Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

PubMed

Terry, Claire; Rasoulpour, Reza J; Saghir, Shakil; Marty, Sue; Gollapudi, B Bhaskar; Billington, Richard

2014-05-01

Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) ( Ellis-Hutchings et al. 2014 ); liver tumors in rodents mediated via CAR/PXR ( LeBaron et al. 2014 ); and Leydig cell tumors in Fischer 344 rats ( Rasoulpour et al. 2014 ).

Technical manual for basic version of the Markov chain nest productivity model (MCnest)

EPA Science Inventory

The Markov Chain Nest Productivity Model (or MCnest) integrates existing toxicity information from three standardized avian toxicity tests with information on species life history and the timing of pesticide applications relative to the timing of avian breeding seasons to quantit...

User’s manual for basic version of MCnest Markov chain nest productivity model

EPA Science Inventory

The Markov Chain Nest Productivity Model (or MCnest) integrates existing toxicity information from three standardized avian toxicity tests with information on species life history and the timing of pesticide applications relative to the timing of avian breeding seasons to quantit...

Prioritizing ToxCast Chemicals Across Multiple Sectors of Toxicity Using ToxPi

EPA Science Inventory

The Toxicological Prioritization Index (ToxPi™) framework was developed as a decision-support tool to aid in the rational prioritization of chemicals for integrated toxicity testing. ToxPi consolidates information from multiple domains—including ToxCast™ in vitro bioactivity prof...

Exposure Space: Integrating Exposure Data and Modeling with Toxicity Information

EPA Science Inventory

Recent advances have been made in high-throughput (HTP) toxicity testing, e.g. from ToxCast, which will ultimately be combined with HTP predictions of exposure potential to support next-generation chemical safety assessment. Rapid exposure methods are essential in selecting chemi...

The role of in vitro methods as alternatives to animals in toxicity testing.

PubMed

Anadón, Arturo; Martínez, María Aranzazu; Castellano, Victor; Martínez-Larrañaga, María Rosa

2014-01-01

It is accepted that animal testing should be reduced, refined or replaced as far as it is practicably possible. There are also a wide variety of in vitro models, which are used as screening studies and mechanistic investigations. The ability of an in vitro assay to be reliable, biomedically, is essential in pharmaceutical development. Furthermore, it is necessary that cells used in in vitro testing mimic the phenotype of cells within the human target tissue. The focus of this review article is to identify the key points of in vitro assays. In doing so, the authors take into account the chemical agents that are assessed and the integrated in vitro testing strategies. There is a transfer of toxicological data from primary in vivo animal studies to in vitro assays. The key element for designing an integrated in vitro testing strategy is summarized as follows: exposure modeling of chemical agents for in vitro testing; data gathering, sharing and read-across for testing a class of chemical; a battery of tests to assemble a broad spectrum of data on different mechanisms of action to predict toxic effects; and applicability of the test and the integrated in vitro testing strategies and flexibility to adjust the integrated in vitro testing strategies to test substance. While these methods will be invaluable if effective, more studies must be done to ensure reliability and suitability of these tests for humans.

Sediment Ecotoxicity Assessment Ring Verification Report and Statement

EPA Science Inventory

The SEA Ring (U.S. Patent No. 8,011,239) is an integrated, field tested, toxicity and bioavailability assessment device. This device was developed at SPAWAR in San Diego, California and is commercially available from Zebra-Tech, Ltd. The SEA Ring was designed to evaluate toxicity...

Neurobehavioral toxicity testing for risk assessment.

EPA Science Inventory

Neurobehavioral evaluations are key components in neurotoxicity testing. In the realm of regulatory testing, these evaluations range from a functional observational battery (FOB) and an Irwin’s screen, which assess the neurological, motor, and functional integrity of the subject...

AN "INJURY-TIME INTEGRAL" MODEL FOR RELATING ACUTE TO CHRONIC INJURY TO PHOSGENE

EPA Science Inventory

ABSTRACT
The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the "concentration x time" (C x T) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (m...

Profiling of the toxicity mechanisms of coated and uncoated silver nanoparticles to yeast Saccharomyces cerevisiae BY4741 using a set of its 9 single-gene deletion mutants defective in oxidative stress response, cell wall or membrane integrity and endocytosis.

PubMed

Käosaar, Sandra; Kahru, Anne; Mantecca, Paride; Kasemets, Kaja

2016-09-01

The widespread use of nanosilver in various antibacterial, antifungal, and antiviral products warrants the studies of the toxicity pathways of nanosilver-enabled materials toward microbes and viruses. We profiled the toxicity mechanisms of uncoated, casein-coated, and polyvinylpyrrolidone-coated silver nanoparticles (AgNPs) using Saccharomyces cerevisiae wild-type (wt) and its 9 single-gene deletion mutants defective in oxidative stress (OS) defense, cell wall/membrane integrity, and endocytosis. The 48-h growth inhibition assay in organic-rich growth medium and 24-h cell viability assay in deionized (DI) water were applied whereas AgNO3, H2O2, and SDS served as positive controls. Both coated AgNPs (primary size 8-12nm) were significantly more toxic than the uncoated (~85nm) AgNPs. All studied AgNPs were ~30 times more toxic if exposed to yeast cells in DI water than in the rich growth medium: the IC50 based on nominal concentration of AgNPs in the growth inhibition test ranged from 77 to 576mg Ag/L and in the cell viability test from 2.7 to 18.7mg Ag/L, respectively. Confocal microscopy showed that wt but not endocytosis mutant (end3Δ) internalized AgNPs. Comparison of toxicity patterns of wt and mutant strains defective in OS defense and membrane integrity revealed that the toxicity of the studied AgNPs to S. cerevisiae was not caused by the OS or cell wall/membrane permeabilization. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integrating toxicogenomics data into cancer adverse outcome pathways

EPA Science Inventory

Integrating toxicogenomics data into adverse outcome pathways for cancer.J. Christopher CortonNHEERL/ORD, EPA, Research Triangle Park, NCAs the toxicology field continues to move towards a new paradigm in toxicity testing and safety assessment, there is the expectation that model...

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...

AN INTEGRATION OF COPEPOD-BASED BAFS, LIFECYCLE TOXICITY TESTING, AND ENDOCRINE DISRUPTION METHODOLOGIES FOR RAPID POPULATION-LEVEL RISK ASSESSMENT OF PERSISTENT BIOACCUMULATIVE TOXICANTS

EPA Science Inventory

Extensive multi-generational microplate culturing (copepod hatching stage through two broods) experiments were completed with the POPs lindane, DDD and fipronil sulfide.  Identical tandem microplate experiments were run concurrently to yield sufficient copepod biomass for li...

Virtual Liver: integrating in vitro and in vivo data to predict chemical-induced toxicity

EPA Science Inventory

It is difficult to assess the health impact of long-term exposure to low levels of contaminants from animal studies. Current methods for testing the toxicity of a single chemical can cost millions of dollars, take up to two years and sacrifice thousands of animals. In vitro model...

INTEGRATING NEW TESTS OF SPERM GENETIC INTEGRITY INTO SEMEN ANALYSIS: BREAKOUT GROUP DISCUSSION

EPA Science Inventory

The First International Conference on Male-Mediated Developmental Toxicity, held in September 1992, reported that the spermatozoon can bring genetic damage into the oocyte at fertilization and thereby contribute to subsequent abnormal pregnancy outcomes. At that time, laboratory ...

Toward the Replacement of Animal Experiments through the Bioinformatics-driven Analysis of 'Omics' Data from Human Cell Cultures.

PubMed

Grafström, Roland C; Nymark, Penny; Hongisto, Vesa; Spjuth, Ola; Ceder, Rebecca; Willighagen, Egon; Hardy, Barry; Kaski, Samuel; Kohonen, Pekka

2015-11-01

This paper outlines the work for which Roland Grafström and Pekka Kohonen were awarded the 2014 Lush Science Prize. The research activities of the Grafström laboratory have, for many years, covered cancer biology studies, as well as the development and application of toxicity-predictive in vitro models to determine chemical safety. Through the integration of in silico analyses of diverse types of genomics data (transcriptomic and proteomic), their efforts have proved to fit well into the recently-developed Adverse Outcome Pathway paradigm. Genomics analysis within state-of-the-art cancer biology research and Toxicology in the 21st Century concepts share many technological tools. A key category within the Three Rs paradigm is the Replacement of animals in toxicity testing with alternative methods, such as bioinformatics-driven analyses of data obtained from human cell cultures exposed to diverse toxicants. This work was recently expanded within the pan-European SEURAT-1 project (Safety Evaluation Ultimately Replacing Animal Testing), to replace repeat-dose toxicity testing with data-rich analyses of sophisticated cell culture models. The aims and objectives of the SEURAT project have been to guide the application, analysis, interpretation and storage of 'omics' technology-derived data within the service-oriented sub-project, ToxBank. Particularly addressing the Lush Science Prize focus on the relevance of toxicity pathways, a 'data warehouse' that is under continuous expansion, coupled with the development of novel data storage and management methods for toxicology, serve to address data integration across multiple 'omics' technologies. The prize winners' guiding principles and concepts for modern knowledge management of toxicological data are summarised. The translation of basic discovery results ranged from chemical-testing and material-testing data, to information relevant to human health and environmental safety. 2015 FRAME.

Toxicity assessment of diesel- and metal-contaminated soils through elutriate and solid phase assays with the slime mold Dictyostelium discoideum.

PubMed

Rodríguez-Ruiz, Amaia; Dondero, Francesco; Viarengo, Aldo; Marigómez, Ionan

2016-06-01

A suite of organisms from different taxonomical and ecological positions is needed to assess environmentally relevant soil toxicity. A new bioassay based on Dictyostelium is presented that is aimed at integrating slime molds into such a testing framework. Toxicity tests on elutriates and the solid phase developmental cycle assay were successfully applied to a soil spiked with a mixture of Zn, Cd, and diesel fuel freshly prepared (recently contaminated) and after 2 yr of aging. The elutriates of both soils provoked toxic effects, but toxicity was markedly lower in the aged soil. In the D. discoideum developmental cycle assay, both soils affected amoeba viability and aggregation, with fewer multicellular units, smaller fruiting bodies and, overall, inhibition of fruiting body formation. This assay is quick and requires small amounts of test soil, which might facilitate its incorporation into a multispecies multiple-endpoint toxicity bioassay battery suitable for environmental risk assessment in soils. Environ Toxicol Chem 2016;35:1413-1421. © 2015 SETAC. © 2015 SETAC.

[Preclinical prognosis of pyracetam and picamilon safety based on acute toxicity data].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2003-01-01

A comparative acute toxicity test of the nootropic drugs piracetam and picamilon was performed on rats. The study was based on the principles of integral evaluation of the drug effect upon the functional and behavioral state of animals. It was found that the conventional therapeutic index does not coincide with the actual therapeutic activity range. Piracetam and picamilon, while exhibiting significantly different toxicity, are characterized by approximately equal ranges of the therapeutic activity.

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

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.

Improving Toxicity Assessment of Pesticide Mixtures: The Use of Polar Passive Sampling Devices Extracts in Microalgae Toxicity Tests

PubMed Central

Kim Tiam, Sandra; Fauvelle, Vincent; Morin, Soizic; Mazzella, Nicolas

2016-01-01

Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS) and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD) extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively, aimed (i) at characterizing the “toxic potential” of waters using dose-response curves, and (ii) at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed. PMID:27667986

Comparative performances of eggs and embryos of sea urchin (Paracentrotus lividus) in toxicity bioassays used for assessment of marine sediment quality.

PubMed

Khosrovyan, A; Rodríguez-Romero, A; Salamanca, M J; Del Valls, T A; Riba, I; Serrano, F

2013-05-15

The potential toxicity of sediments from various ports was assessed by means of two different liquid-phase toxicity bioassays (acute and chronic) with embryos and eggs of sea urchin Paracentrotus lividus. Performances of embryos and eggs of P. lividus in these bioassays were compared for their interchangeable applicability in integrated sediment quality assessment. The obtained endpoints (percentages of normally developed plutei and fertilized eggs) were linked to physical and chemical properties of sediments and demonstrated dependence on sediment contamination. The endpoints in the two bioassays were strongly correlated and generally exhibited similar tendency throughout the samples. Therein, embryos demonstrated higher sensitivity to elutriate exposure, compared to eggs. It was concluded that these tests could be used interchangeably for testing toxicity of marine sediments. Preferential use of any of the bioassays can be determined by the discriminatory capacity of the test or vulnerability consideration of the test subject to the surrounding conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

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.

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

Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

PubMed

Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

2016-02-01

Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers.

[Functional-behavioral profile of new cyclic GABA analogs in acute toxicity tests].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E

2004-01-01

The properties of karphedone and phepyrone--new phenyl derivatives of pyrrolidone possessing nootropic activity--were studied in the course of the acute toxicity tests on rats. The drug effects were evaluated in terms of their integral influence on the state and behavior of test animals. The real therapeutic range and the profit/risk ratio of karphedone were comparable with those of the reference drug pyracetam and exceeded by a factor of 1.3 the corresponding values for phepyrone (irrespective of the LD50 values). The results give grounds for the further preclinical investigation of karphedone.

40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

Code of Federal Regulations, 2013 CFR

2013-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt... Waste, Physical/Chemical Methods,” EPA Publication SW-846, as incorporated by reference in § 260.11 of...

40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

Code of Federal Regulations, 2011 CFR

2011-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt... Waste, Physical/Chemical Methods,” EPA Publication SW-846, as incorporated by reference in § 260.11 of...

40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

Code of Federal Regulations, 2014 CFR

2014-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt... Waste, Physical/Chemical Methods,” EPA Publication SW-846, as incorporated by reference in § 260.11 of...

40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

Code of Federal Regulations, 2012 CFR

2012-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt... Waste, Physical/Chemical Methods,” EPA Publication SW-846, as incorporated by reference in § 260.11 of...

40 CFR Appendix Ix to Part 268 - Extraction Procedure (EP) Toxicity Test Method and Structural Integrity Test (Method 1310B)

Code of Federal Regulations, 2010 CFR

2010-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt... Waste, Physical/Chemical Methods,” EPA Publication SW-846, as incorporated by reference in § 260.11 of...

Transfers and transformations of zinc in flow-through wetland microcosms.

PubMed

Gillespie, W B; Hawkins, W B; Rodgers, J H; Cano, M L; Dorn, P B

1999-06-01

Two microcosm-scale wetlands (570-liter containers) were integratively designed and constructed to investigate transfers and transformations of zinc associated with an aqueous matrix, and to provide future design parameters for pilot-scale constructed wetlands. The fundamental design of these wetland microcosms was based on biogeochemical principles regulating fate and transformations of zinc (pH, redox, etc.). Each wetland consisted of a 45-cm hydrosoil depth inundated with 25 cm of water, and planted with Scirpus californicus. Zinc ( approximately 2 mg/liter) as ZnCl2 was amended to each wetland for 62 days. Individual wetland hydraulic retention times (HRT) were approximately 24 h. Total recoverable zinc was measured daily in microcosm inflow and outflows, and zinc concentrations in hydrosoil and S. californicus tissue were measured pre- and post-treatment. Ceriodaphnia dubia and Pimephales promelas7-day aqueous toxicity tests were performed on wetland inflows and outflows, and Hyalella azteca whole sediment toxicity tests (10-day) were performed pre- and post-treatment. Approximately 75% of total recoverable zinc was transferred from the water column. Toxicity decreased from inflow to outflow based on 7-day C. dubia tests, and survival of H. azteca in hydrosoil was >80%. Data illustrate the ability of integratively designed wetlands to transfer and sequester zinc from the water column while concomitantly decreasing associated toxicity. Copyright 1999 Academic Press.

High-Throughput Screening for Identification of Blood-Brain Barrier Integrity Enhancers: A Drug Repurposing Opportunity to Rectify Vascular Amyloid Toxicity.

PubMed

Qosa, Hisham; Mohamed, Loqman A; Al Rihani, Sweilem B; Batarseh, Yazan S; Duong, Quoc-Viet; Keller, Jeffrey N; Kaddoumi, Amal

2016-07-06

The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins, and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer's disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76-4.56 μM. Of these 7 drugs, 5 were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron, and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD.

High-throughput screening for identification of blood-brain barrier integrity enhancers: a drug repurposing opportunity to rectify vascular amyloid toxicity

PubMed Central

Qosa, Hisham; Mohamed, Loqman A.; Al Rihani, Sweilem B.; Batarseh, Yazan S.; Duong, Quoc-Viet; Keller, Jeffrey N.; Kaddoumi, Amal

2016-01-01

The blood-brain barrier (BBB) is a dynamic interface that maintains brain homeostasis and protects it from free entry of chemicals, toxins and drugs. The barrier function of the BBB is maintained mainly by capillary endothelial cells that physically separate brain from blood. Several neurological diseases, such as Alzheimer’s disease (AD), are known to disrupt BBB integrity. In this study, a high-throughput screening (HTS) was developed to identify drugs that rectify/protect BBB integrity from vascular amyloid toxicity associated with AD progression. Assessing Lucifer Yellow permeation across in-vitro BBB model composed from mouse brain endothelial cells (bEnd3) grown on 96-well plate inserts was used to screen 1280 compounds of Sigma LOPAC®1280 library for modulators of bEnd3 monolayer integrity. HTS identified 62 compounds as disruptors, and 50 compounds as enhancers of the endothelial barrier integrity. From these 50 enhancers, 7 FDA approved drugs were identified with EC50 values ranging from 0.76–4.56 μM. Of these 7 drugs, five were able to protect bEnd3-based BBB model integrity against amyloid toxicity. Furthermore, to test the translational potential to humans, the 7 drugs were tested for their ability to rectify the disruptive effect of Aβ in the human endothelial cell line hCMEC/D3. Only 3 (etodolac, granisetron and beclomethasone) out of the 5 effective drugs in the bEnd3-based BBB model demonstrated a promising effect to protect the hCMEC/D3-based BBB model integrity. These drugs are compelling candidates for repurposing as therapeutic agents that could rectify dysfunctional BBB associated with AD. PMID:27392852

Toxicity assessment strategies, data requirements, and risk assessment approaches to derive health based guidance values for non-relevant metabolites of plant protection products.

PubMed

Dekant, Wolfgang; Melching-Kollmuss, Stephanie; Kalberlah, Fritz

2010-03-01

In Europe, limits for tolerable concentrations of "non-relevant metabolites" for active ingredients (AI) of plant protection products in drinking water between 0.1 and 10 microg/L are discussed depending on the toxicological information available. "Non-relevant metabolites" are degradation products of AIs, which do not or only partially retain the targeted toxicities of AIs. For "non-relevant metabolites" without genotoxicity (to be confirmed by testing in vitro), the application of the concept of "thresholds of toxicological concern" results in a health-based drinking water limit of 4.5 microg/L even for Cramer class III compounds, using the TTC threshold of 90 microg/person/day (divided by 10 and 2). Taking into account the thresholds derived from two reproduction toxicity data bases a drinking water limit of 3.0 microg/L is proposed. Therefore, for "non-relevant metabolites" whose drinking water concentration is below 3.0 microg/L, no toxicity testing is necessary. This work develops a toxicity assessment strategy as a basis to delineate health-based limits for "non-relevant metabolites" in ground and drinking water. Toxicological testing is recommended to investigate, whether the metabolites are relevant or not, based on the hazard properties of the parent AIs, as outlined in the SANCO Guidance document. Also, genotoxicity testing of the water metabolites is clearly recommended. In this publication, tiered testing strategies are proposed for non-relevant metabolites, when drinking water concentrations >3.0 microg/L will occur. Conclusions based on structure-activity relationships and the detailed toxicity database on the parent AI should be included. When testing in animals is required for risk assessment, key aspects are studies along OECD-testing guidelines with "enhanced" study designs addressing additional endpoints such as reproductive toxicity and a developmental screening test to derive health-based tolerable drinking water limits with a limited number of animals. The testing strategies are similar to those used in the initial hazard assessment of high production volume (HPV) chemicals. For "non-relevant metabolites" which are also formed as products of the biotransformation of the parent AI in mammals, the proposed toxicity testing strategies uses the repeat-dose oral toxicity study combined with a reproductive/developmental screening as outlined in OECD test guidelines 407 and 422 with integration of determination of hormonal activities. For "non-relevant metabolites" not formed during biotransformation of the AI in mammals, the strategy relies on an "enhanced" 90-day oral study covering additional endpoints regarding hormonal effects and male and female fertility in combination with a prenatal developmental toxicity study (OECD test guideline 414). The integration of the results of these studies into the risk assessment process applies large minimal margins of exposure (MOEs) to compensate for the shorter duration of the studies. The results of the targeted toxicity testing will provide a science basis for setting tolerable drinking water limits for "non-relevant metabolites" based on their toxicology. Based on the recommendations given in the SANCO guidance document and the work described in this and the accompanying paper, a concise re-evaluation of the Guidance document is proposed. (c) 2009 Elsevier Inc. All rights reserved.

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.

Biodegradability, toxicity and mutagenicity of detergents: Integrated experimental evaluations.

PubMed

Pedrazzani, Roberta; Ceretti, Elisabetta; Zerbini, Ilaria; Casale, Rosario; Gozio, Eleonora; Bertanza, Giorgio; Gelatti, Umberto; Donato, Francesco; Feretti, Donatella

2012-10-01

The widespread use of detergents has raised concern with regard to the environmental pollution caused by their active ingredients, which are biorefractory, toxic and persistent. Since detergents are complex mixtures of different substances, in which synergistic effects may occur, we aimed to assess the mutagenicity of different detergent formulations, taking into account aquatic toxicity and ready biodegradability. We performed a ready biodegradability test (OECD 301 F), Daphnia magna and Vibrio fischeri toxicity tests, and mutagenicity tests (Salmonella/microsome test, Allium cepa test and comet assay). Six detergent formulations were examined, 3 pre-manufacture and 3 commercially available. All detergents presented ready biodegradability. EC50 values varied for all products, according to the marker organism used, but were always higher than the more stringent value considered for aquatic toxicity assessment (V. fischeri 10-60 mg/L; D. magna 25-300 mg/L; A. cepa 250-2000 mg/L). None of the detergents caused mutations in bacteria. However, one commercial ecolabelled product induced an increase in micronucleus frequency in A. cepa root cells. All pre-manufacture detergents and one commercial one, which gave negative results in the Ames and A. cepa tests, induced DNA damage in human leukocytes. A more accurate evaluation of the environmental impact of complex mixtures such as detergents requires a battery of tests to describe degradation, as well as toxicological and mutagenic features. Copyright © 2012 Elsevier Inc. All rights reserved.

Integration of chemical-specific exposure and pharmacokinetic considerations with the chemical-agnostic adverse outcome pathway framework

EPA Science Inventory

Traditional toxicity testing provides insight into the mechanisms underlying toxicological responses but requires a high investment in large numbers of resources. The new paradigm of testing approaches involves rapid screening of thousands of chemicals across hundreds of biologic...

Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity.

PubMed

Clippinger, Amy J; Allen, David; Behrsing, Holger; BéruBé, Kelly A; Bolger, Michael B; Casey, Warren; DeLorme, Michael; Gaça, Marianna; Gehen, Sean C; Glover, Kyle; Hayden, Patrick; Hinderliter, Paul; Hotchkiss, Jon A; Iskandar, Anita; Keyser, Brian; Luettich, Karsta; Ma-Hock, Lan; Maione, Anna G; Makena, Patrudu; Melbourne, Jodie; Milchak, Lawrence; Ng, Sheung P; Paini, Alicia; Page, Kathryn; Patlewicz, Grace; Prieto, Pilar; Raabe, Hans; Reinke, Emily N; Roper, Clive; Rose, Jane; Sharma, Monita; Spoo, Wayne; Thorne, Peter S; Wilson, Daniel M; Jarabek, Annie M

2018-06-20

New approaches are needed to assess the effects of inhaled substances on human health. These approaches will be based on mechanisms of toxicity, an understanding of dosimetry, and the use of in silico modeling and in vitro test methods. In order to accelerate wider implementation of such approaches, development of adverse outcome pathways (AOPs) can help identify and address gaps in our understanding of relevant parameters for model input and mechanisms, and optimize non-animal approaches that can be used to investigate key events of toxicity. This paper describes the AOPs and the toolbox of in vitro and in silico models that can be used to assess the key events leading to toxicity following inhalation exposure. Because the optimal testing strategy will vary depending on the substance of interest, here we present a decision tree approach to identify an appropriate non-animal integrated testing strategy that incorporates consideration of a substance's physicochemical properties, relevant mechanisms of toxicity, and available in silico models and in vitro test methods. This decision tree can facilitate standardization of the testing approaches. Case study examples are presented to provide a basis for proof-of-concept testing to illustrate the utility of non-animal approaches to inform hazard identification and risk assessment of humans exposed to inhaled substances. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Integrating Exposure, Pharmacokinetics, And Dosimetry With In Vitro Dose-Response Data To Evaluate Chemical Risk

EPA Science Inventory

High throughput in vitro toxicity testing of hundreds to thousands of chemicals across any number of biological endpoints allows for rapidly assessing human and ecosystem health impacts, thus reducing resources associated with traditional animal testing. In order to apply these i...

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

PubMed

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

2010-02-01

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

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.

Implementing a framework for integrating toxicokinetics into human health risk assessment for agrochemicals.

PubMed

Terry, Claire; Hays, Sean; McCoy, Alene T; McFadden, Lisa G; Aggarwal, Manoj; Rasoulpour, Reza J; Juberg, Daland R

2016-03-01

A strategic and comprehensive program in which toxicokinetic (TK) measurements are made for all agrochemicals undergoing toxicity testing (both new compounds and compounds already registered for use) is described. This approach provides the data to more accurately assess the toxicokinetics of agrochemicals and their metabolites in laboratory animals and humans. Having this knowledge provides the ability to conduct more insightful toxicity studies, refine and interpret exposure assessments and reduce uncertainty in risk assessments. By developing a better understanding of TK across species, including humans via in vitro metabolism studies, any differences across species in TK can be identified early and the most relevant species can be selected for toxicity tests. It also provides the ability to identify any non-linearities in TK as a function of dose, which in turn can be used to identify a kinetically derived maximum dose (KMD) and avoid dosing inappropriately outside of the kinetic linear range. Measuring TK in key life stages also helps to identify changes in ADME parameters from in utero to adults. A robust TK database can also be used to set internal concentration based "Reference Concentrations" and Biomonitoring Equivalents (BE), and support selection of Chemical Specific Adjustment Factors (CSAF). All of these factors support the reduction of uncertainty throughout the entire risk assessment process. This paper outlines how a TK research strategy can be integrated into new agrochemical toxicity testing programs, together with a proposed Framework for future use. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of surficial sediment toxicity and sediment physico-chemical characteristics of representative sites in the Lagoon of Venice (Italy)

NASA Astrophysics Data System (ADS)

Losso, C.; Arizzi Novelli, A.; Picone, M.; Marchetto, D.; Pessa, G.; Molinaroli, E.; Ghetti, P. F.; Volpi Ghirardini, A.

2004-11-01

Toxic hazard in sites with varying types and levels of contamination in the Lagoon of Venice was estimated by means of toxicity bioassays based on the early life-stages of the autochthonous sea urchin Paracentrotus lividus. Elutriate was chosen as the test matrix, due to its ability to highlight potential toxic effects towards sensitive biological components of the water column caused by sediment resuspension phenomena affecting the Lagoon. Surficial sediments (core-top 5 cm deep), directly influenced by resuspension/redeposition processes, and core sediments (core 20 cm deep), recording time-mediated contamination, were sampled in some sites located in the lagoonal area most greatly influenced by anthropogenic activities. Particle size, organic matter and water content were also analysed. In two sites, the results of physical parameters showed that the core-top sediments were coarser than the 20-cm core sediments. Sperm cell toxicity test results showed the negligible acute toxicity of elutriates from all investigated sites. The embryo toxicity test demonstrated a short-term chronic toxicity gradient for elutriates from the 20-cm core sediments, in general agreement both with the expected contamination gradient and with results of the Microtox® solid-phase test. Elutriates of the core-top 5-cm sediments revealed a totally inverted gradient, in comparison with that for the 20-cm core sediments, and the presence of a "hot spot" of contamination in the site chosen as a possible reference. Investigations on ammonia and sulphides as possible confounding factors excluded their contribution to this "hot spot". Integrated physico-chemical and toxicity results on sediments at various depths demonstrated the presence of disturbed sediments in the central basin of the Lagoon of Venice.

Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology.

PubMed

Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

2015-02-01

To elucidate the effects of chemicals on populations of different species in the environment, efficient testing and modeling approaches are needed that consider multiple stressors and allow reliable extrapolation of responses across species. An adverse outcome pathway (AOP) is a concept that provides a framework for organizing knowledge about the progression of toxicity events across scales of biological organization that lead to adverse outcomes relevant for risk assessment. In this paper, we focus on exploring how the AOP concept can be used to guide research aimed at improving both our understanding of chronic toxicity, including delayed toxicity as well as epigenetic and transgenerational effects of chemicals, and our ability to predict adverse outcomes. A better understanding of the influence of subtle toxicity on individual and population fitness would support a broader integration of sublethal endpoints into risk assessment frameworks. Detailed mechanistic knowledge would facilitate the development of alternative testing methods as well as help prioritize higher tier toxicity testing. We argue that targeted development of AOPs supports both of these aspects by promoting the elucidation of molecular mechanisms and their contribution to relevant toxicity outcomes across biological scales. We further discuss information requirements and challenges in application of AOPs for chemical- and site-specific risk assessment and for extrapolation across species. We provide recommendations for potential extension of the AOP framework to incorporate information on exposure, toxicokinetics and situation-specific ecological contexts, and discuss common interfaces that can be employed to couple AOPs with computational modeling approaches and with evolutionary life history theory. The extended AOP framework can serve as a venue for integration of knowledge derived from various sources, including empirical data as well as molecular, quantitative and evolutionary-based models describing species responses to toxicants. This will allow a more efficient application of AOP knowledge for quantitative chemical- and site-specific risk assessment as well as for extrapolation across species in the future. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Current and future perspectives on the development ...

EPA Pesticide Factsheets

Safety-related problems continue to be one of the major reasons of attrition in drug development. Non-testing approaches to predict toxicity could form part of the solution. This review provides a perspective of current status of non-testing approaches available for the prediction of different toxicity endpoints. A framework for the development, evaluation and assessment of (Q)SARs is presented together with several examples. A workflow for performing read-across predictions within category and analogue approaches is presented and the shortcomings discussed. In light of the advances in high throughput (HT) approaches and constructs such as adverse outcome pathways (AOPs) coming on-line to help in interpreting such HT data, the ways in which non-testing approaches are developed are also evolving. We discuss what the future of these approaches might look like and outline how their integration could be useful in screening toxicity for drug development. Invited review article for CRT for a special issue.

Assessing the status of sediment toxicity and macroinvertebrate communities in the Eighteenmile Creek Area of Concern, New York

USGS Publications Warehouse

George, Scott D.; Duffy, Brian T.; Baldigo, Barry P.

2017-01-01

In 1972, the governments of Canada and the United States committed to restoring the physical, chemical, and biological integrity of the Laurentian Great Lakes under the Great Lakes Water Quality Agreement. Through this framework, the downstream-most section of Eighteenmile Creek, a tributary to the south shore of Lake Ontario in New York, was designated as an Area of Concern (AOC) because water quality and bed sediments were contaminated by past industrial and municipal discharges, waste disposal, and pesticide usage. Five beneficial use impairments (BUIs) have been identified in the AOC including the degradation of the “benthos”, or the benthic macroinvertebrate community. This investigation used sediment toxicity testing and macroinvertebrate community assessments to determine if the toxicity of bed sediments in the AOC differed from that of an unimpacted reference stream. Results from 10-day toxicity tests indicated that survival and growth of the dipteran Chironomus dilutus and the amphipod Hyalella azteca did not differ significantly between sediments from the AOC and reference area. Analyses of benthic macroinvertebrate community integrity and structure also indicated that macroinvertebrate communities, while impacted across most sites on both streams, were generally similar between the AOC and reference area. Despite these findings, the upstream-most AOC site consistently scored poorly in all analyses, which suggests that localized sediment toxicity may exist in the AOC, even if large scale differences between the AOC and a comparable reference stream are minimal.

Evaluation of toxicity and estrogenicity of the landfill-concentrated leachate during advanced oxidation treatment: chemical analyses and bioanalytical tools.

PubMed

Wang, Guifang; Lu, Gang; Zhao, Jiandi; Yin, Pinghe; Zhao, Ling

2016-08-01

Landfill-concentrated leachate from membrane separation processes is a potential pollution source for the surroundings. In this study, the toxicity and estrogenicity potentials of concentrated leachate prior to and during UV-Fenton and Fenton treatments were assessed by a combination of chemical (di (2-ethylhexyl) phthalate and dibutyl phthalate were chosen as targets) and biological (Daphnia magna, Chlorella vulgaris, and E-screen assay) analyses. Removal efficiencies of measured di (2-ethylhexyl) phthalate and dibutyl phthalate were more than 97 % after treatment with the two methods. Biological tests showed acute toxicity effects on D. magna tests in untreated concentrated leachate samples, whereas acute toxicity on C. vulgaris tests was not observed. Both treatment methods were found to be efficient in reducing acute toxicity effects on D. magna tests. The E-screen test showed concentrated leachate had significant estrogenicity, UV-Fenton and Fenton treatment, especially the former, were effective methods for reducing estrogenicity of concentrated leachate. The EEQchem (estradiol equivalent concentration) of all samples could only explain 0.218-5.31 % range of the EEQbio. These results showed that UV-Fenton reagent could be considered as a suitable method for treatment of concentrated leachate, and the importance of the application of an integrated (biological + chemical) analytical approach for a comprehensive evaluation of treatment suitability.

An Integrated In Vitro and Computational Approach to Define the Exposure-Dose-Toxicity Relationships In High-Throughput Screens

EPA Science Inventory

Research efforts by the US Environmental Protection Agency have set out to develop alternative testing programs to prioritize limited testing resources toward chemicals that likely represent the greatest hazard to human health and the environment. Efforts such as EPA’s ToxCast r...

Integrating Aggregate Exposure Pathway (AEP) and Adverse Outcome Pathway (AOP) Frameworks to Estimate Exposure-relevant Responses

EPA Science Inventory

High throughput toxicity testing (HTT) holds the promise of providing data for tens of thousands of chemicals that currently have no data due to the cost and time required for animal testing. Interpretation of these results require information linking the perturbations seen in vi...

"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.

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

Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

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

Theunissen, P.T., E-mail: Peter.Theunissen@rivm.nl; Department of Toxicogenomics, Maastricht University, Maastricht; Robinson, J.F.

Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTnmore » morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.« less

In vitro screening of organotin compounds and sediment extracts for cytotoxicity to fish cells.

PubMed

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

2011-01-01

The present study reports an in vitro screening method for contaminants in sediment samples utilizing an RTG-2 cell line. This technique integrates cytotoxicity testing with analytical chemistry with the aim of achieving a toxicity evaluation of the sediment sample. The toxic effect of individual organotin (OT) compounds and their presence in the sediment sample is the focus of the present study; however, other contaminants are also discussed. The following OT compounds: tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenyltin (DPT), and a sediment solvent extract are exposed to the RTG-2 fish cell line. Both the alamar blue (AB) and neutral red (NR) assays are used to assess cytotoxicity after 24-h and 96-h exposure. Methodology for preparation of a sediment solvent extract suitable for biological testing and analytical determination is also described. With the RTG-2 cells, the AB and NR assays had comparable sensitivity for each individual OT compound exposure after 24 h, with TPT being the most toxic compound tested. The individual OT compound concentrations required to induce a 50% toxic effect on the cells (369 ng ml⁻¹ TBT, 1,905 ng ml⁻¹ DBT) did not equate to the concentrations of these contaminants present in the sediment extract that induced a 50% effect on the cells (294 ng ml⁻¹ TBT, 109 ng ml⁻¹ DBT). The solvent extract therefore exhibited a greater toxicity, and this suggests that the toxic effects observed were not due to OT compounds alone. The presence of other contaminants in the solvent extract is confirmed with chemical analysis, warranting further toxicity testing of contaminant mixtures and exposure to the cell line to further elucidate a complete toxicity evaluation. © 2010 SETAC.

Autonomous, agile micro-satellites and supporting technologies

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

Breitfeller, E; Dittman, M D; Gaughan, R J

1999-07-19

This paper updates the on-going effort at Lawrence Livermore National Laboratory to develop autonomous, agile micro-satellites (MicroSats). The objective of this development effort is to develop MicroSats weighing only a few tens of kilograms, that are able to autonomously perform precision maneuvers and can be used telerobotically in a variety of mission modes. The required capabilities include satellite rendezvous, inspection, proximity-operations, docking, and servicing. The MicroSat carries an integrated proximity-operations sensor-suite incorporating advanced avionics. A new self-pressurizing propulsion system utilizing a miniaturized pump and non-toxic mono-propellant hydrogen peroxide was successfully tested. This system can provide a nominal 25 kg MicroSatmore » with 200-300 m/s delta-v including a warm-gas attitude control system. The avionics is based on the latest PowerPC processor using a CompactPCI bus architecture, which is modular, high-performance and processor-independent. This leverages commercial-off-the-shelf (COTS) technologies and minimizes the effects of future changes in processors. The MicroSat software development environment uses the Vx-Works real-time operating system (RTOS) that provides a rapid development environment for integration of new software modules, allowing early integration and test. We will summarize results of recent integrated ground flight testing of our latest non-toxic pumped propulsion MicroSat testbed vehicle operated on our unique dynamic air-rail.« less

Vitro Pulmonary Toxicity of Metal Oxide Nanoparticles

EPA Science Inventory

The diversity of engineered-nanomaterials and their applications as well as potential unknown health effects of these novel materials are significant challenges to assessing the health risks of nanotechnology. An integrated multi-tier testing strategy (www.epa.gov/nanoscience/) ...

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.

Inhalation toxicity of indoor air pollutants in Drosophila melanogaster using integrated transcriptomics and computational behavior analyses

NASA Astrophysics Data System (ADS)

Eom, Hyun-Jeong; Liu, Yuedan; Kwak, Gyu-Suk; Heo, Muyoung; Song, Kyung Seuk; Chung, Yun Doo; Chon, Tae-Soo; Choi, Jinhee

2017-06-01

We conducted an inhalation toxicity test on the alternative animal model, Drosophila melanogaster, to investigate potential hazards of indoor air pollution. The inhalation toxicity of toluene and formaldehyde was investigated using comprehensive transcriptomics and computational behavior analyses. The ingenuity pathway analysis (IPA) based on microarray data suggests the involvement of pathways related to immune response, stress response, and metabolism in formaldehyde and toluene exposure based on hub molecules. We conducted a toxicity test using mutants of the representative genes in these pathways to explore the toxicological consequences of alterations of these pathways. Furthermore, extensive computational behavior analysis showed that exposure to either toluene or formaldehyde reduced most of the behavioral parameters of both wild-type and mutants. Interestingly, behavioral alteration caused by toluene or formaldehyde exposure was most severe in the p38b mutant, suggesting that the defects in the p38 pathway underlie behavioral alteration. Overall, the results indicate that exposure to toluene and formaldehyde via inhalation causes severe toxicity in Drosophila, by inducing significant alterations in gene expression and behavior, suggesting that Drosophila can be used as a potential alternative model in inhalation toxicity screening.

Inhalation toxicity of indoor air pollutants in Drosophila melanogaster using integrated transcriptomics and computational behavior analyses

PubMed Central

Eom, Hyun-Jeong; Liu, Yuedan; Kwak, Gyu-Suk; Heo, Muyoung; Song, Kyung Seuk; Chung, Yun Doo; Chon, Tae-Soo; Choi, Jinhee

2017-01-01

We conducted an inhalation toxicity test on the alternative animal model, Drosophila melanogaster, to investigate potential hazards of indoor air pollution. The inhalation toxicity of toluene and formaldehyde was investigated using comprehensive transcriptomics and computational behavior analyses. The ingenuity pathway analysis (IPA) based on microarray data suggests the involvement of pathways related to immune response, stress response, and metabolism in formaldehyde and toluene exposure based on hub molecules. We conducted a toxicity test using mutants of the representative genes in these pathways to explore the toxicological consequences of alterations of these pathways. Furthermore, extensive computational behavior analysis showed that exposure to either toluene or formaldehyde reduced most of the behavioral parameters of both wild-type and mutants. Interestingly, behavioral alteration caused by toluene or formaldehyde exposure was most severe in the p38b mutant, suggesting that the defects in the p38 pathway underlie behavioral alteration. Overall, the results indicate that exposure to toluene and formaldehyde via inhalation causes severe toxicity in Drosophila, by inducing significant alterations in gene expression and behavior, suggesting that Drosophila can be used as a potential alternative model in inhalation toxicity screening. PMID:28621308

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

Leachate composition and toxicity assessment: an integrated approach correlating physicochemical parameters and toxicity of leachates from MSW landfill in Delhi.

