Ecological evaluation of proposed dredged material from St. Andrew Bay, Florida

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

Mayhew, H.L.; Word, J.Q.; Kohn, N.P.

1993-10-01

The US Army Corps of Engineers (USACE), Mobile District, requested that the Battelle/Marine Sciences Laboratory (MSL) conduct field sampling and chemical and biological testing to determine the suitability of potential dredged material for open ocean disposal. Sediment from St. Andrew Bay was chemically characterized and evaluated for biological toxicity and bioaccumulation of contaminants. The Tier III guidance for ocean disposal testing requires tests of water column effects (following dredged material disposal), deposited sediment toxicity, and bioaccumulation of contaminants from deposited sediment (dredged material). To meet these requirements, the MSL conducted suspended-particulate-phase (SPP) toxicity tests, solid-phase toxicity tests, and bioaccumulation testingmore » on sediment representing potential dredged material from Panama City Harbor. Physical and chemical characterization of sediment to support toxicity and bioaccumulation results was also conducted on both the test and reference sediments. The MSL collected sediment samples from five sites in St. Andrew Bay and one reference site near Lands End Peninsula. The five test sediments and the reference sediment were analyzed for physical and chemical sediment characteristics, SPP chemical contaminants, solid-phase toxicity, SPP toxicity, and bioaccumulation of contaminants.« less

Toxicity of organic chemical pollution in groundwater downgradient of a landfill (Grindsted, Denmark)

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

Baun, A.; Jensen, S.D.; Bjerg, P.L.

2000-05-01

The aim of the present study was to describe the occurrence and distribution of toxicity related to organic chemical contaminants in the leachate plume downgradient of the Grindsted Landfill (Denmark). A total of 27 groundwater samples were preconcentrated by solid-phase extraction (SPE) using XAD-2 as the resin material. This treatment effectively eliminated sample matrix toxicity caused by inorganic salts and natural organic compounds and produced an aqueous concentrate of the nonvolatile chemical contaminants. The SPE extracts were tested in a battery of standardized short-term aquatic toxicity tests with luminescent bacteria (Vibrio fischeri), algae (Selenastrum capricornutum), and crustaceans (Daphnia magna). Additionalmore » genotoxicity tests were made using the umuC test (Salmonella typhimurium). Biotests with algae and luminescent bacteria were the most sensitive tests. On the basis of results with these two bioassays, it was concluded that SPE extracts of groundwater collected close to the landfill were toxic. The toxicity decreased with the distance from the landfill. At distances greater than 80 m from the border of the landfill, the groundwater toxicity was not significantly different from the background toxicity. SPE extracts were not toxic to Daphnia, and no genotoxicity was observed in the umuC test. The overall findings indicate that a battery of biotests applied on preconcentrated groundwater samples can be a useful tool for toxicity characterization and hazard ranking of groundwater polluted with complex chemical mixtures, such as landfill leachates.« less

Understanding Genetic Toxicity Through Data Mining: The ...

EPA Pesticide Factsheets

This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies. This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies.

Acute oral toxicity test of chemical compounds in silkworms.

PubMed

Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

2016-02-01

This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals.

Ecotoxicologic impacts of agricultural drain water in the Salinas River, California, USA.

PubMed

Anderson, Brian S; Hunt, John W; Phillips, Bryn M; Nicely, Patricia A; Gilbert, Kristine D; de Vlaming, Victor; Connor, Valerie; Richard, Nancy; Tjeerdema, Ronald S

