The toxicity of arsenic(III), chromium(VI) and zinc to groundwater copepods.

PubMed

Hose, G C; Symington, K; Lott, M J; Lategan, M J

2016-09-01

Groundwater ecosystems globally are threatened by anthropogenic contamination, yet there are few ecotoxicological data using obligate groundwater biota on which to base risk assessments. Copepods are found inhabiting aquifers of different geologies around the world and so are a useful taxon for use in ecotoxicological studies of groundwater. The aim of this study was to test the sensitivity of obligate groundwater copepods to metal contaminants (arsenic(III), chromium(VI) and zinc) in groundwater in static 96 h, 14 days and 28 days exposure tests. The copepods were variably sensitive to As, Cr and Zn, with Cr being the most toxic across all taxa. No taxon was consistently most sensitive and there was no apparent relationship between the hardness, pH and organic carbon concentration of the diluent water and the sensitivity of biota. As expected, toxicity increased with exposure period and we encourage the use of longer exposure periods in future toxicity tests with groundwater organisms to reflect the greater exposure periods likely to be associated with groundwater contamination.

Revision of the ICH guideline on detection of toxicity to reproduction for medicinal products: SWOT analysis.

PubMed

Barrow, Paul

2016-09-01

SWOT analysis was used to gain insights and perspectives into the revision of the ICH S5(R2) guideline on detection of toxicity to reproduction for medicinal products. The current ICH guideline was rapidly adopted worldwide and has an excellent safety record for more than 20 years. The revised guideline should aim to further improve reproductive and developmental (DART) safety testing for new drugs. Alternative methods to animal experiments should be used whenever possible. Modern technology should be used to obtain high quality data from fewer animals. Additions to the guideline should include considerations on the following: limit dose setting, maternal toxicity, biopharmaceuticals, vaccines, testing strategies by indication, developmental immunotoxicity, and male-mediated developmental toxicity. Emerging issues, such as epigenetics and the microbiome, will most likely pose challenges to DART testing in the future. It is hoped that the new guideline will be adopted even outside the ICH regions. Copyright © 2016 Elsevier Inc. 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

Biosensors for Mycotoxin Analysis: Recent Developments and Future Prospects

USDA-ARS?s Scientific Manuscript database

The toxicity and prevalence of mycotoxins in commodities and foods has necessitated the development of rapid methods in order to ensure the protection of human food and animal feed supplies. Testing for mycotoxins can be accomplished by many techniques that range from determinative tests in which t...

Toxicity test of xanthone from mangosteen on zebrafish embryos

NASA Astrophysics Data System (ADS)

Noordin, Muhammad Akram Mohd; Noor, Mahanem Mat; Kamaruddin, Wan Mohd Aizat Wan; Lazim, Azwan Mat; Fazry, Shazrul

2016-11-01

Xanthone is a chemical compound identified in mangosteen pericarp. A previous study showed that xanthone has anti-proliferating effect on cancer cells. In this study we investigate the toxicity level of xanthone in zebrafish embryo to for future reference on other animal model. We employed Fish Embryo Toxicity (FET) assay to determine the toxicity level of different concentrations of xanthone. Embryos were observed at 24, 48 and 72 hours post fertilization (hpf) under microscope at 4× magnification. The extract showed toxicity effect on embryo at concentrations of 250, 125 and 62.5 µg/mL. Concentrations at 15.63, 7.81 and 3.91 µg / mL of xanthone did not harm the embryos and showed 100% of survival.

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

PubMed

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

2017-10-01

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

Selection of a battery of rapid toxicity sensors for drinking water evaluation.

PubMed

van der Schalie, William H; James, Ryan R; Gargan, Thomas P

2006-07-15

Comprehensive identification of chemical contaminants in Army field water supplies can be a lengthy process, but rapid analytical methods suitable for field use are limited. A complementary approach is to directly measure toxicity instead of individual chemical constituents. Ten toxicity sensors utilizing enzymes, bacteria, or vertebrate cells were tested to determine the minimum number of sensors that could rapidly identify toxicity in water samples containing one of 12 industrial chemicals. The ideal sensor would respond at a concentration just exceeding the Military Exposure Guideline (MEG) level for the chemical (an estimated threshold for adverse effects) but below the human lethal concentration. Chemical solutions were provided to testing laboratories as blind samples. No sensors responded to deionized water blanks, and only one sensor responded to a hard water blank. No single toxicity sensor responded to more than six chemicals in the desired response range, and one chemical (nicotine) was not detected by any sensor with the desired sensitivity. A combination of three sensors (Microtox, the Electric Cell Substrate Impedance Sensing (ECIS) test, and the Hepatocyte low density lipoprotein (LDL) uptake test) responded appropriately to nine of twelve chemicals. Adding a fourth sensor (neuronal microelectrode array) to the test battery allowed detection of two additional chemicals (aldicarb and methamidophos), but the neuronal microelectrode array was overly sensitive to paraquat. Evaluating sensor performance using a standard set of chemicals and a desired sensitivity range provides a basis both for selecting among available toxicity sensors and for evaluating emerging sensor technologies. Recommendations for future toxicity sensor evaluations are discussed.