PubMed

Gupta, Anshu; Paulraj, R

2017-07-01

Landfills are considered the most widely practiced method for disposal of municipal solid waste (MSW) and 95% of the total MSW collected worldwide is disposed of in landfills. Leachate produced from MSW landfills may contain a number of pollutants and pose a potential environmental risk for surface as well as ground water. In the present study, chemical analysis and toxicity assessment of landfill leachate have been carried out. Leachate samples were collected from Ghazipur landfill site, New Delhi. Leachates were characterized by measuring the concentration of heavy metals (Pb, Cu, Cr and Ni), 5-day biochemical oxygen demand (BOD 5 ), chemical oxygen demand (COD), pH, electrical conductivity and SO 4 2 -. For toxicity testing of leachate, Triticum aestivum (wheat) was selected and testing was done in a time- and dose-dependent manner using the crude leachate. Median lethal concentration after 24 and 48 h of exposure was observed. The main objective of this study was to evaluate toxicity of MSW landfill leachate and establish a possible correlation between the measured physicochemical parameters and resultant toxicity. Statistical analysis showed that toxicity was dependent on the concentration of heavy metals (Pb, Cu), conductivity, and organic matter (COD and BOD5).

Larvicidal and antifeedant activity of some plant-derived compounds to Lymantria dispar L. (Lepidoptera: Limantriidae).

PubMed

Kostić, Miroslav; Popović, Zorica; Brkić, Dejan; Milanović, Slobodan; Sivcev, Ivan; Stanković, Sladjan

2008-11-01

Ethanol solutions of essential oil of Ocimum basilicum and its main component, linalool (both isomer forms), all in three concentrations, as well as botanical standard Bioneem (0.5%), were tested for their toxicity and antifeedant activity against the second instar gypsy moth larvae in the laboratory bioassay. The essential oil of O. basilicum was subjected to gas chromatography analysis, and totally 37 compounds were detected, of which linalool was predominantly present. All tested solutions showed low to moderate larvicidal effect in both residual toxicity test and in chronic larval mortality bioassay. Chronic mortality tests showed that obtained mortality was a consequence of starving rather than ingestion of treated leaves. However, antifeedant index achieved by application of tested solutions in feeding choice assay was remarkable. Foliar application of all tested compounds deterred feeding by L2 in the same percent as Bioneem. Antifeedant index was relatively high at all tested treatments (85-94%); moreover, the larval desensitization to repelling volatiles has not occurred after five days of observation. Low toxic and high antifeedant properties make these plant-derived compounds suitable for incorporation in integrated pest management programs, especially in urban environments.

Comparative toxicity of leachates from 52 textiles to Daphnia magna.

PubMed

Dave, Göran; Aspegren, Pia

2010-10-01

The environmental aspects of textiles are very complex and include production, processing, transport, usage, and recycling. Textiles are made from a variety of materials and can contain a large number of chemicals. Chemicals are used during production of fibres, for preservation and colouring and they are released during normal wear and during washing. The aim of this study was to investigate the release to water of toxic chemicals from various textiles. Altogether 52 samples of textiles made from cotton (21), linen (4), cotton and linen (7), cellulose (3), synthetic fibres (7), cotton and synthetic fibres (8) and wool (2). Seven were eco-labelled. All textiles were cut into squares and placed into Petri dishes with 50 ml ISO test medium in a concentration series (4-256 cm(2)/50 ml) and tested for acute toxicity to Daphnia magna. Estimated EC50s were converted into weight/volume, and 48-h EC50s ranged between <1 and >182 g/L. It was not possible to detect any difference between fibre type and toxicity (ANOVA), but a significantly higher toxicity was found for printed versus unprinted cotton and cotton/linen textiles, while the opposite was found for synthetic textiles. Eco-labelled products were evenly distributed on a toxicity scale, which means that eco-labelling in its present form does not necessarily protect users or the environment from exposure to toxic chemicals. Therefore, the results from the present study suggest that bioassays and toxicity tests should become an integrated part of textile environmental quality control programs. Copyright © 2010 Elsevier Inc. All rights reserved.

Interactions between toxic chemicals and natural environmental factors--a meta-analysis and case studies.

PubMed

Laskowski, Ryszard; Bednarska, Agnieszka J; Kramarz, Paulina E; Loureiro, Susana; Scheil, Volker; Kudłek, Joanna; Holmstrup, Martin

2010-08-15

The paper addresses problems arising from effects of natural environmental factors on toxicity of pollutants to organisms. Most studies on interactions between toxicants and natural factors, including those completed in the EU project NoMiracle (Novel Methods for Integrated Risk Assessment of Cumulative Stressors in Europe) described herein, showed that effects of toxic chemicals on organisms can differ vastly depending purely on external conditions. We compiled data from 61 studies on effects of temperature, moisture and dissolved oxygen on toxicity of a range of chemicals representing pesticides, polycyclic aromatic hydrocarbons, plant protection products of bacterial origin and trace metals. In 62.3% cases significant interactions (p< or =0.05 or less) between natural factors and chemicals were found, reaching 100% for the effect of dissolved oxygen on toxicity of waterborne chemicals. The meta-analysis of the 61 studies showed that the null hypothesis assuming no interactions between toxic chemicals and natural environmental factors should be rejected at p=2.7 x 10(-82) (truncated product method probability). In a few cases of more complex experimental designs, also second-order interactions were found, indicating that natural factors can modify interactions among chemicals. Such data emphasize the necessity of including information on natural factors and their variation in time and across geographic regions in ecological risk assessment. This can be done only if appropriate ecotoxicological test designs are used, in which test organisms are exposed to toxicants at a range of environmental conditions. We advocate designing such tests for the second-tier ecological risk assessment procedures. Copyright 2010 Elsevier B.V. All rights reserved.

Zebrafish – As an Integrative Model for Twenty-first Century Toxicity Testing

EPA Science Inventory

The zebrafish embryo is a useful small model for investigating vertebrate development because of its transparency, low cost, transgenic and morpholino capabilities, conservation of cell signaling, and concordance with mammalian developmental phenotypes. From these advantages, the...

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...

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

EPA Science Inventory

The US EPA National Center for Computational Toxicology (NCCT) has a mission to integrate modern computing and information technology with molecular biology to improve Agency prioritization of data requirements and risk assessment of chemicals. Recognizing the critical need for ...

[Quaternary ammonium cytotoxicity in a human conjunctival cell line].

PubMed

Debbasch, C; de Saint Jean, M; Pisella, P J; Rat, P; Warnet, J M; Baudouin, C

1999-11-01

Ophthalmic preparations can induce conjunctival toxicity, often caused by preservatives. The aim of this study was to evaluate in vitro cytotoxicity of quaternary ammonium. Cytotoxicity tests were done on a continuous human conjunctival cell line using microplate cold light cytofluorimetry. Membrane integrity (neutral red test), DNA condensation (Hoechst 33342 test) and reactive oxygen species (ROS) production (dichlorofluorescein diacetate and hydroethidine tests) were evaluated on living cells treated with different concentrations of benzalkonium chloride, benzododecinium bromide and cetrimide (0.00001 to 0.01%) after 15 minutes of treatment or 15 minutes and 24 hours of cell recovery. All the compounds tested showed similar in vitro effects. Using the neutral red test, we observed a decrease in membrane integrity even at 0.005% and 0.01% (p < 0.001) and after a short time (15 minutes). A stimulation of ROS production (H2O2 and O2) was observed at 0.00001% and above (p < 0.001), associated with a chromatine condensation due to an apoptotic phenomenon. A necrotic phenomenon is suggested at high concentrations of quaternary ammonium preservatives whereas an apoptotic mechanism exists for lower concentrations. This toxicity observed in vitro can explain some of the ocular surface damage caused by long-term use of preserved eye-drops.

Organic compounds removal and toxicity reduction of landfill leachate by commercial bakers' yeast and conventional bacteria based membrane bioreactor integrated with nanofiltration.

PubMed

Reis, Beatriz Gasparini; Silveira, Amanda Lemes; Tostes Teixeira, Luiza Procópio; Okuma, Adriana Akemi; Lange, Liséte Celina; Amaral, Miriam Cristina Santos

2017-12-01

This study aimed to compare the performance of a commercial bakers' yeast (MBRy) and conventional bacteria (MBRb) based membrane bioreactor integrated with nanofiltration (NF) in the removal of landfill leachate toxicity. Performances were evaluated using physicochemical analyses, toxicity tests and identification of organic compounds. The MBR b and MBR y were operated with a hydraulic retention time (HRT) of 48h and solids retention time (SRT) of 60 d. The MBR y demonstrated better removal efficiencies for COD (69±7%), color (54±11%) and ammoniacal nitrogen (34±7%) compared to MBR b , which showed removal efficiencies of 27±5%, 33±4% and 27±7%, for COD, color and ammoniacal nitrogen. Although the MBR y seems to be the configuration that presented the highest efficiency; it generated toxic permeate whose toxicity cannot be explained by physicochemical results. The identification of compounds shows that there is a wide range of compounds in the landfill leachate in addition to others that are produced in the biological treatment steps. The NF plays a crucial role in the polishing of the final effluents by the either complete or partial retention of compounds, that attribute toxicity to the leachate, and inorganic contaminants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selectivity lists of pesticides to beneficial arthropods for IPM programs in carrot--first results.

PubMed

Hautier, L; Jansen, J-P; Mabon, N; Schiffers, B

2005-01-01

In order to improve IPM programs in carrot, 7 fungicides, 12 herbicides and 9 insecticides commonly used in Belgium were tested for their toxicity towards five beneficial arthropods representative of most important natural enemies encountered in carrot: parasitic wasps - Aphidius rhopalosiphi (De Stefani-Perez) (Hym., Aphidiidae), ladybirds - Adalia bipunctata (L.) (Col., Coccinellidae), hoverfly - Episyrphus balteatus (Dipt.. Syrphidae), rove beetle - Aleochara bilineata (Col., Staphylinidae) and carabid beetle - Bembidion lampros (Col., Carabidae). Initialy, all plant protection products were tested on inert substrate glass plates or sand according to the insect. Products with a corrected mortality (CM) or a parasitism reduction (PR) lower than 30% were kept for the constitution of positive list (green list). The other compounds were further tested on plant for A. rhopalosiphi, A. bipunctata, E. balteatus and soil for B. lampros and A. bilineata. With these extended laboratory tests results, products were listed in toxicity class: green category [CM or PR < or = 30%], yellow category [30% < CM or PR < or = 60%] and orange category [60% < CM or PR < or = 80%]. Products with toxicity higher than 80% on plants or that reduce parasitism more than 80% on soil were put in red category and are not recommended to Integrated Pest Management programs in carrot. Results showed that all fungicides tested were harmless to beneficials except Tebuconazole, which was slightly harmful for A. bipunctata. Herbicides were also harmless for soil beneficials, except Chlorpropham. This product was very toxic on sand towards A. bilineata and must be tested on soil. All soil insecticides tested were very toxic for ground beneficials and considered as non-selective. Their use in IPM is subject to questioning in view of negative impacts on beneficials. Among foliar insecticides, Dimethoate and Deltamethrin are not recommended for IPM because their high toxicity for all beneficials. The other foliar insecticides were more selective; any of them were harmless for all species tested.

Circadian dysregulation disrupts bile acid homeostasis

USDA-ARS?s Scientific Manuscript database

Bile acids are potentially toxic compounds and their levels of hepatic production, uptake, and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis. Both restricted feedi...

A structured approach to Exposure Based Waiving of human health endpoints under REACH developed in the OSIRIS project.

PubMed

Marquart, Hans; Meijster, Tim; Van de Bovenkamp, Marja; Ter Burg, Wouter; Spaan, Suzanne; Van Engelen, Jacqueline

2012-03-01

Exposure Based Waiving (EBW) is one of the options in REACH when there is insufficient hazard data on a specific endpoint. Rules for adaptation of test requirements are specified and a general option for EBW is given via Appendix XI of REACH, allowing waiving of repeated dose toxicity studies, reproductive toxicity studies and carcinogenicity studies under a number of conditions if exposure is very low. A decision tree is described that was developed in the European project OSIRIS (Optimised Strategies for Risk Assessment of Industrial Chemicals through Integration of Non-Test and Test Information) to help decide in what cases EBW can be justified. The decision tree uses specific criteria as well as more general questions. For the latter, guidance on interpretation and resulting conclusions is provided. Criteria and guidance are partly based on an expert elicitation process. Among the specific criteria a number of proposed Thresholds of Toxicological Concern are used. The decision tree, expanded with specific parts on absorption, distribution, metabolism and excretion that are not described in this paper, is implemented in the OSIRIS webtool on integrated testing strategies. Copyright © 2011 Elsevier Inc. All rights reserved.

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

The nematode Caenorhabditis elegans as an integrated toxicological tool to assess water quality and pollution.

PubMed

Clavijo, Araceli; Kronberg, María Florencia; Rossen, Ariana; Moya, Aldana; Calvo, Daniel; Salatino, Santa Esmeralda; Pagano, Eduardo Antonio; Morábito, José Antonio; Munarriz, Eliana Rosa

2016-11-01

Determination of water quality status in rivers is critical to establish a sustainable water management policy. For this reason, over the last decades it has been recommended to perform integrated water assessments that include water quantities and physicochemical, ecological and toxicological tests. However, sometimes resources are limited and it is not possible to perform large-scale chemical determinations of pollutants or conduct numerous ecotoxicological tests. To overcome this problem we use and measure the growth, as a response parameter, of the soil nematode Caenorhabditis elegans to assess water quality in rivers. The C. elegans is a ubiquitous organism that has emerged as an important model organism in aquatic and soil toxicology research. The Tunuyán River Basin (Province of Mendoza, Argentina) has been selected as a representative traditional water monitoring system to test the applicability of the C. elegans toxicological bioassay to generate an integrated water quality evaluation. Jointly with the C. elegans toxic assays, physicochemical and bacteriological parameters were determined for each monitoring site. C. elegans bioassays help to identify different water qualities in the river basin. Multivariate statistical analysis (PCA and linear regression models) has allowed us to confirm that traditional water quality studies do not predict potential toxic effects on living organisms. On the contrary, physicochemical and bacteriological analyzes explain <62% of the C. elegans growth response variability, showing that ecotoxicological bioassays are important to obtain a realistic scenario of water quality threats. Our results confirm that the C. elegans bioassay is a sensible and suitable tool to assess toxicity and should be implemented in routine water quality monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

NASA Astrophysics Data System (ADS)

Becker, Holger; Hansen-Hagge, Thomas; Kurtz, Andreas; Mrowka, Ralf; Wölfl, Stefan; Gärtner, Claudia

2017-02-01

The development of new drugs is time-consuming, extremely expensive and often promising drug candidates fail in late stages of the development process due to the lack of suitable tools to either predict toxicological effects or to test drug candidates in physiologically relevant environments prior to clinical tests. We therefore try to develop diagnostic multiorgan microfluidic chips based on patient specific induced pluripotent stem cell (iPS) technology to explore liver dependent toxic effects of drugs on individual human tissues such as liver or kidney cells. Based initially on standardized microfluidic modules for cell culture, we have developed integrated microfluidic devices which contain different chambers for cell/tissue cultivation. The devices are manufactured using injection molding of thermoplastic polymers such as polystyrene or cyclo-olefin polymer. In the project, suitable surface modification methods of the used materials had to be explored. We have been able to successfully demonstrate the seeding, cultivation and further differentiation of modified iPS, as shown by the use of differentiation markers, thus providing a suitable platform for toxicity testing and potential tissue-tissue interactions.

Implementation challenges for designing integrated in vitro testing strategies (ITS) aiming at reducing and replacing animal experimentation.

PubMed

De Wever, Bart; Fuchs, Horst W; Gaca, Marianna; Krul, Cyrille; Mikulowski, Stan; Poth, Albrecht; Roggen, Erwin L; Vilà, Maya R

2012-04-01

At the IVTIP (in vitro testing industrial platform) meeting of November 26th 2009 entitled 'Toxicology in the 21st century ('21C')--working our way towards a visionary reality' all delegates endorsed the emerging concept of the '21C' vision as the way forward to enable a thorough, reliable and systematic approach to future toxicity testing without the use of animals. One of the emerging concepts focused on integrating a defined number of tests modelling in vivo-relevant and well-characterised toxicity pathways representing mechanistic endpoints. At this meeting the importance of Integrated Testing Strategies (ITS) as tools towards reduction and eventually replacement of the animals currently used for hazard identification and risk assessment was recognised. A follow-up IVTIP Spring 2010 meeting entitled 'Integrated In Vitro Testing Strategies (ITS)--Implementation Challenges' was organised to address pending questions about ITS. This report is not a review of the ITS literature, but a summary of the discussions triggered by presented examples on how to develop and implement ITS. Contrasts between pharmaceutical and chemical industry, as well as a list of general but practical aspects to be considered while developing an ITS emerged from the discussions. In addition, current recommendations on the validation of ITS were discussed. In conclusion, the outcome of this workshop improved the understanding of the participants of some important factors that may impact the design of an ITS in function of its purpose (e.g., screening, or early decision making versus regulatory), the context in which they need to be applied (e.g., ICH guidelines, REACH) and the status and quality of the available tools. A set of recommendations of best practices was established and the importance of the applicability of the individual tests as well as the testing strategy itself was highlighted. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Creating a Structured AOP Knowledgebase via Ontology-Based Annotations

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly used to integrate data from traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in terms that can be interpreted computationally. We wil...

Tidal river sediments in the Washington, D.C. area. 111 Biological effects associated with sediment contamination

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

Schlekat, C.E.; McGee, B.L.; Boward, D.M.

1994-06-01

Sediment toxicity and benthic marcroinvertebrate community structure were measured as one component of a study conceived to determine the distribution and effect of sediment contamination in tidal freshwater portions of the Potomac and Anacostia rivers in the Washington, D.C., area. Samples were collected at 15 sites. Analyses included a partial life cycle (28 d) whole sediment test using the amphipod Hyalella azteca (Talitridae) and an assessment of benthic community structure. Survival and growth (as estimated by amphipod length) were experimental endpoints for the toxicity test. Significant mortality was observed in 5 to 10 sites in the lower Anacostia River basinmore » and at the main channel Potomac River site. Sublethal toxicity, as measured by inhibition of amphipod growth, was not observed. Toxicity test results were in general agreement with synoptically measured sediment contaminant concentrations. Porewater total ammonia (NH{sub 3} + NH{sub 4}{sup +}) appears to be responsible for the toxicity of sediments from the Potomac River, while correlation analysis and simultaneously extracted metals: acid volatile sulfide (SEM:AVA) results suggest that the toxicity associated with Anacostia River sediments was due to organic compounds. Twenty-eight macroinvertebrate taxa were identified among all sites, with richness varying from 5 to 17 taxa per site. Groups of benthic assemblages identified by group-average cluster analysis exhibited variable agreement with sediment chemical and sediment toxicity results. Integration of toxicological, chemical, and ecological components suggests that adverse environmental effects manifest in lower Anacostia River benthos result from chemical contamination of sediment. 37 refs., 2 figs., 7 tabs.« less

Sediment toxicity assessment in the Lagoon of Venice (Italy) using Paracentrotus lividus (Echinodermata: Echinoidea) fertilization and embryo bioassays.

PubMed

Volpi Ghirardini, A; Arizzi Novelli, A; Tagliapietra, D

2005-09-01

The capacity of two toxicity bioassays (fertilization and embryo toxicity tests) to discriminate sediment toxicity using the sea urchin Paracentrotus lividus was tested in five stations with different levels of pollution in the Lagoon of Venice. Two stations were located in estuarine sites, two in the industrial zone, and one in a site at the top of our quality gradient (reference). Elutriate was chosen as sediment matrix to assess the potential effects of bioavailable pollutants in the water column as a consequence of sediment resuspension (dredging and dumping, fishing gear, etc.). An experimental design based on Quality Assurance/Quality Control procedures (QA/QC) was adopted in order to set the methodological basis for an effective use of these bioassays in monitoring programs. Results revealed both higher embriotoxicity than spermiotoxicity in all stations and the efficacy of combined use of both toxicity bioassays in discriminating differing pollution/bioavailability between stations and periods. The good representativeness of the integrated sampling scheme and the standardization of all experimental phases yielded high precision of results. Clear Toxicity Fingerprints were evidenced for the investigated sites through the combined use of both bioassays. A good fit between ecotoxicological data and chemical contamination levels was found, except for unnatural sediment texture.

An Integrated Chemical Environment to Support 21st-Century Toxicology.

PubMed

Bell, Shannon M; Phillips, Jason; Sedykh, Alexander; Tandon, Arpit; Sprankle, Catherine; Morefield, Stephen Q; Shapiro, Andy; Allen, David; Shah, Ruchir; Maull, Elizabeth A; Casey, Warren M; Kleinstreuer, Nicole C

2017-05-25

SUMMARY : Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource. The ICE data integrator allows users to retrieve and combine data sets and to develop hypotheses through data exploration. Open-source computational workflows and models will be available for download and application to local data. ICE currently includes curated in vivo test data, reference chemical information, in vitro assay data (including Tox21 TM /ToxCast™ high-throughput screening data), and in silico model predictions. Users can query these data collections focusing on end points of interest such as acute systemic toxicity, endocrine disruption, skin sensitization, and many others. ICE is publicly accessible at https://ice.ntp.niehs.nih.gov. https://doi.org/10.1289/EHP1759.

An Integrated Chemical Environment to Support 21st-Century Toxicology

PubMed Central

Bell, Shannon M.; Phillips, Jason; Sedykh, Alexander; Tandon, Arpit; Sprankle, Catherine; Morefield, Stephen Q.; Shapiro, Andy; Allen, David; Shah, Ruchir; Maull, Elizabeth A.; Casey, Warren M.

2017-01-01

Summary: Access to high-quality reference data is essential for the development, validation, and implementation of in vitro and in silico approaches that reduce and replace the use of animals in toxicity testing. Currently, these data must often be pooled from a variety of disparate sources to efficiently link a set of assay responses and model predictions to an outcome or hazard classification. To provide a central access point for these purposes, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods developed the Integrated Chemical Environment (ICE) web resource. The ICE data integrator allows users to retrieve and combine data sets and to develop hypotheses through data exploration. Open-source computational workflows and models will be available for download and application to local data. ICE currently includes curated in vivo test data, reference chemical information, in vitro assay data (including Tox21TM/ToxCast™ high-throughput screening data), and in silico model predictions. Users can query these data collections focusing on end points of interest such as acute systemic toxicity, endocrine disruption, skin sensitization, and many others. ICE is publicly accessible at https://ice.ntp.niehs.nih.gov. https://doi.org/10.1289/EHP1759 PMID:28557712

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

Transferability and inter-laboratory variability assessment of the in vitro bovine oocyte fertilization test.

PubMed

Tessaro, Irene; Modina, Silvia C; Crotti, Gabriella; Franciosi, Federica; Colleoni, Silvia; Lodde, Valentina; Galli, Cesare; Lazzari, Giovanna; Luciano, Alberto M

2015-01-01

The dramatic increase in the number of animals required for reproductive toxicity testing imposes the validation of alternative methods to reduce the use of laboratory animals. As we previously demonstrated for in vitro maturation test of bovine oocytes, the present study describes the transferability assessment and the inter-laboratory variability of an in vitro test able to identify chemical effects during the process of bovine oocyte fertilization. Eight chemicals with well-known toxic properties (benzo[a]pyrene, busulfan, cadmium chloride, cycloheximide, diethylstilbestrol, ketoconazole, methylacetoacetate, mifepristone/RU-486) were tested in two well-trained laboratories. The statistical analysis demonstrated no differences in the EC50 values for each chemical in within (inter-runs) and in between-laboratory variability of the proposed test. We therefore conclude that the bovine in vitro fertilization test could advance toward the validation process as alternative in vitro method and become part of an integrated testing strategy in order to predict chemical hazards on mammalian fertility. Copyright © 2015 Elsevier Inc. All rights reserved.

Using a modified dredging elutriate testing approach to evaluate potential aquatic impacts associated with dredging a large freshwater industrial harbor.

PubMed

Watson-Leung, Trudy; Graham, Matt; Hartman, Erin; Welsh, Paul G

2017-01-01

Potential adverse impacts to the aquatic environment should be minimized whenever possible during an environmental dredging project by selecting realistic and technically feasible environmental targets. These targets need to balance short term impacts with the longer term benefit of removing contaminated sediments from the environment. Environmental dredging is part of the planned remediation of Randle Reef (a 60 hectare zone of mostly PAH-contaminated sediments) in Hamilton, Ontario, Canada. In this study, we describe the results of dredging elutriate toxicity testing (DETE) to assess the potential risks from dredging this PAH contaminated site. A modified elutriate preparation method intended as an alternative measure of conditions within the dredging plume was assessed with both standard water column species (Daphnia magna and fathead minnow [Pimephales promelas]) and alternative benthic and epibenthic test organisms (Chironomus dilutus and Hyalella azteca). The standard DETE test was also conducted with H. azteca to compare with the modified DETE results. The greatest toxic response was seen in the alternative test species; however, the modified DETE method resulted in less toxicity than the standard protocol. The relationship between toxicity results and chemical and/or physical characteristics of the samples was examined, but differences in toxicity could only be explained by differences in the total suspended solids concentrations in the elutriate samples. Challenges associated with DETE assessment of PAH-contaminated sediments and the implications for establishing dredging benchmarks are discussed. Integr Environ Assess Manag 2017;13:155-166. © 2016 SETAC. © 2016 SETAC.

Use of High-Throughput Testing and Approaches for Evaluating Chemical Risk-Relevance to Humans

EPA Science Inventory

ToxCast is profiling the bioactivity of thousands of chemicals based on high-throughput screening (HTS) and computational models that integrate knowledge of biological systems and in vivo toxicities. Many of these assays probe signaling pathways and cellular processes critical to...

Creating a Structured Adverse Outcome Pathway Knowledgebase via Ontology-Based Annotations

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework is increasingly used to integrate data based on traditional and emerging toxicity testing paradigms. As the number of AOP descriptions has increased, so has the need to define the AOP in computable terms. Herein, we present a comprehens...

Incorporating Population Variability and Susceptible Subpopulations into Dosimetry for High-Throughput Toxicity Testing

EPA Science Inventory

Momentum is growing worldwide to use in vitro high-throughput screening (HTS) to evaluate human health effects of chemicals. However, the integration of dosimetry into HTS assays and incorporation of population variability will be essential before its application in a risk assess...

User's Manual MCnest - Markov Chain Nest Productivity Model Version 2.0

EPA Science Inventory

The Markov chain nest productivity model, or MCnest, is a set of algorithms for integrating the results of avian toxicity tests with reproductive life-history data to project the relative magnitude of chemical effects on avian reproduction. The mathematical foundation of MCnest i...

Evaluation of Short-Term Bioassays to Predict Functional Impairment. Selected Short-Term Cardiovascular Toxicity Tests.

DTIC Science & Technology

1980-10-01

for many cultures at one time (Acosta, 1979). When Nitro Blue tetrazolium (NBT) and phenazine methosulphate react with succinate dehydrogenase...microscopically-observable for- mazan granules are formed. When the structural integrity of the mitochondrial membranes is maintained, NBT and phenazine

Testing of Lithium-Sulfur Dioxide Cells for Waste Disposal Hazards.

DTIC Science & Technology

1980-10-01

r AD-AO90 785 WAPORA INC CHEVY CHASE NO F/G 10/3 TESTING OF LITHIUM-SULFUR DIOXIDE CELLS FOR WASTE DISPOSAL HAZA-ETC(U) OCT 80 D B BOIES OAAK20-79-C... TESTING ION T HUM -SUFU DIXD-EL ORWSEDSOA Daved B. pBli else 69stributonsi nlmied.e OCTOBELE198 Fia PRepr for Peio OCT 23198008 STRYUIO AELETOISRSA...34 cell Toxic waste Sulfur dioxide vapor pressure Structural Integrity Test Ignitable waste Extraction procedure results Corrosive waste ftactive waste

Bivalve embryo bioassay to assess the potential toxicity of dredged material before dumping

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

Quiniou, F.

1995-12-31

Dredged harbor sediments frequently contain a wide spectrum of contaminants in addition to a significant percentage of organic matter. Also, dredging and dumping activities into sea water, of these highly contaminated soil may induce a harmful effect on the environment. In France, in accordance with Oslo convention guidelines, a working group on dredging activities and environment (GEODE) created since 1991 decided to set up a pilot research program to assess the intrinsic toxicity of four harbor sludges. Intrinsic toxicity of harbor muds were tested by solid phase (whole sediment) and aqueous extract bioassays (sea water elutriates) using the sublethal toxicitymore » test bivalve embryo bioassay (Crassostrea gigas). Elutriates enable them to detect the toxicity of contaminants which may be released in the soluble form into the water column during dredging operations. While, whole sediment integrate the synergistic effects of all the contaminants (hydrophilic and hydrophobic) including pore water. Bioassays results, correlated to chemical analysis, are compared to contaminant levels determined by French working group GEODE and Canadian sediment quality criteria.« less

Design and validation of an ontology-driven animal-free testing strategy for developmental neurotoxicity testing.

PubMed

Hessel, Ellen V S; Staal, Yvonne C M; Piersma, Aldert H

2018-03-13

Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of fundamental processes in neural tube formation, brain development and neural specification, aiming at illustrating complexity rather than comprehensiveness. We also give a flavor of the wealth of alternative methods in this area. Given the impressive progress in mechanistic knowledge of human biology and toxicology, the time is right for a conceptual approach for designing testing strategies that cover the integral mechanistic landscape of developmental neurotoxicity. The ontology approach provides a framework for defining this landscape, upon which an integral in silico model for predicting toxicity can be built. It subsequently directs the selection of in vitro assays for rate-limiting events in the biological network, to feed parameter tuning in the model, leading to prediction of the toxicological outcome. Validation of such models requires primary attention to coverage of the biological domain, rather than classical predictive value of individual tests. Proofs of concept for such an approach are already available. The challenge is in mining modern biology, toxicology and chemical information to feed intelligent designs, which will define testing strategies for neurodevelopmental toxicity testing. Copyright © 2018 Elsevier Inc. All rights reserved.

Integrated Proteomic Approaches for Understanding Toxicity of Environmental Chemicals

EPA Science Inventory

To apply quantitative proteomic analysis to the evaluation of toxicity of environmental chemicals, we have developed an integrated proteomic technology platform. This platform has been applied to the analysis of the toxic effects and pathways of many important environmental chemi...

Integration of chemical-specific exposure and pharmacokinetic information with the chemical-agnostic AOP framework to support high throughput risk assessment

EPA Science Inventory

Application of the Adverse Outcome Pathway (AOP) framework and high throughput toxicity testing in chemical-specific risk assessment requires reconciliation of chemical concentrations sufficient to trigger a molecular initiating event measured in vitro and at the relevant target ...

Incorporating High-Throughput Exposure Predictions with Dosimetry-Adjusted In Vitro Bioactivity to Inform Chemical Toxicity Testing

EPA Science Inventory

We previously integrated dosimetry and exposure with high-throughput screening (HTS) to enhance the utility of ToxCast™ HTS data by translating in vitro bioactivity concentrations to oral equivalent doses (OEDs) required to achieve these levels internally. These OEDs were compare...

THE GOOD, THE BAD AND THE UGLY - DETERMINATION OF BACTERIAL VIRULENCE USING ANIMAL MODELS AND MICROARRAY TECHNOLOGY

EPA Science Inventory

In its Computational Toxicology Program, EPA/ORD proposes to integrate genomics and computational methods to provide a mechanistic basis for the prediction of toxicity of chemicals and the pathogenicity of microorganisms. The goal of microbiological water testing is to be able to...

Can avian reproductive outcomes estimated with MCnest be made more robust using stochastic parameterizations?

EPA Science Inventory

The Markov chain nest productivity model, or MCnest, is a set of algorithms for integrating the results of avian toxicity tests with reproductive life-history data to project the relative magnitude of chemical effects on avian reproduction. The mathematical foundation of MCnest i...

ToxPi Prioritization and Profiling of 1060 ToxCast Chemicals Across Multiple Sectors of Toxicological Concern

EPA Science Inventory

The Toxicological Prioritization Index (ToxPi™) framework was developed as a decision-support tool to aid in the prioritization of chemicals for integrated toxicity testing. ToxPi consolidates information from multiple domains - including ToxCast™ in vitro bioactivity profiles (a...

Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development.

PubMed

Kimmel, Gary L; Kimmel, Carole A; Williams, Amy L; DeSesso, John M

2013-02-01

The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission's 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations. In addition, the results of six unpublished developmental toxicity studies in rats were considered. Five of the seven rabbit studies (dose range: 10-500 mg/kg/day) were GLP- and testing guideline-compliant for the era in which the studies were performed; a sixth study predated testing and GLP guidelines, but generally adhered to these principles. The seventh study was judged inadequate. In each of the adequate studies, offspring effects occurred only at doses that also caused maternal toxicity. An integrated evaluation of the six adequate studies, using conservative assumptions, demonstrated that neither the overall malformation rate nor the incidence of cardiovascular malformations increased with dose up to the point where severe maternal toxicity was observed (generally ≥150 mg/kg/day). Random occurrences of cardiovascular malformations were observed across all dose groups (including controls) and did not exhibit a dose-response relationship. In the six rat studies (dose range: 30-3500 mg/kg/day), a low incidence of sporadic cardiovascular malformations was reported that was clearly not related to treatment. In summary, assessment of the entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy.

Evaluation of developmental toxicity studies of glyphosate with attention to cardiovascular development

PubMed Central

Kimmel, Gary L.; Kimmel, Carole A.; Williams, Amy L.

2013-01-01

The herbicide glyphosate has undergone multiple safety tests for developmental toxicity in rats and rabbits. The European Commission’s 2002 review of available glyphosate data discusses specific heart defects observed in several individual rabbit developmental toxicity studies, but describes the evidence for a potential causal relationship as equivocal. The present assessment was undertaken to analyze the current body of information generated from seven unpublished rabbit studies in order to determine if glyphosate poses a risk for cardiovascular malformations. In addition, the results of six unpublished developmental toxicity studies in rats were considered. Five of the seven rabbit studies (dose range: 10–500 mg/kg/day) were GLP- and testing guideline-compliant for the era in which the studies were performed; a sixth study predated testing and GLP guidelines, but generally adhered to these principles. The seventh study was judged inadequate. In each of the adequate studies, offspring effects occurred only at doses that also caused maternal toxicity. An integrated evaluation of the six adequate studies, using conservative assumptions, demonstrated that neither the overall malformation rate nor the incidence of cardiovascular malformations increased with dose up to the point where severe maternal toxicity was observed (generally ≥150 mg/kg/day). Random occurrences of cardiovascular malformations were observed across all dose groups (including controls) and did not exhibit a dose–response relationship. In the six rat studies (dose range: 30–3500 mg/kg/day), a low incidence of sporadic cardiovascular malformations was reported that was clearly not related to treatment. In summary, assessment of the entire body of the developmental toxicity data reviewed fails to support a potential risk for increased cardiovascular defects as a result of glyphosate exposure during pregnancy. PMID:23286529

Characteristics of genomic signatures derived using univariate methods and mechanistically anchored functional descriptors for predicting drug- and xenobiotic-induced nephrotoxicity.

PubMed

Shi, Weiwei; Bugrim, Andrej; Nikolsky, Yuri; Nikolskya, Tatiana; Brennan, Richard J

2008-01-01

ABSTRACT The ideal toxicity biomarker is composed of the properties of prediction (is detected prior to traditional pathological signs of injury), accuracy (high sensitivity and specificity), and mechanistic relationships to the endpoint measured (biological relevance). Gene expression-based toxicity biomarkers ("signatures") have shown good predictive power and accuracy, but are difficult to interpret biologically. We have compared different statistical methods of feature selection with knowledge-based approaches, using GeneGo's database of canonical pathway maps, to generate gene sets for the classification of renal tubule toxicity. The gene set selection algorithms include four univariate analyses: t-statistics, fold-change, B-statistics, and RankProd, and their combination and overlap for the identification of differentially expressed probes. Enrichment analysis following the results of the four univariate analyses, Hotelling T-square test, and, finally out-of-bag selection, a variant of cross-validation, were used to identify canonical pathway maps-sets of genes coordinately involved in key biological processes-with classification power. Differentially expressed genes identified by the different statistical univariate analyses all generated reasonably performing classifiers of tubule toxicity. Maps identified by enrichment analysis or Hotelling T-square had lower classification power, but highlighted perturbed lipid homeostasis as a common discriminator of nephrotoxic treatments. The out-of-bag method yielded the best functionally integrated classifier. The map "ephrins signaling" performed comparably to a classifier derived using sparse linear programming, a machine learning algorithm, and represents a signaling network specifically involved in renal tubule development and integrity. Such functional descriptors of toxicity promise to better integrate predictive toxicogenomics with mechanistic analysis, facilitating the interpretation and risk assessment of predictive genomic investigations.

An Integrated Chemical Reactor-Heat Exchanger Based on Ammonium Carbamate (POSTPRINT)

DTIC Science & Technology

2012-10-01

With the scrubber and exhaust operating, the test cell ammonia concentration remains below 5 ppm. To further reduce NH3 release into the test cell...material has a high decomposition enthalpy and exhibits decomposition over a wide range of temperatures. AC decomposition produces ammonia and carbon...installation due to toxic gas ( ammonia ) generation during operation. Therefore, the experiment is intended to be remotely operated. A secondary control

Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

USGS Publications Warehouse

McCarty, L.S.; Landrum, P.F.; Luoma, S.N.; Meador, J.P.; Merten, A.A.; Shephard, B.K.; van Wezelzz, A.P.

2011-01-01

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residueeffect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions. ??:2010 SETAC.

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.

Integrated field and laboratory tests to evaluate effects of metals-impacted wetlands on amphibians: A case study from Montana

USGS Publications Warehouse

Linder, G.; ,

2003-01-01

Mining activities frequently impact wildlife habitats, and a wide range of habitats may require evaluations of the linkages between wildlife and environmental stressors common to mining activities (e.g., physical alteration of habitat, releases of chemicals such as metals and other inorganic constituents as part of the mining operation). Wetlands, for example, are frequently impacted by mining activities. Within an ecological assessment for a wetland, toxicity evaluations for representative species may be advantageous to the site evaluation, since these species could be exposed to complex chemical mixtures potentially released from the site. Amphibian species common to these transition zones between terrestrial and aquatic habitats are one key biological indicator of exposure, and integrated approaches which involve both field and laboratory methods focused on amphibians are critical to the assessment process. The laboratory and field evaluations of a wetland in western Montana illustrates the integrated approach to risk assessment and causal analysis. Here, amphibians were used to evaluate the potential toxicity associated with heavy metal-laden sediments deposited in a reservoir. Field and laboratory methods were applied to a toxicity assessment for metals characteristic of mine tailings to reduce potential "lab to field" extrapolation errors and provide adaptive management programs with critical site-specific information targeted on remediation.

t4 Workshop Report

PubMed Central

Silbergeld, Ellen K.; Contreras, Elizabeth Q.; Hartung, Thomas; Hirsch, Cordula; Hogberg, Helena; Jachak, Ashish C.; Jordan, William; Landsiedel, Robert; Morris, Jeffery; Patri, Anil; Pounds, Joel G.; de Vizcaya Ruiz, Andrea; Shvedova, Anna; Tanguay, Robert; Tatarazako, Norihasa; van Vliet, Erwin; Walker, Nigel J.; Wiesner, Mark; Wilcox, Neil; Zurlo, Joanne

2014-01-01

Summary In October 2010, a group of experts met as part of the transatlantic think tank for toxicology (t4) to exchange ideas about the current status and future of safety testing of nanomaterials. At present, there is no widely accepted path forward to assure appropriate and effective hazard identification for engineered nanomaterials. The group discussed needs for characterization of nanomaterials and identified testing protocols that incorporate the use of innovative alternative whole models such as zebrafish or C. elegans, as well as in vitro or alternative methods to examine specific functional pathways and modes of action. The group proposed elements of a potential testing scheme for nanomaterials that works towards an integrated testing strategy, incorporating the goals of the NRC report Toxicity Testing in the 21st Century: A Vision and a Strategy by focusing on pathways of toxic response, and utilizing an evidence-based strategy for developing the knowledge base for safety assessment. Finally, the group recommended that a reliable, open, curated database be developed that interfaces with existing databases to enable sharing of information. PMID:21993959

Integrated ecological risk assessment of pesticides in tropical ecosystems: a case study with carbofuran in Brazil.

PubMed

Chelinho, Sónia; Lopes, Isabel; Natal-da-Luz, Tiago; Domene, Xaxier; Nunes, Maria Edna Tenorio; Espíndola, Evaldo L G; Ribeiro, Rui; Sousa, Jose P

2012-02-01

The aim of the present study is to contribute an ecologically relevant assessment of the ecotoxicological effects of pesticide applications in agricultural areas in the tropics, using an integrated approach with information gathered from soil and aquatic compartments. Carbofuran, an insecticide/nematicide used widely on sugarcane crops, was selected as a model substance. To evaluate the toxic effects of pesticide spraying for soil biota, as well as the potential indirect effects on aquatic biota resulting from surface runoff and/or leaching, field and laboratory (using a cost-effective simulator of pesticide applications) trials were performed. Standard ecotoxicological tests were performed with soil (Eisenia andrei, Folsomia candida, and Enchytraeus crypticus) and aquatic (Ceriodaphnia silvestrii) organisms, using serial dilutions of soil, eluate, leachate, and runoff samples. Among soil organisms, sensitivity was found to be E. crypticus < E. andrei < F. candida. Among the aqueous extracts, mortality of C. silvestrii was extreme in runoff samples, whereas eluates were by far the least toxic samples. A generally higher toxicity was found in the bioassays performed with samples from the field trial, indicating the need for improvements in the laboratory simulator. However, the tool developed proved to be valuable in evaluating the toxic effects of pesticide spraying in soils and the potential risks for aquatic compartments. Copyright © 2011 SETAC.

Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

EPA Science Inventory

Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

Ecotoxicological assessment of flocculant modified soil for lake restoration using an integrated biotic toxicity index.

PubMed

Wang, Zhibin; Zhang, Honggang; Pan, Gang

2016-06-15

Flocculant modified soils/clays are being increasingly studied as geo-engineering materials for lake restoration and harmful algal bloom control. However, the potential impacts of adding these materials in aquatic ecological systems remain unclear. This study investigated the potential effects of chitosan, cationic starch, chitosan modified soils (MS-C) and cationic starch modified soils (MS-S) on the aquatic organisms by using a bioassay battery. The toxicity potential of these four flocculants was quantitatively assessed using an integrated biotic toxicity index (BTI). The test system includes four aquatic species, namely Chlorella vulgaris, Daphnia magna, Cyprinus carpio and Limnodrilus hoffmeisteri, which represent four trophic levels in the freshwater ecosystem. Results showed that median effect concentrations (EC50) of the MS-C and MS-S were 31-124 times higher than chitosan and cationic starch, respectively. D. magna was the most sensitive species to the four flocculants. Histological examination of C. carpio showed that significant pathological changes were found in gills. Different from chitosan and cationic starch, MS-C and MS-S significantly alleviated the acute toxicities of chitosan and cationic starch. The toxicity order of the four flocculants based on BTI were cationic starch > chitosan > MS-S > MS-C. The results suggested that BTI can be used as a quantitative and comparable indicator to assess biotic toxicity for aquatic geo-engineering materials. Chitosan or cationic starch modified soil/clay materials can be used at their optimal dosage without causing substantial adverse effects to the bioassay battery in aquatic ecosystem. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plant toxins and trophic cascades alter fire regime and succession on a boral forest landscape

USGS Publications Warehouse

Feng, Zhilan; Alfaro-Murillo, Jorge A.; DeAngelis, Donald L.; Schmidt, Jennifer; Barga, Matthew; Zheng, Yiqiang; Ahmad Tamrin, Muhammad Hanis B.; Olson, Mark; Glaser, Tim; Kielland, Knut; Chapin, F. Stuart; Bryant, John

2012-01-01

Two models were integrated in order to study the effect of plant toxicity and a trophic cascade on forest succession and fire patterns across a boreal landscape in central Alaska. One of the models, ALFRESCO, is a cellular automata model that stochastically simulates transitions from spruce dominated 1 km2 spatial cells to deciduous woody vegetation based on stochastic fires, and from deciduous woody vegetation to spruce based on age of the cell with some stochastic variation. The other model, the ‘toxin-dependent functional response’ model (TDFRM) simulates woody vegetation types with different levels of toxicity, an herbivore browser (moose) that can forage selectively on these types, and a carnivore (wolf) that preys on the herbivore. Here we replace the simple succession rules in each ALFRESCO cell by plant–herbivore–carnivore dynamics from TDFRM. The central hypothesis tested in the integrated model is that the herbivore, by feeding selectively on low-toxicity deciduous woody vegetation, speeds succession towards high-toxicity evergreens, like spruce. Wolves, by keeping moose populations down, can help slow the succession. Our results confirmed this hypothesis for the model calibrated to the Tanana floodplain of Alaska. We used the model to estimate the effects of different levels of wolf control. Simulations indicated that management reductions in wolf densities could reduce the mean time to transition from deciduous to spruce by more than 15 years, thereby increasing landscape flammability. The integrated model can be useful in estimating ecosystem impacts of wolf control and moose harvesting in central Alaska.

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

Changing patterns in water toxicity associated with current use pesticides in three California agriculture regions.

PubMed

Anderson, Brian S; Phillips, Bryn M; Voorhees, Jennifer P; Deng, Xin; Geraci, Jeff; Worcester, Karen; Tjeerdema, Ron S

2018-03-01

Regulation of agriculture irrigation water discharges in California, USA, is assessed and controlled by its 9 Regional Water Quality Control Boards under the jurisdiction of the California State Water Resources Control Board. Each Regional Water Board has developed programs to control pesticides in runoff as part of the waste discharge requirements implemented through each region's Irrigated Lands Regulatory Program. The present study assessed how pesticide use patterns differ in the Imperial (Imperial County) and the Salinas and Santa Maria (Monterey County) valleys, which host 3 of California's prime agriculture areas. Surface-water toxicity associated with current use pesticides was monitored at several sites in these areas in 2014 and 2015, and results were linked to changes in pesticide use patterns in these areas. Pesticide use patterns appeared to coincide with differences in the way agriculture programs were implemented by the 2 respective Regional Water Quality Control Boards, and these programs differed in the 2 Water Board Regions. Different pesticide use patterns affected the occurrence of pesticides in agriculture runoff, and this influenced toxicity test results. Greater detection frequency and higher concentrations of the organophosphate pesticide chlorpyrifos were detected in agriculture runoff in Imperial County compared to Monterey County, likely due to more rigorous monitoring requirements for growers using this pesticide in Monterey County. Monterey County agriculture runoff contained toxic concentrations of pyrethroid and neonicotinoid pesticides, which impacted amphipods (Hyalella azteca) and midge larvae (Chironomus dilutus) in toxicity tests. Study results illustrate how monitoring strategies need to evolve as regulatory actions affect change in pesticide use and demonstrate the importance of using toxicity test indicator species appropriate for the suite of contaminants in runoff in order to accurately assess environmental risk. Integr Environ Assess Manag 2018;14:270-281. © 2017 SETAC. © 2017 SETAC.

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

Using ultrahigh-resolution mass spectrometry and toxicity identification techniques to characterize the toxicity of oil sands process-affected water: The case for classical naphthenic acids.

PubMed

Hughes, Sarah A; Mahaffey, Ashley; Shore, Bryon; Baker, Josh; Kilgour, Bruce; Brown, Christine; Peru, Kerry M; Headley, John V; Bailey, Howard C

2017-11-01

Previous assessments of oil sands process-affected water (OSPW) toxicity were hampered by lack of high-resolution analytical analysis, use of nonstandard toxicity methods, and variability between OSPW samples. We integrated ultrahigh-resolution mass spectrometry with a toxicity identification evaluation (TIE) approach to quantitatively identify the primary cause of acute toxicity of OSPW to rainbow trout (Oncorhynchus mykiss). The initial characterization of OSPW toxicity indicated that toxicity was associated with nonpolar organic compounds, and toxicant(s) were further isolated within a range of discrete methanol fractions that were then subjected to Orbitrap mass spectrometry to evaluate the contribution of naphthenic acid fraction compounds to toxicity. The results showed that toxicity was attributable to classical naphthenic acids, with the potency of individual compounds increasing as a function of carbon number. Notably, the mass of classical naphthenic acids present in OSPW was dominated by carbon numbers ≤16; however, toxicity was largely a function of classical naphthenic acids with ≥17 carbons. Additional experiments found that acute toxicity of the organic fraction was similar when tested at conductivities of 400 and 1800 μmhos/cm and that rainbow trout fry were more sensitive to the organic fraction than larval fathead minnows (Pimephales promelas). Collectively, the results will aid in developing treatment goals and targets for removal of OSPW toxicity in water return scenarios both during operations and on mine closure. Environ Toxicol Chem 2017;36:3148-3157. © 2017 SETAC. © 2017 SETAC.

Health effects research in direct coal liquefaction. Studies of H-coal distillates: Phase I. PDU samples - the effects of hydrotreatment

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

Epler, J.L.; Fry, R.J.M.; Larimer, F.W.

1981-11-01

A multi-divisional effort aimed at the integrated assessment of the health and environmental effects of various coal conversion and shale oil technologies is being carried out. The feasibility of using health effects bioassays to predict the potential biohazard of various H-Coal derived test materials is examined in a coupled chemical and biological approach. The primary focus of the research is the use of preliminary chemical characterizations and preparation for bioassay, followed by testing in short-term assays in order to rapidly ascertain the potential biohazard. Mammalian toxicological assays parallel the testing. Raw and hydrotreated product liquids from process development units ofmore » H-Coal and the pilot plant solvent refined coal process were examined for acute toxicity monitored as population growth impairment of Tetrahymena exposed to aqueous extracts and for mutagenic activity monitored as revertants of Salmonella exposed to metabolically activated chemical class fractions. Medium to high severity hydrotreatment appears to be an effective means of reducing biological activity, presumably by reducing the aromaticity and heteroatom content. Five basic mammalian, acute toxicity tests have been conducted with selected H-coal samples and shale oil derivatives. The data show that H-Coal samples are moderately toxic whereas the toxicity of shale oil derived products is slight and comparable to samples obtained from naturally occurring petroleums. No overt skin or eye toxicity was found. The present data reveal that coal-derived distillates generated by the H-coal process are highly carcinogenic to mouse skin. An extreme form of neurotoxicity associated with dermal exposure to one of the lighter, minimally carcinogenic, materials was noted. (DMC)« less

76 FR 59142 - Guidance for Industry on Reproductive and Developmental Toxicities-Integrating Study Results To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

...--Integrating Study Results To Assess Concerns; Availability AGENCY: Food and Drug Administration, HHS. ACTION... industry entitled ``Reproductive and Developmental Toxicities--Integrating Study Results to Assess Concerns.'' This guidance describes an approach to estimating possible human developmental or reproductive risks...

Lung Toxicity of Condensed Aerosol from E-CIG Liquids: Influence of the Flavor and the In Vitro Model Used.

PubMed

Bengalli, Rossella; Ferri, Emanuele; Labra, Massimo; Mantecca, Paride

2017-10-20

The diffusion of e-cigarette (e-CIG) opens a great scientific and regulatory debate about its safety. The huge number of commercialized devices, e-liquids with almost infinite chemical formulations and the growing market demand for a rapid and efficient toxicity screen system that is able to test all of these references and related aerosols. A consensus on the best protocols for the e-CIG safety assessment is still far to be achieved, since the huge number of variables characterizing these products (e.g., flavoring type and concentration, nicotine concentration, type of the device, including the battery and the atomizer). This suggests that more experimental evidences are needed to support the regulatory frameworks. The present study aims to contribute in this field by testing the effects of condensed aerosols (CAs) from three main e-liquid categories (tobacco, mint, and cinnamon as food-related flavor), with (18 mg/mL) or without nicotine. Two in vitro models, represented by a monoculture of human epithelial alveolar cells and a three-dimensional (3D) co-culture of alveolar and lung microvascular endothelial cells were used. Cell viability, pro-inflammatory cytokines release and alveolar-blood barrier (ABB) integrity were investigated as inhalation toxicity endpoints. Results showed that nicotine itself had almost no influence on the modulation of the toxicity response, while flavor composition did have. The cell viability was significantly decreased in monoculture and ABB after exposure to the mints and cinnamon CAs. The barrier integrity was significantly affected in the ABB after exposure to cytotoxic CAs. With the exception of the significant IL-8 release in the monoculture after Cinnamon exposure, no increase of inflammatory cytokines (IL-8 and MCP-1) release was observed. These findings point out that multiple assays with different in vitro models are able to discriminate the acute inhalation toxicity of CAs from liquids with different flavors, providing the companies and regulatory bodies with useful tools for the preliminary screening of marketable products.

SEURAT: Safety Evaluation Ultimately Replacing Animal Testing--recommendations for future research in the field of predictive toxicology.

PubMed

Daston, George; Knight, Derek J; Schwarz, Michael; Gocht, Tilman; Thomas, Russell S; Mahony, Catherine; Whelan, Maurice

2015-01-01

The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained in SEURAT-1 and appreciating international advancement in both basic and regulatory science, we reflect here on how SEURAT should evolve and propose that further research and development should be directed along two complementary and interconnecting work streams. The first work stream would focus on developing new 'paradigm' approaches for regulatory science. The goal here is the identification of 'critical biological targets' relevant for toxicity and to test their suitability to be used as anchors for predicting toxicity. The second work stream would focus on integration and application of new approach methods for hazard (and risk) assessment within the current regulatory 'paradigm', aiming for acceptance of animal-free testing strategies by regulatory authorities (i.e. translating scientific achievements into regulation). Components for both work streams are discussed and may provide a structure for a future research programme in the field of predictive toxicology.

Deriving site-specific soil clean-up values for metals and metalloids: Rationale for including protection of soil microbial processes

PubMed Central

Kuperman, Roman G; Siciliano, Steven D; Römbke, Jörg; Oorts, Koen

2014-01-01

Although it is widely recognized that microorganisms are essential for sustaining soil fertility, structure, nutrient cycling, groundwater purification, and other soil functions, soil microbial toxicity data were excluded from the derivation of Ecological Soil Screening Levels (Eco-SSL) in the United States. Among the reasons for such exclusion were claims that microbial toxicity tests were too difficult to interpret because of the high variability of microbial responses, uncertainty regarding the relevance of the various endpoints, and functional redundancy. Since the release of the first draft of the Eco-SSL Guidance document by the US Environmental Protection Agency in 2003, soil microbial toxicity testing and its use in ecological risk assessments have substantially improved. A wide range of standardized and nonstandardized methods became available for testing chemical toxicity to microbial functions in soil. Regulatory frameworks in the European Union and Australia have successfully incorporated microbial toxicity data into the derivation of soil threshold concentrations for ecological risk assessments. This article provides the 3-part rationale for including soil microbial processes in the development of soil clean-up values (SCVs): 1) presenting a brief overview of relevant test methods for assessing microbial functions in soil, 2) examining data sets for Cu, Ni, Zn, and Mo that incorporated soil microbial toxicity data into regulatory frameworks, and 3) offering recommendations on how to integrate the best available science into the method development for deriving site-specific SCVs that account for bioavailability of metals and metalloids in soil. Although the primary focus of this article is on the development of the approach for deriving SCVs for metals and metalloids in the United States, the recommendations provided in this article may also be applicable in other jurisdictions that aim at developing ecological soil threshold values for protection of microbial processes in contaminated soils. PMID:24376192

Active biomonitoring in freshwater environments: early warning signals from biomarkers in assessing biological effects of diffuse sources of pollutants

NASA Astrophysics Data System (ADS)

Wepener, V.; van Vuren, J. H. J.; Chatiza, F. P.; Mbizi, Z.; Slabbert, L.; Masola, B.

Effluents are a main source of direct and continuous input of pollutants in aquatic ecosystems. Relating observed effects to specific pollutants or even classes of pollutants remains a very difficult task due to the usually unknown, complex and often highly variable composition of effluents. It is recognized that toxicants interfere with organism integrity at the biochemical level and give rise to effects at the individual level and is manifested in reduced ecologically relevant characteristics such as growth, reproduction and survival, and ultimately at the ecosystem level. By integrating multiple endpoints at different ecologically relevant levels of organization within one test organism, it should be possible to gain understanding in how different levels of organization within this organism respond to toxic exposure and how responses at these different levels are interrelated. This paper presents results from a field study in the Rietvlei Wetland system, Gauteng, South Africa using the freshwater mollusk ( Melanoides tuberculata) and freshwater fish ( Oreochromis mossambicus) as bioindicator organisms. Active biomonitoring (ABM) exposures were conducted where organisms were exposed for 28 days in an effluent dominated river during high flow conditions in April 2003. The river receives effluent from a wastewater treatment plant and an industrial complex, so that up to 75% of the total flow of the river is effluent-based. Effects of field exposure were determined using cellular biomarkers e.g. DNA damage, HSP 70, metallothionein, acetylcholine esterase, lactate dehydrogenase and ethoxyresorufin-o-deethylase activity. The results clearly indicate that although the traditional mortality-based whole effluent toxicity testing did not indicate any toxicity, the in situ exposed organisms were stressed. A multivariate statistical approach was particularly useful for integrating the biomarker responses and highlighting sites at which more detailed analysis of chemical contamination would be useful. Based on the individual biomarker results’ contributing towards the distinct groupings it is possible to conclude that Site 1 is subjected to organic pollutants, whereas Sites 2 and 3 undergo a combination of metallic and organic pollutant stress. However, it is essential that a rapid and sensitive biomarker that is representative of the responses of a suite of biomarkers be tested before ABM can be implemented as a routine biomonitoring practice in water resource management.

Use of high-throughput and in vivo data to support read ...

EPA Pesticide Factsheets

Disrupting normal function of mitochondria can culminate in a variety of organ-level toxicities. A number of mechanisms - such as uncoupling of oxidative phosphorylation and inhibition of the electron transport chain - have been implicated in mitochondrial toxicity. The presence of mitochondrial toxicity has led to a number of drugs being withdrawn from the market highlighting the need to identify potential mitochondrial toxicants within the environment. High-throughput screening (HTS) assays provide a means of rapidly gathering toxicity data for a large number of chemicals; however, information as to the associated in vivo effect is typically unknown. The Adverse Outcome Pathway (AOP) concept provides a valuable scaffold onto which mechanistic data from different levels of biological organisation can be arranged.Information pertaining to mitochondrial toxicity from the U.S. EPA’s ToxCast program were integrated with rodent in vivo data from U.S. EPA’s ToxRefDB to connect the high throughput ToxCast assay results with potential adverse outcome data. Previously developed structural alerts were utilized to profile the chemicals with both in vitro mitochondrial toxicity and in vivo rodent data. Structural similarity guided by the toxicity profile as measured in the ToxCast assay battery was then used to group those chemicals which either were not tested in a mitochondrial toxicity assay or were not considered a “hit” and read-across was performed. Subsequen

Low toxicity of HfO2, SiO2, Al2O3 and CeO2 nanoparticles to the yeast, Saccharomyces cerevisiae.

PubMed

García-Saucedo, Citlali; Field, James A; Otero-Gonzalez, Lila; Sierra-Álvarez, Reyes

2011-09-15

Increasing use of nanomaterials necessitates an improved understanding of their potential impact on environment health. This study evaluated the cytotoxicity of nanosized HfO(2), SiO(2), Al(2)O(3) and CeO(2) towards the eukaryotic model organism Saccharomyces cerevisiae, and characterized their state of dispersion in bioassay medium. Nanotoxicity was assessed by monitoring oxygen consumption in batch cultures and by analysis of cell membrane integrity. CeO(2), Al(2)O(3), and HfO(2) nanoparticles were highly unstable in yeast medium and formed micron-sized, settleable agglomerates. A non-toxic polyacrylate dispersant (Dispex A40) was used to improve nanoparticle stability and determine the impact of enhanced dispersion on toxicity. None of the NPs tested without dispersant inhibited O(2) uptake by yeast at concentrations as high as 1000 mg/L. Dispersant supplementation only enhanced the toxicity of CeO(2) (47% at 1000 mg/L). Dispersed SiO(2) and Al(2)O(3) (1000 mg/L) caused cell membrane damage, whereas dispersed HfO(2) and CeO(2) did not cause significant disruption of membrane integrity at the same concentration. These results suggest that the O(2) uptake inhibition observed with dispersed CeO(2) NPs was not due to reduced cell viability. This is the first study evaluating toxicity of nanoscale HfO(2), SiO(2), Al(2)O(3) and CeO(2) to S. cerevisiae. Overall the results obtained demonstrate that these nanomaterials display low or no toxicity to yeast. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Integrative assessment of coastal pollution: Development and evaluation of sediment quality criteria from chemical contamination and ecotoxicological data

NASA Astrophysics Data System (ADS)

Bellas, Juan; Nieto, Óscar; Beiras, Ricardo

2011-04-01

Elutriate embryo-larval bioassays with sea-urchins ( Paracentrotus lividus) were conducted concurrently with chemical analyses of sediments and biota as part of an integrative assessment of pollution in highly productive coastal regions. High metal contents and organic compounds in sediments and mussels were found in localised areas from the inner part of the estuaries indicating a clear anthropogenic influence. In particular, average maximum concentrations of 2803 mg Cu/kg dw, 776 mg Pb/kg dw, 2.5 mg Hg/kg dw and 5803 μg ∑ 7PAHs/kg dw were measured in sediments from the most polluted sites. Significant correlations were observed between sediment chemistry and toxicity bioassays. Moreover, the Mantel test revealed a significant correlation ( rM=0.80; p<0.01) between sediment pollutant concentrations and toxicity data profiles. In addition, sediment quality criteria were used to help in the ecological interpretation of sediment chemistry data and to identify pollutants of concern. The toxicity bioassays identified polluted sites and quantified the level of toxicity, providing a cost-effective tool to complement the routine chemical monitoring currently conducted in European coastal waters with ecologically relevant information. This is in line with the recent European legislation that advocates the use of biological tools with the ultimate aim of protecting marine resources from anthropogenic substances that will affect their sensitive early life stages.

Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells.

PubMed

Kim, In-Sun; Baek, Miri; Choi, Soo-Jin

2010-05-01

The increased applications of nanoparticles in a wide range of industrial fields raise the concern about their potential toxicity to human. The aim of this study was to assess and compare the toxicity of four different oxide nanoparticles (Al2O3, CeO2, TiO2 and ZnO) to human lung epithelial cells, A549 carcinoma cells and L-132 normal cells, in vitro. We focused on the toxicological effects of the present nanoparticles on cell proliferation, cell viability, membrane integrity and oxidative stress. The long-term cytotoxicity of nanoparticles was also evaluated by employing the clonogenic assay. Among four nanoparticles tested, ZnO exhibited the highest cytotoxicity in terms of cell proliferation, cell viability, membrane integrity and colony formation in both cell lines. Al2O3, CeO2 and TiO2 showed little adverse effects on cell proliferation and cell viability. However, TiO2 induced oxidative stress in a concentration- and time-dependent manner. CeO2 caused membrane damage and inhibited colony formation in long-term, but with different degree depending on cell lines. Al2O3 seems to be less toxic than the other nanoparticles even after long time exposure. These results highlight the need for caution during manufacturing process of nanomaterials as well as further investigation on the toxicity mechanism.

Integrated in silico strategy for PBT assessment and prioritization under REACH.

PubMed

Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Cappelli, Claudia I; Petoumenou, Maria I; Albanese, Federica; Roncaglioni, Alessandra; Brandt, Marc; Benfenati, Emilio

2016-11-01

Chemicals may persist in the environment, bioaccumulate and be toxic for humans and wildlife, posing great concern. These three properties, persistence (P), bioaccumulation (B), and toxicity (T) are the key targets of the PBT-hazard assessment. The European regulation for the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) requires assessment of PBT-properties for all chemicals that are produced or imported in Europe in amounts exceeding 10 tonnes per year, checking whether the criteria set out in REACH Annex XIII are met, so the substance should therefore be considered to have properties of very high concern. Considering how many substances can fall under the REACH regulation, there is a pressing need for new strategies to identify and screen large numbers fast and inexpensively. An efficient non-testing screening approach to identify PBT candidates is necessary, as a valuable alternative to money- and time-consuming laboratory tests and a good start for prioritization since few tools exist (e.g. the PBT profiler developed by US EPA). The aim of this work was to offer a conceptual scheme for identifying and prioritizing chemicals for further assessment and if appropriate further testing, based on their PBT-potential, using a non-testing screening approach. We integrated in silico models (using existing and developing new ones) in a final algorithm for screening and ranking PBT-potential, which uses experimental and predicted values as well as associated uncertainties. The Multi-Criteria Decision-Making (MCDM) theory was used to integrate the different values. Then we compiled a new set of data containing known PBT and non-PBT substances, in order to check how well our approach clearly differentiated compounds labeled as PBT from those labeled as non-PBT. This indicated that the integrated model distinguished between PBT from non-PBT compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

EPA Pesticide Factsheets

Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

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

Post-exposure temperature influence on the toxicity of conventional and new chemistry insecticides to green lacewing Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae)

PubMed Central

Mansoor, Muhammad Mudassir; Afzal, Muhammad; Raza, Abu Bakar M.; Akram, Zeeshan; Waqar, Adil; Afzal, Muhammad Babar Shahzad

2014-01-01

Chrysoperla carnea (Stephens) is an important biological control agent currently being used in many integrated pest management (IPM) programs to control insect pests. The effect of post-treatment temperature on insecticide toxicity of a spinosyn (spinosad), pyrethroid (lambda cyhalothrin), organophosphate (chlorpyrifos) and new chemistry (acetamiprid) to C. carnea larvae was investigated under laboratory conditions. Temperature coefficients of each insecticide tested were evaluated. From 20 to 40 °C, toxicity of lambda cyhalothrin and spinosad decreased by 2.15- and 1.87-fold while toxicity of acetamiprid and chlorpyrifos increased by 2.00 and 1.79-fold, respectively. The study demonstrates that pesticide effectiveness may vary according to environmental conditions. In cropping systems where multiple insecticide products are used, attention should be given to temperature variation as a key factor in making pest management strategies safer for biological control agents. Insecticides with a negative temperature coefficient may play a constructive role to conserve C. carnea populations. PMID:25972753

Post-exposure temperature influence on the toxicity of conventional and new chemistry insecticides to green lacewing Chrysoperla carnea (Stephens) (Neuroptera: Chrysopidae).

PubMed

Mansoor, Muhammad Mudassir; Afzal, Muhammad; Raza, Abu Bakar M; Akram, Zeeshan; Waqar, Adil; Afzal, Muhammad Babar Shahzad

2015-05-01

Chrysoperla carnea (Stephens) is an important biological control agent currently being used in many integrated pest management (IPM) programs to control insect pests. The effect of post-treatment temperature on insecticide toxicity of a spinosyn (spinosad), pyrethroid (lambda cyhalothrin), organophosphate (chlorpyrifos) and new chemistry (acetamiprid) to C. carnea larvae was investigated under laboratory conditions. Temperature coefficients of each insecticide tested were evaluated. From 20 to 40 °C, toxicity of lambda cyhalothrin and spinosad decreased by 2.15- and 1.87-fold while toxicity of acetamiprid and chlorpyrifos increased by 2.00 and 1.79-fold, respectively. The study demonstrates that pesticide effectiveness may vary according to environmental conditions. In cropping systems where multiple insecticide products are used, attention should be given to temperature variation as a key factor in making pest management strategies safer for biological control agents. Insecticides with a negative temperature coefficient may play a constructive role to conserve C. carnea populations.

Phase I/II adaptive design for drug combination oncology trials

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2014-01-01

Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329

Effect of new and old pesticides on Orius armatus (Gross) - an Australian predator of western flower thrips, Frankliniella occidentalis (Pergande).

PubMed

Broughton, Sonya; Harrison, Jessica; Rahman, Touhidur

2014-03-01

Orius armatus (Gross) is an important predator of western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) in Australian glasshouse grown sweet pepper. The failure of O. armatus to establish in some glasshouses has been attributed to the use of newer, more non-selective pesticides, some of which are regarded to be compatible with integrated pest management. The residual toxicity (via direct and indirect contact) of several older and newer chemistry pesticides were evaluated. In addition, the effect of several systemic insecticides through insecticide-treated food-chain uptake was tested. Older chemistry pesticides (methamidophos, dimethoate) were toxic to Orius armatus, except pirimicarb which was non-toxic. Newer chemistry pesticides differed in their suitability. Abamectin was toxic to adults and nymphs. Chlorantraniliprole, imidacloprid and spirotetramat were non-toxic. Spinosad and spinetoram were moderately toxic to O. armatus. Spinosad also reduced fecundity by 20% compared to the untreated control. Pymetrozine was non-toxic, but females exposed to treated beans produced 30% fewer eggs and 20% fewer nymphs hatched compared to the untreated control. The selective pesticides do not necessarily facilitate the conservation of beneficials, and further assessment of the various developmental stages and other sub-lethal effects of chlorantraniliprole, imidacloprid, pymetrozine, spinetoram, and spirotetramat is recommended. © 2013 Society of Chemical Industry.

Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs.

PubMed

Beker van Woudenberg, Anna; Snel, Cor; Rijkmans, Eke; de Groot, Didima; Bouma, Marga; Hermsen, Sanne; Piersma, Aldert; Menke, Aswin; Wolterbeek, André

2014-11-01

To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60μM. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180μM. For ETH, all endpoints showed similar sensitivity (6.6mM), whereas MA was the most sensitive parameter for LEV (40mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET. Copyright © 2014 Elsevier Inc. All rights reserved.

Swimming speed alteration of Artemia sp. and Brachionus plicatilis as a sub-lethal behavioural end-point for ecotoxicological surveys.

PubMed

Garaventa, Francesca; Gambardella, Chiara; Di Fino, Alessio; Pittore, Massimiliano; Faimali, Marco

2010-03-01

In this study, we investigated the possibility to improve a new behavioural bioassay (Swimming Speed Alteration test-SSA test) using larvae of marine cyst-forming organisms: e.g. the brine shrimp Artemia sp. and the rotifer Brachionus plicatilis. Swimming speed was investigated as a behavioural end-point for application in ecotoxicology studies. A first experiment to analyse the linear swimming speed of the two organisms was performed to verify the applicability of the video-camera tracking system, here referred to as Swimming Behavioural Recorder (SBR). A second experiment was performed, exposing organisms to different toxic compounds (zinc pyrithione, Macrotrol MT-200, and Eserine). Swimming speed alteration was analyzed together with mortality. The results of the first experiment indicate that SBR is a suitable tool to detect linear swimming speed of the two organisms, since the values have been obtained in accordance with other studies using the same organisms (3.05 mm s(-1) for Artemia sp. and 0.62 mm s(-1) for B. plicatilis). Toxicity test results clearly indicate that swimming speed of Artemia sp. and B. plicatilis is a valid behavioural end-point to detect stress at sub-lethal toxic substance concentrations. Indeed, alterations in swimming speed have been detected at toxic compound concentrations as low as less then 0.1-5% of their LC(50) values. In conclusion, the SSA test with B. plicatilis and Artemia sp. can be a good behavioural integrated output for application in marine ecotoxicology and environmental monitoring programs.

Accurate prediction of acute fish toxicity of fragrance chemicals with the RTgill-W1 cell assay.

PubMed

Natsch, Andreas; Laue, Heike; Haupt, Tina; von Niederhäusern, Valentin; Sanders, Gordon

2018-03-01

Testing for acute fish toxicity is an integral part of the environmental safety assessment of chemicals. A true replacement of primary fish tissue was recently proposed using cell viability in a fish gill cell line (RTgill-W1) as a means of predicting acute toxicity, showing good predictivity on 35 chemicals. To promote regulatory acceptance, the predictivity and applicability domain of novel tests need to be carefully evaluated on chemicals with existing high-quality in vivo data. We applied the RTgill-W1 cell assay to 38 fragrance chemicals with a wide range of both physicochemical properties and median lethal concentration (LC50) values and representing a diverse range of chemistries. A strong correlation (R 2  = 0.90-0.94) between the logarithmic in vivo LC50 values, based on fish mortality, and the logarithmic in vitro median effect concentration (EC50) values based on cell viability was observed. A leave-one-out analysis illustrates a median under-/overprediction from in vitro EC50 values to in vivo LC50 values by a factor of 1.5. This assay offers a simple, accurate, and reliable alternative to in vivo acute fish toxicity testing for chemicals, presumably acting mainly by a narcotic mode of action. Furthermore, the present study provides validation of the predictivity of the RTgill-W1 assay on a completely independent set of chemicals that had not been previously tested and indicates that fragrance chemicals are clearly within the applicability domain. Environ Toxicol Chem 2018;37:931-941. © 2017 SETAC. © 2017 SETAC.

Toxicity of electronic waste leachates to Daphnia magna: screening and toxicity identification evaluation of different products, components, and materials.

PubMed

Lithner, Delilah; Halling, Maja; Dave, Göran

2012-05-01

Electronic waste has become one of the fastest growing waste problems in the world. It contains both toxic metals and toxic organics. The aim of this study was to (1) investigate to what extent toxicants can leach from different electronic products, components, and materials into water and (2) identify which group of toxicants (metals or hydrophobic organics) that is causing toxicity. Components from five discarded electronic products (cell phone, computer, phone modem, keyboard, and computer mouse) were leached in deionised water for 3 days at 23°C in concentrations of 25 g/l for metal components, 50 g/l for mixed-material components, and 100 g/l for plastic components. The water phase was tested for acute toxicity to Daphnia magna. Eighteen of 68 leachates showed toxicity (with immobility of D. magna ≥ 50% after 48 h) and came from metal or mixed-material components. The 8 most toxic leachates, with 48 h EC(50)s ranging from 0.4 to 20 g/l, came from 2 circuit sheets (key board), integrated drive electronics (IDE) cable clips (computer), metal studs (computer), a circuit board (computer mouse), a cord (phone modem), mixed parts (cell phone), and a circuit board (key board). All 5 electronic products were represented among them. Toxicity identification evaluations (with C18 and CM resins filtrations and ethylenediaminetetraacetic acid addition) indicated that metals caused the toxicity in the majority of the most toxic leachates. Overall, this study has shown that electronic waste can leach toxic compounds also during short-term leaching with pure water.

Toxicity of waters from the St. Lawrence River at Massena Area-of-Concern to the plankton species Selenastrum capricornutum and Ceriodaphnia dubia

USGS Publications Warehouse

Baldigo, Barry P.; Duffy, Brian T.; Nally, Christopher J.; David, Anthony M.

2012-01-01

In 1972, the US and Canada committed to restore the chemical, physical, and biological integrity of the Great Lakes Ecosystem under the first Great Lakes Water Quality Agreement. During subsequent amendments, part of the St. Lawrence River at Massena NY, and segments of three tributaries, were designated as one Area of Concern (AOC) due to various beneficial use impairments (BUIs). Plankton beneficial use was designated impaired within this AOC because phytoplankton and zooplankton population data were unavailable or needed “further assessment”. Contaminated sediments from industrial waste disposal have been largely remediated, thus, the plankton BUI may currently be obsolete. The St. Lawrence River at Massena AOC remedial action plan established two criteria which may be used to assess the plankton BUI; the second states that, “in the absence of community structure data, plankton bioassays confirm no toxicity impact in ambient waters”. This study was implemented during 2011 to determine whether this criterion was achieved. Acute toxicity and chronic toxicity of local waters were quantified seasonally using standardized bioassays with green alga Selenastrum capricornutum and water flea Ceriodaphnia dubia to test the hypothesis that waters from sites within the AOC were no more toxic than were waters from adjacent reference sites. The results of univariate and multivariate analyses confirm that ambient waters from most AOC sites (and seasons) were not toxic to both species. Assuming both test species represent natural plankton assemblages, the quality of surface waters throughout most of this AOC should not seriously impair the health of resident plankton communities.

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.

"Watching the Detectives" report of the general assembly of the EU project DETECTIVE Brussels, 24-25 November 2015.

PubMed

Fernando, Ruani N; Chaudhari, Umesh; Escher, Sylvia E; Hengstler, Jan G; Hescheler, Jürgen; Jennings, Paul; Keun, Hector C; Kleinjans, Jos C S; Kolde, Raivo; Kollipara, Laxmikanth; Kopp-Schneider, Annette; Limonciel, Alice; Nemade, Harshal; Nguemo, Filomain; Peterson, Hedi; Prieto, Pilar; Rodrigues, Robim M; Sachinidis, Agapios; Schäfer, Christoph; Sickmann, Albert; Spitkovsky, Dimitry; Stöber, Regina; van Breda, Simone G J; van de Water, Bob; Vivier, Manon; Zahedi, René P; Vinken, Mathieu; Rogiers, Vera

2016-06-01

SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro- and in silico-based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and "-omics" technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitute a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich "-omics" databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project.

“Watching the Detectives” Report of the general assembly of the EU project DETECTIVE Brussels, 24-25 November, 2015

PubMed Central

Fernando, Ruani N.; Chaudhari, Umesh; Escher, Sylvia E.; Hengstler, Jan G.; Hescheler, Jürgen; Jennings, Paul; Keun, Hector C.; Kleinjans, Jos C. S.; Kolde, Raivo; Kollipara, Laxmikanth; Kopp-Schneider, Annette; Limonciel, Alice; Nemade, Harshal; Nguemo, Filomain; Peterson, Hedi; Prieto, Pilar; Rodrigues, Robim M.; Sachinidis, Agapios; Schäfer, Christoph; Sickmann, Albert; Spitkovsky, Dimitry; Stöber, Regina; van Breda, Simone G.J.; van de Water, Bob; Vivier, Manon; Zahedi, René P.

2017-01-01

SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro and in silico based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and “-omics” technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitutes a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich “-omics” databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project. PMID:27129694

Integrated microfluidic technology for sub-lethal and behavioral marine ecotoxicity biotests

NASA Astrophysics Data System (ADS)

Huang, Yushi; Reyes Aldasoro, Constantino Carlos; Persoone, Guido; Wlodkowic, Donald

2015-06-01

Changes in behavioral traits exhibited by small aquatic invertebrates are increasingly postulated as ethically acceptable and more sensitive endpoints for detection of water-born ecotoxicity than conventional mortality assays. Despite importance of such behavioral biotests, their implementation is profoundly limited by the lack of appropriate biocompatible automation, integrated optoelectronic sensors, and the associated electronics and analysis algorithms. This work outlines development of a proof-of-concept miniaturized Lab-on-a-Chip (LOC) platform for rapid water toxicity tests based on changes in swimming patterns exhibited by Artemia franciscana (Artoxkit M™) nauplii. In contrast to conventionally performed end-point analysis based on counting numbers of dead/immobile specimens we performed a time-resolved video data analysis to dynamically assess impact of a reference toxicant on swimming pattern of A. franciscana. Our system design combined: (i) innovative microfluidic device keeping free swimming Artemia sp. nauplii under continuous microperfusion as a mean of toxin delivery; (ii) mechatronic interface for user-friendly fluidic actuation of the chip; and (iii) miniaturized video acquisition for movement analysis of test specimens. The system was capable of performing fully programmable time-lapse and video-microscopy of multiple samples for rapid ecotoxicity analysis. It enabled development of a user-friendly and inexpensive test protocol to dynamically detect sub-lethal behavioral end-points such as changes in speed of movement or distance traveled by each animal.

Control of zoonotic cutaneous leishmaniasis vector, Phlebotomus papatasi, using attractive toxic sugar baits (ATSB).

PubMed

Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Rassi, Yavar; Karami Jooshin, Moharram; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad

2017-01-01

Attractive Toxic Sugar Baits (ATSB) is a new vector control method that meets Integrated Vector Management (IVM) goals. In an experimental design, this study aimed to determine effects of ATSB on control of Phlebotomus papatasi, as a main vector of Zoonotic Cutaneous Leishmaniasis (ZCL), in Qom Province, center of Iran. In a cross-sectional design, boric acid was mixed with brown sugar solution and tested as toxic baits for P. papatasi. Two methods were utilized to use the baits: (a) spraying ATSB on vegetation, bushes, and shrubs; and (b) setting ATSB-treated barrier fences in front of colonies at 500 m distance from the houses in outskirts of villages. In order to examine the residual efficacy rate of ATSB-treated barrier fences, the bioassay test was used. Density of P. papatasi sandflies was measured using sticky and light traps biweekly. For data analysis, Mann-Whitney U Test and Kruskal-Wallis were used. Results ATSB-treated barrier fences led to 3 times reduction in P. papatasi population. Besides that, ATSB spraying on plants led to more than 5 times reduction in P. papatasi population. Comparing the incidence of leishmaniasis in treated villages before and after the study showed that the incidence was statistically reduced. Therefore, ATSB is an effective method to control vectors and prevent leishmaniasis.

Monitoring and Management of Toxicities of Novel B Cell Signaling Agents.

PubMed

Rhodes, Joanna; Mato, Anthony; Sharman, Jeff P

2018-04-11

B cell signaling agents, including ibrutinib, idelalisib, and the BCL-2 inhibitor venetoclax have become an integral part of therapy for patients with non-Hodgkin's lymphomas. The toxicity profiles of these medications is distinct from chemoimmunotherapy. Here, we will review the mechanism of action of these drugs, their efficacy, and toxicity management. Ibrutinib use is associated with increased risk of atrial fibrillation and bleeding which can be managed using dose interruptions and modifications. Patients on idelalisib require close clinical and frequent laboratory monitoring, particularly of liver function tests to ensure there are no serious adverse events. Monitoring for infections is important in patients on both idelalisib and ibrutinib. Venetoclax requires close clinical and laboratory monitoring to prevent significant tumor lysis. Targeted B cell receptor therapies each have unique side effect profiles which require careful clinical monitoring. As we continue to use these therapies, optimal management strategies will continue to be elucidated.

Integrated testing strategies for toxicity employing new and existing technologies.