2003-10-01

The Salinas River is the largest of the three rivers that drain into the Monterey Bay National Marine Sanctuary in central California (USA). Large areas of this watershed are cultivated year-round in row crops, and previous laboratory studies have demonstrated that acute toxicity of agricultural drain water to Ceriodaphnia dubia is caused by the organophosphate (OP) pesticides chlorpyrifos and diazinon. We investigated chemical contamination and toxicity in waters and sediments in the river downstream of an agricultural drain water input. Ecological impacts of drain water were investigated by using bioassessments of macroinvertebrate community structure. Toxicity identification evaluations were used to characterize chemicals responsible for toxicity. Salinas River water downstream of the agricultural drain was acutely toxic to the cladoceran Ceriodaphnia dubia, and toxicity to C. dubia was highly correlated with combined toxic units (TUs) of chlorpyrifos and diazinon. Laboratory tests were used to demonstrate that sediments in this system were acutely toxic to the amphipod Hyalella azteca, a resident invertebrate. Toxicity identification evaluations (TIEs) conducted on sediment pore water suggested that toxicity to amphipods was due in part to OP pesticides; concentrations of chlorpyrifos in pore water sometimes exceeded the 10-d mean lethal concentration (LC50) for H. azteca. Potentiation of toxicity with addition of the metabolic inhibitor piperonyl butoxide suggested that sediment toxicity also was due to other non-metabolically activated compounds. Macroinvertebrate community structure was highly impacted downstream of the agricultural drain input, and a number of macroinvertebrate community metrics were negatively correlated with combined TUs of chlorpyrifos and diazinon, as well as turbidity associated with the drain water. Some macroinvertebrate metrics were also correlated with bank vegetation cover. This study suggests that pesticide pollution is the likely cause of ecological damage in the Salinas River, and this factor may interact with other stressors associated with agricultural drain water to impact the macroinvertebrate community in the system.

Static renewal tests using Pimephales promelas (fathead minnows) and Ceriodaphnia dubia (daphnids). Clinch River-Environmental Restoration Program (CR-ERP) study, ambient water toxicity

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

Simbeck, D.J.

1994-12-31

Clinch River-Environmental Restoration Program (CR-ERP) personnel and Tennessee Valley Authority (TVA) personnel conducted a study during the week of January 25--February 1, 1994. The organisms specified for testing were larval fathead minnows, Pimephales promelas, and the daphnid, Ceriodaphnia dubia. Surface water samples were collected from Clinch River Mile 9.0, Poplar Creek Mile 1.0, and Poplar Creek Mile 2.9 on January 24, 26, and 28. Samples were partitioned and provided to the CR-ERP and TVA toxicology laboratories for testing. Exposure of test organisms to these samples resulted in no toxicity (survival or growth) to fathead minnows; however, toxicity to daphnids wasmore » demonstrated in undiluted samples from Poplar Creek Mile 1.0 in testing conducted by TVA based on hypothesis testing of data. Point estimation (IC{sub 25}) analysis of the data, however, showed no toxicity in PCM 1.0 samples. Attachments to this report include: Chain of custody forms -- originals; Toxicity test bench sheets and statistical analyses; Meter calibrations; and Reference toxicant test information.« less

16 CFR 1500.40 - Method of testing toxic substances.

Code of Federal Regulations, 2014 CFR

2014-01-01

... not require animals, are presented in the CPSC's animal testing policy set forth in 16 CFR 1500.232. A... test animals. The method of testing the toxic substances referred to in § 1500.3(c)(1)(ii)(C) and (c)(2... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Method of testing toxic substances. 1500.40...

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...

Evaluation of the toxic properties of naturally weathered Exxon Valdez crude oil to surrogate wildlife species

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

Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.

1995-12-31

The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) to avian and mammalian wildlife species were evaluated using the surrogate species, mallard duck, Anas platyrhynchos, and European ferret, Mustela putorius. This study was conducted to evaluate the potential for toxic (rather than physical) injury to wildlife species that may have been exposed to WEVC, either through external contact or through dietary uptake. Previous studies have assessed the toxicity of unweathered crude oils, including Alaska North Slope Crude, but little information exists regarding the toxicity of a naturally weathered crude oil, typical of that encountered following a spill. Amore » battery of laboratory toxicity tests was conducted, in compliance with standard and published test procedures, to evaluate acute and subchronic toxicity of WEVC. These included tests of food avoidance, reproductive effects, and direct eggshell application toxicity. Naturally weathered EVC, recovered postspill from Prince William Sound, was used as the test material. 36 refs., 7 figs., 4 tabs.« less

In vitro transcriptomic prediction of hepatotoxicity for early drug discovery

PubMed Central

Cheng, Feng; Theodorescu, Dan; Schulman, Ira G.; Lee, Jae K.