Weathering and aging of 2,4,6-trinitrotoluene in soil increases toxicity to potworm Enchytraeus crypticus.

PubMed

Kuperman, Roman G; Checkai, Ronald T; Simini, Michael; Phillips, Carlton T; Kolakowski, Jan E; Kurnas, Carl W

2005-10-01

Energetic materials are employed in a wide range of commercial and military activities and often are released into the environment. Scientifically based ecological soil-screening levels (Eco-SSLs) are needed to identify contaminant explosive levels in soil that present an acceptable ecological risk. Insufficient information for 2,4,6-trinitrotoluene (TNT) to generate Eco-SSLs for soil invertebrates necessitated toxicity testing. We adapted the standardized Enchytraeid Reproduction Test and selected Enchytraeus crypticus for these studies. Tests were conducted in Sassafras sandy loam soil, which supports relatively high bioavailability of TNT. Weathering and aging procedures for TNT amended to test soil were incorporated into the study design to produce toxicity data that better reflect the soil exposure conditions in the field compared with toxicity in freshly amended soils. This included exposing hydrated TNT-amended soils in open glass containers in the greenhouse to alternating wetting and drying cycles. Definitive tests showed that toxicity for E. crypticus adult survival and juvenile production was increased significantly in weathered and aged soil treatments compared with toxicity in freshly amended soil based on 95% confidence intervals. The median effect concentration and 20% effective concentration for reproduction were 98 and 77 mg/kg, respectively, for TNT freshly amended into soil and 48 and 37 mg/kg, respectively, for weathered and aged TNT soil treatments. These findings of increased toxicity to E. crypticus in weathered and aged TNT soil treatments compared with exposures in freshly amended soils show that future investigations should include a weathering and aging component to generate toxicity data that provide more complete information on ecotoxicological effects of energetic contaminants in soil.

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.

In honor of the Teratology Society's 50th anniversary: The role of Teratology Society members in the development and evolution of in vivo developmental toxicity test guidelines.

PubMed

Tyl, Rochelle W

2010-06-01

Members of the Teratology Society (established in 1960) were involved in the first governmental developmental and reproductive toxicity testing guidelines (1966) by FDA following the thalidomide epidemic, followed by other national and international governmental testing guidelines. The Segment II (developmental toxicity) study design, described in rodents and rabbits, has evolved with additional enhanced endpoints and better descriptions, mechanistic insights, range-finding studies, and toxico/pharmacokinetic ADME information (especially for pharmaceuticals). Society members were also involved in the development of the current screening assays and tests for endocrine disruptors (beginning in 1996) and are now involved with developing new testing guidelines (e.g., the extended one-generation protocol), and evaluating the current test guidelines and new initiatives under ILSI/HESI sponsorship. New initiatives include ToxCast from the U.S. EPA to screen, prioritize, and predict toxic chemicals by high throughput and high-content in vitro assays, bioinformation, and modeling to reduce (or eliminate) in vivo whole animal studies. Our Society and its journal have played vital roles in the scientific and regulatory accomplishments in birth defects research over the past 50 years and will continue to do so in the future. Happy 50th anniversary! (c) 2010 Wiley-Liss, Inc.

Different influences of field aging on nickel toxicity to Folsomia candida in two types of soil.

PubMed

Liu, Yu-Rong; Li, Jing; He, Ji-Zheng; Ma, Yi-Bing; Zheng, Yuan-Ming

2015-06-01

Metal aging in soils has been considered an important factor influencing its availability and toxicity to organisms. In this study, we report the influence of 5 years field aging on the nickel (Ni) toxicity to collembolan Folsomia candida based on two different types of soil from Dezhou (DZ) and Qiyang (QY) counties in China. Acute and chronic toxicity of Ni to F. candida was assessed in both freshly spiked and field aging contaminated soils. We found that 5 years field aging increased the EC50 and 2d-LC50 values of Ni to F. candida in the DZ soil, while little influence on the Ni toxicity was observed in the QY soil. There was no adverse effect of the long-term field aging on the Ni toxicity to the survival of F. candida in the two tested soils. In addition, field aging of the two soils impacted differently the water-soluble Ni concentrations, which were significantly correlated to the juvenile production of F. candida based on a logistic model. Our study highlights different effects of long-term field aging on the Ni toxicity to F. candida between divergent types of soil, and this should be taken into account in future toxicity testing and risk assessment practices.

Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

PubMed

Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

2015-10-01

To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

Genetic Toxicology in the 21st Century: Reflections and Future Directions

PubMed Central

Mahadevan, Brinda; Snyder, Ronald D.; Waters, Michael D.; Benz, R. Daniel; Kemper, Raymond A.; Tice, Raymond R.; Richard, Ann M.

2011-01-01

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high-throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast™, a related research program of the U.S. Environmental Protection Agency, using a broad array of high throughput and high content technologies for toxicity profiling of environmental chemicals, and computational toxicology modeling. Progress and challenges, including the pressing need to incorporate metabolic activation capability, are summarized. PMID:21538556

Toxicity evaluation of 2-hydroxybiphenyl and other compounds involved in studies of fossil fuels biodesulphurisation.

PubMed

Alves, L; Paixão, S M

2011-10-01

The acute toxicity of some compounds used in fossil fuels biodesulphurisation studies, on the respiration activity, was evaluated by Gordonia alkanivorans and Rhodococcus erythropolis. Moreover, the effect of 2-hydroxybiphenyl on cell growth of both strains was also determined, using batch (chronic bioassays) and continuous cultures. The IC₅₀ values obtained showed the toxicity of all the compounds tested to both strains, specially the high toxicity of 2-HBP. These results were confirmed by the chronic toxicity data. The toxicity data sets highlight for a higher sensitivity to the toxicant by the strain presenting a lower growth rate, due to a lower cells number in contact with the toxicant. Thus, microorganisms exhibiting faster generation times could be more resistant to 2-HBP accumulation during a BDS process. The physiological response of both strains to 2-HBP pulse in a steady-state continuous culture shows their potential to be used in a future fossil fuel BDS process. Copyright © 2011 Elsevier Ltd. All rights reserved.

U.S. Coast Guard 1994 Oil Pollution Research Grants Publications - Part II.

DTIC Science & Technology

1996-09-01

preparations. However, toxicity testing in various salinities may be of future interest in a number of cases. We have no direct data on the effect of different...of oil toxicity. Factors such as temperature (Korn et al. 1979), salinity (Linden et al. 1979), pH and route of exposure (Lee et al. 1976) may effect ...Evidence of altered metabolic pathways provides information concerning enzyme systems sensitive to oil-dispersant expostre. Any factors effecting these

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

PubMed

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

2015-01-01

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

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.

Acute toxicity tests and meta-analysis identify gaps in tropical ecotoxicology for amphibians.

PubMed

Ghose, Sonia L; Donnelly, Maureen A; Kerby, Jacob; Whitfield, Steven M

2014-09-01

Amphibian populations are declining worldwide, particularly in tropical regions where amphibian diversity is highest. Pollutants, including agricultural pesticides, have been identified as a potential contributor to decline, yet toxicological studies of tropical amphibians are very rare. The present study assesses toxic effects on amphibians of 10 commonly used commercial pesticides in tropical agriculture using 2 approaches. First, the authors conducted 8-d toxicity assays with formulations of each pesticide using individually reared red-eyed tree frog (Agalychnis callidryas) tadpoles. Second, they conducted a review of available data for the lethal concentration to kill 50% of test animals from the US Environmental Protection Agency's ECOTOX database to allow comparison with their findings. Lethal concentration estimates from the assays ranged over several orders of magnitude. The nematicides terbufos and ethoprophos and the fungicide chlorothalonil were very highly toxic, with evident effects within an order of magnitude of environmental concentrations. Acute toxicity assays and meta-analysis show that nematicides and fungicides are generally more toxic than herbicides yet receive far less research attention than less toxic herbicides. Given that the tropics have a high diversity of amphibians, the findings emphasize the need for research into the effects of commonly used pesticides in tropical countries and should help guide future ecotoxicological research in tropical regions. © 2014 SETAC.

Genetic toxicology in the 21st century: Reflections and future ...

EPA Pesticide Factsheets

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high-throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast™, a related research program of the

Toxicology of a Peruvian botanical remedy to support healthy liver function.