PubMed

Combes, Robert D; Balls, Michael

2011-07-01

We have developed individual, integrated testing strategies (ITS) for predicting the toxicity of general chemicals, cosmetics, pharmaceuticals, inhaled chemicals, and nanoparticles. These ITS are based on published schemes developed previously for the risk assessment of chemicals to fulfil the requirements of REACH, which have been updated to take account of the latest developments in advanced in chemico modelling and in vitro technologies. In addition, we propose an ITS for neurotoxicity, based on the same principles, for incorporation in the other ITS. The technologies are deployed in a step-wise manner, as a basis for decision-tree approaches, incorporating weight-of-evidence stages. This means that testing can be stopped at the point where a risk assessment and/or classification can be performed, with labelling in accordance with the requirements of the regulatory authority concerned, rather than following a checklist approach to hazard identification. In addition, the strategies are intelligent, in that they are based on the fundamental premise that there is no hazard in the absence of exposure - which is why pharmacokinetic modelling plays a key role in each ITS. The new technologies include the use of complex, three-dimensional human cell tissue culture systems with in vivo-like structural, physiological and biochemical features, as well as dosing conditions. In this way, problems of inter-species extrapolation and in vitro/in vivo extrapolation are minimised. This is reflected in the ITS placing more emphasis on the use of volunteers at the whole organism testing stage, rather than on existing animal testing, which is the current situation. 2011 FRAME.

Integration of genomic endpoints into toxicity identification evaluations

EPA Science Inventory

Toxicity identification and evaluations (TIEs) use physical/chemical manipulation of a sample to isolate or change the potency of different groups of toxicants potentially present in a sample. Organisms are then exposed to these fractions to determine if their toxicity has change...

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

EPA Science Inventory

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

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

Lung Toxicity of Condensed Aerosol from E-CIG Liquids: Influence of the Flavor and the In Vitro Model Used

PubMed Central

Bengalli, Rossella; Ferri, Emanuele; Labra, Massimo; Mantecca, Paride

2017-01-01

The diffusion of e-cigarette (e-CIG) opens a great scientific and regulatory debate about its safety. The huge number of commercialized devices, e-liquids with almost infinite chemical formulations and the growing market demand for a rapid and efficient toxicity screen system that is able to test all of these references and related aerosols. A consensus on the best protocols for the e-CIG safety assessment is still far to be achieved, since the huge number of variables characterizing these products (e.g., flavoring type and concentration, nicotine concentration, type of the device, including the battery and the atomizer). This suggests that more experimental evidences are needed to support the regulatory frameworks. The present study aims to contribute in this field by testing the effects of condensed aerosols (CAs) from three main e-liquid categories (tobacco, mint, and cinnamon as food-related flavor), with (18 mg/mL) or without nicotine. Two in vitro models, represented by a monoculture of human epithelial alveolar cells and a three-dimensional (3D) co-culture of alveolar and lung microvascular endothelial cells were used. Cell viability, pro-inflammatory cytokines release and alveolar-blood barrier (ABB) integrity were investigated as inhalation toxicity endpoints. Results showed that nicotine itself had almost no influence on the modulation of the toxicity response, while flavor composition did have. The cell viability was significantly decreased in monoculture and ABB after exposure to the mints and cinnamon CAs. The barrier integrity was significantly affected in the ABB after exposure to cytotoxic CAs. With the exception of the significant IL-8 release in the monoculture after Cinnamon exposure, no increase of inflammatory cytokines (IL-8 and MCP-1) release was observed. These findings point out that multiple assays with different in vitro models are able to discriminate the acute inhalation toxicity of CAs from liquids with different flavors, providing the companies and regulatory bodies with useful tools for the preliminary screening of marketable products. PMID:29053606

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

EPA Science Inventory

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

HUMAN EXPOSURE MEASUREMENTS OF AIR TOXICS

EPA Science Inventory

EPA's air toxics program is moving toward a risk-based focus. The framework for such a focus was laid out in the National Air Toxics Program: Integrated Urban Strategy which included the requirement for EPA to conduct a National-Scale Air Toxics Assessment (NATA) of human expos...

Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010.

PubMed

Adler, Sarah; Basketter, David; Creton, Stuart; Pelkonen, Olavi; van Benthem, Jan; Zuang, Valérie; Andersen, Klaus Ejner; Angers-Loustau, Alexandre; Aptula, Aynur; Bal-Price, Anna; Benfenati, Emilio; Bernauer, Ulrike; Bessems, Jos; Bois, Frederic Y; Boobis, Alan; Brandon, Esther; Bremer, Susanne; Broschard, Thomas; Casati, Silvia; Coecke, Sandra; Corvi, Raffaella; Cronin, Mark; Daston, George; Dekant, Wolfgang; Felter, Susan; Grignard, Elise; Gundert-Remy, Ursula; Heinonen, Tuula; Kimber, Ian; Kleinjans, Jos; Komulainen, Hannu; Kreiling, Reinhard; Kreysa, Joachim; Leite, Sofia Batista; Loizou, George; Maxwell, Gavin; Mazzatorta, Paolo; Munn, Sharon; Pfuhler, Stefan; Phrakonkham, Pascal; Piersma, Aldert; Poth, Albrecht; Prieto, Pilar; Repetto, Guillermo; Rogiers, Vera; Schoeters, Greet; Schwarz, Michael; Serafimova, Rositsa; Tähti, Hanna; Testai, Emanuela; van Delft, Joost; van Loveren, Henk; Vinken, Mathieu; Worth, Andrew; Zaldivar, José-Manuel

2011-05-01

The 7th amendment to the EU Cosmetics Directive prohibits to put animal-tested cosmetics on the market in Europe after 2013. In that context, the European Commission invited stakeholder bodies (industry, non-governmental organisations, EU Member States, and the Commission's Scientific Committee on Consumer Safety) to identify scientific experts in five toxicological areas, i.e. toxicokinetics, repeated dose toxicity, carcinogenicity, skin sensitisation, and reproductive toxicity for which the Directive foresees that the 2013 deadline could be further extended in case alternative and validated methods would not be available in time. The selected experts were asked to analyse the status and prospects of alternative methods and to provide a scientifically sound estimate of the time necessary to achieve full replacement of animal testing. In summary, the experts confirmed that it will take at least another 7-9 years for the replacement of the current in vivo animal tests used for the safety assessment of cosmetic ingredients for skin sensitisation. However, the experts were also of the opinion that alternative methods may be able to give hazard information, i.e. to differentiate between sensitisers and non-sensitisers, ahead of 2017. This would, however, not provide the complete picture of what is a safe exposure because the relative potency of a sensitiser would not be known. For toxicokinetics, the timeframe was 5-7 years to develop the models still lacking to predict lung absorption and renal/biliary excretion, and even longer to integrate the methods to fully replace the animal toxicokinetic models. For the systemic toxicological endpoints of repeated dose toxicity, carcinogenicity and reproductive toxicity, the time horizon for full replacement could not be estimated.

Green toxicology.

PubMed

Maertens, Alexandra; Anastas, Nicholas; Spencer, Pamela J; Stephens, Martin; Goldberg, Alan; Hartung, Thomas

2014-01-01

Historically, early identification and characterization of adverse effects of industrial chemicals was difficult because conventional toxicological test methods did not meet R&D needs for rapid, relatively inexpensive methods amenable to small amounts of test material. The pharmaceutical industry now front-loads toxicity testing, using in silico, in vitro, and less demanding animal tests at earlier stages of product development to identify and anticipate undesirable toxicological effects and optimize product development. The Green Chemistry movement embraces similar ideas for development of less toxic products, safer processes, and less waste and exposure. Further, the concept of benign design suggests ways to consider possible toxicities before the actual synthesis and to apply some structure/activity rules (SAR) and in silico methods. This requires not only scientific development but also a change in corporate culture in which synthetic chemists work with toxicologists. An emerging discipline called Green Toxicology (Anastas, 2012) provides a framework for integrating the principles of toxicology into the enterprise of designing safer chemicals, thereby minimizing potential toxicity as early in production as possible. Green Toxicology`s novel utility lies in driving innovation by moving safety considerations to the earliest stage in a chemical`s lifecycle, i.e., to molecular design. In principle, this field is no different than other subdisciplines of toxicology that endeavor to focus on a specific area - for example, clinical, environmental or forensic toxicology. We use the same principles and tools to evaluate an existing substance or to design a new one. The unique emphasis is in using 21st century toxicology tools as a preventative strategy to "design out" undesired human health and environmental effects, thereby increasing the likelihood of launching a successful, sustainable product. Starting with the formation of a steering group and a series of workshops, the Green Toxicology concept is currently spreading internationally and is being refined via an iterative process.

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

PubMed Central

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

2017-01-01

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

Integrated assessment of contaminated sediments in the lower Fox River and Green Bay, Wisconsin

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

Ankley, G.T.; Lodge, K.; Call, D.J.

Samples of sediment and biota were collected from sites in the lower Fox River and southern Green Bay to determine existing or potential impacts of sediment-associated contaminants on different ecosystem components of this Great Lakes area of concern. Evaluation of benthos revealed a relatively depauperate community, particularly at the lower Fox River sites. Sediment pore water and bulk sediments from several lower Fox River sites were toxic to a number of test species including Pimephales promelas, Ceriodaphnia dubia, Hexagenia limbata, Selenastrum capricornutum, and Photobacterium phosphorum. An important component of the observed toxicity appeared to be due to ammonia. Evaluation ofmore » three bullhead (Ictalurus) species from the lower Fox River revealed an absence of preneoplastic or neoplastic liver lesions, and the Salmonella typhimurium bioassay indicated relatively little mutagenicity in sediment extracts. Apparent adverse reproductive effects were noted in two species of birds nesting along the lower Fox River and on a confined disposal facility for sediments near the mouth of the river, and there were measurable concentrations of potentially toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), and planar polychlorinated biphenyls (PCBs) both in the birds and in sediments from several of the study sites. Based on toxic equivalency factors and the results of an in vitro bioassay with H4IIE rat hepatoma cells, it appeared that the majority of potential toxicity of the PCB/PCDF/PCDD mixture in biota from the lower Fox River/Green Bay system was due to the planar PCBs. The results of these studies are discussed in terms of an integrated assessment focused on providing data for remedial action planning.« less

Approaches for describing and communicating overall uncertainty in toxicity characterizations: U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) as a case study.

PubMed

Beck, Nancy B; Becker, Richard A; Erraguntla, Neeraja; Farland, William H; Grant, Roberta L; Gray, George; Kirman, Christopher; LaKind, Judy S; Jeffrey Lewis, R; Nance, Patricia; Pottenger, Lynn H; Santos, Susan L; Shirley, Stephanie; Simon, Ted; Dourson, Michael L

2016-01-01

Single point estimates of human health hazard/toxicity values such as a reference dose (RfD) are generally used in chemical hazard and risk assessment programs for assessing potential risks associated with site- or use-specific exposures. The resulting point estimates are often used by risk managers for regulatory decision-making, including standard setting, determination of emission controls, and mitigation of exposures to chemical substances. Risk managers, as well as stakeholders (interested and affected parties), often have limited information regarding assumptions and uncertainty factors in numerical estimates of both hazards and risks. Further, the use of different approaches for addressing uncertainty, which vary in transparency, can lead to a lack of confidence in the scientific underpinning of regulatory decision-making. The overarching goal of this paper, which was developed from an invited participant workshop, is to offer five approaches for presenting toxicity values in a transparent manner in order to improve the understanding, consideration, and informed use of uncertainty by risk assessors, risk managers, and stakeholders. The five approaches for improving the presentation and communication of uncertainty are described using U.S. Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) as a case study. These approaches will ensure transparency in the documentation, development, and use of toxicity values at EPA, the Agency for Toxic Substances and Disease Registry (ATSDR), and other similar assessment programs in the public and private sector. Further empirical testing will help to inform the approaches that will work best for specific audiences and situations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Importance of supply integrity for in vitro fertilization and embryo culture.

PubMed

Morbeck, Dean E

2012-06-01

The quality of in vitro culture conditions is a key component of a successful clinical embryology laboratory. Many, but not all, supplies used in the embryology laboratory are screened by the supplier with a bioassay. Embryology laboratories use a variety of approaches to verify the quality of mineral oil, protein, and disposables before clinical use; however, a best practice has not been determined. Some laboratories test every supply, even those already screened by the supplier, whereas other laboratories perform as little testing as possible. Despite screening by the supplier, recent reports of embryo toxicity, specifically with mineral oil, highlight that the integrity of the supply system has gaps. This review describes current bioassay quality control testing and discusses how it applies to screening of products with documented lot-to-lot variation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

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

Comparative Cytotoxicity Study of Silver Nanoparticles (AgNPs) in a Variety of Rainbow Trout Cell Lines (RTL-W1, RTH-149, RTG-2) and Primary Hepatocytes

PubMed Central

Connolly, Mona; Fernandez-Cruz, Maria-Luisa; Quesada-Garcia, Alba; Alte, Luis; Segner, Helmut; Navas, Jose M.

2015-01-01

Among all classes of nanomaterials, silver nanoparticles (AgNPs) have potentially an important ecotoxicological impact, especially in freshwater environments. Fish are particularly susceptible to the toxic effects of silver ions and, with knowledge gaps regarding the contribution of dissolution and unique particle effects to AgNP toxicity, they represent a group of vulnerable organisms. Using cell lines (RTL-W1, RTH-149, RTG-2) and primary hepatocytes of rainbow trout (Oncorhynchus mykiss) as in vitro test systems, we assessed the cytotoxicity of the representative AgNP, NM-300K, and AgNO3 as an Ag+ ion source. Lack of AgNP interference with the cytotoxicity assays (AlamarBlue, CFDA-AM, NRU assay) and their simultaneous application point to the compatibility and usefulness of such a battery of assays. The RTH-149 and RTL-W1 liver cell lines exhibited similar sensitivity as primary hepatocytes towards AgNP toxicity. Leibovitz’s L-15 culture medium composition (high amino acid content) had an important influence on the behaviour and toxicity of AgNPs towards the RTL-W1 cell line. The obtained results demonstrate that, with careful consideration, such an in vitro approach can provide valuable toxicological data to be used in an integrated testing strategy for NM-300K risk assessment. PMID:26006119

IN SILICO METHODOLOGIES FOR PREDICTIVE EVALUATION OF TOXICITY BASED ON INTEGRATION OF DATABASES

EPA Science Inventory

In silico methodologies for predictive evaluation of toxicity based on integration of databases

Chihae Yang1 and Ann M. Richard2, 1LeadScope, Inc. 1245 Kinnear Rd. Columbus, OH. 43212 2National Health & Environmental Effects Research Lab, U.S. EPA, Research Triangle Park, ...

Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

PubMed

Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

2014-12-01

Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

Treatment of copper industry waste and production of sintered glass-ceramic.

PubMed

Coruh, Semra; Ergun, Osman Nuri; Cheng, Ta-Wui

2006-06-01

Copper waste is iron-rich hazardous waste containing heavy metals such as Cu, Zn, Co, Pb. The results of leaching tests show that the concentration of these elements exceeds the Turkish and EPA regulatory limits. Consequently, this waste cannot be disposed of in its present form and therefore requires treatment to stabilize it or make it inert prior to disposal. Vitrification was selected as the technology for the treatment of the toxic waste under investigation. During the vitrification process significant amounts of the toxic organic and inorganic chemical compounds could be destroyed, and at the same time, the metal species are immobilized as they become an integral part of the glass matrix. The copper flotation waste samples used in this research were obtained from the Black Sea Copper Works of Samsun, Turkey. The samples were vitrified after being mixed with other inorganic waste and materials. The copper flotation waste and their glass-ceramic products were characterized by X-ray analysis (XRD), scanning electron microscopy and by the toxicity characteristic leaching procedure test. The products showed very good chemical durability. The glass-ceramics fabricated at 850 degrees C/2 h have a large application potential especially as construction and building materials.

Computational toxicology using the OpenTox application programming interface and Bioclipse

PubMed Central

2011-01-01

Background Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications. Findings This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources. Conclusions A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers. PMID:22075173

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

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

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model

PubMed Central

Jackson, George R.; Maione, Anna G.; Klausner, Mitchell

2018-01-01

Abstract Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (in vitro) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1–2 and EPA Acute Inhalation Toxicity Category I–II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity. PMID:29904643

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model.

PubMed

Jackson, George R; Maione, Anna G; Klausner, Mitchell; Hayden, Patrick J

2018-06-01

Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal ( in vitro ) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1-2 and EPA Acute Inhalation Toxicity Category I-II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity.

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.

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…

The SEURAT-1 approach towards animal free human safety assessment.

PubMed

Gocht, Tilman; Berggren, Elisabet; Ahr, Hans Jürgen; Cotgreave, Ian; Cronin, Mark T D; Daston, George; Hardy, Barry; Heinzle, Elmar; Hescheler, Jürgen; Knight, Derek J; Mahony, Catherine; Peschanski, Marc; Schwarz, Michael; Thomas, Russell S; Verfaillie, Catherine; White, Andrew; Whelan, Maurice

2015-01-01

SEURAT-1 is a European public-private research consortium that is working towards animal-free testing of chemical compounds and the highest level of consumer protection. A research strategy was formulated based on the guiding principle to adopt a toxicological mode-of-action framework to describe how any substance may adversely affect human health.The proof of the initiative will be in demonstrating the applicability of the concepts on which SEURAT-1 is built on three levels:(i) Theoretical prototypes for adverse outcome pathways are formulated based on knowledge already available in the scientific literature on investigating the toxicological mode-of-actions leading to adverse outcomes (addressing mainly liver toxicity);(ii)adverse outcome pathway descriptions are used as a guide for the formulation of case studies to further elucidate the theoretical model and to develop integrated testing strategies for the prediction of certain toxicological effects (i.e., those related to the adverse outcome pathway descriptions);(iii) further case studies target the application of knowledge gained within SEURAT-1 in the context of safety assessment. The ultimate goal would be to perform ab initio predictions based on a complete understanding of toxicological mechanisms. In the near-term, it is more realistic that data from innovative testing methods will support read-across arguments. Both scenarios are addressed with case studies for improved safety assessment. A conceptual framework for a rational integrated assessment strategy emerged from designing the case studies and is discussed in the context of international developments focusing on alternative approaches for evaluating chemicals using the new 21st century tools for toxicity testing.

Interlaboratory study for the validation of an ecotoxicological procedure to monitor the quality of septic sludge received at a wastewater treatment plant.

PubMed

Robidoux, P Y; Choucri, A; Bastien, C; Sunahara, G I; López-Gastey, J

2001-01-01

Septic tank sludge is regularly hauled to the Montreal Urban Community (MUC) wastewater treatment plant. It is then discharged and mixed with the wastewater inflow before entering the primary chemical treatment process. An ecotoxicological procedure integrating chemical and toxicological analyses has been recently developed and applied to screen for the illicit discharge of toxic substances in septic sludge. The toxicity tests used were the Microtox, the bacterial-respiration, and the lettuce (Lactuca sativa) root elongation tests. In order to validate the applicability of the proposed procedure, a two-year interlaboratory study was carried out. In general, the results obtained by two independent laboratories (MUC and the Centre d'expertise en analyse environnementale du Quebec) were comparable and reproducible. Some differences were found using the Microtox test. Organic (e.g., phenol and formaldehyde) and inorganic (e.g., nickel and cyanide) spiked septic sludge were detected with good reliability and high efficiency. The relative efficiency to detect spiked substances was > 70% and confirms the results of previous studies. In addition, the respiration test was the most efficient toxicological tool to detect spiked substances, whereas the Microtox was the least efficient (< 15%). Efficiencies to detect spiked contaminants were also similar for both laboratories. These results support previous data presented earlier and contribute to the validation of the ecotoxicological procedure used by the MUC to screen toxicity in septic sludge.

Residual Acute Toxicity of Some Modern Insecticides Toward Two Mirid Predators of Tomato Pests.

PubMed

Wanumen, Andrea C; Carvalho, Geraldo A; Medina, Pilar; Viñuela, Elisa; Adán, Ángeles

2016-03-31

The successful integration of chemical and biological control strategies for crop pests depends on a thorough evaluation of the effects of pesticides on the natural enemies of pests. A case-by-case review is difficult to achieve because of the many combinations of pests, natural enemies, and crops that need to be tested. Within this framework, we tested and compared seven insecticides representative of four different modes of action (MoAs) groups on closely related predators (Miridae): flubendiamide, spirotetramat, metaflumizone, and sulfoxaflor onNesidiocoris tenuisReuter and flubendiamide, spiromesifen, indoxacarb, and imidacloprid onMacrolophus basicornis(Stal). We follow the standardized methodology of the International Organization for Biological Control, a sequential testing exposure scheme. The lethal effect of each insecticide was evaluated in adults after three days of contact with treated surfaces in the laboratory, extended laboratory, and semifield tests (inert substrate, tomato leaves, and tomato plant as the treated surface, respectively). Flubendiamide, spiromesifen, and spirotetramat were classified as harmless (class 1), metaflumizone was slightly harmful (class 2) but persistent, indoxacarb was harmless (class 1), and sulfoxaflor and imidacloprid were toxic (class 4) and exhibited a long residual activity. Our results suggest similarities in the acute toxicities of insecticides from the same MoA group on related species of natural enemies. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reproductive and Developmental Toxicity of Dioxin in Fish1

PubMed Central

King-Heiden, Tisha C.; Mehta, Vatsal; Xiong, Kong M.; Lanham, Kevin A.; Antkiewicz, Dagmara S.; Ganser, Alissa; Heideman, Warren

2011-01-01

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is a global environmental contaminant and the prototypical ligand for investigating aryl hydrocarbon receptor (AHR)-mediated toxicity. Environmental exposure to TCDD results in developmental and reproductive toxicity in fish, birds and mammals. To resolve the ecotoxicological relevance and human health risks posed by exposure to dioxin-like AHR agonists, a vertebrate model is needed that allows for toxicity studies at various levels of biological organization, assesses adverse reproductive and developmental effects and establishes appropriate integrative correlations between different levels of effects. Here we describe the reproductive and developmental toxicity of TCDD in feral fish species and summarize how using the zebrafish model to investigate TCDD toxicity has enabled us to characterize the AHR signaling in fish and to better understand how dioxin-like chemicals induce toxicity. We propose that such studies can be used to predict the risks that AHR ligands pose to feral fish populations and provide a platform for integrating risk assessments for both ecologically relevant organisms and humans. PMID:21958697

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

Genotoxicity testing of peptides: Folate deprivation as a marker of exaggerated pharmacology

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

Guérard, Melanie, E-mail: melanie.guerard@roche.com; Zeller, Andreas; Festag, Matthias

2014-09-15

The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidencemore » of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. - Highlights: • A synthetic peptide has been evaluated for potential genotoxicity • Small increases in an integrated (13-weeks) micronucleus test were observed • Further, animals had a pronounced reductions in food intake and body weight gain • A dose-dependent decrease in plasma folate levels was evident from week 4 onwards • Elevated micronuclei-incidence due to the exaggerated pharmacology.« less

Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

NASA Astrophysics Data System (ADS)

Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

2018-03-01

Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

Integrative Approaches for Predicting in vivo Effects of Chemicals from their Structural Descriptors and the Results of Short-term Biological Assays

PubMed Central

Low, Yen S.; Sedykh, Alexander; Rusyn, Ivan; Tropsha, Alexander

2017-01-01

Cheminformatics approaches such as Quantitative Structure Activity Relationship (QSAR) modeling have been used traditionally for predicting chemical toxicity. In recent years, high throughput biological assays have been increasingly employed to elucidate mechanisms of chemical toxicity and predict toxic effects of chemicals in vivo. The data generated in such assays can be considered as biological descriptors of chemicals that can be combined with molecular descriptors and employed in QSAR modeling to improve the accuracy of toxicity prediction. In this review, we discuss several approaches for integrating chemical and biological data for predicting biological effects of chemicals in vivo and compare their performance across several data sets. We conclude that while no method consistently shows superior performance, the integrative approaches rank consistently among the best yet offer enriched interpretation of models over those built with either chemical or biological data alone. We discuss the outlook for such interdisciplinary methods and offer recommendations to further improve the accuracy and interpretability of computational models that predict chemical toxicity. PMID:24805064

Mode of action and the assessment of chemical hazards in the presence of limited data: use of structure-activity relationships (SAR) under TSCA, Section 5.

PubMed Central

Auer, C M; Nabholz, J V; Baetcke, K P

1990-01-01

Section 5 of the Toxic Substances Control Act (TSCA) requires that manufacturers and importers of new chemicals must submit a Premanufacture Notification (PMN) to the U.S. Environmental Protection Agency 90 days before they intend to commence manufacture or import. Certain information such as chemical identity, uses, etc., must be included in the notification. The submission of test data on the new substance, however, is not required, although any available health and environmental information must be provided. Nonetheless, over half of all PMNs submitted to the agency do not contain any test data; because PMN chemicals are new, no test data is generally available in the scientific literature. Given this situation, EPA has had to develop techniques for hazard assessment that can be used in the presence of limited test data. EPA's approach has been termed "structure-activity relationships" (SAR) and involves three major components: the first is critical evaluation and interpretation of available toxicity data on the chemical; the second component involves evaluation of test data available on analogous substances and/or potential metabolites; and the third component involves the use of mathematical expressions for biological activity known as "quantitative structure-activity relationships" (QSARs). At present, the use of QSARs is limited to estimating physical chemical properties, environmental toxicity, and bioconcentration factors. An important overarching element in EPA's approach is the experience and judgment of scientific assessors in interpreting and integrating the available data and information. Examples are provided that illustrate EPA's approach to hazard assessment for PMN chemicals. PMID:2269224

Opportunities to integrate new approaches in genetic toxicology: an ILSI-HESI workshop report.

PubMed

Zeiger, Errol; Gollapudi, Bhaskar; Aardema, Marilyn J; Auerbach, Scott; Boverhof, Darrell; Custer, Laura; Dedon, Peter; Honma, Masamitsu; Ishida, Seiichi; Kasinski, Andrea L; Kim, James H; Manjanatha, Mugimane G; Marlowe, Jennifer; Pfuhler, Stefan; Pogribny, Igor; Slikker, William; Stankowski, Leon F; Tanir, Jennifer Y; Tice, Raymond; van Benthem, Jan; White, Paul; Witt, Kristine L; Thybaud, Véronique

2015-04-01

Genetic toxicity tests currently used to identify and characterize potential human mutagens and carcinogens rely on measurements of primary DNA damage, gene mutation, and chromosome damage in vitro and in rodents. The International Life Sciences Institute Health and Environmental Sciences Institute (ILSI-HESI) Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity Testing held an April 2012 Workshop in Washington, DC, to consider the impact of new understanding of biology and new technologies on the identification and characterization of genotoxic substances, and to identify new approaches to inform more accurate human risk assessment for genetic and carcinogenic effects. Workshop organizers and speakers were from industry, academe, and government. The Workshop focused on biological effects and technologies that would potentially yield the most useful information for evaluating human risk of genetic damage. Also addressed was the impact that improved understanding of biology and availability of new techniques might have on genetic toxicology practices. Workshop topics included (1) alternative experimental models to improve genetic toxicity testing, (2) Biomarkers of epigenetic changes and their applicability to genetic toxicology, and (3) new technologies and approaches. The ability of these new tests and technologies to be developed into tests to identify and characterize genotoxic agents; to serve as a bridge between in vitro and in vivo rodent, or preferably human, data; or to be used to provide dose response information for quantitative risk assessment was also addressed. A summary of the workshop and links to the scientific presentations are provided. © 2014 Wiley Periodicals, Inc.

Lime sulfur toxicity to broad mite, to its host plants and to natural enemies.

PubMed

Venzon, Madelaine; Oliveira, Rafael M; Perez, André L; Rodríguez-Cruz, Fredy A; Martins Filho, Sebastião

2013-06-01

An acaricidal effect of lime sulfur has not been demonstrated for Polyphagotarsonemus latus. However, lime sulfur can cause toxicity to natural enemies and to host plants. In this study, the toxicity of different concentrations of lime sulfur to P. latus, to the predatory mite Amblyseius herbicolus and to the predatory insect Chrysoperla externa was evaluated. Additionally, the phytotoxicity of lime sulfur to two P. latus hosts, chili pepper and physic nut plants, was determined. Lime sulfur at a concentration of 9.5 mL L(-1) restrained P. latus population growth. However, this concentration was deleterious to natural enemies. The predatory mite A. herbicolus showed a negative value of instantaneous growth rate, and only 50% of the tested larvae of C. externa reached adulthood when exposed to 10 mL L(-1) . Physic nut had severe injury symptoms when sprayed with all tested lime sulfur concentrations. For chili pepper plants, no phytoxicity was observed at any tested concentration. Lime sulfur might be used for P. latus control on chili pepper but not on physic nut owing to phytotoxicity. Care should be taken when using lime sulfur in view of negative effects on natural enemies. Selective lime sulfur concentration integrated with other management tactics may provide an effective and sustainable P. latus control on chili pepper. © 2012 Society of Chemical Industry.

Control of zoonotic cutaneous leishmaniasis vector, Phlebotomus papatasi, using attractive toxic sugar baits (ATSB)

PubMed Central

Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Rassi, Yavar; Karami Jooshin, Moharram; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad

2017-01-01

Introduction Attractive Toxic Sugar Baits (ATSB) is a new vector control method that meets Integrated Vector Management (IVM) goals. In an experimental design, this study aimed to determine effects of ATSB on control of Phlebotomus papatasi, as a main vector of Zoonotic Cutaneous Leishmaniasis (ZCL), in Qom Province, center of Iran. Methods In a cross-sectional design, boric acid was mixed with brown sugar solution and tested as toxic baits for P. papatasi. Two methods were utilized to use the baits: (a) spraying ATSB on vegetation, bushes, and shrubs; and (b) setting ATSB-treated barrier fences in front of colonies at 500 m distance from the houses in outskirts of villages. In order to examine the residual efficacy rate of ATSB-treated barrier fences, the bioassay test was used. Density of P. papatasi sandflies was measured using sticky and light traps biweekly. For data analysis, Mann-Whitney U Test and Kruskal-Wallis were used. Results ATSB-treated barrier fences led to 3 times reduction in P. papatasi population. Besides that, ATSB spraying on plants led to more than 5 times reduction in P. papatasi population. Conclusions Comparing the incidence of leishmaniasis in treated villages before and after the study showed that the incidence was statistically reduced. Therefore, ATSB is an effective method to control vectors and prevent leishmaniasis. PMID:28426679

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

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 ...

Design and methods of the Southeast Stream Quality Assessment (SESQA), 2014

USGS Publications Warehouse

Journey, Celeste A.; Van Metre, Peter C.; Bell, Amanda H.; Button, Daniel T.; Garrett, Jessica D.; Nakagaki, Naomi; Qi, Sharon L.; Bradley, Paul M.

2015-07-15

This report provides a detailed description of the SESQA study components, including surveys of ecological conditions, routine water sampling, deployment of passive polar organic compound integrative samplers for pesticides and contaminants of emerging concern, and synoptic sediment sampling and toxicity testing at all urban, confined animal feeding operation, and reference sites. Continuous water-quality monitoring and daily pesticide sampling efforts conducted at a subset of urban sites are also described.

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...

MONITORING THE AIR FOR TOXIC AND GENOTOXIC COMPOUNDS

EPA Science Inventory

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

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.

Silibinin pretreatment attenuates biochemical and behavioral changes induced by intrastriatal MPP+ injection in rats.

PubMed

Geed, Milind; Garabadu, Debapriya; Ahmad, Ausaf; Krishnamurthy, Sairam

2014-02-01

Silymarin commonly known for its hepatoprotective effect is reported to show protection against 6-hydroxydopamine-induced neurotoxicity. Silibinin forms the major active constituent of silymarin. Therefore, the neuroprotective effect of silibinin (50, 100 and 200 mg/kg) was evaluated in the unilaterally injected 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neurotoxicity in male rats. A battery of tests such as elevated plus maze (EPM), narrow beam walk, open field, bar catalepsy, grip strength, and foot print analysis was performed to evaluate the behavioral symptoms of striatal dopaminergic toxicity. Furthermore, the mechanism of action of silibinin was investigated by evaluating the mitochondrial complex enzyme activities, mitochondrial integrity and oxidative status. Striatal caspase-3 and NFκB were expressed to evaluate the effect of silibinin on apoptosis and inflammation respectively. Silibinin (100 and 200 mg/kg) protected against MPP(+)-induced dopamine depletion in striatum. Silibinin reversed MPP(+)-induced decrease in transfer latency indicating memory consolidation in the EPM test. Silibinin (100 and 200 mg/kg) attenuated MPP(+)-induced motor deficits, such as fine motor movements and gait. MPP(+)-induced mitochondrial dysfunction, loss of integrity and oxidative stress were attenuated by silibinin. Silibinin decreased striatal caspase-3 and NFκB expression indicating potential anti-apoptotic and anti-inflammatory effects respectively. Hence, silibinin exhibited neuroprotective effect in the MPP(+) induced striatal toxicity augmenting dopamine levels. The mechanism of action may be linked to maintenance of mitochondrial bioenergetics and integrity apart from anti-apoptotic and anti-inflammatory activities. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of particle size and coating on nanoscale Ag and TiO₂ exposure in zebrafish (Danio rerio) embryos.

PubMed

Osborne, Olivia J; Johnston, Blair D; Moger, Julian; Balousha, Mohammed; Lead, Jamie R; Kudoh, Tetsuhiro; Tyler, Charles R

2013-12-01

Manufactured metal (oxide) nanoparticles are entering the aquatic environment with little understanding on their potential health impacts for exposed organisms. Adopting an integrative approach, we investigated effects of particle size and coating on biological responses for two of the most commonly used metal (oxide) nanoscale particles, silver (Ag) and titanium dioxide (TiO₂) in zebrafish embryos. Titanium dioxide nanoparticles (nominally, 4 nm, 10 nm, 30 nm and 134 nm) had little or no toxicity on the endpoints measured. Ag both in nano form (10 nm and 35 nm) and its larger counterpart (600-1600 nm) induced dose-dependent lethality and morphological defects, occurring predominantly during gastrula stage. Of the silver material tested 10 nm nanoparticles appeared to be the most toxic. Coating Ag nanoparticles with citrate or fulvic acid decreased toxicity significantly. In situ hybridisation analysis identified the yolk syncytial layer (YSL) as a target tissue for Ag-nano toxicity where there was a significant induction of the heavy metal stress response gene, metallothionein 2 (Mt2) at sub-lethal exposures. Coherent Anti-stroke Raman Scattering (CARS) microscopy provided no evidence for silver particles crossing the chorionic membrane in exposed embryos. Collectively, our data suggest that silver ions play a major role in the toxicity of Ag nanoparticles.

Integrated testing strategy (ITS) for bioaccumulation assessment under REACH.

PubMed

Lombardo, Anna; Roncaglioni, Alessandra; Benfentati, Emilio; Nendza, Monika; Segner, Helmut; Fernández, Alberto; Kühne, Ralph; Franco, Antonio; Pauné, Eduard; Schüürmann, Gerrit

2014-08-01

REACH (registration, evaluation, authorisation and restriction of chemicals) regulation requires that all the chemicals produced or imported in Europe above 1 tonne/year are registered. To register a chemical, physicochemical, toxicological and ecotoxicological information needs to be reported in a dossier. REACH promotes the use of alternative methods to replace, refine and reduce the use of animal (eco)toxicity testing. Within the EU OSIRIS project, integrated testing strategies (ITSs) have been developed for the rational use of non-animal testing approaches in chemical hazard assessment. Here we present an ITS for evaluating the bioaccumulation potential of organic chemicals. The scheme includes the use of all available data (also the non-optimal ones), waiving schemes, analysis of physicochemical properties related to the end point and alternative methods (both in silico and in vitro). In vivo methods are used only as last resort. Using the ITS, in vivo testing could be waived for about 67% of the examined compounds, but bioaccumulation potential could be estimated on the basis of non-animal methods. The presented ITS is freely available through a web tool. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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.

Determination of the toxicity of intravitreal minocycline in rabbit eyes.

PubMed

Falavarjani, Khalil Ghasemi; Pourhabibi, Arash; Aghdam, Kaveh Abri; Hosseini, Seyed Bagher; Modarres, Mehdi; Pazouki, Abdolreza; Khanamiri, Hossein Nazari

2016-09-01

To evaluate the retinal toxicity of intravitreal minocycline in rabbit eyes. Intravitreal injection of minocycline with concentrations of 1000, 500, 250, 125 and 62.5 μg in 0.1 ml was performed in 10 New Zealand albino rabbits. Each concentration was injected into two rabbit eyes. For each dose, normal saline was injected in one contralateral eye and the other fellow eye remained non-injected. Electrophysiologic testing was performed before and 4 weeks after injections. The eyes were enucleated 4 weeks after injections and examined using light microscopy. The clinical examination was unremarkable after injections. Electroretinography recordings were significantly affected at all doses in at least one of the a- or b-waves of photopic or scotopic responses. Histopathologic examination revealed marked atrophy and loss of integrity in all retinal layers in all minocycline injected eyes. Contralateral eyes were normal. In our study, intravitreal minocycline was toxic to the retina in albino rabbits even at a concentration of 62.5 µg/0.1 ml.

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.

Variation in toxicity response of Ceriodaphnia dubia to Athabasca oil sands coke leachates.

PubMed

Puttaswamy, Naveen; Turcotte, Dominique; Liber, Karsten

2010-07-01

Coke from the Athabasca (Alberta, Canada) oil sands operations may someday be integrated into reclamation landscapes. It is hypothesized that the metals associated with the solid coke may leach into the surrounding environment. Therefore, the main objectives of this study were to characterize the toxicity and chemistry of coke leachates collected from two field lysimeters (i.e. shallow lysimeter and deep lysimeter) over a period of 20months, as well as from other oil sands coke storage sites. In addition, a batch renewal leaching of coke was conducted to examine the rate of metals release. Chronic toxicity of key metals (e.g. Al, Mn, Ni and V) found in lysimeter coke leachate was evaluated separately. Toxicity test results revealed that whole coke leachates (100% v/v) were acutely toxic to Ceriodaphnia dubia; the 7-day LC50 values were always <25% v/v coke leachate. The deep lysimeter leachate was generally more toxic than the shallow lysimeter leachate, likely because of significantly higher concentrations of vanadium (V) found in the deep lysimeter leachate at all sampling times. Vanadium concentrations were higher than all other metals found in the leachate from both lysimeters, and in the batch renewal leaching study. Furthermore, V found in leachates collected from other oil sands field sites showed a concentration-response relationship with C. dubia survival. Mass balance calculations indicated that 94-98% of potentially leachable V fraction was still present in the coke from two field lysimeters. Evidence gathered from these assessments, including toxic unit (TU) calculations for the elements of concern, suggests that V was the likely cause of toxicity of the deep lysimeter leachate, whereas in the shallow lysimeter leachate both Ni and V could be responsible for the observed toxicity. 2010 Elsevier Ltd. All rights reserved.

Toxicity of tomato red, a popular food dye blend on male albino mice.

PubMed

Sharma, Shipra; Goyal, Rajendra P; Chakravarty, Geetanjali; Sharma, Anjali

2008-06-01

Colour in food is an integral part of our culture and is also indispensable to the modern day consumer. During the past several decades, the technology of food processing has changed dramatically and the growth in the use of synthetic food colours as an individual dye or in the form of blends has increased enormously. In the present investigation, an attempt has been made to evaluate the toxic effects of a commonly used dye blend, tomato red on male Swiss albino mice. The mice were treated orally with 2 and 6g/kg body weight/day for 42 days. The present study revealed an increase in the body weight and liver weight. However, a decrease was recorded in the weights of kidneys and testes. Histopathological study revealed severe degenerative changes in the liver, kidney and testes. In conclusion, the use of the dye blend in various food items has adverse effect on the vital organs.

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.

Toxicity of six insecticides to predatory mite Amblyseius cucumeris (Oudemans) (Acari: Phytoseiidae) in- and off-field.

PubMed

Cheng, Shenhang; Lin, Ronghua; Zhang, Nan; Yuan, Shankui; Zhou, Xinxin; Huang, Jian; Ren, Xiaodong; Wang, Shoushan; Jiang, Hui; Yu, Caihong

2018-06-22

Amblyseius cucumeris (Oudemans) is a beneficial non-target arthropod (NTA) and a key predator of tetranychid mites in integrated pest management (IPM) programs across China. Evaluating the toxic effects of insecticides on such predatory mites is essential for the success and development of IPM. We tested six insecticides to determine the risk of neonicotinoid insecticide toxicity to predatory mites, using the 'open glass plate method' and adult female A. cucumeris in a "worst case laboratory exposure" scenario. A 48-h toxicity test was performed using the hazard quotient (HQ) approach to evaluate the risk of each insecticide. The LR 50 values (application rate that caused 50% mortality) of acetamiprid, thiamethoxam, imidacloprid, and dinotefuran were 76.4, 104.5, 84.9, and 224.6 g active ingredient (a.i.) ha -1 , respectively, with in-field HQ values of 0.40, 1.28, 0.49, and 0.82, respectively. The HQ values were lower than the trigger value of 2, and were consistent with off-field values. The risks of the four neonicotinoid insecticides to adult female A. cucumeris were acceptable in two exposure scenarios in field and off field. The 48-h LR 50 values for bifenthrin and malathion were 0.008 and 0.062 g. a.i. ha -1 , respectively, which were much lower than the recommended field application rates. The HQ values were much higher than the trigger values for both in- and off-field, indicating that the risks of these two insecticides were unacceptable. Bifenthrin and malathion posed an extremely high risk to the test species, and their use should be restricted to reduce risks to the field with augmentative releases of A. cucumeris. Copyright © 2018 Elsevier Inc. All rights reserved.