2012-01-01

Liver toxicity (hepatotoxicity) is a critical issue in drug discovery and development. Standard preclinical evaluation of drug hepatotoxicity is generally performed using in vivo animal systems. However, only a small number of preselected compounds can be examined in vivo due to high experimental costs. A more efficient yet accurate screening technique which can identify potentially hepatotoxic compounds in the early stages of drug development would thus be valuable. Here, we develop and apply a novel genomic prediction technique for screening hepatotoxic compounds based on in vitro human liver cell tests. Using a training set of in vivo rodent experiments for drug hepatotoxicity evaluation, we discovered common biomarkers of drug-induced liver toxicity among six heterogeneous compounds. This gene set was further triaged to a subset of 32 genes that can be used as a multi-gene expression signature to predict hepatotoxicity. This multi-gene predictor was independently validated and showed consistently high prediction performance on five test sets of in vitro human liver cell and in vivo animal toxicity experiments. The predictor also demonstrated utility in evaluating different degrees of toxicity in response to drug concentrations which may be useful not only for discerning a compound’s general hepatotoxicity but also for determining its toxic concentration. PMID:21884709

Biologically Relevant Exposure Science for 21st Century Toxicity Testing

EPA Science Inventory

High visibility efforts in toxicity testing and computational toxicology including the recent NRC report, Toxicity Testing in the 21st Century: a Vision and Strategy (NRC, 2007), raise important research questions and opportunities for the field of exposure science. The authors ...

Overview of T.E.S.T. (Toxicity Estimation Software Tool)

EPA Science Inventory

This talk provides an overview of T.E.S.T. (Toxicity Estimation Software Tool). T.E.S.T. predicts toxicity values and physical properties using a variety of different QSAR (quantitative structure activity relationship) approaches including hierarchical clustering, group contribut...

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.

Aquatic assessment of the Ely Copper Mine Superfund site, Vershire, Vermont

USGS Publications Warehouse

Seal, Robert R.; Kiah, Richard G.; Piatak, Nadine M.; Besser, John M.; Coles, James F.; Hammarstrom, Jane M.; Argue, Denise M.; Levitan, Denise M.; Deacon, Jeffrey R.; Ingersoll, Christopher G.

2010-01-01

The information was used to develop an overall assessment of the impact on the aquatic system that appears to be a result of the acid rock drainage at the Ely Mine. More than 700 meters of Ely Brook, including two of the six ponds, were found to be severely impacted, on the basis of water-quality data and biological assessments. The reference location was of good quality based on the water quality and biological assessment. More than 3,125 meters of Schoolhouse Brook are also severely impacted, on the basis of water-quality data and biological assessments. The biological community begins to recover near the confluence with the Ompompanoosuc River. The evidence is less conclusive regarding the Ompompanoosuc River. The sediment data suggest that the sediments could be a source of toxicity in Ely Brook and Schoolhouse Brook. The surface-water assessment is consistent with the outcome of a surface-water toxicity testing program performed by the U.S. Environmental Protection Agency for Ely Brook and Schoolhouse Brook and a surface-water toxicity testing program and in situ amphibian testing program for the ponds.

Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

PubMed

Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

2015-06-02

The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish acute toxicity test or application of assessment factors while considering the very good fish embryo-acute fish toxicity correlation for other compounds.

Effect of low-purity Fenton reagents on toxicity of textile dyeing effluent to Daphnia magna.

PubMed

Na, Joorim; Yoo, Jisu; Nam, Gwiwoong; Jung, Jinho

2017-09-20

This study aimed to identify the source of toxicity in textile dyeing effluent collected from February to July 2016, using Daphnia magna as a test organism. Toxicity identification evaluation (TIE) procedures were used to identify the toxicants in textile dyeing effluent, and Jar testing to simulate the Fenton process was conducted to identify the source of toxicants. Textile dyeing effluent was acutely toxic to D. magna [from 1.5 to 9.7 toxic units (TU)] during the study period. TIE results showed that Zn derived from the Fenton process was a key toxicant in textile dyeing effluent. Additionally, Jar testing revealed that low-purity Fenton reagents (FeCl 2 and FeSO 4 ), which contained large amounts of Zn (89 838 and 610 mg L -1 , respectively), were the source of toxicity. Although we were unable to conclusively identify the residual toxicity (approx. 1.4 TU of 9.71 TU) attributable to unknown toxicants in textile dyeing effluent, the findings of this study suggest that careful operation of the Fenton treatment process could contribute to eliminating its unintended toxic effects on aquatic organisms.

Kupffer Cell Isolation for Nanoparticle Toxicity Testing

PubMed Central

Bourgognon, Maxime; Klippstein, Rebecca; Al-Jamal, Khuloud T.

2015-01-01

The large majority of in vitro nanotoxicological studies have used immortalized cell lines for their practicality. However, results from nanoparticle toxicity testing in immortalized cell lines or primary cells have shown discrepancies, highlighting the need to extend the use of primary cells for in vitro assays. This protocol describes the isolation of mouse liver macrophages, named Kupffer cells, and their use to study nanoparticle toxicity. Kupffer cells are the most abundant macrophage population in the body and constitute part of the reticulo-endothelial system (RES), responsible for the capture of circulating nanoparticles. The Kupffer cell isolation method reported here is based on a 2-step perfusion method followed by purification on density gradient. The method, based on collagenase digestion and density centrifugation, is adapted from the original protocol developed by Smedsrød et al. designed for rat liver cell isolation and provides high yield (up to 14 x 106 cells per mouse) and high purity (>95%) of Kupffer cells. This isolation method does not require sophisticated or expensive equipment and therefore represents an ideal compromise between complexity and cell yield. The use of heavier mice (35-45 g) improves the yield of the isolation method but also facilitates remarkably the procedure of portal vein cannulation. The toxicity of functionalized carbon nanotubes f-CNTs was measured in this model by the modified LDH assay. This method assesses cell viability by measuring the lack of structural integrity of Kupffer cell membrane after incubation with f-CNTs. Toxicity induced by f-CNTs can be measured consistently using this assay, highlighting that isolated Kupffer cells are useful for nanoparticle toxicity testing. The overall understanding of nanotoxicology could benefit from such models, making the nanoparticle selection for clinical translation more efficient. PMID:26327223

Monkey Feeding Assay for Testing Emetic Activity of Staphylococcal Enterotoxin.

PubMed

Seo, Keun Seok

2016-01-01

Staphylococcal enterotoxins (SEs) are unique bacterial toxins that cause gastrointestinal toxicity as well as superantigenic activity. Since systemic administration of SEs induces superantigenic activity leading to toxic shock syndrome that may mimic enterotoxic activity of SEs such as vomiting and diarrhea, oral administration of SEs in the monkey feeding assay is considered as a standard method to evaluate emetic activity of SEs. This chapter summarizes and discusses practical considerations of the monkey feeding assay used in studies characterizing classical and newly identified SEs.

Comparison of effluent toxicity results using Ceriodaphnia dubia cultured on several diets

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

Norberg-King, T.J.; Schmidt, S.

1993-10-01

Several diets have been proposed for Ceriodaphnia dubia, but no single diet has been universally accepted as optimal for toxicity testing. Although several diets for Ceriodaphnia dubia culturing and testing are commonly used, little or no data exist on whether toxicity varies with the diet. This study evaluated several combinations of yeast-Cerophyl-trout chow (YCT), Selenastrum capricornutum, and Selenastrum capricornutum-Cerophyl foods for routine culture performance and the sensitivity of the offspring in subsequent acute toxicity tests with effluents. Variations in the diets included use of a vitamin-fortified yeast added to the YCT, algae (Selenastrum capricornutum) grown in two different algal media,more » and different feeding rates of the algae-Cerophyl diets. Eleven diets were evaluated in a multigeneration feeding study, but only seven were used in subsequent toxicity tests. The young produced from each of the seven diets were tested in 48-h acute tests with three different effluents across the generations. Toxicity tests with the effluents gave LC50s that were within a factor of two of one another, regardless of the food used for culturing. These results indicate that several diets are satisfactory for culturing Ceriodaphnia dubia and that the results of the toxicity tests are comparable.« less

Coastal circulation and sediment dynamics in Hanalei Bay, Kaua'i, Hawaii, part III, studies of sediment toxicity

USGS Publications Warehouse

Carr, Robert S.; Nipper, Marion; Field, Michael; Biedenbach, James M.