Toxicokinetics and toxicodynamics of differently coated silver nanoparticles and silver nitrate in Enchytraeus crypticus upon aqueous exposure in an inert sand medium.

PubMed

Topuz, Emel; van Gestel, Cornelis A M

2015-12-01

The aim of the present study was to evaluate the effect of silver nanoparticles (AgNPs) on Enchytraeus crypticus, applying a combined toxicokinetics and toxicodynamics approach to understand the relationship between survival and the development of internal Ag concentrations in the animals over time. Toxicity tests were conducted in medium composed of well-defined aqueous solutions added to inert quartz sand to avoid the complexity of soil conditions. Citrate-coated AgNPs (AgNP-Cit) and polyvinylpyrrolidone-coated AgNPs (AgNP-PVP) were tested and compared with silver nitrate (AgNO3), which was used as a positive control for Ag ion effects. The median lethal concentration (LC50) values based on Ag concentrations in the solution phase of the test medium decreased over time and reached steady state after 7 d, with AgNO3 and AgNP-PVP being more toxic than AgNP-Cit. Slow dissolution may explain the low uptake kinetics and lower toxicity of AgNP-Cit compared with the other 2 Ag forms. The LC50 values based on internal Ag concentrations in the animals were almost stable over time, highlighting the importance of integrating toxicokinetics and toxicodynamics and relating survival with internal Ag concentrations. Neither survival-based elimination rates nor internal LC50s in the organisms showed any significant evidence of nano-specific effects for both AgNPs, although they suggested some uptake of particulate Ag for AgNP-Cit. The authors conclude that the toxicity of both types of AgNP probably is mainly attributable to the release of Ag ions. © 2015 SETAC.

Assessing condition of macroinvertebrate communities and sediment toxicity in the St. Lawrence River at Massena Area-of-Concern

USGS Publications Warehouse

Duffy, Brian T.; Baldigo, Barry P.; Smith, Alexander J.; George, Scott D.; David, Anthony M.

2016-01-01

In 1972, the USA and Canada agreed to restore the chemical, physical, and biological integrity of the Great Lakes ecosystem under the first Great Lakes Water Quality Agreement. In subsequent amendments, part of the St. Lawrence River at Massena, New York and segments of three tributaries, were designated as an Area of Concern (AOC) due to the effects of polychlorinated biphenyls (PCBs), lead and copper contamination, and habitat degradation and resulting impairment to several beneficial uses. Because sediments have been largely remediated, the present study was initiated to evaluate the current status of the benthic macroinvertebrate (benthos) beneficial use impairment (BUI). Benthic macroinvertebrate communities and sediment toxicity tests using Chironomus dilutus were used to test the hypotheses that community condition and sediment toxicity at AOC sites were not significantly different from those of adjacent reference sites. Grain size was found to be the main driver of community composition and macroinvertebrate assemblages, and bioassessment metrics did not differ significantly between AOC and reference sites of the same sediment class. Median growth of C. dilutus and its survival in three of the four river systems did not differ significantly in sediments from AOC and reference sites. Comparable macroinvertebrate assemblages and general lack of toxicity across most AOC and reference sites suggest that the quality of sediments should not significantly impair benthic macroinvertebrate communities in most sites in the St. Lawrence River AOC.

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.

Methods, safety, and early clinical outcomes of dose escalation using simultaneous integrated and sequential boosts in patients with locally advanced gynecologic malignancies.

PubMed

Boyle, John; Craciunescu, Oana; Steffey, Beverly; Cai, Jing; Chino, Junzo

2014-11-01

To evaluate the safety of dose escalated radiotherapy using a simultaneous integrated boost technique in patients with locally advanced gynecological malignancies. Thirty-nine women with locally advanced gynecological malignancies were treated with intensity modulated radiation therapy utilizing a simultaneous integrated boost (SIB) technique for gross disease in the para-aortic and/or pelvic nodal basins, sidewall extension, or residual primary disease. Women were treated to 45Gy in 1.8Gy fractions to elective nodal regions. Gross disease was simultaneously treated to 55Gy in 2.2Gy fractions (n=44 sites). An additional sequential boost of 10Gy in 2Gy fractions was delivered if deemed appropriate (n=29 sites). Acute and late toxicity, local control in the treated volumes (LC), overall survival (OS), and distant metastases (DM) were assessed. All were treated with a SIB to a dose of 55Gy. Twenty-four patients were subsequently treated with a sequential boost to a median dose of 65Gy. Median follow-up was 18months. Rates of acute>grade 2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 2.5%, 0%, and 30%, respectively. There were no grade 4 acute toxicities. At one year, grade 1-2 late GI toxicities were 24.5%. There were no grade 3 or 4 late GI toxicities. Rates of grade 1-2 late GU toxicities were 12.7%. There were no grade 3 or 4 late GU toxicities. Dose escalated radiotherapy using a SIB results in acceptable rates of acute toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

An Overview of the Toxicity of Naphthalene, EDB and Ethanol

EPA Science Inventory

This presentation is a short summary of information on the toxicity and carcinogenicity of naphthalene and 1,2-dibromoethane (EDB) that is available in the EPA Integrated Risk Information System (IRIS) and information on the toxicity of ethanol available from the Health, Environm...

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

EPA Science Inventory

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

Integration of gene expression biomarkers and whole sediment toxicity identification evaluations

EPA Science Inventory

Toxicity identification and evaluations (TIEs) use physical/chemical manipulation of a sample to isolate or change the potency of different groups of chemicals potentially toxic in a sample. Organisms are then exposed to these fractions pre- and post-manipulation to determine if ...

Provisional Peer-Reviewed Toxicity Values for Acenaphthene

EPA Science Inventory

A Provisional Peer-Reviewed Toxicity Values (PPRTV) is defined as a toxicity value derived for use in the Superfund Program when such a value is not available from EPA’s Integrated Risk Information System (IRIS) Database. PPRTVs are developed according to a Standard Operating Pr...

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.

Aquatic information and retrieval (AQUIRE) database system

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

Hunter, R.; Niemi, G.; Pilli, A.

The AQUIRE database system is one of the foremost international resources for finding aquatic toxicity information. Information in the system is organized around the concept of an 'aquatic toxicity test.' A toxicity test record contains information about the chemical, species, endpoint, endpoint concentrations, and test conditions under which the toxicity test was conducted. For the past 10 years aquatic literature has been reviewed and entered into the system. Currently, the AQUIRE database system contains data on more than 2,400 species, 160 endpoints, 5,000 chemicals, 6,000 references, and 104,000 toxicity tests.

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 ...

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).

Antibacterial activity of Aquilaria crassna leaf extract against Staphylococcus epidermidis by disruption of cell wall

PubMed Central

2013-01-01

Background Aquilaria crassna Pierre ex Lecomte has been traditionally used in Thailand for treatment of infectious diseases such as diarrhoea and skin diseases for a long time. The main objectives of this study were to examine antibacterial activity of the Aquilaria crassna leaf extract against Staphylococcus epidermidis and its underlying mechanism. The antioxidant activity and acute toxicity were studied as well. Methods Antioxidant activities were examined by FRAP, ABTS and DPPH scavenging methods. Antibacterial activity was conducted using disc diffusion assay and the minimum inhibitory concentration (MIC) was determined by dilution method. The minimum bactericidal concentration (MBC) was reported as the lowest concentration producing no growth of microbes in the subcultures. Morphological changes of the microbe were observed by scanning electron microscopy, while an inhibitory effect on biofilm formation was evaluated by phase contrast microscopic analysis. Bacterial cell wall integrity was assessed by transmission electron microscopy. Acute toxicity was conducted in accordance with the OECD for Testing of Chemicals (2001) guidelines. Results The extract exhibited considerable antioxidant activity. Staphylococcus epidermidis was susceptible to the extract with the MIC and MBC of 6 and 12 mg/ml, respectively. The extract caused swelling and distortion of bacterial cells and inhibited bacterial biofilm formation. Rupture of bacterial cell wall occurred after treated with the extract for 24 h. Acute toxicity test in mice showed no sign of toxicity or death at the doses of 2,000 and 15,000 mg/kg body weight. Conclusion The aqueous extract of Aquilaria crassna leaves possesses an in vitro antibacterial activity against Staphylococcus epidermidis, with no sign of acute oral toxicity in mice, probably by interfering with bacterial cell wall synthesis and inhibiting biofilm formation. PMID:23962360

Toxicity of effluents from gasoline stations oil-water separators to early life stages of zebrafish Danio rerio.

PubMed

Alves, Romulo Nepomuceno; Mariz, Célio Freire; Paulo, Driele Ventura de; Carvalho, Paulo S M

2017-07-01

Used petroleum hydrocarbons and gasoline stations runoff are significant sources of polycyclic aromatic hydrocarbons (PAHs) to aquatic ecosystems. Samples of the final effluent of oil-water-separators were collected at gasoline stations in the metropolitan region of Recife, Brazil, before release to sewage or rainwater systems. Effluent soluble fractions (ESF) were prepared and bioassays were performed according to the Fish Embryo Toxicity Test. The test involved exposing zebrafish Danio rerio embryos to dilutions of the ESFs for 96 h, with daily examination of lethality and sublethal morphological effects integrated through the General Morphology Score (GMS), based on the achievement of developmental hallmarks. Frequencies of abnormalities were recorded after exposures. ESF LC50-96h (lethal concentration to 50% of exposed embryos) in the most toxic effluent achieved 8.9% (v/v), equivalent to 11 μg phenanthrene equivalents L -1 . GMS scores indicated significantly delayed embryo-larval development at ESF dilutions of 10% and 20% from effluents of all gas stations. Major abnormalities detected after the 96 h exposure included the presence of a yolk sac not fully absorbed coupled with the lack of an inflated swim bladder, lack of both pectoral fins, and the failure to develop a protruding mouth. Effective equivalent PAH concentrations that induce a 50% frequency of larvae without an inflated swim bladder (EC50) were 4.9 μg phenanthrene L -1 , 21.8 μg naphthalene L -1 , and 34.1 μg chrysene L -1 . This study shows that PAHs in ESFs from gas stations oil water separators are toxic to zebrafish, contributing to the toxicity of urban storm waters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic variance of tolerance and the toxicant threshold model.

PubMed

Tanaka, Yoshinari; Mano, Hiroyuki; Tatsuta, Haruki

2012-04-01

A statistical genetics method is presented for estimating the genetic variance (heritability) of tolerance to pollutants on the basis of a standard acute toxicity test conducted on several isofemale lines of cladoceran species. To analyze the genetic variance of tolerance in the case when the response is measured as a few discrete states (quantal endpoints), the authors attempted to apply the threshold character model in quantitative genetics to the threshold model separately developed in ecotoxicology. The integrated threshold model (toxicant threshold model) assumes that the response of a particular individual occurs at a threshold toxicant concentration and that the individual tolerance characterized by the individual's threshold value is determined by genetic and environmental factors. As a case study, the heritability of tolerance to p-nonylphenol in the cladoceran species Daphnia galeata was estimated by using the maximum likelihood method and nested analysis of variance (ANOVA). Broad-sense heritability was estimated to be 0.199 ± 0.112 by the maximum likelihood method and 0.184 ± 0.089 by ANOVA; both results implied that the species examined had the potential to acquire tolerance to this substance by evolutionary change. Copyright © 2012 SETAC.

Biodegradability and toxicity assessment of a real textile wastewater effluent treated by an optimized electrocoagulation process.

PubMed

Manenti, Diego R; Módenes, Aparecido N; Soares, Petrick A; Boaventura, Rui A R; Palácio, Soraya M; Borba, Fernando H; Espinoza-Quiñones, Fernando R; Bergamasco, Rosângela; Vilar, Vítor J P

2015-01-01

In this work, the application of an iron electrode-based electrocoagulation (EC) process on the treatment of a real textile wastewater (RTW) was investigated. In order to perform an efficient integration of the EC process with a biological oxidation one, an enhancement in the biodegradability and low toxicity of final compounds was sought. Optimal values of EC reactor operation parameters (pH, current density and electrolysis time) were achieved by applying a full factorial 3(3) experimental design. Biodegradability and toxicity assays were performed on treated RTW samples obtained at the optimal values of: pH of the solution (7.0), current density (142.9 A m(-2)) and different electrolysis times. As response variables for the biodegradability and toxicity assessment, the Zahn-Wellens test (Dt), the ratio values of dissolved organic carbon (DOC) relative to low-molecular-weight carboxylates anions (LMCA) and lethal concentration 50 (LC50) were used. According to the Dt, the DOC/LMCA ratio and LC50, an electrolysis time of 15 min along with the optimal values of pH and current density were suggested as suitable for a next stage of treatment based on a biological oxidation process.

Risk assessment in the 21st century: roadmap and matrix.

PubMed

Embry, Michelle R; Bachman, Ammie N; Bell, David R; Boobis, Alan R; Cohen, Samuel M; Dellarco, Michael; Dewhurst, Ian C; Doerrer, Nancy G; Hines, Ronald N; Moretto, Angelo; Pastoor, Timothy P; Phillips, Richard D; Rowlands, J Craig; Tanir, Jennifer Y; Wolf, Douglas C; Doe, John E

2014-08-01

Abstract The RISK21 integrated evaluation strategy is a problem formulation-based exposure-driven risk assessment roadmap that takes advantage of existing information to graphically represent the intersection of exposure and toxicity data on a highly visual matrix. This paper describes in detail the process for using the roadmap and matrix. The purpose of this methodology is to optimize the use of prior information and testing resources (animals, time, facilities, and personnel) to efficiently and transparently reach a risk and/or safety determination. Based on the particular problem, exposure and toxicity data should have sufficient precision to make such a decision. Estimates of exposure and toxicity, bounded by variability and/or uncertainty, are plotted on the X- and Y-axes of the RISK21 matrix, respectively. The resulting intersection is a highly visual representation of estimated risk. Decisions can then be made to increase precision in the exposure or toxicity estimates or declare that the available information is sufficient. RISK21 represents a step forward in the goal to introduce new methodologies into 21st century risk assessment. Indeed, because of its transparent and visual process, RISK21 has the potential to widen the scope of risk communication beyond those with technical expertise.

INTEGRATED CHEMICAL INFORMATION TECHNOLOGIES ...

EPA Pesticide Factsheets

A central regulatory mandate of the Environmental Protection Agency, spanning many Program Offices and issues, is to assess the potential health and environmental risks of large numbers of chemicals released into the environment, often in the absence of relevant test data. Models for predicting potential adverse effects of chemicals based primarily on chemical structure play a central role in prioritization and screening strategies yet are highly dependent and conditional upon the data used for developing such models. Hence, limits on data quantity, quality, and availability are considered by many to be the largest hurdles to improving prediction models in diverse areas of toxicology. Generation of new toxicity data for additional chemicals and endpoints, development of new high-throughput, mechanistically relevant bioassays, and increased generation of genomics and proteomics data that can clarify relevant mechanisms will all play important roles in improving future SAR prediction models. The potential for much greater immediate gains, across large domains of chemical and toxicity space, comes from maximizing the ability to mine and model useful information from existing toxicity data, data that represent huge past investment in research and testing expenditures. In addition, the ability to place newer “omics” data, data that potentially span many possible domains of toxicological effects, in the broader context of historical data is the means for opti

Computational Modeling and Simulation of Developmental ...

EPA Pesticide Factsheets

Developmental and Reproductive Toxicity (DART) testing is important for assessing the potential consequences of drug and chemical exposure on human health and well-being. Complexity of pregnancy and the reproductive cycle makes DART testing challenging and costly for traditional (animal-based) methods. A compendium of in vitro data from ToxCast/Tox21 high-throughput screening (HTS) programs is available for predictive toxicology. ‘Predictive DART’ will require an integrative strategy that mobilizes HTS data into in silico models that capture the relevant embryology. This lecture addresses progress on EPA's 'virtual embryo'. The question of how tissues and organs are shaped during development is crucial for understanding (and predicting) human birth defects. While ToxCast HTS data may predict developmental toxicity with reasonable accuracy, mechanistic models are still necessary to capture the relevant biology. Subtle microscopic changes induced chemically may amplify to an adverse outcome but coarse changes may override lesion propagation in any complex adaptive system. Modeling system dynamics in a developing tissue is a multiscale problem that challenges our ability to predict toxicity from in vitro profiling data (ToxCast/Tox21). (DISCLAIMER: The views expressed in this presentation are those of the presenter and do not necessarily reflect the views or policies of the US EPA). This was an invited seminar presentation to the National Institute for Public H

Ectopic Bone Matrix Mineralization: Unveiling the Osteoinductive Nature of Crab Cuticle

NASA Astrophysics Data System (ADS)

Omokanwaye, Tiffany Suella

Engineered nanomaterials are increasingly used in a variety of industrial processes and consumer products. Numerous studies have reported toxicity of different NPs during the last years. Thus, there are growing concerns about the potential impacts to the health and environment of engineered nanoparticles (NPs). However, some methodological problems complicate the interpretation of nanotoxicity studies. On the one hand, some NPs have shown to interfere with classical toxicity assays based on colorimetric or fluorescent measurements. On the other hand, most NPs tend to aggregate in media used in toxicity tests, which complicates the interpretation of the toxicity results. The first objective of this dissertation was to evaluate a novel impedance-based and label-free real time cell analyzer (RTCA) as a high throughput method for screening the cytotoxicity of nanoparticles and to validate the RTCA results using a conventional cytotoxicity test (MTT). Several inorganic NPs were tested for potential cytotoxicity to human bronchial epithelial cells (16HBE14o-). In general, there was a good correlation in cytotoxicity measurements between the two methods. Moreover, none of the NPs tested showed interference with the impedance measurements performed by the RTCA system. The results demonstrate the potential and validity of the impedance-based RTCA technique to rapidly screen for NP toxicity. The second objective of this dissertation was to assess the toxicity of different inorganic NPs to the eukaryotic cell model Saccharomyces cerevisiae, and to test the influence of NP aggregation state in their toxicity. Nanotoxicity was assessed by monitoring oxygen consumption in batch cultures and by analysis of cell membrane integrity. Mn2O3 NPs showed the highest inhibition of O2 consumption and cell membrane damage, while the other NPs caused low or no toxicity to the yeast. Most NPs showed high tendency to aggregate in the assay medium, so a non-toxic dispersant was used to improve NP stability. In contrast to aggregated CeO2 NPs, dispersed CeO 2 NPs showed toxicity to the yeast. However, dispersant supplementation decreased the inhibition caused by Mn2O3 NPs at low concentrations, which could indicate that dispersant association with the particles may have an impact on the interaction between the NPs and the cells. The proven toxicity of some NPs raises concerns about their environmental fate. Municipal and industrial wastewaters are considered primary sources of NPs to the environment. However, information on the behavior and impact of NPs on wastewater treatment processes is very limited. A third objective of this dissertation was to evaluate the fate and long-term effect of ZnO and CuO NPs during wastewater treatment in high-rate anaerobic bioreactors. Laboratory-scale upflow anaerobic sludge blanket (UASB) reactors were fed with synthetic wastewater containing NPs for extended periods of time (> 90 d). Extensive removal (62-82%) of ZnO and CuO NPs was observed during wastewater treatment in the UASB reactors. Scanning electron microscopy and chemical analysis confirmed that NPs were associated with the anaerobic sludge. While short-term exposure to low levels of ZnO and CuO NPs only caused minor inhibition to methanogenesis, extended exposure to NPs accumulated in the sludge bed led to a gradual and partial inhibitory response in the reactors. The inhibitory effect was also evident in the decline in the acetoclastic methanogenic activity of the biomass.

Integrating toxicogenomics into human health risk assessment: lessons learned from the benzo[a]pyrene case study.

PubMed

Chepelev, Nikolai L; Moffat, Ivy D; Labib, Sarah; Bourdon-Lacombe, Julie; Kuo, Byron; Buick, Julie K; Lemieux, France; Malik, Amal I; Halappanavar, Sabina; Williams, Andrew; Yauk, Carole L

2015-01-01

The use of short-term toxicogenomic tests to predict cancer (or other health effects) offers considerable advantages relative to traditional toxicity testing methods. The advantages include increased throughput, increased mechanistic data, and significantly reduced costs. However, precisely how toxicogenomics data can be used to support human health risk assessment (RA) is unclear. In a companion paper ( Moffat et al. 2014 ), we present a case study evaluating the utility of toxicogenomics in the RA of benzo[a]pyrene (BaP), a known human carcinogen. The case study is meant as a proof-of-principle exercise using a well-established mode of action (MOA) that impacts multiple tissues, which should provide a best case example. We found that toxicogenomics provided rich mechanistic data applicable to hazard identification, dose-response analysis, and quantitative RA of BaP. Based on this work, here we share some useful lessons for both research and RA, and outline our perspective on how toxicogenomics can benefit RA in the short- and long-term. Specifically, we focus on (1) obtaining biologically relevant data that are readily suitable for establishing an MOA for toxicants, (2) examining the human relevance of an MOA from animal testing, and (3) proposing appropriate quantitative values for RA. We describe our envisioned strategy on how toxicogenomics can become a tool in RA, especially when anchored to other short-term toxicity tests (apical endpoints) to increase confidence in the proposed MOA, and emphasize the need for additional studies on other MOAs to define the best practices in the application of toxicogenomics in RA.

Short-term exposure to low doses of rotenone induces developmental, biochemical, behavioral, and histological changes in fish.

PubMed

Melo, Karina Motta; Oliveira, Rhaul; Grisolia, Cesar Koppe; Domingues, Inês; Pieczarka, Julio Cesar; de Souza Filho, José; Nagamachi, Cleusa Yoshiko

2015-09-01

Rotenone, a natural compound derived from plants of the genera Derris and Lonchocarpus, is used worldwide as a pesticide and piscicide. This study aims to assess short-term toxicity of rotenone to early-life stages of the fish Danio rerio and Poecilia reticulata using a wide and integrative range of biomarkers (developmental, biochemical, behavioral, and histopathological). Moreover, the species sensitivity distribution (SSD) approach was used to compare rotenone acute toxicity to fish species. Toxicity tests were based on the OECD protocols, fish embryo toxicity test (for D. rerio embryos), and fish acute toxicity test (for P. reticulata juveniles). D. rerio embryos were used to estimate lethal concentrations and analyze embryonic and enzymatic alterations (activity of catalase, glutathione-S-transferase, and cholinesterase), while P. reticulata juveniles were used for the assessment of histological damage in the gills and liver. Rotenone induced significant mortality in zebrafish embryos with a 96-h lethal concentration 50% (LC50) = 12.2 μg/L. Rotenone was embryotoxic, affecting the development of D. rerio embryos, which showed cardiac edema; tail deformities; loss of equilibrium; and a general delay characterized by lack of tail detachment, delayed somite formation, yolk sac absorption, and lack of pigmentation. Biochemical biomarker inhibition was observed for concentrations ≥1 μg/L for CAT and glutathione-S-transferase (GST) and for cholinesterase (ChE) in concentration from 10 μg/L. Behavioral changes were observed for P. reticulata juveniles exposed to concentrations equal to or above 25 μg/L of rotenone; moreover, histological damage in the liver and gills of fish exposed to concentrations equal to or above 2.5 μg/L could be observed. A hazard concentration 5% (HC5) of 3.2 μg/L was estimated considering the acute toxicity data for different fish species (n = 49). Lethal and sublethal effects of rotenone raise a concern about its effects on nontarget fish species, especially because rotenone and its metabolite rotenolone are frequently reported in the microgram range in natural environments for several days after field applications. Rotenone should be used with caution. Given the high toxicity and wide range of sublethal effects here reported, further studies in a chronic exposure scenario are recommended.

Acute toxicity of some nerve agents and pesticides in rats.

PubMed

Misik, Jan; Pavlikova, Ruzena; Cabal, Jiri; Kuca, Kamil

2015-01-01

Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure. V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/). The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.

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.

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...

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.

Comparing probabilistic and descriptive analyses of time–dose–toxicity relationship for determining no-observed-adverse-effect level in drug development

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

Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder

The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; andmore » then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. - Highlights: • Simulations revealed issues with NOAEL concept, determination and application. • Probabilistic modelling was used to address these issues. • The model integrated time-dose-toxicity data from multiple studies. • The approach uses data efficiently and may allow more meaningful human translation.« less

Phase I Trial of Simultaneous In-Field Boost With Helical Tomotherapy for Patients With One to Three Brain Metastases

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

Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Yartsev, Slav; Yaremko, Brian

2011-07-15

Purpose: Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. Methods and Materials: The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lowermore » dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. Results: A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. Conclusion: The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.« less

DEPLOYMENT OF A WATER QUALITY EARLY WARNING SYSTEM USING ON-LINE TOXICITY MONITORS

EPA Science Inventory

Contaminants are of concern when they are found in concentrations that are toxic to plants and/or animals. On–line Toxicity Monitors (OTMs) integrate all factors resulting in stress including physical and chemical qualities. This is important because of the limitations of c...

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

In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity

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

Boisvert, Annie; Jones, Steven; Issop, Leeyah

Plasticizers are indispensable additives providing flexibility and malleability to plastics. Among them, several phthalates, including di (2-ethylhexyl) phthalate (DEHP), have emerged as endocrine disruptors, leading to their restriction in consumer products and creating a need for new, safer plasticizers. The goal of this project was to use in vitro functional screening tools to select novel non-toxic plasticizers suitable for further in vivo evaluation. A panel of novel compounds with satisfactory plasticizer properties and biodegradability were tested, along with several commercial plasticizers, such as diisononyl-cyclohexane-1,2-dicarboxylate (DINCH®). MEHP, the monoester metabolite of DEHP was also included as reference compound. Because phthalates targetmore » mainly testicular function, including androgen production and spermatogenesis, we used the mouse MA-10 Leydig and C18-4 spermatogonial cell lines as surrogates to examine cell survival, proliferation, steroidogenesis and mitochondrial integrity. The most promising compounds were further assessed on organ cultures of rat fetal and neonatal testes, corresponding to sensitive developmental windows. Dose-response studies revealed the toxicity of most maleates and fumarates, while identifying several dibenzoate and succinate plasticizers as innocuous on Leydig and germ cells. Interestingly, DINCH®, a plasticizer marketed as a safe alternative to phthalates, exerted a biphasic effect on steroid production in MA-10 and fetal Leydig cells. MEHP was the only plasticizer inducing the formation of multinucleated germ cells (MNG) in organ culture. Overall, organ cultures corroborated the cell line data, identifying one dibenzoate and one succinate as the most promising candidates. The adoption of such collaborative approaches for developing new chemicals should help prevent the development of compounds potentially harmful to human health. - Highlights: • Phthalate plasticizers exert toxic effects on male reproduction. • Reproductive toxicity of new plasticizers was assessed by functional assays. • Mouse Leydig and germ cell lines, and rat perinatal testis cultures were used. • Survival, proliferation, steroidogenesis, abnormal germ cell formation were examined. • Reproductive toxic and innocuous plasticizer candidates were identified.« less

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.

Genotoxicity testing of peptides: folate deprivation as a marker of exaggerated pharmacology.

PubMed

Guérard, Melanie; Zeller, Andreas; Festag, Matthias; Schubert, Christine; Singer, Thomas; Müller, Lutz

2014-09-15

The incidence of micronucleated-cells is considered to be a marker of a genotoxic event and can be caused by direct- or indirect-DNA reactive mechanisms. In particular, small increases in the incidence of micronuclei, which are not associated with toxicity in the target tissue or any structurally altering properties of the compound, trigger the suspicion that an indirect mechanism could be at play. In a bone marrow micronucleus test of a synthetic peptide (a dual agonist of the GLP-1 and GIP receptors) that had been integrated into a regulatory 13-week repeat-dose toxicity study in the rat, small increases in the incidence of micronuclei had been observed, together with pronounced reductions in food intake and body weight gain. Because it is well established that folate plays a crucial role in maintaining genomic integrity and pronounced reductions in food intake and body weight gain were observed, folate levels were determined from plasma samples initially collected for toxicokinetic analytics. A dose-dependent decrease in plasma folate levels was evident after 4 weeks of treatment at the mid and high dose levels, persisted until the end of the treatment duration of 13-weeks and returned to baseline levels during the recovery period of 4 weeks. Based on these properties, and the fact that the compound tested (peptide) per se is not expected to reach the nucleus and cause DNA damage, the rationale is supported that the elevated incidence of micronucleated polychromatic erythrocytes is directly linked to the exaggerated pharmacology of the compound resulting in a decreased folate level. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

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

Control of aliphatic halogenated DBP precursors with multiple drinking water treatment processes: Formation potential and integrated toxicity.

PubMed

Zhang, Yimeng; Chu, Wenhai; Yao, Dechang; Yin, Daqiang

2017-08-01

The comprehensive control efficiency for the formation potentials (FPs) of a range of regulated and unregulated halogenated disinfection by-products (DBPs) (including carbonaceous DBPs (C-DBPs), nitrogenous DBPs (N-DBPs), and iodinated DBPs (I-DBPs)) with the multiple drinking water treatment processes, including pre-ozonation, conventional treatment (coagulation-sedimentation, pre-sand filtration), ozone-biological activated carbon (O 3 -BAC) advanced treatment, and post-sand filtration, was investigated. The potential toxic risks of DBPs by combing their FPs and toxicity values were also evaluated. The results showed that the multiple drinking water treatment processes had superior performance in removing organic/inorganic precursors and reducing the formation of a range of halogenated DBPs. Therein, ozonation significantly removed bromide and iodide, and thus reduced the formation of brominated and iodinated DBPs. The removal of organic carbon and nitrogen precursors by the conventional treatment processes was substantially improved by O 3 -BAC advanced treatment, and thus prevented the formation of chlorinated C-DBPs and N-DBPs. However, BAC filtration leads to the increased formation of brominated C-DBPs and N-DBPs due to the increase of bromide/DOC and bromide/DON. After the whole multiple treatment processes, the rank order for integrated toxic risk values caused by these halogenated DBPs was haloacetonitriles (HANs)≫haloacetamides (HAMs)>haloacetic acids (HAAs)>trihalomethanes (THMs)>halonitromethanes (HNMs)≫I-DBPs (I-HAMs and I-THMs). I-DBPs failed to cause high integrated toxic risk because of their very low FPs. The significant higher integrated toxic risk value caused by HANs than other halogenated DBPs cannot be ignored. Copyright © 2017. Published by Elsevier B.V.

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)

Considerations for test design to accommodate energy-budget models in ecotoxicology: a case study for acetone in the pond snail Lymnaea stagnalis.

PubMed

Barsi, Alpar; Jager, Tjalling; Collinet, Marc; Lagadic, Laurent; Ducrot, Virginie

2014-07-01

Toxicokinetic-toxicodynamic (TKTD) modeling offers many advantages in the analysis of ecotoxicity test data. Calibration of TKTD models, however, places different demands on test design compared with classical concentration-response approaches. In the present study, useful complementary information is provided regarding test design for TKTD modeling. A case study is presented for the pond snail Lymnaea stagnalis exposed to the narcotic compound acetone, in which the data on all endpoints were analyzed together using a relatively simple TKTD model called DEBkiss. Furthermore, the influence of the data used for calibration on accuracy and precision of model parameters is discussed. The DEBkiss model described toxic effects on survival, growth, and reproduction over time well, within a single integrated analysis. Regarding the parameter estimates (e.g., no-effect concentration), precision rather than accuracy was affected depending on which data set was used for model calibration. In addition, the present study shows that the intrinsic sensitivity of snails to acetone stays the same across different life stages, including the embryonic stage. In fact, the data on egg development allowed for selection of a unique metabolic mode of action for the toxicant. Practical and theoretical considerations for test design to accommodate TKTD modeling are discussed in the hope that this information will aid other researchers to make the best possible use of their test animals. © 2014 SETAC.

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.

Bioavailability and Environmental Regulation - Integrating a Fate & Effects Model with a Biotic Ligand Model for Copper in Seawater

NASA Astrophysics Data System (ADS)

Rivera, I.; Chadwick, B.; Rosen, G.; Wang, P. F.; Paquin, P.; Santore, R.; Ryan, A.

2015-12-01

Understanding the bioavailability of metals in the aquatic environment is important for defining appropriate regulatory constraints. A failure to recognize the importance of bioavailability factors on metal toxicity can result in criteria that are over- or under-protective. USEPA addresses the tendency of the national Water Quality Criterion (WQC) for regulation of copper in marine waters to underestimate the natural attenuation of copper toxicity in harbors by the application of site-specific Water Quality Standards (WQS). Which provides the level of protection intended by the WQC, and establishes realistic regulatory objectives. However, development of site-specific WQS involves a long-term effort, and does not account for temporal variation. The toxicity model seawater-Biotic Ligand Model (BLM) was developed and integrated with the existing Curvilinear Hydrodynamics in 3 Dimensions (CH3D) transport & fate model to create an efficient tool for development of site-specific WQS in harbors. The integrated model was demonstrated at a harbor-wide scale in San Diego Bay and Pearl Harbor, and accounted for the natural physical, chemical, biological and toxicological characteristics of the harbor to achieve more scientifically based compliance. In both harbors the spatial and temporal distributions of copper species, toxic effects, and Water Effect Ratio predicted by the integrated model are comparable to previous data. The model was further demonstrated in Shelter Island Yacht Basin (SIYB) marina in San Diego Bay. The integrated model agreed with toxicological and chemical approaches by indicating negligible bioavailability as well as no toxicity; but for a single event, even though an increasing gradient in Cu was observed both horizontally and vertically, with concentrations that reached levels well above current regulatory thresholds. These results support the incorporation by USEPA of the seawater-BLM in a full-strength seawater criterion.

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.

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.

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.

Mapping sediment contamination and toxicity in Winter Quarters Bay, McMurdo Station, Antarctica.

PubMed

Crockett, Alan B; White, Gregory J

2003-07-01

Winter Quarters Bay (WQB) is a small embayment located adjacent to McMurdo Station, the largest research base in Antarctica. The bay is approximately 250 m wide and long, with a maximum depth of 33 m. Historically, trash from the McMurdo Station was piled on the steep shoreline of WQB, doused with fuel and ignited. That practice has ceased, and the adjacent land area has been regraded to cover the residual waste. The bottom of WQB remains littered with drums, equipment, tanks, tires, cables, and other objects, especially the southeastern side of the bay where dumping took place. Sediments are contaminated with PCBs, metals, and hydrocarbon fuels. The objectives of this study were to map the distribution of organic contaminants in WQB, assess the toxicity of WQB sediments using a simple microbial test, and determine correlations between toxicity and contaminant levels. The study suggests that adverse ecological effects have occurred from one or more of the contaminants found in WQB but the source of the toxic impacts to bay sediments remains unknown. Whole sediment toxicity was only correlated with oil-equivalent while solvent extracts of sediments were correlated with PAHs and oil-equivalent. The authors recommend that an integrated research plan be developed that focuses on determining what additional information is needed to make informed decisions on possible remediation of WQB.

Assessment of the application of an ecotoxicological procedure to screen illicit toxic discharges in domestic septic tank sludge.

PubMed

López-Gastey, J; Choucri, A; Robidoux, P Y; Sunahara, G I

2000-06-01

An innovative screening procedure has been developed to detect illicit toxic discharges in domestic septic tank sludge hauled to the Montreal Urban Community waste-water treatment plant. This new means of control is based on an integrative approach, using bioassays and chemical analyses. Conservative criteria are applied to detect abnormal toxicity with great reliability while avoiding false positive results. The complementary data obtained from toxicity tests and chemical analyses support the use of this efficient and easy-to-apply procedure. This study assesses the control procedure in which 231 samples were analyzed over a 30-month period. Data clearly demonstrate the deterrent power of an efficient control procedure combined with a public awareness campaign among the carriers. In the first 15 months of application, between January 1996 and March 1997, approximately 30% of the 123 samples analyzed showed abnormal toxicity. Between April 1997 and June 1998, that is, after a public hearing presentation of this procedure, this proportion dropped significantly to approximately 9% based on 108 analyzed samples. The results of a 30-month application of this new control procedure show the superior efficiency of the ecotoxicological approach compared with the previously used chemical control procedure. To be able to apply it effectively and, if necessary, to apply the appropriate coercive measures, ecotoxicological criteria should be included in regulatory guidelines.

Continuation of the Ecological Risk Assessment of Explosive Residues in Rodents, Reptiles, Amphibians, Fish and Invertebrates: An Integrated Laboratory and Field Investigation Related to Live-Fire Ranges in the Department of Defense

DTIC Science & Technology

2008-08-01

malicum strain HAAP-1 isolated from a methanogenic mixed culture. Current Microbiology 48:332-340. Army. 1985h. HMX: Acute toxicity tests in...explosives: biotransformation versus mineralization. Applied Microbiology and Biotechnology 54:605-618. Hawari J, Halasz A, Sheremata T, Beaudet S...triazine (RDX) with municipal anaerobic sludge. Applied and Environmental Microbiology 66:2652-2657. Kudo, H., and Y. Oki. 1984. Microtus species

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.

Integration of QSAR and in vitro toxicology.

PubMed Central

Barratt, M D

1998-01-01

The principles of quantitative structure-activity relationships (QSAR) are based on the premise that the properties of a chemical are implicit in its molecular structure. Therefore, if a mechanistic hypothesis can be proposed linking a group of related chemicals with a particular toxic end point, the hypothesis can be used to define relevant parameters to establish a QSAR. Ways in which QSAR and in vitro toxicology can complement each other in development of alternatives to live animal experiments are described and illustrated by examples from acute toxicological end points. Integration of QSAR and in vitro methods is examined in the context of assessing mechanistic competence and improving the design of in vitro assays and the development of prediction models. The nature of biological variability is explored together with its implications for the selection of sets of chemicals for test development, optimization, and validation. Methods are described to support the use of data from in vivo tests that do not meet today's stringent requirements of acceptability. Integration of QSAR and in vitro methods into strategic approaches for the replacement, reduction, and refinement of the use of animals is described with examples. PMID:9599692

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

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 ...

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.

Guidelines for performing systematic reviews in the development of toxicity factors.

PubMed

Schaefer, Heather R; Myers, Jessica L

2017-12-01

The Texas Commission on Environmental Quality (TCEQ) developed guidance on conducting systematic reviews during the development of chemical-specific toxicity factors. Using elements from publicly available frameworks, the TCEQ systematic review process was developed in order to supplement the existing TCEQ Guidelines for developing toxicity factors (TCEQ Regulatory Guidance 442). The TCEQ systematic review process includes six steps: 1) Problem Formulation; 2) Systematic Literature Review and Study Selection; 3) Data Extraction; 4) Study Quality and Risk of Bias Assessment; 5) Evidence Integration and Endpoint Determination; and 6) Confidence Rating. This document provides guidance on conducting a systematic literature review and integrating evidence from different data streams when developing chemical-specific reference values (ReVs) and unit risk factors (URFs). However, this process can also be modified or expanded to address other questions that would benefit from systematic review practices. The systematic review and evidence integration framework can improve regulatory decision-making processes, increase transparency, minimize bias, improve consistency between different risk assessments, and further improve confidence in toxicity factor development. Copyright © 2017 The Author(s). Published by Elsevier Inc. 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...

A novel continuous toxicity test system using a luminously modified freshwater bacterium.

PubMed

Cho, Jang-Cheon; Park, Kyung-Je; Ihm, Hyuk-Soon; Park, Ji-Eun; Kim, Se-Young; Kang, Ilnam; Lee, Kyu-Ho; Jahng, Deokjin; Lee, Dong-Hun; Kim, Sang-Jong

2004-09-15

An automated continuous toxicity test system was developed using a recombinant bioluminescent freshwater bacterium. The groundwater-borne bacterium, Janthinobacterium lividum YH9-RC, was modified with luxAB and optimized for toxicity tests using different kinds of organic carbon compounds and heavy metals. luxAB-marked YH9-RC cells were much more sensitive (average 7.3-8.6 times) to chemicals used for toxicity detection than marine Vibrio fischeri cells used in the Microtox assay. Toxicity tests for wastewater samples using the YH9-RC-based toxicity assay showed that EC50-5 min values in an untreated raw wastewater sample (23.9 +/- 12.8%) were the lowest, while those in an effluent sample (76.7 +/- 14.9%) were the highest. Lyophilization conditions were optimized in 384-multiwell plates containing bioluminescent bacteria that were pre-incubated for 15 min in 0.16 M of trehalose prior to freeze-drying, increasing the recovery of bioluminescence and viability by 50%. Luminously modified cells exposed to continuous phenol or wastewater stream showed a rapid decrease in bioluminescence, which fell below detectable range within 1 min. An advanced toxicity test system, featuring automated real-time toxicity monitoring and alerting functions, was designed and finely tuned. This novel continuous toxicity test system can be used for real-time biomonitoring of water toxicity, and can potentially be used as a biological early warning system.

Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle.