2006-01-01

Toxicity tests are commonly conducted as a measure of the bioavailability of toxic chemicals to biota in an environment. Chemical analyses alone are insufficient to determine whether contaminants pose a threat to biota. Porewater toxicity tests are extremely sensitive to a broad range of contaminants in marine environments and provide ecologically relevant data on sensitive life stages. The inclusion of porewater toxicity testing as an additional indicator of sediment quality provides a more comprehensive picture of contaminant effects in these sensitive habitats. In this study purple-spined sea urchin (Arbacia punctulata) fertilization and embryological development porewater toxicity tests were used to evaluate the sediments collected from the coastal environment around Hanalei Bay, Kaua’i, Hawaii. These tests have been used previously to assess the bioavailability of contaminants associated with sediments in the vicinity of coral reefs.

Aquatic Toxicity Information Retrieval Data Base (ACQUIRE). Data file

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

Not Available

The purpose of Acquire is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for ACQUIRE. Independently compiled data files that meet ACQUIRE parameter and quality assurance criteria are also included. Selected toxicity test results and related testing information for any individual chemical from laboratory and field aquatic toxicity effects are included for tests with freshwater and marine organisms. The total number of data records in ACQUIRE is now over 105,300.more » This includes data from 6000 references, for 5200 chemicals and 2400 test species. A major data file, Acute Toxicity of Organic Chemicals (ATOC), has been incorporated into ACQUIRE. The ATOC file contains laboratory acute test data on 525 organic chemicals using juvenile fathead minnows.« less

Are we in the dark ages of environmental toxicology?

PubMed

McCarty, L S

2013-12-01

Environmental toxicity is judged to be in a "dark ages" period due to longstanding limitations in the implementation of the simple conceptual model that is the basis of current aquatic toxicity testing protocols. Fortunately, the environmental regulatory revolution of the last half-century is not substantially compromised as development of past regulatory guidance was designed to deal with limited amounts of relatively poor quality toxicity data. However, as regulatory objectives have substantially increased in breadth and depth, aquatic toxicity data derived with old testing methods are no longer adequate. In the near-term explicit model description and routine assumption validation should be mandatory. Updated testing methods could provide some improvements in toxicological data quality. A thorough reevaluation of toxicity testing objectives and methods resulting in substantially revised standard testing methods, plus a comprehensive scheme for classification of modes/mechanisms of toxic action, should be the long-term objective. Copyright © 2013 Elsevier Inc. All rights reserved.

A Way Forward Commentary

EPA Science Inventory

Models for predicting adverse outcomes can help reduce and focus animal testing with new and existing chemicals. This short "thought starter" describes how quantitative-structure activity relationship and systems biology models can be used to help define toxicity pathways and li...

Meta-analysis of toxicity and teratogenicity of 133 chemicals from zebrafish developmental toxicity studies

EPA Science Inventory

Zebrafish developmental toxicity testing is an emerging field, which faces considerable challenges regarding data meta-analysis and the establishment of standardized test protocols. Here, we present an initial correlation study on toxicity of 133 chemicals based on data in the li...

A TOXICITY ASSESSMENT APPROACH TO EVALUATING IN-SITU BIOREMEDIATION OF PAH CONTAMINATED SEDIMENTS

EPA Science Inventory

Freshwater and marine sediment toxicity tests were used to measure baseline toxicity of sediment samples collected from New Jersey/New York Harbor (NJ/NY) (non-PAH- contaminated) sediment (ERC). Four freshwater toxicity tests were used: 1) amphipod (Hyalella azteca) mortality and...

Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.

PubMed

Kovács, Róbert; Bakos, Katalin; Urbányi, Béla; Kövesi, Judit; Gazsi, Gyöngyi; Csepeli, Andrea; Appl, Ádám János; Bencsik, Dóra; Csenki, Zsolt; Horváth, Ákos

2016-08-01

The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU), cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio rerio) were investigated. Acute tests were carried out in a static system in accordance with the OECD guideline 203 for adult fish and the draft guideline for fish embryos (FET test) in order to find the LC50 values of the four cytostatic drugs. Early-life stage toxicity test on zebrafish was conducted according the OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system with the objective of investigating the sub-chronic effects of the cytostatic drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1). In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant delay in the hatch of larvae. In case of ET, LC50 values were not calculable as they were higher than 300 mg L(-1) at which concentration the substance crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72 hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the Early-life Stage Test with 5-FU, embryonic deformities were not detected during the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered as LOEC, as statistically significant difference in mortalities was detected in this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be considered LOEC for mortalities, however, the treatment did not have an effect on the other investigated parameters (dry and wet weight, standard length). All four cytostatic drugs were characterized by low toxicity in zebrafish in acute and sub-chronic tests.