PubMed

Zore, Gajanan B; Thakre, Archana D; Jadhav, Sitaram; Karuppayil, S Mohan

2011-10-15

Anti-Candida potential of six terpenoids were evaluated in this study against various isolates of Candida albicans (n=39) and non-C. albicans (n=9) that are differentially susceptible to fluconazole. All the six terpenoids tested, showed excellent activity and were equally effective against isolates of Candida sps., tested in this study. Linalool and citral were the most effective ones, inhibiting all the isolates at ≤0.064% (v/v). Five among the six terpenoids tested were fungicidal. Time dependent kill curve assay showed that MFCs of linalool and eugenol were highly toxic to C. albicans, killing 99.9% inoculum within seven min of exposure, while that of citronellal, linalyl acetate and citral required 15min, 1h and 2h, respectively. FIC index values (Linalool - 0.140, benzyl benzoate - 0.156, eugenol - 0.265, citral - 0.281 and 0.312 for linalyl acetate and citronellal) and isobologram obtained by checker board assay showed that all the six terpenoids tested exhibit excellent synergistic activity with fluconazole against a fluconazole resistant strain of C. albicans. Terpenoids tested arrested C. albicans cells at different phases of the cell cycle i.e. linalool and LA at G1, citral and citronellal at S phase and benzyl benzoate at G2-M phase and induced apoptosis. Linalool, citral, citronellal and benzyl benzoate caused more than 50% inhibition of germ tube induction at 0.008%, while eugenol and LA required 0.032 and 0.016% (v/v) concentrations, respectively. MICs of all the terpenoids for the C. albicans growth were non toxic to HeLa cells. Terpenoids tested exhibited excellent activity against C. albicans yeast and hyphal form growth at the concentrations that are non toxic to HeLa cells. Terpenoids tested in this study may find use in antifungal chemotherapy, not only as antifungal agents but also as synergistic agents along with conventional drugs like fluconazole. Copyright © 2011 Elsevier GmbH. All rights reserved.

Is the risk for soil arthropods covered by new data requirements under the EU PPP Regulation No. 1107/2009?

PubMed

Kohlschmid, E; Ruf, D

2016-12-01

Testing of effects on earthworms and non-target foliar arthropods is an integral part of the ecotoxicological risk assessment for the authorization of plant protection products. According to the new data requirements, which came into force in 2014 for active substances and in 2016 for plant protection products, the chronic earthworm toxicity test with Eisenia fetida based on reproductive, growth, and behavioral effects instead of the acute earthworm toxicity test based on mortality, has to be conducted routinely. Additional testing of effects on soil arthropods (Folsomia candida, Hyposaspis aculeifer) is required if the risk assessment of foliar applications raises concerns regarding non-target foliar arthropods (Aphidius rhopalosiphi, Typhlodromus pyri) or if the product is applied directly on or into the soil. Thus, it was investigated whether the sublethal earthworm endpoint is more sensitive than the sublethal soil arthropod endpoint for different types of pesticides and whether the risk assessment for non-target arthropods would trigger the testing of effects on soil arthropods in the cases where soil arthropods are more sensitive than earthworms. Toxicity data were obtained from Swiss ecotoxicological database, EFSA Conclusions and scientific literature. For insecticides and herbicides, no general conclusion regarding differences in sensitivity of either earthworms or soil arthropods based on sublethal endpoints were possible. For fungicides, the data indicated that in general, earthworms seemed to be more sensitive than soil arthropods. In total, the sublethal F. candida or H. aculeifer endpoint was lower than the sublethal E. fetida endpoint for 23 (34 %) out of 68 active substances. For 26 % of these 23 active substances, testing of soil arthropods would not have been triggered due to the new data requirement. These results based on sublethal endpoints show that earthworms and soil arthropods differ in sensitivity toward certain active substances and that the risk assessment for non-target foliar arthropods did not always trigger soil arthropod testing in the cases where soil arthropods were more sensitive than earthworms.

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.

PH DEPENDENT TOXICITY OF FIVE METALS TO THREE MARINE ORGANISMS

EPA Science Inventory

The pH of natural marine systems is relatively stable; this may explain why metal toxicity changes with pH have not been well documented. However, changes in metal toxicity with pH in marine waters are of concern in toxicity testing. During porewater toxicity testing pH can chang...

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

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.

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

ECVAM and new technologies for toxicity testing.

PubMed

Bouvier d'Yvoire, Michel; Bremer, Susanne; Casati, Silvia; Ceridono, Mara; Coecke, Sandra; Corvi, Raffaella; Eskes, Chantra; Gribaldo, Laura; Griesinger, Claudius; Knaut, Holger; Linge, Jens P; Roi, Annett; Zuang, Valérie

2012-01-01

The development of alternative empirical (testing) and non-empirical (non-testing) methods to traditional toxicological tests for complex human health effects is a tremendous task. Toxicants may potentially interfere with a vast number of physiological mechanisms thereby causing disturbances on various levels of complexity of human physiology. Only a limited number of mechanisms relevant for toxicity ('pathways' of toxicity) have been identified with certainty so far and, presumably, many more mechanisms by which toxicants cause adverse effects remain to be identified. Recapitulating in empirical model systems (i.e., in vitro test systems) all those relevant physiological mechanisms prone to be disturbed by toxicants and relevant for causing the toxicity effect in question poses an enormous challenge. First, the mechanism(s) of action of toxicants in relation to the most relevant adverse effects of a specific human health endpoint need to be identified. Subsequently, these mechanisms need to be modeled in reductionist test systems that allow assessing whether an unknown substance may operate via a specific (array of) mechanism(s). Ideally, such test systems should be relevant for the species of interest, i.e., based on human cells or modeling mechanisms present in humans. Since much of our understanding about toxicity mechanisms is based on studies using animal model systems (i.e., experimental animals or animal-derived cells), designing test systems that model mechanisms relevant for the human situation may be limited by the lack of relevant information from basic research. New technologies from molecular biology and cell biology, as well as progress in tissue engineering, imaging techniques and automated testing platforms hold the promise to alleviate some of the traditional difficulties associated with improving toxicity testing for complex endpoints. Such new technologies are expected (1) to accelerate the identification of toxicity pathways with human relevance that need to be modeled in test methods for toxicity testing (2) to enable the reconstruction of reductionist test systems modeling at a reduced level of complexity the target system/organ of interest (e.g., through tissue engineering, use of human-derived cell lines and stem cells etc.), (3) to allow the measurement of specific mechanisms relevant for a given health endpoint in such test methods (e.g., through gene and protein expression, changes in metabolites, receptor activation, changes in neural activity etc.), (4) to allow to measure toxicity mechanisms at higher throughput rates through the use of automated testing. In this chapter, we discuss the potential impact of new technologies on the development, optimization and use of empirical testing methods, grouped according to important toxicological endpoints. We highlight, from an ECVAM perspective, the areas of topical toxicity, skin absorption, reproductive and developmental toxicity, carcinogenicity/genotoxicity, sensitization, hematopoeisis and toxicokinetics and discuss strategic developments including ECVAM's database service on alternative methods. Neither the areas of toxicity discussed nor the highlighted new technologies represent comprehensive listings which would be an impossible endeavor in the context of a book chapter. However, we feel that these areas are of utmost importance and we predict that new technologies are likely to contribute significantly to test development in these fields. We summarize which new technologies are expected to contribute to the development of new alternative testing methods over the next few years and point out current and planned ECVAM projects for each of these areas.

Inhibition of CYP6B1-mediated detoxification of xanthotoxin by plant allelochemicals in the black swallowtail (Papilio polyxenes).

PubMed

Wen, Zhimou; Berenbaum, May R; Schuler, Mary A

2006-03-01

The structural and biosynthetic diversity of allelochemicals in plants is thought to arise from selection for additive toxicity as a consequence of toxin mixture or for enhanced toxicity as a result of synergism. In order to understand how insects cope with this type of plant defense, we tested the effects of some allelochemicals in host plants of the black swallowtail Papilio polyxenes on the xanthotoxin-metabolic activity of CYP6B1, the principal enzyme responsible for the detoxification of furanocoumarins in this caterpillar. Additionally, the effects of some synthetic compounds not normally encountered by P. polyxenes on CYP6B1 were tested. These studies demonstrate that the integrity of furanocoumarin structure is important for competitive binding to the active site of CYP6B1, even though the carbonyl group on the pyranone ring apparently does not affect its inhibitory capacity, as in the case of furanochromones. Angular furanocoumarins are generally less phototoxic to many organisms than linear furanocoumarins due to their reduced capacity for cross-linking DNA strands, yet they are more toxic than linear furanocoumarins to black swallowtail larvae. This enhanced toxicity in vivo may be due to the ability of angular furanocoumarins to bind to the active site of CYP6B1 without being rapidly metabolized. This binding reduces the availability of CYP6B1 to metabolize other linear furanocoumarins. The structure-activity relationships for methylenedioxyphenyl compounds, flavonoids, imidazole, and imidazole derivatives are also discussed in light of their capacity to inhibit the xanthotoxin-metabolic activity of CYP6B1.

Effect of bis(tributyltin) oxide on reproduction and population growth rate of calanoid copepod Schmackeria poplesia

NASA Astrophysics Data System (ADS)

Huang, Ying; Zhu, Liyan; Qiu, Xuchun; Zhang, Tianwen

2010-03-01

A full life-cycle toxicity test, combined with histology, on calanoid copepod Schmackeria poplesia was used to study the effect of bis(tributyltin) oxide (TBTO). The results indicate no sex-specific differences in TBTO toxicity. Long-term mortalities of the copepods exposed to concentrations higher than 20 ng TBTO L-1 were significantly elevated compared with that of control, and larval development was inhibited when they were exposed to 40 and 60 ng TBTO L-1. The percentages of ovigerous females were reduced compared with the control ( P<0.01) after 24 days exposure to concentrations higher than 10 ng TBTO L-1. Histological examinations suggest that exposure to TBTO might block the posterior end of the diverticula and inhibits the production of egg sacs. A modified Euler-Lotka equation was used to calculate a population-level endpoint, the intrinsic rate of natural increase ( r m), from individual life-table endpoints, i.e. mortality rate, time of release of first brood, sex ratio, the fraction of ovigerous females among all females as well as the number of nauplii per ovigerous female. Apart from the highest TBTO concentration (60 ng L-1), where all females aborted their egg sacs, 20 ng TBTO L-1 was the only concentration that significantly decreased r m compared with that of control (an effect associated with decreased sex ratio). The results show that the S. poplesia is affected by prolonged exposure to low concentrations of TBTO. The full life-cycle toxicity test combined with histology experiments provides more integral understanding of the toxicity of endocrine disrupters.

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.

Cytotoxicity of metal and semiconductor nanoparticles indicated by cellular micromotility.

PubMed

Tarantola, Marco; Schneider, David; Sunnick, Eva; Adam, Holger; Pierrat, Sebastien; Rosman, Christina; Breus, Vladimir; Sönnichsen, Carsten; Basché, Thomas; Wegener, Joachim; Janshoff, Andreas

2009-01-27

In the growing field of nanotechnology, there is an urgent need to sensitively determine the toxicity of nanoparticles since many technical and medical applications are based on controlled exposure to particles, that is, as contrast agents or for drug delivery. Before the in vivo implementation, in vitro cell experiments are required to achieve a detailed knowledge of toxicity and biodegradation as a function of the nanoparticles' physical and chemical properties. In this study, we show that the micromotility of animal cells as monitored by electrical cell-substrate impedance analysis (ECIS) is highly suitable to quantify in vitro cytotoxicity of semiconductor quantum dots and gold nanorods. The method is validated by conventional cytotoxicity testing and accompanied by fluorescence and dark-field microscopy to visualize changes in the cytoskeleton integrity and to determine the location of the particles within the cell.

Health risk evaluation associated to Planktothrix rubescens: An integrated approach to design tailored monitoring programs for human exposure to cyanotoxins.

PubMed

Manganelli, Maura; Scardala, Simona; Stefanelli, Mara; Vichi, Susanna; Mattei, Daniela; Bogialli, Sara; Ceccarelli, Piegiorgio; Corradetti, Ernesto; Petrucci, Ines; Gemma, Simonetta; Testai, Emanuela; Funari, Enzo

2010-03-01

Increasing concern for human health related to cyanotoxin exposure imposes the identification of pattern and level of exposure; however, current monitoring programs, based on cyanobacteria cell counts, could be inadequate. An integrated approach has been applied to a small lake in Italy, affected by Planktothrix rubescens blooms, to provide a scientific basis for appropriate monitoring program design. The cyanobacterium dynamic, the lake physicochemical and trophic status, expressed as nutrients concentration and recycling rates due to bacterial activity, the identification/quantification of toxic genotype and cyanotoxin concentration have been studied. Our results indicate that low levels of nutrients are not a marker for low risk of P. rubescens proliferation and confirm that cyanobacterial density solely is not a reliable parameter to assess human exposure. The ratio between toxic/non-toxic cells, and toxin concentrations, which can be better explained by toxic population dynamic, are much more diagnostic, although varying with time and environmental conditions. The toxic fraction within P. rubescens population is generally high (30-100%) and increases with water depth. The ratio toxic/non-toxic cells is lowest during the bloom, suggesting a competitive advantage for non-toxic cells. Therefore, when P. rubescens is the dominant species, it is important to analyze samples below the thermocline, and quantitatively estimate toxic genotype abundance. In addition, the identification of cyanotoxin content and congeners profile, with different toxic potential, are crucial for risk assessment. Copyright 2009 Elsevier Ltd. All rights reserved.

Acute aquatic toxicity of biodiesel fuels

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

Wright, B.; Haws, R.; Little, D.

1995-12-31

This study develops data on the acute aquatic toxicity of selected biodiesel fuels which may become subject to environmental effects test regulations under the US Toxic Substances Control Act (TSCA). The test substances are Rape Methyl Ester (RME), Rape Ethyl Ester (REE), Methyl Soyate (MS), a biodiesel mixture of 20% REE and 80% Diesel, a biodiesel mixture of 50% REE and diesel, and a reference substance of Phillips D-2 Reference Diesel. The test procedure follows the Daphnid Acute Toxicity Test outlined in 40 CFR {section} 797.1300 of the TSCA regulations. Daphnia Magna are exposed to the test substance in amore » flow-through system consisting of a mixing chamber, a proportional diluter, and duplicate test chambers. Novel system modifications are described that accommodate the testing of oil-based test substances with Daphnia. The acute aquatic toxicity is estimated by an EC50, an effective concentration producing immobility in 50% of the test specimen.« less

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...

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.

Anatomy of a decision III: Evaluation of national disposal at sea program action level efficacy considering 2 chemical action levels.

PubMed

Apitz, Sabine E; Vivian, Chris; Agius, Suzanne

2017-11-01

The potential performance (i.e., ability to separate nontoxic from toxic sediments) of a range of international Disposal at Sea (DaS) chemical Action Levels (ALs) was compared using a sediment chemical and toxicological database. The use of chemistry alone (without the use of further lines of evidence) did not perform well at reducing costs and protecting the environment. Although some approaches for interpreting AL1 results are very effective at filtering out the majority of acutely toxic sediments, without subsequent toxicological assessment, a large proportion of nontoxic sediments would be unnecessarily subjected to treatment and containment, and a number of sublethally toxic sediments would be missed. Even the best tiered systems that collect and evaluate information sequentially resulted in the failure to catch at least some sublethally or acutely toxic sediments. None of the AL2s examined were particularly effective in distinguishing between non-, sublethally, or acutely toxic sediments. Thus, this review did not support the use of chemical AL2s to predict the degree to which sediments will be toxic. Integr Environ Assess Manag 2017;13:1086-1099.© 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

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.

Development of an Integrated Toxicity Assessment System for use in Operational Deployment and Materials Development

DTIC Science & Technology

2006-05-01

In addition to NBC concerns, there are issues in many current military settings for exposures to toxic industrial chemicals or materials (TICs or TIMs...Significant health issues caused by use of legacy chemicals have emphasized the need for more effective predication of chemical toxicity . This paper...current military settings for exposures to toxic industrial chemicals or materials (TICs or TIMs). Significant health issues caused by use of legacy

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.

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.

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

Galleria mellonella larvae allow the discrimination of toxic and non-toxic chemicals.

PubMed

Allegra, Enrico; Titball, Richard W; Carter, John; Champion, Olivia L

2018-05-01

The acute toxicities of 19 chemicals were assessed using G. mellonella larvae. The results obtained were compared against LD50 values derived from in vitro cytotoxicity tests and against in vivo acute oral LD50 values. In general, cell culture systems overestimated the toxicity of chemicals, especially low toxicity chemicals. In contrast, toxicity testing in G. mellonella larvae was found to be a reliable predictor for low toxicity chemicals. For the 9 chemicals tested which were assigned to Globally Harmonised System (GHS) category 5, the toxicity measured in G. mellonella larvae was consistent with their GHS categorisation but cytotoxicity measured in 3T3 or NHK cells predicted 4 out of 9 chemicals as having low toxicity. A more robust assessment of the likely toxicity of chemicals in mammals could be made by taking into account their toxicities in both cell cultures and in G. mellonella larvae. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Conceptual Framework To Extend Life Cycle Assessment Using Near-Field Human Exposure Modeling and High-Throughput Tools for Chemicals.

PubMed

Csiszar, Susan A; Meyer, David E; Dionisio, Kathie L; Egeghy, Peter; Isaacs, Kristin K; Price, Paul S; Scanlon, Kelly A; Tan, Yu-Mei; Thomas, Kent; Vallero, Daniel; Bare, Jane C

2016-11-01

Life Cycle Assessment (LCA) is a decision-making tool that accounts for multiple impacts across the life cycle of a product or service. This paper presents a conceptual framework to integrate human health impact assessment with risk screening approaches to extend LCA to include near-field chemical sources (e.g., those originating from consumer products and building materials) that have traditionally been excluded from LCA. A new generation of rapid human exposure modeling and high-throughput toxicity testing is transforming chemical risk prioritization and provides an opportunity for integration of screening-level risk assessment (RA) with LCA. The combined LCA and RA approach considers environmental impacts of products alongside risks to human health, which is consistent with regulatory frameworks addressing RA within a sustainability mindset. A case study is presented to juxtapose LCA and risk screening approaches for a chemical used in a consumer product. The case study demonstrates how these new risk screening tools can be used to inform toxicity impact estimates in LCA and highlights needs for future research. The framework provides a basis for developing tools and methods to support decision making on the use of chemicals in products.

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.

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 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.

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

Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Biswas, Jaydip; Bhattacharya, Sudin

2015-07-01

Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid peroxidation as evident by increased in reactive oxygen species, nitric oxide level, and malondialdehyde (MDA) formation with decreased in level of antioxidants such as reduced glutathione, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. Furthermore, CP at a dose of 25 mg/kg b.w. increased pulmonary DNA damage ('comet tail') and triggered DNA fragmentation and apoptosis in mouse bone marrow cells. On the other hand, Nano-Se at a dose of 2 mg Se/kg b.w., significantly inhibited CP-induced DNA damage in bronchoalveolar lavage cells, and decreased the apoptosis and percentage of DNA fragmentation in bone marrow cells and also antagonized the reduction of the activities of antioxidant enzymes and the increase level of MDA. Thus, our results suggest that Nano-Se in pre- and co-administration may serve as a promising preventive strategy against CP-induced pulmonary toxicity.

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.

Petroleum coke adsorption as a water management option for oil sands process-affected water.

PubMed

Zubot, Warren; MacKinnon, Michael D; Chelme-Ayala, Pamela; Smith, Daniel W; Gamal El-Din, Mohamed

2012-06-15

Water is integral to both operational and environmental aspects of the oil sands industry. A water treatment option based on the use of petroleum coke (PC), a by-product of bitumen upgrading, was examined as an opportunity to reduce site oil sands process-affected water (OSPW) inventories and net raw water demand. Changes in OSPW quality when treated with PC included increments in pH levels and concentrations of vanadium, molybdenum, and sulphate. Constituents that decreased in concentration after PC adsorption included total acid-extractable organics (TAO), bicarbonate, calcium, barium, magnesium, and strontium. Changes in naphthenic acids (NAs) speciation were observed after PC adsorption. A battery of bioassays was used to measure the OSPW toxicity. The results indicated that untreated OSPW was toxic towards Vibrio fischeri and rainbow trout. However, OSPW treated with PC at appropriate dosages was not acutely toxic towards these test organisms. Removal of TAO was found to be an adsorption process, fitting the Langmuir and Langmuir-Freundlich isotherm models. For TAO concentrations of 60 mg/L, adsorption capacities ranged between 0.1 and 0.46 mg/g. This study demonstrates that freshly produced PC from fluid cokers provides an effective treatment of OSPW in terms of key constituents' removal and toxicity reduction. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of plant essential oils as acaricides against the poultry red mite, Dermanyssus gallinae, with special focus on exposure time.

PubMed

George, D R; Olatunji, G; Guy, J H; Sparagano, O A E

2010-04-19

Essential oils from thyme and cade have been shown to be effective acaricides against the poultry red mite, Dermanyssus gallinae (De Geer) when tested over a 24h period. Data on the actual rate of knock-down achieved with these products is lacking and potentially important as essential oils are likely to display only short-term toxicity. When tested over periods of less than 24h, thyme essential oil killed D. gallinae relatively quickly and so may make for an effective acaricide even if the residual toxicity of this product is low. However, cade essential oil did not display such a high level of mite knock-down, suggesting it may hold less promise in D. gallinae management. Comparison of the results with those obtained elsewhere using alternative D. gallinae products further confirms the possibility that thyme essential may be useful in control of this pest. This might be especially true if thyme essential oil were employed as part of an integrated pest management approach.

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

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

Fumigant Toxicity and Sublethal Effects of Artemisia khorassanica and Artemisia sieberi on Sitotroga cerealella (Lepidoptera: Gelechiidae)

PubMed Central

Abedi, Z; Abdolmaleki, A; Jafary-Jahed, M; Borzoui, E; Mozaffar Mansouri, Seyed

2017-01-01

Abstract Fumigant toxicity and sublethal effects of essential oils from Artemisia khorassanica Podl. and Artemisia sieberi Bess were investigated against adults of Sitotroga cerealella Olivier. To assess the sublethal effects, adult moths were exposed to the LC30 of each essential oil, and life table parameters of the surviving S. cerealella were studied. Higher fumigant toxicity of A. khorassanica (LC50: 7.38 µl/liter air) than A. sieberi (LC50: 9.26 µl/liter air) was observed against S. cerealella. Also, the insecticidal effects of A. khorassanica (LT50: 9.01 h) were faster than A. sieberi (LT50: 14.37 h). A significant extension was observed in the developmental time (egg to adult) of S. cerealella treated with the essential oils. In addition, fecundity of S. cerealella reduced by 25.29 and 35.78% following exposure to sublethal concentrations of A. sieberi and A. khorassanica, respectively. Both tested essential oils caused a significant reduction in the gross and net reproductive rates, intrinsic rate of increase (rm), and finite rate of increase of S. cerealella. The rm values following exposure to A. sieberi, A. khorassanica, and control were 0.098, 0.094, and 0.107 d−1, respectively. The results of this study suggest that tested essential oils have a good potential to apply in integrated pest management of S. cerealella. PMID:29117375

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

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.

Exploring an herbal "wonder cure" for cancer: a multidisciplinary approach.

PubMed

Ben-Arye, Eran; Mahajna, Jamal; Aly, Radi; Ali-Shtayeh, Mohammed Saleem; Bentur, Yedidia; Lev, Efraim; Deng, Gary; Samuels, Noah

2016-07-01

The unmonitored use of herbal medicinal remedies by patients with cancer presents a significant challenge to oncology healthcare professionals. We describe an increasingly popular herbal "wonder drug," Ephedra foeminea (Alanda in Arabic), whose use has spread from the Palestinian patient population throughout the Middle East. We conducted a multicentered and multidisciplinary collaborative research effort in order to understand the potential benefits and harms of this popular herbal remedy. We conducted an in-depth search of the medical literature, both traditional and modern, for any mention of the clinical use of Alanda for the treatment of cancer. We then tested the remedy, first for toxic ephedra alkaloid components and then for anticancer effects, as well as effects on the cytotoxic activity of chemotherapy agents (cisplatin and carboplatin) on breast cancer cell cultures. We found no mention in the literature, both conventional and traditional, on the use of Alanda for the treatment of cancer. Laboratory testing did not find any toxic components (i.e., ephedra alkaloids) in the preparation. However, in vitro exposure to Alanda led to a reduced cytotoxic effect of chemotherapy on breast cancer cell cultures. The use of an integrative ethnobotanical, laboratory and clinical research-based approach can be extremely helpful when providing nonjudgmental and evidence-based guidance to patients with cancer, especially on the use of traditional herbal medicine. The effectiveness and safety of these products need to be examined by integrative physicians who are dually trained in both complementary medicine and supportive cancer care.

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...

Development of an in vitro test battery for assessing chemical effects on bovine germ cells under the ReProTect umbrella

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

Lazzari, Giovanna; Tessaro, Irene; Crotti, Gabriella

2008-12-15

Current European legislation for the registration and authorisation of chemicals (REACH) will require a dramatic increase in the use of animals for reproductive toxicity testing. Since one objective of REACH is to use vertebrates only as last resort, the development and validation of alternative methods is urgently needed. For this purpose ReProTect, an integrated research project funded by the European Union, joining together 33 partners with complementary expertise in reproductive toxicology, was designed. The study presented here describes a battery of two tests developed within ReProTect. The objective of these tests is the detection of chemical effects during the processesmore » of oocyte maturation and fertilisation in a bovine model. The corresponding toxicological endpoints are the reaching of metaphase II and the formation of the pronuclei respectively. Fifteen chemicals have been tested (Benzo[a]pyrene, Busulfan, Butylparaben, Cadmium Chloride, Carbendazim, Cycloheximide, Diethylstilbestrol, Genistein, Ionomycin, Ketoconazole, Lindane, Methylacetoacetate, Mifepristone, Nocodazole and DMSO as solvent) demonstrating high intra-laboratory reproducibility of the tests. Furthermore, the responses obtained in both tests, for several substances, had a good correlation with the available in vivo and in vitro data. These tests therefore, could predictably become part of an integrated testing strategy that combines the bovine models with additional in vitro tests, in order to predict chemical hazards on mammalian fertility.« less

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.

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.

Behavioural and biochemical responses to metals tested alone or in mixture (Cd-Cu-Ni-Pb-Zn) in Gammarus fossarum: From a multi-biomarker approach to modelling metal mixture toxicity.

PubMed

Lebrun, Jérémie D; Uher, Emmanuelle; Fechner, Lise C

2017-12-01

Metals are usually present as mixtures at low concentrations in aquatic ecosystems. However, the toxicity and sub-lethal effects of metal mixtures on organisms are still poorly addressed in environmental risk assessment. Here we investigated the biochemical and behavioural responses of Gammarus fossarum to Cu, Cd, Ni, Pb and Zn tested individually or in mixture (M2X) at concentrations twice the levels of environmental quality standards (EQSs) from the European Water Framework Directive. The same metal mixture was also tested with concentrations equivalent to EQSs (M1X), thus in a regulatory context, as EQSs are proposed to protect aquatic biota. For each exposure condition, mortality, locomotion, respiration and enzymatic activities involved in digestive metabolism and moult were monitored over a 120h exposure period. Multi-metric variations were summarized by the integrated biomarker response index (IBR). Mono-metallic exposures shed light on biological alterations occurring at environmental exposure levels in gammarids and depending on the considered metal and gender. As regards mixtures, biomarkers were altered for both M2X and M1X. However, no additive or synergistic effect of metals was observed comparing to mono-metallic exposures. Indeed, bioaccumulation data highlighted competitive interactions between metals in M2X, decreasing subsequently their internalisation and toxicity. IBR values indicated that the health of gammarids was more impacted by M1X than M2X, because of reduced competitions and enhanced uptakes of metals for the mixture at lower, EQS-like concentrations. Models using bioconcentration data obtained from mono-metallic exposures generated successful predictions of global toxicity both for M1X and M2X. We conclude that sub-lethal effects of mixtures identified by the multi-biomarker approach can lead to disturbances in population dynamics of gammarids. Although IBR-based models offer promising lines of enquiry to predict metal mixture toxicity, further studies are needed to confirm their predictive quality on larger ranges of metallic combinations before their use in field conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

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 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 a human neurite growth assay as specific screen for developmental neurotoxicants.

PubMed

Krug, Anne K; Balmer, Nina V; Matt, Florian; Schönenberger, Felix; Merhof, Dorit; Leist, Marcel

2013-12-01

Organ-specific in vitro toxicity assays are often highly sensitive, but they lack specificity. We evaluated here examples of assay features that can affect test specificity, and some general procedures are suggested on how positive hits in complex biological assays may be defined. Differentiating human LUHMES cells were used as potential model for developmental neurotoxicity testing. Forty candidate toxicants were screened, and several hits were obtained and confirmed. Although the cells had a definitive neuronal phenotype, the use of a general cell death endpoint in these cultures did not allow specific identification of neurotoxicants. As alternative approach, neurite growth was measured as an organ-specific functional endpoint. We found that neurite extension of developing LUHMES was specifically inhibited by diverse compounds such as colchicine, vincristine, narciclasine, rotenone, cycloheximide, or diquat. These compounds reduced neurite growth at concentrations that did not compromise cell viability, and neurite growth was affected more potently than the integrity of developed neurites of mature neurons. A ratio of the EC50 values of neurite growth inhibition and cell death of >4 provided a robust classifier for compounds associated with a developmental neurotoxic hazard. Screening of unspecific toxicants in the test system always yielded ratios <4. The assay identified also compounds that accelerated neurite growth, such as the rho kinase pathway modifiers blebbistatin or thiazovivin. The negative effects of colchicine or rotenone were completely inhibited by a rho kinase inhibitor. In summary, we suggest that assays using functional endpoints (neurite growth) can specifically identify and characterize (developmental) neurotoxicants.

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.

Carbon nanotube sensors integrated inside a microfluidic channel for water quality monitoring

NASA Astrophysics Data System (ADS)

Liu, Yu; Li, Xinghui; Dokmeci, Mehmet R.; Wang, Ming L.

2011-04-01

Single-walled carbon nanotubes (SWNTs) with their unique electrical properties and large surface area are remarkable materials for detecting low concentration of toxic and hazardous chemicals (both from the gaseous and liquid phases). Ionic adsorbates in water will attach on to SWNTs and drastically alter their electrical properties. Several SWNTs based pH and chemical sensors have been demonstrated. However, most of them require external components to test and analyze the response of SWNTs to ions inside the liquid samples. Here, we report a water quality monitoring sensor composed of SWNTs integrated inside microfluidic channels and on-chip testing components with a wireless transmission board. To detect multiple analytes in water requires the functionalization of SWNTs with different chemistries. In addition, microfluidic channels are used to guide liquid samples to individual nanotube sensors in an efficient manner. Furthermore, the microfluidic system enables sample mixing and separation before testing. To realize the nanosensors, first microelectrodes were fabricated on an oxidized silicon substrate. Next, PDMS micro channels were fabricated and bonded on the substrate. These channels can be incorporated with a microfluidic system which can be designed to manipulate different analytes for specific molecule detection. Low temperature, solution based Dielectrophoretic (DEP) assembly was conducted inside this microfluidic system which successfully bridged SWNTs between the microelectrodes. The SWNTs sensors were next characterized with different pH buffer solutions. The resistance of SWNTs had a linearly increase as the pH values ranged from 5 to 8. The nanosensor incorporated within the microfluidic system is a versatile platform and can be utilized to detect numerous water pollutants, including toxic organics and microorganisms down to low concentrations. On-chip processing and wireless transmission enables the realization of a full autonomous system for real time monitoring of water quality.

77 FR 43089 - Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity Testing: Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... Systemic Toxicity Testing: Request for Nominations for an Independent Expert Panel and Submission of... systemic toxicity testing. NICEATM requests nominations of scientific experts who can be considered for the...) Test Guideline 425 in 2001 (OECD, 2001). The oral UDP reduces animal use by up to 70% compared to the...

GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?

PubMed

Van Cott, Andrew; Hastings, Charles E; Landsiedel, Robert; Kolle, Susanne; Stinchcombe, Stefan

2018-02-01

In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formulations tested for inhalation toxicity and 31 formulations tested for dermal toxicity. The GHS additivity formula was applied to each of these formulations and compared with the experimental in vivo result. In the acute oral assay, the GHS additivity formula misclassified 110 formulations using the GHS classification criteria (48% accuracy) and 119 formulations using the USEPA classification criteria (43% accuracy). With acute inhalation, the GHS additivity formula misclassified 50 formulations using the GHS classification criteria (61% accuracy) and 34 formulations using the USEPA classification criteria (73% accuracy). For acute dermal toxicity, the GHS additivity formula misclassified 16 formulations using the GHS classification criteria (48% accuracy) and 20 formulations using the USEPA classification criteria (36% accuracy). This data indicates the acute systemic toxicity of many formulations is not the sum of the ingredients' toxicity (additivity); but rather, ingredients in a formulation can interact to result in lower or higher toxicity than predicted by the GHS additivity formula. Copyright © 2018 Elsevier Inc. All rights reserved.

Pilot study for ambient toxicity testing in Chesapeake bay. Year two report

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

Hall, L.W.; Ziegenfuss, M.C.; Fischer, S.A.

1992-11-01

The primary goal of the ambient toxicity testing pilot study was to identify toxic areas in living resource habitats of the Chesapeake Bay watershed by using a battery of standardized, directly modified or recently developed water column, sediment and suborganismal toxicity tests. Tests were conducted twice at the following stations: Potomac River-Morgantown, Potomac River-Dahlgren, Patapsco River and Wye River. A suite of inorganic and organic contaminants was evaluated in the water column and sediment during these tests. Standard water quality conditions were also evaluated in water and sediment from all stations.

The sensitivity of relative toxicity rankings by the USF/NASA test method to some test variables

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Labossiere, L. A.; Leon, H. A.; Kourtides, D. A.; Parker, J. A.; Hsu, M.-T. S.

1976-01-01

Pyrolysis temperature and the distance between the source and sensor of effluents are two important variables in tests for relative toxicity. Modifications of the USF/NASA toxicity screening test method to increase the upper temperature limit of pyrolysis, reduce the distance between the sample and the test animals, and increase the chamber volume available for animal occupancy, did not significantly alter rankings of relative toxicity of four representative materials. The changes rendered some differences no longer significant, but did not reverse any rankings. The materials studied were cotton, wool, aromatic polyamide, and polybenzimidazole.

Assessing time-integrated dissolved concentrations and predicting toxicity of metals during diel cycling in streams

USGS Publications Warehouse

Balistrieri, Laurie S.; Nimick, David A.; Mebane, Christopher A.

2012-01-01

Evaluating water quality and the health of aquatic organisms is challenging in systems with systematic diel (24 hour) or less predictable runoff-induced changes in water composition. To advance our understanding of how to evaluate environmental health in these dynamic systems, field studies of diel cycling were conducted in two streams (Silver Bow Creek and High Ore Creek) affected by historical mining activities in southwestern Montana. A combination of sampling and modeling tools were used to assess the toxicity of metals in these systems. Diffusive Gradients in Thin Films (DGT) samplers were deployed at multiple time intervals during diel sampling to confirm that DGT integrates time-varying concentrations of dissolved metals. Thermodynamic speciation calculations using site specific water compositions, including time-integrated dissolved metal concentrations determined from DGT, and a competitive, multiple-metal biotic ligand model incorporated into the Windemere Humic Aqueous Model Version 6.0 (WHAM VI) were used to determine the chemical speciation of dissolved metals and biotic ligands. The model results were combined with previously collected toxicity data on cutthroat trout to derive a relationship that predicts the relative survivability of these fish at a given site. This integrative approach may prove useful for assessing water quality and toxicity of metals to aquatic organisms in dynamic systems and evaluating whether potential changes in environmental health of aquatic systems are due to anthropogenic activities or natural variability.

Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: a workshop summary.

PubMed

Boverhof, Darrell R; Ladics, Greg; Luebke, Bob; Botham, Jane; Corsini, Emanuela; Evans, Ellen; Germolec, Dori; Holsapple, Michael; Loveless, Scott E; Lu, Haitian; van der Laan, Jan Willem; White, Kimber L; Yang, Yung

2014-02-01

As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity. Copyright © 2013 Elsevier Inc. All rights reserved.

Toxic Hazards Research Unit

NASA Technical Reports Server (NTRS)

Macewen, J. D.; Vernot, E. H.

1971-01-01

The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

Acute toxicity of fire control chemicals to Daphnia magna(Straus) and Selenastrum capricornutum(Printz)

USGS Publications Warehouse

McDonald, Susan F.; Hamilton, Steven J.; Buhl, Kevin J.; Heisinger, James F.

1996-01-01

Acute toxicity tests were conducted exposingDaphnia magnaStraus (daphnid) in soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3, respectively), andSelenastrum capricornutumPrintz (algae) in ASTM algal assay medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Chek WD-881 and Silv-Ex. The chemicals were slightly toxic to practically harmless to daphnids and moderately toxic to algae. Water quality did not consistently alter the toxicity of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv-Ex (48-hr EC507 mg/liter in soft and hard waters), whereas the least toxic chemical to daphnids was Fire-Trol LCG-R (48-hr EC50848 mg/liter in soft water, 813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R (96-hr IC5010 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr IC5079 mg/liter). Un-ionized ammonia concentrations near the EC50or IC50value in tests with the Fire-Trol compounds were frequently equal to or above reported LC50un-ionized ammonia concentrations. Un-ionized ammonia concentrations in tests with Phos-Chek D75-F were low, thus other toxic components present in the compounds probably contributed to the toxicity. When compared to the daphnids tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae, whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids. The results of these tests are comparable to those obtained from research conducted in other laboratories with the same species and similar chemicals. Accidental entry of fire-fighting chemicals into aquatic environments could adversely affect algae and aquatic invertebrates, thus disrupting ecosystem function.

EVALUATION OF ALTERNATIVE REFERENCE TOXICANTS FOR USE IN THE EARTHWORM TOXICITY TEST

EPA Science Inventory

The use of the 14-d earthworm toxicity test to aid in the evaluation of the ecological impact of contaminated soils is becoming increasingly widespread. However,the method is in need of further standardization. As part of this continuing process, the choice of reference toxicants...

Toxicity of selected insecticides applied to western spruce budworm

Treesearch

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

1975-01-01

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

Static renewal tests using Anodonta imbecillis (freshwater mussels). Anodonta imbecillis copper sulfate reference toxicant/food 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. Two different foods, phytoplankton and YCT-Selenastrum (YCT-S), were tested in side by side tests to compare food quality. Toxicity testing of copper sulfate reference toxicant was conducted from July 6--15, 1993. The organisms used for testing were juvenile fresh-water mussels (Anodonta imbecillis). Although significant reduction in growth, compared tomore » the phytoplankton control, was seen in all treatments, including the YCT-S Control, the consequence of this observation has not been established. Ninety-day testing of juvenile mussels exhibited large variations in growth within treatment and replicate groups. Attachments to this report include: Toxicity test bench sheets and statistical analyses; and Copper analysis request and results.« less

Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.

PubMed

Ducharme, Nicole A; Reif, David M; Gustafsson, Jan-Ake; Bondesson, Maria

2015-08-01

With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates. Copyright © 2014 Elsevier Inc. All rights reserved.

Promoting the 3Rs to enhance the OECD fish toxicity testing framework.

PubMed

Hutchinson, Thomas H; Wheeler, James R; Gourmelon, Anne; Burden, Natalie

2016-04-01

Fish toxicity testing has been conducted since the 1860's in order to help define safe levels of chemical contaminants in lakes, rivers and coastal waters. The historical emphasis on acute lethality testing of chemicals has more recently focussed on long term sublethal effects of chemicals on fish and their prey species. Fish toxicity testing is now embedded in much environment legislation on chemical safety while it is recognized that animal use should be Replaced, Reduced and Refined (the 3Rs) where possible. The OECD Fish Toxicity Testing Framework provides a useful structure with which to address the needs of environmental safety assessment whilst implementing the 3Rs. This commentary aims to promote the implementation of the recommendations of the OECD Fish Toxicity Testing Framework. Copyright © 2016 Elsevier Inc. All rights reserved.

Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests.

PubMed

Arts, Gertie H P; Belgers, J Dick M; Hoekzema, Conny H; Thissen, Jac T N M

2008-05-01

The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root endpoints, reflecting root growth, were most sensitive in the toxicity tests, while endpoints relating to biomass, growth and shoot length were less sensitive. The endpoints with the lowest coefficients of variation were not necessarily the endpoints, which were toxicologically most sensitive. Differences in sensitivity were in the range of 10-1000 for different macrophyte-specific endpoints. No macrophyte species was consistently the most sensitive. Criteria to select endpoints in macrophyte toxicity tests should include toxicological sensitivity, variance and ecological relevance. Hence, macrophyte toxicity tests should comprise an array of endpoints, including very sensitive endpoints like those relating to root growth.

What food and feeding rates are optimum for the Chironomus dilutus sediment toxicity test method?

EPA Science Inventory

Laboratory tests with benthic macroinvertebrates conducted using standard toxicity test procedures are used to assess the potential toxicity of contaminated sediments. Results are compared across sites or for batches of samples, and the performance of organisms in control treatme...

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

NASA Technical Reports Server (NTRS)

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

1977-01-01

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

A COMPARISON OF BULK SEDIMENT TOXICITY TESTING METHODS AND SEDIMENT ELUTRIATE TOXICITY

EPA Science Inventory

Bulk sediment toxicity tests are routinely used to assess the level and extent of contamination in natural sediments. While reliable, these tests can be resource intensive, requiring significant outlays of time and materials. The purpose of this study was to compare the results ...

Integrative assessment of coastal marine pollution in the Bay of Santander and the Upper Galician Rias

NASA Astrophysics Data System (ADS)

Rial, Diego; León, Víctor M.; Bellas, Juan

2017-12-01

Sediments from the Rias of A Coruña, Ferrol, Betanzos and Ares (n = 26) and the Bay of Santander (n = 11) were sampled in July 2012. The concentration of organic contaminants in sediment elutriates (CBs, PAHs, pesticides and personal care products) and sea urchin (Paracentrotus lividus) embryotoxicity were assessed. Relevant concentrations of organic pollutants were detected in the elutriates (ΣContaminants < 400 ng/L) but their interpretation in terms of the observed toxicity was not straightforward. A clear gradient of toxicity from the inner to the outer areas of the Bay of Santander was observed. Sediment elutriates from three stations situated close to the city of A Coruña showed moderate toxicity values, whereas sediment elutriates from the Rias of Ares and Betanzos showed no marked toxicity. Stations located close to the city of Ferrol showed moderate to high toxicity, which is indicative of a nearby source of contamination. On the contrary, the outer area of the Ria of Ferrol was classified as "Good" according to the calculated toxic units. These results allowed for an integrative assessment of the environmental quality of the studied areas.

Toxcast and the Use of Human Relevant In Vitro Exposures ...

EPA Pesticide Factsheets

The path for incorporating new approach methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. These challenges include sufficient coverage of toxicological mechanisms to meaningfully interpret negative test results, development of increasingly relevant test systems, computational modeling to integrate experimental data, putting results in a dose and exposure context, characterizing uncertainty, and efficient validation of the test systems and computational models. The presentation will cover progress at the U.S. EPA in systematically addressing each of these challenges and delivering more human-relevant risk-based assessments. This abstract does not necessarily reflect U.S. EPA policy. Presentation at the British Toxicological Society Annual Congress on ToxCast and the Use of Human Relevant In Vitro Exposures: Incorporating high-throughput exposure and toxicity testing data for 21st century risk assessments .

Comprehensive summary--Predict-IV: A systems toxicology approach to improve pharmaceutical drug safety testing.

PubMed

Mueller, Stefan O; Dekant, Wolfgang; Jennings, Paul; Testai, Emanuela; Bois, Frederic

2015-12-25

This special issue of Toxicology in Vitro is dedicated to disseminating the results of the EU-funded collaborative project "Profiling the toxicity of new drugs: a non animal-based approach integrating toxicodynamics and biokinetics" (Predict-IV; Grant 202222). The project's overall aim was to develop strategies to improve the assessment of drug safety in the early stage of development and late discovery phase, by an intelligent combination of non animal-based test systems, cell biology, mechanistic toxicology and in silico modeling, in a rapid and cost effective manner. This overview introduces the scope and overall achievements of Predict-IV. Copyright © 2014 Elsevier Ltd. All rights reserved.

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2011 CFR

2011-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2013 CFR

2013-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2012 CFR

2012-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

40 CFR 799.5087 - Chemical testing requirements for second group of high production volume chemicals (HPV2).

Code of Federal Regulations, 2014 CFR

2014-07-01

...: ASTM E 729-96 (Reapproved 2007) 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97 (Reapproved 2004) 2. Toxicity to Plants (Algae): ASTM E 1218... Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E 1193-97...

Protocol Development and Preliminary Toxicity Study of CBRN Nanomaterials

DTIC Science & Technology

2013-12-05

Program Army Institute of Public Health Specialty: 500C, Toxicity Tests Toxicology Study No. 87-XE-0EJ5-11 (FY12 Continuation) Use of trademarked name(s...toxicity by Microtox test and human cytotoxicity by NRU assay. These studies fill the data gaps and provide toxicity information useful in risk...Transepithelial Permeability (TEP) assays were developed and tested on EpiAirway. a 3-D human tracheal/bronchial epithelial equivalent. Further evaluation of the

Dempster-Shafer theory applied to regulatory decision process for selecting safer alternatives to toxic chemicals in consumer products.

PubMed

Park, Sung Jin; Ogunseitan, Oladele A; Lejano, Raul P

2014-01-01

Regulatory agencies often face a dilemma when regulating chemicals in consumer products-namely, that of making decisions in the face of multiple, and sometimes conflicting, lines of evidence. We present an integrative approach for dealing with uncertainty and multiple pieces of evidence in toxics regulation. The integrative risk analytic framework is grounded in the Dempster-Shafer (D-S) theory that allows the analyst to combine multiple pieces of evidence and judgments from independent sources of information. We apply the integrative approach to the comparative risk assessment of bisphenol-A (BPA)-based polycarbonate and the functionally equivalent alternative, Eastman Tritan copolyester (ETC). Our results show that according to cumulative empirical evidence, the estimated probability of toxicity of BPA is 0.034, whereas the toxicity probability for ETC is 0.097. However, when we combine extant evidence with strength of confidence in the source (or expert judgment), we are guided by a richer interval measure, (Bel(t), Pl(t)). With the D-S derived measure, we arrive at various intervals for BPA, with the low-range estimate at (0.034, 0.250), and (0.097,0.688) for ETC. These new measures allow a reasonable basis for comparison and a justifiable procedure for decision making that takes advantage of multiple sources of evidence. Through the application of D-S theory to toxicity risk assessment, we show how a multiplicity of scientific evidence can be converted into a unified risk estimate, and how this information can be effectively used for comparative assessments to select potentially less toxic alternative chemicals. © 2013 SETAC.

Mixture cytotoxicity assessment of ionic liquids and heavy metals in MCF-7 cells using mixtox.

PubMed

Zhu, Xiang-Wei; Ge, Hui-Lin; Cao, Yu-Bin

2016-11-01

Ionic liquids (ILs) are widely used as extractants for heavy metals. However, the effect of mixtures of ILs and heavy metals is rarely understood. In this study, we tested the cytotoxicity of four ILs, four heavy metals and their mixtures on human MCF-7 cells in 96-well microplates. The toxicity of single compounds in MCF-7 cells ranges from 3.07 × 10(-6) M for Cu(II) to 2.20 × 10(-3) M for 1-ethyl-3-methylimidazolium tetrafluoroborate. The toxicity of heavy metals in MCF-7 is generally higher than the toxicity of ILs. A uniform experimental design was used to simulate environmentally realistic mixtures. Two classical reference models (concentration addition and independent action) were used to predict their mixture. The experiments to evaluate the toxicity of the mixture revealed antagonism among four ILs and four heavy metals in MCF-7 cells. Pearson correlation analysis showed that Ni(II) and 1-dodecyl-3-methylimidazolium chloride are positively correlated with the extent of antagonism, while 1-hexyl-3-methylimidazolium tetrafluoroborate showed a negative correlation. Data analysis was conducted in the R package mixtox, which integrates features such as curve fitting, experimental design, and mixture toxicity prediction. The international community of toxicologists is welcome to use this package and provide feedback as suggestions and comments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Static renewal tests using Anodonta imbecillis (freshwater mussels). Anodonta imbecillis QA test 1, Clinch River-Environmental Restoration Program (CR-ERP)

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

Simbeck, D.J.

1993-12-31

Toxicity testing of split whole sediment samples using juvenile freshwater mussels (Anodonta imbecillis) was conducted by TVA and CR-ERP personnel as part of the CR-ERP biomonitoring study of Clinch River sediments to provide a quality assurance mechanism for test organism quality and overall performance of the test. In addition, testing included procedures comparing daily renewal versus non-renewal of test sediments. Testing of sediment samples collected July 15 from Poplar Creek Miles 6.0 and 5.1 was conducted from July 21--30, 1993. Results from this test showed no toxicity (survival effects) to fresh-water mussels during a 9-day exposure to the sediments. Sidemore » by side testing of sediments with daily sediment renewal and no sediment renewal showed no differences between methods. This may be due to the absence of toxicity in both samples and may not reflect true differences between the two methods for toxic sediment. Attachments to this report include: Chain of custody forms -- originals; Toxicity test bench sheets and statistical analyses; and Ammonia analysis request and results.« less

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

Aquatic toxicity of petroleum products and dispersant agents ...

EPA Pesticide Factsheets

The U.S. EPA Office of Research and Development has developed baseline data on the ecotoxicity of selected petroleum products and several chemical dispersants as part of its oil spills research program. Two diluted bitumens (dilbits) from the Alberta Tar Sands were tested for acute and chronic toxicity to standard freshwater and marine organisms given their spill potential during shipment within the United States. Separately, two reference crude oils representing a range of characteristics, and their mixtures with four representative dispersants, were tested to evaluate acute and chronic toxicity to marine organisms in support of Subpart J of the U.S. National Contingency Plan. Water accommodated fractions (WAF) of oil were prepared using traditional slow-stir methods and toxicity tests generally followed U.S. EPA standard effluent testing guidelines. WAFs were characterized for petroleum hydrocarbons including alkyl PAH homologs. The results of these studies will assist the U.S. EPA to assess toxicity data for unconventional oils (dilbits), and establish baseline toxicity data for selected crude oils and dispersant in support of planning and response activities. Abstract reporting the results of EPA's oil and dispersant toxicity testing program

Aquatic toxicity testing for aquatic life impact assessments and recent scientific advancements

EPA Science Inventory

The focus of this presentation is to provide an overview of the use of aquatic toxicity testing for assessing possible impacts to aquatic life and how new scientific approaches are being researched. Toxicity testing of both ambient and effluent monitoring samples will be discusse...

New technologies and approaches in toxicity testing and risk assessment (ESOT)

EPA Science Inventory

The release of the National Research Council’s Report “Toxicity Testing in the 21st Century: A Vision and a Strategy” in 2007 initiated a broad-based movement in the toxicology community to re-think how toxicity testing and risk assessment are performed. Multiple efforts in the ...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

40 CFR 799.9325 - TSCA 90-day dermal toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Health Effects Test Guidelines § 799.9325 TSCA 90-day dermal toxicity. (a) Scope. This section is...-observed-effects level (NOEL) and toxic effects associated with continuous or repeated exposure to a test... human exposure. (b) Source. The source material used in developing this TSCA test guideline is the...

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

EPA Science Inventory

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

The Adverse Outcome Pathway: A conceptual framework to support toxicity testing in the 21st century

EPA Science Inventory

The field of regulatory toxicity testing is at a turning point. The U.S. National Research Council (NRC) envisioned a shift away from traditional toxicity testing and towards a focused effort to explore and understand pathways perturbed by biologically active substances or their ...

Relative toxicity of pyrolysis products of some materials used in home furnishings

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Furst, A.

1976-01-01

Seventy samples of cushioning and upholstery materials used in home furnishings were evaluated for relative toxicity by means of the USF/NASA toxicity screening test. The materials were variably toxic under pyrolysis conditions, and this test appeared suitable for discriminating among them on the bases of time to incapacitation and time to death. The addition of fire retardants to these materials to comply with flammability regulations either had no significant effect on toxicity, or resulted in a reduction in relative toxicity. The modification of materials to comply with California upholstered furniture flammability regulations appears to have resulted in desirable limitations on toxicity. Fifty percent of the 70 materials tested caused incapacitation earlier than did the materials in compliance, and 30 percent caused death earlier.

Advanced Development of a Compact 5-15 lbf Lox/Methane Thruster for an Integrated Reaction Control and Main Engine Propulsion System

NASA Technical Reports Server (NTRS)

Hurlbert, Eric A.; McManamen, John Patrick; Sooknanen, Josh; Studak, Joseph W.

2011-01-01

This paper describes the advanced development and testing of a compact 5 to 15 lbf LOX/LCH4 thruster for a pressure-fed integrated main engine and RCS propulsion system to be used on a spacecraft "vertical" test bed (VTB). The ability of the RCS thruster and the main engine to operate off the same propellant supply in zero-g reduces mass and improves mission flexibility. This compact RCS engine incorporates several features to dramatically reduce mass and parts count, to ease manufacturing, and to maintain acceptable performance given that specific impulse (Isp) is not the driver. For example, radial injection holes placed on the chamber body for easier drilling, and high temperature Haynes 230 were selected for the chamber over other more expensive options. The valve inlets are rotatable before welding allowing different orientations for vehicle integration. In addition, the engine design effort selected a coil-on-plug ignition system which integrates a relay and coil with the plug electrode, and moves some exciter electronics to avionics driver board. The engine injector design has small dribble volumes to target minimum pulse widths of 20 msec. and an efficient minimum impulse bit of less than 0.05 lbf-sec. The propellants, oxygen and methane, were chosen because together they are a non-toxic, Mars-forward, high density, space storable, and high performance propellant combination that is capable of pressure-fed and pump-fed configurations and integration with life support and power subsystems. This paper will present the results of the advanced development testing to date of the RCS thruster and the integration with a vehicle propulsion system.

Toxicity study of Vernonia cinerea.

PubMed

Latha, L Yoga; Darah, I; Jain, K; Sasidharan, S

2010-01-01

The methanol extract of Vernonia cinerea Less (Asteraceae), which exhibited antimicrobial activity, was tested for toxicity. In an acute toxicity study using mice, the median lethal dose (LD(50)) of the extract was greater than 2000 mg/kg, and we found no pathological changes in macroscopic examination by necropsy of mice treated with extract. As well as the oral acute toxicity study, the brine shrimp lethality test was also done. Brine shrimp test LC(50) values were 3.87 mg/mL (6 h) and 2.72 mg/mL (24 h), exhibiting no significant toxicity result. In conclusion, the methanol extract of V. cinerea did not produce toxic effects in mice and brine shrimp.

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

Evaluating the zebrafish embryo toxicity test for pesticide hazard screening.

PubMed

Glaberman, Scott; Padilla, Stephanie; Barron, Mace G

2017-05-01

Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more resource-intensive, juvenile fish acute toxicity tests. However, there is also evidence that fish embryos are less sensitive than juvenile fish for certain types of chemicals, including neurotoxicants. The utility of fish embryos for pesticide hazard assessment was investigated by comparing published zebrafish embryo toxicity data from pesticides with median lethal concentration 50% (LC50) data for juveniles of 3 commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead minnow. A poor, albeit significant, relationship (r 2  = 0.28; p < 0.05) was found between zebrafish embryo and juvenile fish toxicity when pesticides were considered as a single group, but a much better relationship (r 2  = 0.64; p < 0.05) when pesticide mode of action was factored into an analysis of covariance. This discrepancy is partly explained by the large number of neurotoxic pesticides in the dataset, supporting previous findings that commonly used fish embryo toxicity test endpoints are particularly insensitive to neurotoxicants. These results indicate that it is still premature to replace juvenile fish toxicity tests with embryo-based tests such as the Organisation for Economic Co-operation and Development Fish Embryo Acute Toxicity Test for routine pesticide hazard assessment, although embryo testing could be used with other screening tools for testing prioritization. Environ Toxicol Chem 2017;36:1221-1226. © 2016 SETAC. © 2016 SETAC.

WATERSHED EARLY WARNING SYSTEMS

EPA Science Inventory

Contaminants are of concern when they are found in concentrations that are toxic to plants and/or animals. On-line Toxicity Monitors (OTMs) integrate all factors resulting in stress including physical and chemical qualities. This is important because of the limitations of chemic...

Early Evolution of the Toxicity Identification Evaluation Process: Contributions from the USEPA Effluent Testing Program

EPA Science Inventory

As part of its whole effluent testing program, the USEPA developed an effects-directed analysis (EDA) approach to identifying the cause of toxicity in toxic effluents or ambient waters, an EDA process termed a “Toxicity Identification Evaluation” (TIE), which is the focus of this...

Prediction of toxicity and comparison of alternatives using WebTEST (Web-services Toxicity Estimation Software Tool)

EPA Science Inventory

A Java-based web service is being developed within the US EPA’s Chemistry Dashboard to provide real time estimates of toxicity values and physical properties. WebTEST can generate toxicity predictions directly from a simple URL which includes the endpoint, QSAR method, and ...

Prediction of toxicity and comparison of alternatives using WebTEST (Web-services Toxicity Estimation Software Tool)(Bled Slovenia)

EPA Science Inventory

A Java-based web service is being developed within the US EPA’s Chemistry Dashboard to provide real time estimates of toxicity values and physical properties. WebTEST can generate toxicity predictions directly from a simple URL which includes the endpoint, QSAR method, and ...

40 CFR 799.5089 - Chemical testing requirements for third group of high production volume chemicals (HPV3).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 2007). 2. Acute Toxicity to Daphnia: ASTM E 729-96 (Reapproved 2007). 3. Toxicity to Plants (Algae...). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 The following are the special conditions for C1, C2... (Reapproved 2007). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity...

40 CFR 799.5089 - Chemical testing requirements for third group of high production volume chemicals (HPV3).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 2007). 2. Acute Toxicity to Daphnia: ASTM E 729-96 (Reapproved 2007). 3. Toxicity to Plants (Algae...). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 The following are the special conditions for C1, C2... (Reapproved 2007). 2. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity...

Toxicity of an herbicide and adjuvant to saltmarsh invertebrates in the management of invasive grass; Comparative laboratory and field tests.

PubMed

Kleinhenz, Linda S; Nugegoda, Dayanthi; Verspaandonk, Emily R; Coombes, Darcy C; Howe, Steffan; Shimeta, Jeff

2016-08-15

Coastal weeds are often treated with herbicides without knowledge of non-target impacts, and toxicity data from standardized test species can have limited applicability. We evaluated toxicity to invertebrates from Fusilade Forte® and the adjuvant Hasten® in the control of invasive salt marsh grass, Spartina anglica. For 3 of 4 local invertebrates, Fusilade Forte® was moderately toxic (96h LC50 5.4-144mgL(-1)), whereas Hasten® was less toxic (14.2-450mgL(-1)). For most species, the mixture was more toxic than the herbicide alone, with 96h LC50 reduced 23-45%. However, a field experiment applying typical concentrations (1000×the lowest 96h LC50) showed low concentrations of herbicide residues and no detrimental impacts on invertebrates over 6months. The results reveal the importance of testing locally relevant species for potential toxicity, and of comparison tests with field exposures to determine the realised toxicity in nature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative toxicant sensitivity of sexual and asexual reproduction in the rotifer Brachionus calyciflorus

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

Snell, T.W.; Carmona, M.J.

Cyclically parthenogenetic zooplankters like rotifers are important tools for assessing toxicity in aquatic environments. Sexual reproduction is an essential component of rotifer life cycles, but current toxicity tests utilize only asexual reproduction. The authors compared the effects of four toxicants on asexual and sexual reproduction of the rotifer Brachionus calyciflorus. Toxicants had a differential effect on sexual and asexual reproduction, with sexual reproduction consistently the most sensitive. Concentrations of 0.2 {mu}g/ml PCP (sodium pentachlorophenate) had no effect on the asexual reproductive rate, but significantly reduced sexual reproduction. Likewise, chlorpyrifos concentrations of 0.3 {mu}g/ml had no significant effect on asexual reproduction,more » but sexual reproduction was significantly reduced. There was no difference in NOECs, LOECs, and chronic values for asexual and sexual reproduction for cadmium and naphthol tests. However, comparison of toxicant effect levels revealed that sexual reproduction was more strongly reduced at each toxicant concentration. The four toxicants tested inhibited sexual reproduction 2 to 68 times more than asexual reproduction at the lowest observed effect concentrations. Toxicants inhibited sexual reproduction in its initial step: sexual female production. Because sexual reproduction is more sensitive, toxicity tests based exclusively on asexual reproduction may not be protective of rotifer life cycles.« less

Application of different enzyme assays and biomarkers for pollution monitoring of the marine environment.

PubMed

Seitkalieva, Alexandra V; Menzorova, Natalie I; Rasskazov, Valerу A

2016-01-01

New phosphatase and DNase inhibition tests for assessing the total pollution of a natural marine ecosystem were applied. The seawater samples with different pollution degrees were collected in the Troitsa Bay of the Peter the Great Bay (the Sea of Japan). The sensitivity of the alkaline phosphatase test to integrated pollution was in accordance with the sensitivity of the standard sea urchin sperm cell toxicity test. The increased seawater pollution level was shown to result in an up to fourfold increase in specific activities of acid and alkaline phosphatases from the mussel Crenomytilus grayanus. It was demonstrated that a complex methodological approach can be used to assess marine water areas, as well as to assess the biological conditions of invertebrates adapting to different environmental and anthropogenic effects.

Using enzyme bioassays as a rapid screen for metal toxicity

USGS Publications Warehouse

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

2005-01-01

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

Sensitivity or artifact? -- IQ Toxicity Test -- effluent values

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

Hayes, K.R.; Novotny, A.N.; Batista, N.

1995-12-31

Several complex effluents were DAPHNIA MAGNA IQ TOXICITY TESTED -- (1.25 hours) and conventionally tested with Daphnia magna (48 hours). In many samples the IQ Technology yielded low EC50 values while the 48 hour exposures yielded no acute toxicity. Possible explanations have been suggested for this occurrence such as: genotoxicity, mutagenicity, substrate interference, and enzyme satiation. To identify the causative agent(s) of this response a Toxicity Identification Evaluation was performed on one of the samples. To define the nature of the response, THE SOS-CHROMOTEST KIT and THE MUTA-CHROMOPLATE KIT were utilized to characterize genotoxicity and mutagenicity respectively. The sample didmore » not test positive for genotoxicity but tested positive for mutagenicity only after activation with S9 enzymes, suggesting the presence of promutagens. Additional work needs to be performed to correlate IQ TOXICITY TEST sensitivity with positive MUTA-CHROMOPLATE response.« less

Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

PubMed

de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

2017-07-01

Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (p<0.05); and neonates' heart rate decreased 72.7% (p<0.05). In the chronic toxicity test, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

PubMed

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition.

PubMed

Sørli, Jorid B; Huang, Yishi; Da Silva, Emilie; Hansen, Jitka S; Zuo, Yi Y; Frederiksen, Marie; Nørgaard, Asger W; Ebbehøj, Niels E; Larsen, Søren T; Hougaard, Karin S

2018-01-01

Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21 impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if the products inhibited surfactant function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e., the in vitro method predicted all the products that were toxic for mice to inhale. The specificity of the in vitro test was 63%, i.e., the in vitro method found three false positives in the 21 tested products. Six of the products had been involved in accidental human inhalation where they caused acute inhalation toxicity. All of these six products inhibited lung surfactant function in vitro and were toxic to mice.

Influence of container adsorption upon observed pyrethroid toxicity to Ceriodaphnia dubia and Hyalella azteca

PubMed Central

Wheelock, Craig E.; Miller, Jeff L.; Miller, Mike J.; Phillips, Bryn M.; Gee, Shirley J.; Tjeerdema, Ronald S.; Hammock, Bruce D.

2006-01-01

Pyrethroid insecticides are known for their potential toxicity to aquatic invertebrates and many fish species. A significant problem in the study of pyrethroid toxicity is their extreme hydrophobicity. They can adsorb to test container surfaces and many studies, therefore, report pyrethroid levels as nominal water concentrations. In this study, pyrethroid adsorption to sampling and test containers was measured and several container treatments were examined for their ability to decrease pyrethroid adsorption. None of the chemical treatments were successful at preventing pyrethroid loss from aqueous samples, but vortexing of containers served to resuspend pyrethroids. The effects of the observed adsorption on Ceriodaphnia dubia and Hyalella azteca permethrin toxicity were examined. Species-specific results showed a time-dependent decrease in toxicity following pyrethroid adsorption to test containers for C. dubia, but not for H. azteca. These results demonstrate that pyrethroid adsorption to containers can significantly affect the observed outcome in toxicity-testing and serves as a caution for researchers and testing laboratories. PMID:15951033

Acute toxicity of multi-walled carbon nanotubes, sodium pentachlorophenate, and their complex on earthworm Eisenia fetida.

PubMed

Zhang, Liujun; Hu, Changwei; Wang, Weili; Ji, Funian; Cui, Yibin; Li, Mei

2014-05-01

Laboratory experiments were undertaken to relate biomarker responses to the toxicities of multi-walled carbon nanotubes (MWCNTs) and sodium pentachlorophenate (PCP-Na), both individually and combined. The acute toxicities of MWCNTs and PCP-Na on earthworm Eisenia fetida were studied through different exposure methods (filter paper contact test, immersion contact test, and artificial soil contact test). Enzyme activity and malondialdehyde (MDA) content in the earthworm E. fetida exposed to MWCNTs and PCP-Na in filter paper contact test, both individually and under combined exposure, were determined. After exposure, PCP-Na induced observable acute toxicity while the MWCNTs induced slight toxicity. Interestingly the earthworms exposed to the mixture of MWCNTs and PCP-Na demonstrated different expression of enzymatic biomarkers from those exposed to MWCNTs or PCP-Na alone. Our results indicated that the toxicity of PCP-Na on E. fetida may be alleviated by the appearance of MWCNTs for all exposure methods except for immersion contact test. Copyright © 2014 Elsevier Inc. All rights reserved.

Edaravone Protects against Methylglyoxal-Induced Barrier Damage in Human Brain Endothelial Cells

PubMed Central

Tóth, Andrea E.; Walter, Fruzsina R.; Bocsik, Alexandra; Sántha, Petra; Veszelka, Szilvia; Nagy, Lajos; Puskás, László G.; Couraud, Pierre-Olivier; Takata, Fuyuko; Dohgu, Shinya; Kataoka, Yasufumi; Deli, Mária A.

2014-01-01

Background Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. Methodology Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and β-catenin. Cell morphology was also examined by holographic phase imaging. Principal Findings Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 µM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. Conclusion These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases. PMID:25033388

Assessing condition of macroinvertebrate communities and bed sediment toxicity in the Rochester Embayment Area of Concern, New York, USA

USGS Publications Warehouse

Duffy, Brian; George, Scott D.; Baldigo, Barry P.; Smith, Alexander J.

2017-01-01

The United States and Canada agreed to restore the chemical, physical, and biological integrity of the Great Lakes ecosystem under the first Great Lakes Water Quality Agreement in 1972. The lowest reach of the Genesee River and the Rochester Embayment on Lake Ontario between Bogus Point and Nine Mile Point, including Braddock Bay, were designated as an Area of Concern (AOC) due to effects of contaminated sediments and physical disturbance on several beneficial uses. Following sediment remedial efforts and with conditions improving in the AOC, the present study was conducted to reevaluate the status of the benthic macroinvertebrate (benthos) beneficial use impairment (BUI). Benthic macroinvertebrate community assessments and 10-day Chironomus dilutus bioassays were used to test the hypotheses that sediments within the AOC were no more toxic than sediments from surrounding reference areas. The study was separated into three discrete systems (Genesee River, Lake Ontario, and Braddock Bay) and non-parametric analyses determined that a multimetric index of benthic macroinvertebrate community integrity was significantly higher at AOC sites compared to reference sites on the Genesee River and in Braddock Bay while AOC and reference sites on Lake Ontario did not differ significantly. Survival and growth of C. dilutus were also similar between AOC and reference sites for each system with the exception of significantly higher growth at reference sites on Lake Ontario. Results generally indicated that the condition of benthos and toxicity of sediment of the Rochester Embayment AOC are similar to or better than that in the surrounding area.

Update on the DNT In Vitro Alternative Methods Project at the USEPA

EPA Science Inventory

Current approaches to toxicity testing rely heavily on the use of animals, can cost millions of dollars and can take years to complete for a single chemical. To implement the predictive toxicity testing envisioned in the NAS report on Toxicity Testing in the 21st century, rapid a...

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

Effects of deltamethrin, dimethoate, and chlorpyrifos on survival and reproduction of the collembolan Folsomia candida and the predatory mite Hypoaspis aculeifer in two African and two European soils.

PubMed

Jaabiri Kamoun, Ikram; Jegede, Olukayode O; Owojori, Olugbenga J; Bouzid, Jalel; Gargouri, Radhia; Römbke, Jörg

2018-01-01

Indiscriminate use of pesticides is rampant in most parts of Africa, but only scanty ecotoxicological data exist for the protection of soil organisms-and these data were usually obtained under temperate conditions, including the use of Organisation for Economic Co-operation and Development (OECD) standard test protocols. In order to assess the effects of 3 commonly used pesticides (deltamethrin, dimethoate, chlorpyrifos) on soil fauna in Africa, noncontaminated natural soils were collected from Nigeria and Tunisia. In addition, 2 common test soils, OECD artificial soil and European (Landwirtschaftliche Untersichungs- und Forschungsanstalt [LUFA]) 2.3 soil, were used in OECD standard reproduction tests. Two microarthropod species, the springtail Folsomia candida and the predatory mite Hypoaspis aculeifer, were exposed in these 4 soils spiked individually with the 3 insecticides. Results show that the collembolan F. candida was more sensitive than the mite H. aculeifer for all 3 insecticides. The toxicity of each insecticide in the 4 soils differed, with few exceptions, by less than an order of magnitude. However, the pattern of toxicity was not consistent, that is, the lowest toxicity was often but not always found in OECD artificial soil. Soil- and pesticide-specific patterns of toxicity to F. candida and H. aculeifer might be related to the physicochemical properties of the soils and thus the availability of the 3 pesticides. Following the rules laid down in the European Union for the registration of pesticides and using standard European exposure scenarios, neither an acute nor a chronic risk of dimethoate and chlorpyrifos can be excluded (with few exceptions) in all 4 soils. Lower risks were identified for deltamethrin. For pesticide used in Africa, an environmental risk assessment based on data gained in tests with at least 1 additional natural field soil, preferably of African origin, should be performed using the same risk assessment principles as in the European Union. Integr Environ Assess Manag 2018;14:92-104. © 2017 SETAC. © 2017 SETAC.

Critical dose and toxicity index of organs at risk in radiotherapy: Analyzing the calculated effects of modified dose fractionation in non–small cell lung cancer

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

Pedicini, Piernicola, E-mail: ppiern@libero.it; Strigari, Lidia; Benassi, Marcello

2014-04-01

To increase the efficacy of radiotherapy for non–small cell lung cancer (NSCLC), many schemes of dose fractionation were assessed by a new “toxicity index” (I), which allows one to choose the fractionation schedules that produce less toxic treatments. Thirty-two patients affected by non resectable NSCLC were treated by standard 3-dimensional conformal radiotherapy (3DCRT) with a strategy of limited treated volume. Computed tomography datasets were employed to re plan by simultaneous integrated boost intensity-modulated radiotherapy (IMRT). The dose distributions from plans were used to test various schemes of dose fractionation, in 3DCRT as well as in IMRT, by transforming the dose-volumemore » histogram (DVH) into a biological equivalent DVH (BDVH) and by varying the overall treatment time. The BDVHs were obtained through the toxicity index, which was defined for each of the organs at risk (OAR) by a linear quadratic model keeping an equivalent radiobiological effect on the target volume. The less toxic fractionation consisted in a severe/moderate hyper fractionation for the volume including the primary tumor and lymph nodes, followed by a hypofractionation for the reduced volume of the primary tumor. The 3DCRT and IMRT resulted, respectively, in 4.7% and 4.3% of dose sparing for the spinal cord, without significant changes for the combined-lungs toxicity (p < 0.001). Schedules with reduced overall treatment time (accelerated fractionations) led to a 12.5% dose sparing for the spinal cord (7.5% in IMRT), 8.3% dose sparing for V{sub 20} in the combined lungs (5.5% in IMRT), and also significant dose sparing for all the other OARs (p < 0.001). The toxicity index allows to choose fractionation schedules with reduced toxicity for all the OARs and equivalent radiobiological effect for the tumor in 3DCRT, as well as in IMRT, treatments of NSCLC.« less

WATERSHED EARLY WARNING SYSTEMS

EPA Science Inventory

Contaminants are of concern when they are found in concentrations that are toxic to plants and/or animals. On-line Toxicity Monitors (OTM) integrate all dissolved and bound chemicals found in water. This is important because of the limitations of chemical specific monitoring; yo...

MULTIDISCIPLINARY APPROACH TO TOXICOLOGICAL SCREENING: II. DEVELOPMENTAL TOXICITY

EPA Science Inventory

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

An integrated approach with the zebrafish model for biomonitoring of municipal wastewater effluent and receiving waters.

PubMed

Li, Caixia; Chen, Qiyu; Zhang, Xiaoyan; Snyder, Shane A; Gong, Zhiyuan; Lam, Siew Hong

2017-12-11

Comprehensive monitoring of water pollution is challenging. With the increasing amount and types of anthropogenic compounds being released into water, there are rising concerns of undetected toxicity. This is especially true for municipal wastewater effluents that are discharged to surface waters. This study was designed to integrate zebrafish toxicogenomics, targeted gene expression, and morphological analyses, for toxicity evaluation of effluent discharged from two previously characterized wastewater treatment plants (WWTPs) in Pima County, Arizona, and their receiving surface water. Zebrafish embryos were exposed to organic extracts from the WWTP1 effluent that were reconstituted to represent 1× and 0.5× of the original concentration. Microarray analyses identified deregulated gene probes that mapped to 1666, 779, and 631 unique human homologs in the 1×, 0.5×, and the intersection of both groups, respectively. These were associated with 18 cellular and molecular functions ranging from cell cycle to metabolism and are involved in the development and function of 10 organ systems including nervous, cardiovascular, haematological, reproductive, and hepatic systems. Superpathway of cholesterol biosynthesis, retinoic acid receptor activation, glucocorticoid receptor and prolactin signaling were among the top 11 perturbed canonical pathways. Real-time quantitative PCR validated the expression changes of 12 selected genes. These genes were then tested on zebrafish embryos exposed to the reconstituted extract of water sampled downstream of WWTP1 and another nearby WWTP2. The expression of several targeted genes were significantly affected by the WWTP effluents and some of the downstream receiving waters. Morphological analyses using four transgenic zebrafish lines revealed potential toxicity associated with nervous, hepatic, endothelial-vascular and myeloid systems. This study demonstrated how information can be obtained using adverse outcome pathway framework to derive biological effect-based monitoring tools. This integrated approach using zebrafish can supplement analytical chemistry to provide more comprehensive monitoring of discharged effluents and their receiving waters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Toxicity assessment of sediments from the Grand Calumet River and Indiana Harbor Canal in northwestern Indiana, USA

USGS Publications Warehouse

Ingersoll, C.G.; MacDonald, D.D.; Brumbaugh, W.G.; Johnson, B. Thomas; Kemble, N.E.; Kunz, J.L.; May, T.W.; Wang, N.; Smith, J.R.; Sparks, D.W.; Ireland, D.S.

2002-01-01

The objective of this study was to evaluate the toxicity of sediments from the Grand Calumet River and Indiana Harbor Canal located in northwestern Indiana, USA. Toxicity tests used in this assessment included 10-day sediment exposures with the amphipod Hyalella azteca, 31-day sediment exposures with the oligochaete Lumbriculus variegatus, and the Microtox® Solid-Phase Sediment Toxicity Test. A total of 30 sampling stations were selected in locations that had limited historic matching toxicity and chemistry data. Toxic effects on amphipod survival were observed in 60% of the samples from the assessment area. Results of a toxicity test with oligochaetes indicated that sediments from the assessment area were too toxic to be used in proposed bioaccumulation testing. Measurement of amphipod length after the 10-day exposures did not provide useful information beyond that provided by the survival endpoint. Seven of the 15 samples that were identified as toxic in the amphipod tests were not identified as toxic in the Microtox test, indicating that the 10-day H. azteca test was more sensitive than the Microtox test. Samples that were toxic tended to have the highest concentrations of metals, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs). The toxic samples often had an excess of simultaneously extracted metals (SEM) relative to acid volatile sulfide (AVS) and had multiple exceedances of probable effect concentrations (PECs). Metals may have contributed to the toxicity of samples that had both an excess molar concentration of SEM relative to AVS and elevated concentrations of metals in pore water. However, of the samples that had an excess of SEM relative to AVS, only 38% of these samples had elevated concentration of metals in pore water. The lack of correspondence between SEM-AVS and pore water metals indicates that there are variables in addition to AVS controlling the concentrations of metals in pore water. A mean PEC quotient of 3.4 (based on concentrations of metals, PAHs, and PCBs) was exceeded in 33% of the sediment samples and a mean quotient of 0.63 was exceeded in 70% of the thirty sediment samples from the assessment area. A 50% incidence of toxicity has been previously reported in a database for sediment tests with H. azteca at a mean quotient of 3.4 in 10-day exposures and at a mean quotient of 0.63 in 28-day exposures. Among the Indiana Harbor samples, most of the samples with a mean PEC quotient above 0.63 (i.e., 15 of 21; 71%) and above 3.4 (i.e., 10 of 10; 100%) were toxic to amphipods. Results of this study and previous studies demonstrate that sediments from this assessment area are among the most contaminated and toxic that have ever been reported.

Computerized In Vitro Test for Chemical Toxicity Based on Tetrahymena Swimming Patterns

NASA Technical Reports Server (NTRS)

Noever, David A.; Matsos, Helen C.; Cronise, Raymond J.; Looger, Loren L.; Relwani, Rachna A.; Johnson, Jacqueline U.

1994-01-01

An apparatus and a method for rapidly determining chemical toxicity have been evaluated as an alternative to the rabbit eye initancy test (Draize). The toxicity monitor includes an automated scoring of how motile biological cells (Tetrahymena pyriformis) slow down or otherwise change their swimming patterns in a hostile chemical environment. The method, called the motility assay (MA), is tested for 30 s to determine the chemical toxicity in 20 aqueous samples containing trace organics and salts. With equal or better detection limits, results compare favorably to in vivo animal tests of eye irritancy.

Comparative ecotoxicity of potential biofuels to water flea (Daphnia magna), zebrafish (Danio rerio) and Chinese hamster (Cricetulus griseus) V79 cells.

PubMed

Heger, Sebastian; Du, Miaomiao; Bauer, Kevin; Schäffer, Andreas; Hollert, Henner

2018-08-01

The ecotoxicity of two biofuel candidates (1‑octanol and 2‑butanone) was investigated by an integrative test strategy using three bioassays: the acute immobilisation test with water flea (D. magna), the fish embryo acute toxicity test with zebrafish (Danio rerio) and the in vitro micronucleus assay with Chinese hamster (Cricetulus griseus) V79 cells. The median effective concentration (EC 50 ) values were 14.9±0.66mgL -1 for 1‑octanol, and 2152.1±44.6mgL -1 for 2‑butanone in the D. magna test. Both 1‑octanol and 2‑butanone caused teratogenic and lethal effects on zebrafish embryos, while exposure to 1‑octanol significantly induced these effects at concentrations ≥2.0mgL -1 . These results indicate that 1‑octanol exert much higher ecotoxicity than 2‑butanone to D. magna and zebrafish embryos. Moreover, both 1‑octanol and 2‑butanone did not cause significant genotoxic effects, while their metabolites significantly induced micronuclei in V79 cells. The present study proposed an integrative test approach to evaluate the potential ecotoxicity of biofuels using simple, quick and inexpensive bioassays. Copyright © 2018 Elsevier B.V. All rights reserved.

Toxicity Assessment of Pelvic Intensity-Modulated Radiotherapy With Hypofractionated Simultaneous Integrated Boost to Prostate for Intermediate- and High-Risk Prostate Cancer

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

McCammon, Robert; Rusthoven, Kyle E.; Kavanagh, Brian

Purpose: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. Methods and Materials: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to scoremore » toxicity. Results: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving {>=}25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving {>=}50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Conclusion: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.« less

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PubMed

Franzese, C; Fogliata, A; D'Agostino, G R; Di Brina, L; Comito, T; Navarria, P; Cozzi, L; Scorsetti, M

2017-07-01

The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm 3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

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.

40 CFR 799.5089 - Chemical testing requirements for third group of high production volume chemicals (HPV3).

Code of Federal Regulations, 2014 CFR

2014-07-01

... Toxicity to Daphnia: ASTM E 729-96 (Reapproved 2007). 3. Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test... (Algae): ASTM E 1218-04 e1 The following are the special conditions for C1, C2, C3, C4, C5, and C7.... Toxicity to Plants (Algae): ASTM E 1218-04 e1 Test Group 2 for C2: 1. Chronic Toxicity to Daphnia: ASTM E...

Ecological Risk Assessment of a Metal-Contaminated Area in the Tropics. Tier II: Detailed Assessment.

PubMed

Niemeyer, Júlia Carina; Moreira-Santos, Matilde; Ribeiro, Rui; Rutgers, Michiel; Nogueira, Marco Antonio; da Silva, Eduardo Mendes; Sousa, José Paulo

2015-01-01

This study presents data on the detailed evaluation (tier 2) of a site-specific ecological risk assessment (ssERA) in a former smelter area contaminated with metals (Santo Amaro, Bahia, Brazil). Combining information from three lines of evidence (LoE), chemical (ChemLoE), ecotoxicological (EcotoxLoE) and ecological (EcoLoE), in the Triad approach, integrated risk values were calculated to rank sites and confirm the potential risk disclosed with tier 1. Risk values were calculated for the habitat and for the retention functions in each sampling point. Habitat function included the ChemLoE calculated from total metal concentrations. The EcotoxLoE was based on reproduction tests with terrestrial invertebrates (Folsomia candida, Enchytraeus crypticus, Eisenia andrei), shoot length and plant biomass (Avena sativa, Brassica rapa). For the EcoLoE, ecological parameters (microbial parameters, soil invertebrate community, litter breakdown) were used to derive risk values. Retention function included the ChemLoE, calculated from extractable metal concentrations, and the EcotoxLoE based on eluate tests with aquatic organisms (Daphnia magna reproduction and Pseudokirchneriella subcapitata growth). Results related to the habitat function indicated that the metal residues are sufficient to cause risk to biota, while the low metal levels in extracts and the general lack of toxicity in aquatic tests indicated a high soil retention capacity in most sampling points. Integrated risk of tier 2 showed the same trend of tier 1, suggesting the need to proceed with remediation actions. The high risk levels were related to direct toxicity to organisms and indirect effects, such as failure in the establishment of vegetation and the consequent loss of habitat quality for microorganisms and soil fauna. This study shed some light on the selection of tools for the tier 2 of an ssERA in tropical metal-contaminated sites, focusing on ecological receptors at risk and using available chemical methods, ecological surveys and ecotoxicity tests.