75 FR 40729 - Residues of Quaternary Ammonium Compounds, N-Alkyl (C12-14

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

.... Systemic toxicity occurs after absorption and distribution of the chemical to tissues in the body. Such... identified (the LOAEL) or a Benchmark Dose (BMD) approach is sometimes used for risk assessment. Uncertainty.... No systemic effects observed up to 20 mg/ kg/day, highest dose of technical that could be tested...

ASSESSMENT OF CHEMICAL EFFECTS ON NEURONAL DIFFERENTIATION USING THE ARRAYSCAN HIGH CONTENT SCREENING SYSTEM

EPA Science Inventory

The development of alternative methods for toxicity testing is driven by the need for scientifically valid data that can be obtained in a rapid and cost-efficient manner. In vitro systems provide a model in which chemical effects on cellular events can be examined using technique...

Acute toxicity of anionic and non-ionic surfactants to aquatic organisms.

PubMed

Lechuga, M; Fernández-Serrano, M; Jurado, E; Núñez-Olea, J; Ríos, F

2016-03-01

The environmental risk of surfactants requires toxicity measurements. As different test organisms have different sensitivity to the toxics, it is necessary to establish the most appropriate organism to classify the surfactant as very toxic, toxic, harmful or safe, in order to establish the maximum permissible concentrations in aquatic ecosystems. We have determined the toxicity values of various anionic surfactants ether carboxylic derivatives using four test organisms: the freshwater crustacean Daphnia magna, the luminescent bacterium Vibrio fischeri, the microalgae Selenastrum capricornutum (freshwater algae) and Phaeodactylum tricornutum (seawater algae). In addition, in order to compare and classify the different families of surfactants, we have included a compilation of toxicity data of surfactants collected from literature. The results indicated that V. fischeri was more sensitive to the toxic effects of the surfactants than was D. magna or the microalgae, which was the least sensitive. This result shows that the most suitable toxicity assay for surfactants may be the one using V. fischeri. The toxicity data revealed considerable variation in toxicity responses with the structure of the surfactants regardless of the species tested. The toxicity data have been related to the structure of the surfactants, giving a mathematical relationship that helps to predict the toxic potential of a surfactant from its structure. Model-predicted toxicity agreed well with toxicity values reported in the literature for several surfactants previously studied. Predictive models of toxicity is a handy tool for providing a risk assessment that can be useful to establish the toxicity range for each surfactant and the different test organisms in order to select efficient surfactants with a lower impact on the aquatic environment. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of marine toxicity data for ordnance compounds

USGS Publications Warehouse

Nipper, M.; Carr, R.S.; Biedenbach, J.M.; Hooten, R.L.; Miller, K.; Saepoff, S.

2001-01-01

A toxicity database for ordnance compounds was generated using eight compounds of concern and marine toxicity tests with five species from different phyla. Toxicity tests and endpoints included fertilization success and embryological development with the sea urchin Arbacia punctulata; zoospore germination, germling length, and cell number with the green macroalga Ulva fasciata; survival and reproductive success of the polychaete Dinophilus gyrociliatus; larvae hatching and survival with the redfish Sciaenops ocellatus; and survival of juveniles of the opossum shrimp Americamysis bahia (formerly Mysidopsis bahia). The studied ordnance compounds were 2,4- and 2,6-dinitrotoluene, 2,4,6-trinitrotoluene, 1,3-dinitrobenzene, 1,3,5-trinitrobenzene, 2,4,6-trinitrophenylmethylnitramine (tetryl), 2,4,6-trinitrophenol (picric acid), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The most sensitive toxicity test endpoints overall were the macroalga zoospore germination and the polychaete reproduction tests. The most toxic ordnance compounds overall were tetryl and 1,3,5-trinitrobenzene. These were also the most degradable compounds, often being reduced to very low or below-detection levels at the end of the test exposure. Among the dinitro- and trinitrotoluenes and benzenes, toxicity tended to increase with the level of nitrogenation. Picric acid and RDX were the least toxic chemicals tested overall.

Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

PubMed

Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L

2017-02-01

Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC. © 2016 SETAC.

Ecotoxicological studies of environmental samples from Buenos Aires area using a standardized amphibian embryo toxicity test (AMPHITOX).

PubMed

Herkovits, Jorge; Perez-Coll, Cristina; Herkovits, Francisco D

2002-01-01

The toxicity of 34 environmental samples from potentially polluted and reference stations were evaluated by means of the AMPHITOX test from acute to chronic exposure according to the toxicity found in each sample. The samples were obtained from surface and ground water, leaches, industrial effluents and soils. The data, expressed in acute, short-term chronic and chronic Toxicity Units (TUa, TUstc and TUc) resulted in a maximal value of 1000 TUc, found in a leach, while the lower toxicity value was 1.4 TUa corresponding to two surface water samples. In five samples (four providing from reference places) no toxicity was detected. The results point out the possibility of evaluating the toxicity of a wide diversity of samples by means of AMPHITOX as a customized toxicity test. The fact that almost all samples with suspected toxicity in rivers and streams from the Metropolitan area of Buenos Aires city resulted toxic, indicates the need of enhanced stewardship of chemical substances for environmental and human health protection purposes.

Evaluation of processed borax as antidote for aconite poisoning.

PubMed

Sarkar, Prasanta Kumar; Prajapati, Pradeep K; Shukla, Vinay J; Ravishankar, Basavaiah

2017-06-09

Aconite root is very poisonous; causes cardiac arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is mentioned for management of aconite poisoning. The investigation evaluated antidotal effect of processed borax against acute and sub-acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw aconite. For acute protection Study, single dose of toxicant (35mg/kg) and test drug (22.5mg/kg and 112.5mg/kg) was administered orally, and then 24h survival of animals was observed. The schedule was continued for 30 days in sub-acute protection Study with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg and 112.5mg/kg) and vehicle. Hematological and biochemical tests of blood and serum, histopathology of vital organs were carried out. The cardiac activity Study was continued for 30 days with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg), processed borax solution (22.5mg/kg) and vehicle; ECG was taken after 1h of drug administration on 1 TB , 15th and on 30th day. For neuro-muscular activity Study, the leech dorsal muscle response to 2.5µg of acetylcholine followed by response of toxicant at 25µg and 50µg doses and then response of test drug at 25µg dose were recorded. Protection index indicates that treated borax gave protection to 50% rats exposed to the lethal dose of toxicant in acute protection Study. Most of the changes in hematological, biochemical parameters and histopathological Study induced by the toxicant in sub-acute protection Study were reversed significantly by the test drug treatment. The ventricular premature beat and ventricular tachyarrhythmia caused by the toxicant were reversed by the test drug indicate reversal of toxicant induced cardio-toxicity. The acetylcholine induced contractions in leech muscle were inhibited by toxicant and it was reversed by test drug treatment. The processed borax solution is found as an effective protective agent to acute and sub-acute aconite poisoning, and aconite induced cardiac and neuro-muscular toxicity. Processed borax at therapeutic dose (22.5mg/kg) has shown better antidotal activity profile than five times more than therapeutic dose (112.5mg/kg). Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Towards personalized medicine with a three-dimensional micro-scale perfusion-based two-chamber tissue model system

PubMed Central

Ma, Liang; Barker, Jeremy; Zhou, Changchun; Li, Wei; Zhang, Jing; Lin, Biaoyang; Foltz, Gregory; Küblbeck, Jenni; Honkakoski, Paavo