Ecological Risk Assessment of a Metal-Contaminated Area in the Tropics. Tier II: Detailed Assessment

PubMed Central

Niemeyer, Júlia Carina; Moreira-Santos, Matilde; Ribeiro, Rui; Rutgers, Michiel; Nogueira, Marco Antonio; da Silva, Eduardo Mendes; Sousa, José Paulo

2015-01-01

This study presents data on the detailed evaluation (tier 2) of a site-specific ecological risk assessment (ssERA) in a former smelter area contaminated with metals (Santo Amaro, Bahia, Brazil). Combining information from three lines of evidence (LoE), chemical (ChemLoE), ecotoxicological (EcotoxLoE) and ecological (EcoLoE), in the Triad approach, integrated risk values were calculated to rank sites and confirm the potential risk disclosed with tier 1. Risk values were calculated for the habitat and for the retention functions in each sampling point. Habitat function included the ChemLoE calculated from total metal concentrations. The EcotoxLoE was based on reproduction tests with terrestrial invertebrates (Folsomia candida, Enchytraeus crypticus, Eisenia andrei), shoot length and plant biomass (Avena sativa, Brassica rapa). For the EcoLoE, ecological parameters (microbial parameters, soil invertebrate community, litter breakdown) were used to derive risk values. Retention function included the ChemLoE, calculated from extractable metal concentrations, and the EcotoxLoE based on eluate tests with aquatic organisms (Daphnia magna reproduction and Pseudokirchneriella subcapitata growth). Results related to the habitat function indicated that the metal residues are sufficient to cause risk to biota, while the low metal levels in extracts and the general lack of toxicity in aquatic tests indicated a high soil retention capacity in most sampling points. Integrated risk of tier 2 showed the same trend of tier 1, suggesting the need to proceed with remediation actions. The high risk levels were related to direct toxicity to organisms and indirect effects, such as failure in the establishment of vegetation and the consequent loss of habitat quality for microorganisms and soil fauna. This study shed some light on the selection of tools for the tier 2 of an ssERA in tropical metal-contaminated sites, focusing on ecological receptors at risk and using available chemical methods, ecological surveys and ecotoxicity tests. PMID:26528915

Toxic effects of lead on biochemical and histological alterations in green mussel (Perna viridis) induced by environmentally relevant concentrations.

PubMed

Hariharan, G; Purvaja, R; Ramesh, R

2014-01-01

Acute and chronic toxicity tests were conducted on green mussel (Perna viridis) to determine the adverse effects of lead (Pb). Exposure of organisms to acute toxicity test for 96 h and lethal concentration (LC(50)) was the endpoint of the test. Acute toxicity for 96-h LC(50) and 95% confidence intervals of P. viridis was 2.62 ± 0.12 (2.62-3.24) mg/L Pb. Chronic toxicity tests revealed that survival of exposed organisms decreased with elevated exposure concentrations. No-observed-effect concentration (NOEC) and lowest-observed-effect concentration (LOEC) were calculated based on survival of test organisms. Results of this study demonstrated an increase in toxicity in test organisms with rise in exposure time and concentration. In this study, histology and biochemical enzymes, namely, catalase, reduced glutathione, glutathione S-transferase, and lipid peroxides, were correlated with chronic value and survival endpoints of P. viridis after chronic exposure to Pb. Biochemical and histological responses to different concentrations of Pb were assessed and significant differences were observed between control and increasing exposure concentrations. Biomarker studies in internal organs confirmed that the observed changes are due to adverse effects of Pb. This assessment of toxicity was the first step to determining the seawater quality criteria for marine organisms.

Development of an acute toxicity test with the tropical marine amphipod Parhyale hawaiensis.

PubMed

Artal, Mariana Coletty; Dos Santos, Amanda; Henry, Theodore Burdick; Umbuzeiro, Gisela de Aragão

2018-03-01

There is a lack of suitable tropical marine species for ecotoxicity tests. An attractive model organism for ecotoxicology is the marine amphipod Parhyale hawaiensis, which is already a model for genetic and developmental studies. This species is widespread, can tolerate changes in salinity, is easy to handle and is representative of circumtropical regions. The aim of this work was to describe standardized procedures for laboratory husbandry, define conditions for acute toxicity tests, and to provide acute toxicity test results for some reference toxicants. Culturing conditions for the organism in the laboratory were established in reconstituted seawater (30 ± 2 salinity), 24 ± 2 °C, photoperiod 12/12 h light/dark. Acute toxicity test procedures were developed for 96 h-exposure time, and organisms at ages <7 days. The miniaturized version of the test, based on 96-well microplates and 200 µL of exposure media provided consistent results compared to larger exposure volumes (80-mL vials protocol). Acute toxicity of Ag, Cd, Cu, Zn and ammonia determined for P. hawaiensis were consistent to previous results for other marine amphipods. We conclude that P. hawaiensis can be successfully cultured in standardized conditions and be effectively used in acute toxicity testing. Further development and use of this model will enable standardized and reproducible ecotoxicology investigations in understudied and vulnerable tropical marine ecosystems.

Evaluating the Zebrafish Embryo Toxicity Test for Pesticide ...

EPA Pesticide Factsheets

Given the numerous chemicals used in society, it is critical to develop tools for accurate and efficient evaluation of potential risks to human and ecological receptors. Fish embryo acute toxicity tests are 1 tool that has been shown to be highly predictive of standard, more resource-intensive, juvenile fish acute toxicity tests. However, there is also evidence that fish embryos are less sensitive than juvenile fish for certain types of chemicals, including neurotoxicants. The utility of fish embryos for pesticide hazard assessment was investigated by comparing published zebrafish embryo toxicity data from pesticides with median lethal concentration 50% (LC50) data for juveniles of 3 commonly tested fish species: rainbow trout, bluegill sunfish, and sheepshead minnow. A poor, albeit significant, relationship (r2 = 0.28; p < 0.05) was found between zebrafish embryo and juvenile fish toxicity when pesticides were considered as a single group, but a much better relationship (r2 = 0.64; p < 0.05) when pesticide mode of action was factored into an analysis of covariance. This discrepancy is partly explained by the large number of neurotoxic pesticides in the dataset, supporting previous findings that commonly used fish embryo toxicity test endpoints are particularly insensitive to neurotoxicants. These results indicate that it is still premature to replace juvenile fish toxicity tests with embryo-based tests such as the Organisation for Economic Co-op

The weaker points of fish acute toxicity tests and how tests on embryos can solve some issues.

PubMed

Wedekind, Claus; von Siebenthal, Beat; Gingold, Ruth

2007-07-01

Fish acute toxicity tests play an important role in environmental risk assessment and hazard classification because they allow for first estimates of the relative toxicity of various chemicals in various species. However, such tests need to be carefully interpreted. Here we shortly summarize the main issues which are linked to the genetics and the condition of the test animals, the standardized test situations, the uncertainty about whether a given test species can be seen as representative to a given fish fauna, the often missing knowledge about possible interaction effects, especially with micropathogens, and statistical problems like small sample sizes and, in some cases, pseudoreplication. We suggest that multi-factorial embryo tests on ecologically relevant species solve many of these issues, and we shortly explain how such tests could be done to avoid the weaker points of fish acute toxicity tests.

Draft Test Guideline: Daphnid Chronic Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Gammarid Acute Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Chironomid Sediment Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Mysid Acute Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Penaeid Acute Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Mysid Chronic Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

New EPA Guidance for Testing Pesticides Will Reduce Animal Testing

EPA Pesticide Factsheets

EPA is issuing guidance for requesting waivers of acute dermal toxicity testing requirements for pesticide formulations, which will lead to fewer animal tests for acute dermal toxicity for pesticides.

Toxicity assessment in marine sediment for the Terra Nova environmental effects monitoring program (1997-2010)

NASA Astrophysics Data System (ADS)

Whiteway, Sandra A.; Paine, Michael D.; Wells, Trudy A.; DeBlois, Elisabeth M.; Kilgour, Bruce W.; Tracy, Ellen; Crowley, Roger D.; Williams, Urban P.; Janes, G. Gregory

2014-12-01

This paper discusses toxicity test results on sediments from the Terra Nova offshore oil development. The Terra Nova Field is located on the Grand Banks approximately 350 km southeast of Newfoundland (Canada). The amphipod (Rhepoxynius abronius) survival and solid phase luminescent bacteria (Vibrio fischeri, or Microtox) assays were conducted on sediment samples collected from approximately 50 stations per program year around Terra Nova during baseline (1997), prior to drilling, and in 2000, 2001, 2002, 2004, 2006, 2008 and 2010 after drilling began. The frequency of toxic responses in the amphipod toxicity test was low. Of the ten stations that were toxic in environmental effects monitoring (EEM) years, only one (station 30(FE)) was toxic in more than one year and could be directly attributed to Terra Nova project activities. In contrast, 65 (18%) of 364 EEM samples were toxic to Microtox. Microtox toxicity in EEM years was not related to distance from Terra Nova drill centres or concentrations of >C10-C21 hydrocarbons or barium, the primary constituents of the synthetic-based drill muds used at Terra Nova. Of the variables tested, fines and strontium levels showed the strongest (positive) correlations with toxicity. Neither fines nor strontium levels were affected by drill cuttings discharge at Terra Nova, except at station 30(FE) (and that station was not toxic to Microtox). Benthic macro-invertebrate abundance, richness and diversity were greater in toxic than in non-toxic sediments. Therefore, Microtox responses indicating toxicity were associated with positive biological responses in the field. This result may have been an indirect function of the increased abundance of most invertebrate taxa in less sandy sediments with higher gravel content, where fines and strontium levels and, consequently, toxicity to Microtox were high; or chemical substances released by biodegradation of organic matter, where invertebrates are abundant, may be toxic to Microtox. Given the lack of association between Microtox results and discharge from Terra Nova, coupled with the confounding effects of other variables, the usefulness of Microtox toxicity tests within the context of environmental monitoring for the Terra Nova and, potentially, other offshore oil operations needs to be questioned. The amphipod toxicity tests showed that sediments in the vicinity of discharges of synthetic-based drilling mud cuttings are rarely toxic.

Intelligent Launch and Range Operations Virtual Test Bed (ILRO-VTB)

NASA Technical Reports Server (NTRS)

Bardina, Jorge; Rajkumar, T.

2003-01-01

Intelligent Launch and Range Operations Virtual Test Bed (ILRO-VTB) is a real-time web-based command and control, communication, and intelligent simulation environment of ground-vehicle, launch and range operation activities. ILRO-VTB consists of a variety of simulation models combined with commercial and indigenous software developments (NASA Ames). It creates a hybrid software/hardware environment suitable for testing various integrated control system components of launch and range. The dynamic interactions of the integrated simulated control systems are not well understood. Insight into such systems can only be achieved through simulation/emulation. For that reason, NASA has established a VTB where we can learn the actual control and dynamics of designs for future space programs, including testing and performance evaluation. The current implementation of the VTB simulates the operations of a sub-orbital vehicle of mission, control, ground-vehicle engineering, launch and range operations. The present development of the test bed simulates the operations of Space Shuttle Vehicle (SSV) at NASA Kennedy Space Center. The test bed supports a wide variety of shuttle missions with ancillary modeling capabilities like weather forecasting, lightning tracker, toxic gas dispersion model, debris dispersion model, telemetry, trajectory modeling, ground operations, payload models and etc. To achieve the simulations, all models are linked using Common Object Request Broker Architecture (CORBA). The test bed provides opportunities for government, universities, researchers and industries to do a real time of shuttle launch in cyber space.

Evaluation of Short-Term Bioassays to Predict Functional Impairment. Development of Hepatic Bioassays in Laboratory Animals, Directory of Institutions/Individuals.

DTIC Science & Technology

1980-10-01

Organizations Compounds Tested Morphological Tests Toxic Substances Functional Tests rR ACT Cutlue OM v.a e sif nemooery ad Identify by block number) %MITRE has...demonstrated ability to evaluate and predict hepatic impairment rvsulting from toxicant exposures. This directory is a companion to Selected Short-Term...Hepatic Toxicity Tests, which describes the available hepatic testing protocols and assesses their suitability for a screening program. This direc

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.

Provisional Peer-Reviewed Toxicity Values for Benzaldehyde

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

Provisional Peer-Reviewed Toxicity Values for Azodicarbonamide

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

Provisional Peer-Reviewed Toxicity Values for Lewisite

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

Provisional Peer-Reviewed Toxicity Values for Dicyclopentadiene

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

MECHANISMS OF MALE REPRODUCTIVE TOXICITY: BED, BATH AND BEYOND

EPA Science Inventory

Male reproductive function depends upon the integration of a great number of highly complex biological processes and their endocrine support. Therefore it is not surprising that male reproductive health can be impaired by exposures to drugs and environmental toxicants that impact...

Provisional Peer-Reviewed Toxicity Values for Aluminum

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

Provisional Peer-Reviewed Toxicity Values for Guanidine

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

Provisional Peer-Reviewed Toxicity Values for Acrolein

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

Provisional Peer-Reviewed Toxicity Values for Acenaphthylene

EPA Science Inventory

Provisional Peer-Reviewed Toxicity Values (PPRTV) assessments are developed for use by the Agency’s Office of Land and Emergency Management (OLEM) to support informed decisions in the Superfund program and at hazardous waste sites when a values is not available in the Integrated ...

Contact toxicity of 40 insecticides tested on pandora moth larvae

Treesearch

Robert L. Lyon

1971-01-01

Forty insecticides and an antifeeding compound were tested on pandora moth larvae (Coloradia pandora Blake) in the second and third instars. A total of 21 insecticides were more toxic at LD90 than DDT, providing a good choice of candidates for field testing. Ten exceeded DDT in toxicity tenfold or more. These were, in...

Automated Test Systems for Toxic Vapor Detectors

NASA Technical Reports Server (NTRS)

Mattson, C. B.; Hammond, T. A.; Schwindt, C. J.

1997-01-01

The NASA Toxic Vapor Detection Laboratory (TVDL) at the Kennedy Space Center (KSC), Florida, has been using Personal Computer based Data Acquisition and Control Systems (PCDAS) for about nine years. These systems control the generation of toxic vapors of known concentrations under controlled conditions of temperature and humidity. The PCDAS also logs the test conditions and the test article responses in data files for analysis by standard spreadsheets or custom programs. The PCDAS was originally developed to perform standardized qualification and acceptance tests in a search for a commercial off-the-shelf (COTS) toxic vapor detector to replace the hydrazine detectors for the Space Shuttle launch pad. It has since become standard test equipment for the TVDL and is indispensable in producing calibration standards for the new hydrazine monitors at the 10 part per billion (ppb) level. The standard TVDL PCDAS can control two toxic vapor generators (TVG's) with three channels each and two flow/ temperature / humidity (FTH) controllers and it can record data from up to six toxic vapor detectors (TVD's) under test and can deliver flows from 5 to 50 liters per minute (L/m) at temperatures from near zero to 50 degrees Celsius (C) using an environmental chamber to maintain the sample temperature. The concentration range for toxic vapors depends on the permeation source installed in the TVG. The PCDAS can provide closed loop control of temperature and humidity to two sample vessels, typically one for zero gas and one for the standard gas. This is required at very low toxic vapor concentrations to minimize the time required to passivate the sample delivery system. Recently, there have been several requests for information about the PCDAS by other laboratories with similar needs, both on and off KSC. The purpose of this paper is to inform the toxic vapor detection community of the current status and planned upgrades to the automated testing of toxic vapor detectors at the Kennedy Space Center.

Automated Test Systems for Toxic Vapor Detectors

NASA Technical Reports Server (NTRS)

Mattson, C. B.; Hammond, T. A.; Schwindt, C. J.

1997-01-01

The NASA Toxic Vapor Detection Laboratory (TVDL) at the Kennedy Space Center (KSC), Florida, has been using Personal Computer based Data Acquisition and Control Systems (PCDAS) for about nine years. These systems control the generation of toxic vapors of known concentrations under controlled conditions of temperature and humidity. The PCDAS also logs the test conditions and the test article responses in data files for analysis by standard spreadsheets or custom programs. The PCDAS was originally developed to perform standardized qualification and acceptance tests in a search for a commercial off-the-shelf (COTS) toxic vapor detector to replace the hydrazine detectors for the Space Shuttle launch pad. It has since become standard test equipment for the TVDL and is indispensable in producing calibration standards for the new hydrazine monitors at the 10 part per billion (ppb) level. The standard TVDL PCDAS can control two toxic vapor generators (TVG's) with three channels each and two flow/temperature/humidity (FIFH) controllers and it can record data from up to six toxic vapor detectors (TVD's) under test and can deliver flows from 5 to 50 liters per minute (L/m) at temperatures from near zero to 50 degrees Celsius (C) using an environmental chamber to maintain the sample temperature. The concentration range for toxic vapors depends on the permeation source installed in the TVG. The PCDAS can provide closed loop control of temperature and humidity to two sample vessels, typically one for zero gas and one for the standard gas. This is required at very low toxic vapor concentrations to minimize the time required to passivate the sample delivery system. Recently, there have been several requests for information about the PCDAS by other laboratories with similar needs, both on and off KSC. The purpose of this paper is to inform the toxic vapor detection community of the current status and planned upgrades to the automated testing of toxic vapor detectors at the Kennedy Space Center.

Acute toxicity of leachates of tire wear material to Daphnia magna--variability and toxic components.

PubMed

Wik, Anna; Dave, Göran

2006-09-01

Large amounts of tire rubber are deposited along the roads due to tread wear. Several compounds may leach from the rubber and cause toxicity to aquatic organisms. To investigate the toxic effects of tire wear material from different tires, rubber was abraded from the treads of twenty-five tires. Leachates were prepared by allowing the rubber to equilibrate with dilution water at 44 degrees C for 72 h. Then the rubber was filtered from the leachates, and test organisms (Daphnia magna) were added. Forty-eight hour EC50s ranged from 0.5 to >10.0 g l(-1). The toxicity identification evaluation (TIE) indicated that non-polar organic compounds caused most of the toxicity. UV exposure of the filtered tire leachates caused no significant increase in toxicity. However, when tested as unfiltered leachates (the rubber was not filtered from the leachates before addition of D. magna) photo-enhanced toxicity was considerable for some tires, which means that test procedures are important when testing tire leachates for aquatic (photo) toxicity. The acute toxicity of tire wear for Daphnia magna was found to be <40 times a predicted environmental concentration based on reports on the concentration of a tire component found in environmental samples, which emphasizes the need for a more extensive risk assessment of tire wear for the environment.

Toxicity of CeO2 nanoparticles - the effect of nanoparticle properties.

PubMed

Leung, Yu Hang; Yung, Mana M N; Ng, Alan M C; Ma, Angel P Y; Wong, Stella W Y; Chan, Charis M N; Ng, Yip Hang; Djurišić, Aleksandra B; Guo, Muyao; Wong, Mabel Ting; Leung, Frederick C C; Chan, Wai Kin; Leung, Kenneth M Y; Lee, Hung Kay

2015-04-01

Conflicting reports on the toxicity of CeO2 nanomaterials have been published in recent years, with some studies finding CeO2 nanoparticles to be toxic, while others found it to have protective effects against oxidative stress. To investigate the possible reasons for this, we have performed a comprehensive study on the physical and chemical properties of nanosized CeO2 from three different suppliers as well as CeO2 synthesized by us, and tested their toxicity. For toxicity tests, we have studied the effects of CeO2 nanoparticles on a Gram-negative bacterium Escherichia coli in the dark, under ambient and UV illuminations. We have also performed toxicity tests on the marine diatom Skeletonema costatum under ambient and UV illuminations. We found that the CeO2 nanoparticle samples exhibited significantly different toxicity, which could likely be attributed to the differences in interactions with cells, and possibly to differences in nanoparticle compositions. Our results also suggest that toxicity tests on bacteria may not be suitable for predicting the ecotoxicity of nanomaterials. The relationship between the toxicity and physicochemical properties of the nanoparticles is explicitly discussed in the light of the current results. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

PubMed

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

2012-06-01

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

Corrosion protection products as a source of bisphenol A and toxicity to the aquatic environment.

PubMed

Vermeirssen, Etiënne L M; Dietschweiler, Conrad; Werner, Inge; Burkhardt, Michael

2017-10-15

Steel components are typically treated with anti-corrosion coatings like epoxy or polyurethane resins to protect the integrity and functioning of steel. Such resins may contain substances, such as bisphenol A (BPA), that have caused concern in a human and environmental toxicological context. We investigated the release of toxicity from four anti-corrosion coatings used in hydraulic and civil engineering. Resins were applied onto glass plates and leachate samples produced by horizontally shaking the plates in water for 7 days. Two experiments were conducted, one with a 1 day and one with a 7 day curing period. Using a suite of bioassays, we tested samples for: agonistic and antagonistic effects on various mammalian nuclear receptors; inhibition of photosynthesis and growth in algae; inhibition of bacterial bioluminescence; and inhibition of water flea reproduction. Concentrations of BPA, bisphenol F and various BPA transformation products were determined by chemical analysis (LC-MS/MS). Bioassay results were evaluated using a scheme developed by DIBt (Centre of Competence for Construction, Berlin, Germany). Three products induced responses in one or more of the measured endpoints and toxicity profiles varied markedly in intensity across products. One product released high amounts of BPA which was associated with effects on nuclear receptor transactivation, requiring a more than 700-fold dilution for effect induction to fall below 20%. The same product was also the most toxic to water flea reproduction, requiring ca. 70-fold dilution for effects to fall below 20%. Another product was highly toxic in terms of bacterial bioluminescence, particularly after a shorter curing time, requiring a ca. 1'300-fold dilution for effects to fall below 20%. The third product required a 22-fold dilution for inhibition of water flea reproduction to drop below 20%. Results show that anti-corrosion coatings based on epoxy resins can be a source of toxicity to the aquatic environment. The fact that some products are more toxic than others highlights opportunities for the development of low risk formulations and products with better environmental performance. Finally, the DIBt scheme provides a useful starting point to develop further ecotoxicity guidelines for testing and data evaluation of leachates from construction materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

A prospective pilot study on early toxicity from a simultaneously integrated boost technique for canine sinonasal tumours using image-guided intensity-modulated radiation therapy.

PubMed

Soukup, A; Meier, V; Pot, S; Voelter, K; Rohrer Bley, C

2018-05-14

In order to overcome the common local treatment failure of canine sinonasal tumours, integrated boost techniques were tried in the cobalt/orthovoltage era, but dismissed because of unacceptable early (acute) toxicity. Intriguingly, a recent calculation study of a simultaneously integrated boost (SIB) technique for sinonasal irradiation using intensity-modulated radiation therapy (IMRT) predicted theoretical feasibility. In this prospective pilot study we applied a commonly used protocol of 10 × 4.2 Gy to the planning target volume (PTV) with a 20%-SIB dose to the gross tumour volume (GTV). Our hypothesis expected this dose escalation to be clinically tolerable if applied with image-guided IMRT. We included 9 dogs diagnosed with sinonasal tumours without local/distant metastases. For treatment planning, organs at risk were contoured according to strict anatomical guidelines. Planning volume extensions (GTV/CTV/PTV) were standardized to minimize interplanner variability. Treatments were applied with rigid patient positioning and verified daily with image guidance. After radiation therapy, we set focus on early ophthalmologic complications as well as mucosal and cutaneous toxicity. Early toxicity was evaluated at week 1, 2, 3, 8 and 12 after radiotherapy. Only mild ophthalmologic complications were found. Three patients (33%) had self-limiting moderate to severe early toxicity (grade 3 mucositis) which was managed medically. No patient developed ulcerations/haemorrhage/necrosis of skin/mucosa. The SIB protocol applied with image-guided IMRT to treat canine sinonasal tumours led to clinically acceptable side effects. The suspected increased tumour control probability and the risk of late toxicity with the used dose escalation of 20% has to be further investigated. © 2018 John Wiley & Sons Ltd.

User’s Guide for T.E.S.T. (version 4.2) (Toxicity Estimation Software Tool) A Program to Estimate Toxicity from Molecular Structure

EPA Science Inventory

The user's guide describes the methods used by TEST to predict toxicity and physical properties (including the new mode of action based method used to predict acute aquatic toxicity). It describes all of the experimental data sets included in the tool. It gives the prediction res...

Draft Test Guideline: Tadpole/Sediment Subchronic Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Bivalve Acute Toxicity Test (Embryo Larval)

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Oyster Acute Toxicity Test (Shell Deposition)

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Draft Test Guideline: Fish Early-Life Stage Toxicity Test

EPA Pesticide Factsheets

The following draft test guideline is part of a series of test guidelines that have been developed by EPA for use in the testing of pesticides and toxic substances, and the development of test data for submission to the Agency for review.

Effects of Jatropha curcas oil in Lactuca sativa root tip bioassays.

PubMed

Andrade-Vieira, Larissa F; Botelho, Carolina M; Laviola, Bruno G; Palmieri, Marcel J; Praça-Fontes, Milene M

2014-03-01

Jatropha curcas L. (Euphorbiaceae) is important for biofuel production and as a feed ingredient for animal. However, the presence of phorbol esters in the oil and cake renders the seeds toxic. The toxicity of J. curcas oil is currently assessed by testing in animals, leading to their death. The identification of toxic and nontoxic improved varieties is important for the safe use of J. curcas seeds and byproducts to avoid their environmental toxicity. Hence, the aim of this study was to propose a short-term bioassay using a plant as a model to screen the toxicity of J. curcas oil without the need to sacrifice any animals. The toxicity of J. curcas oil was evident in germination, root elongation and chromosomal aberration tests in Lactuca sativa. It was demonstrated that J. curcas seeds contain natural compounds that exert phyto-, cyto- and genotoxic effects on lettuce, and that phorbol esters act as aneugenic agents, leading to the formation of sticky chromosomes and c-metaphase cells. In conclusion, the tests applied have shown reproducibility, which is important to verify the extent of detoxification and to determine toxic doses, thus reducing the numbers of animals that would be used for toxicity tests.

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

PubMed

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

2017-11-01

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

Integrating in silico models to enhance predictivity for developmental toxicity.

PubMed

Marzo, Marco; Kulkarni, Sunil; Manganaro, Alberto; Roncaglioni, Alessandra; Wu, Shengde; Barton-Maclaren, Tara S; Lester, Cathy; Benfenati, Emilio

2016-08-31

Application of in silico models to predict developmental toxicity has demonstrated limited success particularly when employed as a single source of information. It is acknowledged that modelling the complex outcomes related to this endpoint is a challenge; however, such models have been developed and reported in the literature. The current study explored the possibility of integrating the selected public domain models (CAESAR, SARpy and P&G model) with the selected commercial modelling suites (Multicase, Leadscope and Derek Nexus) to assess if there is an increase in overall predictive performance. The results varied according to the data sets used to assess performance which improved upon model integration relative to individual models. Moreover, because different models are based on different specific developmental toxicity effects, integration of these models increased the applicable chemical and biological spaces. It is suggested that this approach reduces uncertainty associated with in silico predictions by achieving a consensus among a battery of models. The use of tools to assess the applicability domain also improves the interpretation of the predictions. This has been verified in the case of the software VEGA, which makes freely available QSAR models with a measurement of the applicability domain. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Observed and predicted reproduction of Ceriodaphnia dubia exposed to chloride, sulfate, and bicarbonate

USGS Publications Warehouse

Lasier, Peter J.; Hardin, Ian R.

2010-01-01

Chronic toxicities of Cl-, SO42-, and HCO3- to Ceriodaphnia dubia were evaluated in low- and moderate-hardness waters using a three-brood reproduction test method. Toxicity tests of anion mixtures were used to determine interaction effects and to produce models predicting C. dubia reproduction. Effluents diluted with low- and moderate-hardness waters were tested with animals acclimated to low- and moderate-hardness conditions to evaluate the models and to assess the effects of hardness and acclimation. Sulfate was significantly less toxic than Cl- and HCO3- in both types of water. Chloride and HCO3- toxicities were similar in low-hardness water, but HCO3- was the most toxic in moderate-hardness water. Low acute-to-chronic ratios indicate that toxicities of these anions will decrease quickly with dilution. Hardness significantly reduced Cl- and SO42- toxicity but had little effect on HCO3-. Chloride toxicity decreased with an increase in Na+ concentration, and CO3- toxicity may have been reduced by the dissolved organic carbon in effluent. Multivariate models using measured anion concentrations in effluents with low to moderate hardness levels provided fairly accurate predictions of reproduction. Determinations of toxicity for several effluents differed significantly depending on the hardness of the dilution water and the hardness of the water used to culture test animals. These results can be used to predict the contribution of elevated anion concentrations to the chronic toxicity of effluents; to identify effluents that are toxic due to contaminants other than Cl-, SO42-, and HCO3-; and to provide a basis for chemical substitutions in manufacturing processes.

Sediment pore-water toxicity test results and preliminary toxicity identification of post-landfall pore-water samples collected following the Deepwater Horizon oil release, Gulf of Mexico, 2010

USGS Publications Warehouse

Biedenbach, James M.; Carr, Robert S.

2011-01-01

Pore water from coastal beach and marsh sediments from the northern Gulf of Mexico, pre- and post-landfall of the Deepwater Horizon oil release, were collected and evaluated for toxicity with the sea urchin fertilization and embryological development assays. There were 17 pre-landfall samples and 49 post-landfall samples tested using both assays. Toxicity was determined in four pre-landfall sites and in seven post-landfall sites in one or both assays as compared to a known reference sediment pore-water sample collected in Aransas Bay, Texas. Further analysis and testing of five of the post-landfall toxic samples utilizing Toxicity Identification Evaluation techniques indicated that ammonia, and to a lesser extent metals, contributed to most, if not all, of the observed toxicity in four of the five samples. Results of one sample (MS-39) indicated evidence that ammonia, metals, and non-ionic organics were contributing to the observed toxicity.

Parental exposure to heavy fuel oil induces developmental toxicity in offspring of the sea urchin Strongylocentrotus intermedius.

PubMed

Duan, Meina; Xiong, Deqi; Yang, Mengye; Xiong, Yijun; Ding, Guanghui

2018-05-03

The present study investigated the toxic effects of parental (maternal/paternal) exposure to heavy fuel oil (HFO) on the adult reproductive state, gamete quality and development of the offspring of the sea urchin Strongylocentrotus intermedius. Adult sea urchins were exposed to effluents from HFO-oiled gravel columns for 7 days to simulate an oil-contaminated gravel shore, and then gametes of adult sea urchins were used to produce embryos to determine developmental toxicity. For adult sea urchins, no significant difference in the somatic size and weight was found between the various oil loadings tested, while the gonad weight and gonad index were significantly decreased at higher oil loadings. The spawning ability of adults and fecundity of females significantly decreased. For gametes, no effect was observed on the egg size and fertilization success in any of the groups. However, a significant increase in the percentage of anomalies in the offspring was observed and then quantified by an integrative toxicity index (ITI) at 24 and 48 h post fertilization. The offspring from exposed parents showed higher ITI values with more malformed embryos. The results confirmed that parental exposure to HFO can cause adverse effects on the offspring and consequently affect the recruitment and population maintenance of sea urchins. Copyright © 2018 Elsevier Inc. All rights reserved.

Review on toxicity testing with marine macroalgae and the need for method standardization--exemplified with copper and phenol.

PubMed

Eklund, Britta T; Kautsky, Lena

2003-02-01

Toxic effects on macroalgae have been compiled. Eighty-two articles have been found in literature during 1959-2000. A total of 120 substances were investigated using 65 different macroalgae species. About one-third of the tested compounds were organic substances (33%), another third metal-organic substances (35%), and the last third were oils (14%), metals (8%), detergents (7.5%) and other inorganic chemicals (2.5%). Half of the substances were only tested once on a single species. Likewise, toxicity data has only been reported for one chemical tested on a single occasion for about half of the 65 species. Thus little is known about the toxic effects on marine macroalgae. The objectives of the previous studies undertaken varied and therefore the toxicity data was presented in numerous ways, e.g. using different exposure times, temperature, light intensity, light regime, salinity, and nutrients, which makes a direct comparison of the data difficult. This review also shows that many stages in the lifecycle of macroalgae are often more sensitive to toxic substances than other aquatic organisms. Consequently, tests using macroalgae may discover toxicity earlier, which would in turn also protect the fauna. If toxic compounds have a negative affect on the distribution and growth of structurally and functionally dominating macroalgae, there may indirectly be a large and harmful influence on the whole marine coastal ecosystem. For this reason tests on macroalgae should be included in control programs along the coasts.

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.

Characterizing toxicity of metal-contaminated sediments from mining areas

USGS Publications Warehouse

Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.

2015-01-01

This paper reviews methods for testing the toxicity of metals associated with freshwater sediments, linking toxic effects with metal exposure and bioavailability, and developing sediment quality guidelines. The most broadly applicable approach for characterizing metal toxicity is whole-sediment toxicity testing, which attempts to simulate natural exposure conditions in the laboratory. Standard methods for whole-sediment testing can be adapted to test a wide variety of taxa. Chronic sediment tests that characterize effects on multiple endpoints (e.g., survival, growth, and reproduction) can be highly sensitive indicators of adverse effects on resident invertebrate taxa. Methods for testing of aqueous phases (pore water, overlying water, or elutriates) are used less frequently. Analysis of sediment toxicity data focuses on statistical comparisons between responses in sediments from the study area and responses in one or more uncontaminated reference sediments. For large or complex study areas, a greater number of reference sediments is recommended to reliably define the normal range of responses in uncontaminated sediments – the ‘reference envelope’. Data on metal concentrations and effects on test organisms across a gradient of contamination may allow development of concentration-response models, which estimate metal concentrations associated with specified levels of toxic effects (e.g. 20% effect concentration or EC20). Comparisons of toxic effects in laboratory tests with measures of impacts on resident benthic invertebrate communities can help document causal relationships between metal contamination and biological effects. Total or total-recoverable metal concentrations in sediments are the most common measure of metal contamination in sediments, but metal concentrations in labile sediment fractions (e.g., determined as part of selective sediment extraction protocols) may better represent metal bioavailability. Metals released by the weak-acid extraction of acid-volatile sulfide (AVS), termed simultaneously-extracted metals (SEM), are widely used to estimate the ‘potentially-bioavailable’ fraction of metals that is not bound to sulfides (i.e., SEM-AVS). Metal concentrations in pore water are widely considered to be direct measures of metal bioavailability, and predictions of toxicity based on pore-water metal concentrations may be further improved by modeling interactions of metals with other pore-water constituents using Biotic Ligand Models. Data from sediment toxicity tests and metal analyses has provided the basis for development of sediment quality guidelines, which estimate thresholds for toxicity of metals in sediments. Empirical guidelines such as Probable Effects Concentrations or (PECs) are based on associations between sediment metal concentrations and occurrence of toxic effects in large datasets. PECs do not model bioavailable metals, but they can be used to estimate the toxicity of metal mixtures using by calculation of probable effect quotients (PEQ = sediment metal concentration/PEC). In contrast, mechanistic guidelines, such as Equilibrium Partitioning Sediment Benchmarks (ESBs) attempt to predict both bioavailability and mixture toxicity. Application of these simple bioavailability models requires more extensive chemical characterization of sediments or pore water, compared to empirical guidelines, but may provide more reliable estimates of metal toxicity across a wide range of sediment types.

Toxicity of major geochemical ions to freshwater species

EPA Science Inventory

Extensive testing regarding the toxicity of major geochemical ions to Ceriodaphnia dubia, Hyalella azteca, and Pimephales promelas will be presented. For C. dubia, tests of single salts and binary mixtures in various dilution waters demonstrated multiple mechanisms of toxicity an...

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...

Fumigant Toxicity and Sublethal Effects of Artemisia khorassanica and Artemisia sieberi on Sitotroga cerealella (Lepidoptera: Gelechiidae).

PubMed

Naseri, B; Abedi, Z; Abdolmaleki, A; Jafary-Jahed, M; Borzoui, E; Mozaffar Mansouri, Seyed

2017-09-01

Fumigant toxicity and sublethal effects of essential oils from Artemisia khorassanica Podl. and Artemisia sieberi Bess were investigated against adults of Sitotroga cerealella Olivier. To assess the sublethal effects, adult moths were exposed to the LC30 of each essential oil, and life table parameters of the surviving S. cerealella were studied. Higher fumigant toxicity of A. khorassanica (LC50: 7.38 µl/liter air) than A. sieberi (LC50: 9.26 µl/liter air) was observed against S. cerealella. Also, the insecticidal effects of A. khorassanica (LT50: 9.01 h) were faster than A. sieberi (LT50: 14.37 h). A significant extension was observed in the developmental time (egg to adult) of S. cerealella treated with the essential oils. In addition, fecundity of S. cerealella reduced by 25.29 and 35.78% following exposure to sublethal concentrations of A. sieberi and A. khorassanica, respectively. Both tested essential oils caused a significant reduction in the gross and net reproductive rates, intrinsic rate of increase (rm), and finite rate of increase of S. cerealella. The rm values following exposure to A. sieberi, A. khorassanica, and control were 0.098, 0.094, and 0.107 d-1, respectively. The results of this study suggest that tested essential oils have a good potential to apply in integrated pest management of S. cerealella. © The Author 2017. Published by Oxford University Press on behalf of Entomological Society of America.

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

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.

Causes of toxicity in stormwater runoff from sawmills

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

Bailey, H.C.; Elphick, J.R.; Potter, A.

1999-07-01

Samples of stormwater runoff from nine sawmills in British Columbia, Canada, were tested for acute toxicity with juvenile rainbow trout over a 23-month period. Forty-two of the 58 samples tested exhibited toxicity. Causes of toxicity were investigated using toxicity identification evaluation techniques. Toxicity was attributed to divalent cations, particularly zinc, in 32 of the samples. The low hardness associated with most of the samples increased the potential for metal toxicity. For example, the LC50 of zinc was 14 {micro}g/L at a hardness of 5 mg/L. Toxicity in the remaining samples was largely attributed to tannins and lignins and was associatedmore » with areas of bulk log handling. No evidence was found to indicate that antisapstain chemicals applied to freshly cut wood contributed to toxicity.« less

Cytotoxicity of the association of pesticides Roundup Transorb® and Furadan 350 SC® on the zebrafish cell line, ZF-L.

PubMed

Goulart, T L S; Boyle, R T; Souza, M M

2015-10-01

The present study aimed to ascertain the cytotoxicity of pesticides commonly used in rice cultivation, through in vitro assays employing the ZF-L cell line. The in vitro analyses investigated three cellular targets (cell membrane integrity, mitochondrial activity and lysosomal stability) in cells exposed to concentrations of Roundup Transorb® (67.7 μg L(-1), 135.4 μg L(-1) and 270.8 μg L(-1)), Furadan 350 SC® (0.1 μg L(-1), 0.05 μg L(-1) and 0.02 μg L(-1)). We also tested these products in combination. We analyzed the defensive capacity of the cells by measuring the activity of xenobiotic extruder proteins, as well as the expression of these same proteins. Cytotoxic effects of both pesticides were observed individually, as well as with the mixture of both products; including an inhibitory effect on the activity of xenobiotic extrusion. When exposed to the insecticide Furadan, and also the mixture of Furadan and Roundup, there was an increase in the expression of P glycoproteins (P-gps). There was also a negative correlation with cytotoxicity, mainly exhibited by mitochondrial activity and lysosomal integrity, but also with respect to the activity of P-gps. We observed that concentrations below those allowed by law were toxic regarding all parameters tested in this study, with the exception of mitochondrial function. Taken together, our results suggest that toxicity may be due to the surfactants present in the commercial formulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Causes of highway road dust toxicity to an estuarine amphipod: Evaluating the effects of nicotine.

PubMed

Hiki, Kyoshiro; Nakajima, Fumiyuki; Tobino, Tomohiro

2017-02-01

Urban road dust can potentially have adverse effects on ecosystems if it is discharged into receiving waters. This study investigated the causes of highway road dust toxicity by performing sediment toxicity identification evaluation (TIE) tests with an estuarine amphipod, Grandidierella japonica. In addition to metals and polycyclic aromatic hydrocarbons, which are traditionally considered to be the major toxicants in road runoff, we focused on dissolved nicotine as a causative toxicant. The sediment TIE results suggested that organic contaminants contributed to the majority of toxicity, and that the contribution of unionized nicotine to the toxicity was the highest among the chemicals considered. However, additional mortality tests with 48-h pulsed nicotine exposure demonstrated that exposure to nicotine at the same concentration as the baseline level in TIE tests did not cause significant 10-day amphipod mortality. Thus, the road dust toxicity could not be explained only by unionized nicotine, thereby suggesting contributions from joint effects of the measured toxicants and the presence of other unmeasured factors. Copyright © 2016 Elsevier Ltd. All rights reserved.