2013-01-01

A three-dimensional micro-scale perfusion-based two-chamber (3D-μPTC) tissue model system was developed to test the cytotoxicity of anticancer drugs in conjunction with liver metabolism. Liver cells with different cytochrome P450 (CYP) subtypes and glioblastoma multiforme (GBM) brain cancer cells were cultured in two separate chambers connected in tandem. Both chambers contained a 3D tissue engineering scaffold fabricated with biodegradable poly(lactic acid) (PLA) using a solvent-free approach. We used this model system to test the cytotoxicity of anticancer drugs, including temozolomide (TMZ) and ifosfamide (IFO). With the liver cells, TMZ showed a much lower toxicity to GBM cells under both 2D and 3D cell culture conditions. Comparing 2D, GBM cells cultured in 3D had much high viability under TMZ treatment. IFO was used to test the CYP-related metabolic effects. Cells with different expression levels of CYP3A4 differed dramatically in their ability to activate IFO, which led to strong metabolism-dependent cytotoxicity to GBM cells. These results demonstrate that our 3D-μPTC system could provide a more physiologically realistic in vitro environment than the current 2D monolayers for testing metabolism-dependent toxicity of anticancer drugs. It could therefore be used as an important platform for better prediction of drug dosing and schedule towards personalized medicine. PMID:22429982

Synthetic antimicrobial peptides as agricultural pesticides for plant-disease control.

PubMed

Montesinos, Emilio; Bardají, Eduard

2008-07-01

There is a need of antimicrobial compounds in agriculture for plant-disease control, with low toxicity and reduced negative environmental impact. Antimicrobial peptides are produced by living organisms and offer strong possibilities in agriculture because new compounds can be developed based on natural structures with improved properties of activity, specificity, biodegradability, and toxicity. Design of new molecules has been achieved using combinatorial-chemistry procedures coupled to high-throughput screening systems and data processing with design-of-experiments (DOE) methodology to obtain QSAR equation models and optimized compounds. Upon selection of best candidates with low cytotoxicity and moderate stability to protease digestion, anti-infective activity has been evaluated in plant-pathogen model systems. Suitable compounds have been submitted to acute toxicity testing in higher organisms and exhibited a low toxicity profile in a mouse model. Large-scale production can be achieved by solution organic or chemoenzymatic procedures in the case of very small peptides, but, in many cases, production can be performed by biotechnological methods using genetically modified microorganisms (fermentation) or transgenic crops (plant biofactories).

Animal Exposure During Burn Tests

NASA Technical Reports Server (NTRS)

Gaume, J. G.

1978-01-01

An animal exposure test system (AETS) was designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consisted of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram (ECG) and respiration. Cage temperature is measured by a thermistor located in the upper portion of the rat compartment. Animal activity is monitored by the ECG and the records indicate an increase in EMG (electromyograph) noise super-imposed by the increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases and specific events occurring during the test. The AETS was shown to be a useful tool in screening materials for the relative toxicity of their outgassing products during pyrolysis and combustion.

The interactive effects of essential ions and salinity on the survival of Mysidopsis bahia in 96-H acute toxicity tests of effluents discharged to marine and estuarine receiving waters

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

Douglas, W.S.; Horne, M.T.

1997-10-01

The importance of salinity in whole effluent toxicity tests using marine organisms has been acknowledged in most testing protocols. However, little if any attention has been given to the specific effects of alteration of the ionic composition of seawater solutions to the test organism. The presence of persistent toxicity in effluents with no apparent toxic agents prompted examination of the potential influence of essential ions on the survival of the opossum shrimp, Mysidopsis bahia, a common effluent toxicity indicator organism. Through stepwise additions of ionic salts to deionized water, the minimum complement of salts to maintain survival of M. bahiamore » during 96-h exposures was determined to be Ca, Mg, K, Br, Na, and Cl. The toxicity curves for Ca, Mg, K, and Br were then determined across test salinity ranging from 10 to 35 parts per thousand. These curves for Ca, Mg, and K revealed that there are significant negative effects on survival when the essential ions are present in either low or high concentrations relative to the levels in natural seawater. Although there were no statistically detectable effects of Br on organism survival over the concentration range tested (5--480 mg/L). Br toxicity at concentrations less than 5 mg/L and greater than 700 mg/L have been shown in other studies. In addition, the tolerance ranges for K, Ca, and Mg were shown to shift significantly with changes in salinity, with lower salinity causing an apparent decrease in tolerance to an excess of essential ions. Tests with toxic effluents from five industrial and municipal sources revealed that adjustment of the ionic balance prior to testing reduced or eliminated toxicity in four of the five whole effluents tested. Suggestions for integrating this information into biomonitoring programs and toxicity identification evaluations are presented.« less