PubMed

Semple, Hugh A; Sloley, B Duff; Cabanillas, José; Chiu, Andrea; Aung, Steven K H; Green, Francis H Y

2016-06-01

The purpose of these studies was to determine the safety of a botanical treatment for supporting healthy liver function developed in Peru. The formulation, A4+, contains extracts of Curcuma longa L. rhizome (A4R), Cordia lutea Lam. flower (A4F) and Annona muricata L. leaf (A4L). The tests were used to support an application for a non-traditional Natural Health Product Licence from the Natural Health Product Directorate of Health Canada and future clinical trials. Besides reviewing the scientific and clinical information from Peru on the ingredients and conducting an initial Ames test for mutagenicity, we analysed A4+ for its chemical profile and tested genotoxicity (micronucleus test) and general toxicity (28-day repeated dose). A4+ and extracts from the three plants provided distinctive chemical fingerprints. A4L contained acetogenins, requiring a second chromatographic method to produce a specific fingerprint. The Ames test proved positive at the highest concentration (5,000 μg/mL) but A4+ showed no evidence of genotoxicity in the more specific mouse micronucleus test. The 28-day repeated dose (general toxicity) study in rats showed no toxicity at 2,000 mg/kg. We conclude that under the conditions of these studies, A4+ shows no evidence of toxicity at the levels indicated. A no observed adverse effect level (NOAEL) of 2,000 mg/kg was assigned.

An expert consortium review of the EC-commissioned report "alternative (Non-Animal) methods for cosmetics testing: current status and future prospects - 2010".

PubMed

Hartung, Thomas; Blaauboer, Bas J; Bosgra, Sieto; Carney, Edward; Coenen, Joachim; Conolly, Rory B; Corsini, Emanuela; Green, Sidney; Faustman, Elaine M; Gaspari, Anthony; Hayashi, Makoto; Wallace Hayes, A; Hengstler, Jan G; Knudsen, Lisbeth E; Knudsen, Thomas B; McKim, James M; Pfaller, Walter; Roggen, Erwin L

2011-01-01

The European cosmetics legislation foresees a review in 2011 and possible postponement of the 2013 marketing ban to enforce the testing ban for systemic and repeated-dose animal tests. For this purpose, a 119-page report commissioned by the European Commission was published recently. Here, a group of 17 independent experts from the US, Europe, and Japan was brought together to evaluate the report. The expert panel strongly endorsed the report and its conclusions. A number of important options not considered were identified; these do not, however, affect the overall conclusions regarding the current lack of availability of a full replacement, especially for the areas of repeated dose toxicity, carcinogenicity testing, and reproductive toxicity, though a roadmap for change is emerging. However, some of these options may provide adequate data for replacement of some animal studies in the near future pending validation. Various recommendations expand the original report. The reviewers agree with the report that there is greater promise in the short term for the areas of sensitization and toxicokinetics. Additional opportunities lie in more global collaborations and the inclusion of other industry sectors.

The repellent and persistent toxic effects of essential oils against the poultry red mite, Dermanyssus gallinae.

PubMed

Nechita, I S; Poirel, M T; Cozma, V; Zenner, L

2015-12-15

The economic impact of the poultry red mite, Dermanyssus gallinae, the lack of new acaricides, the occurrence of resistance and tighter legislation have all led to the need to find new ways to control this pest. One promising alternative method of control focuses on employing repellent and/or toxic effects of selected plant essential oils against D. gallinae. Ten essential oils (basil, thyme, coriander, eucalyptus, lavender, lemon, fir tree, oregano, mint, and juniper) were tested for the persistence of toxic and repellent effects. In filter-paper toxicity bioassays against D. gallinae, the best results were observed for lavender (more than 97% mortality after 48 and 72 h) and thyme (84% at 72 h) at a dose of 0.12 mg/cm(2). In addition, two oils showed significant persistent toxic effects 15 and 30 days post application to filter papers. Thyme was the most effective (100% mortality at 72 h), followed by lavender (nearly 80% mortality after 72 h). Out of the ten oils tested for their repellent effect, thyme was the strongest, with nearly 80% of the tested area avoided by mites; oregano caused a 60% avoidance and lavender exhibited an effect close to 40%. All other oils exhibited a repellent effect of less than 30%. None of the experiments showed a repellent effect for HM (commercial alimentary oil) or negative controls. We found that the thyme and lavender essential oils exhibited promising results when tested in vitro for toxic and repellent effects against D. gallinae; thus, we suggest that future experiments focus on in vivo tests using these oils in farm units. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of sediment contamination at Great Lakes Areas of Concern: the ARCS Program Toxicity-Chemistry Work Group strategy

USGS Publications Warehouse

Ross, P.E.; Burton, G.A.; Crecelius, E.A.; Filkins, J. C.; Giesy, J.P.; Ingersoll, C.G.; Landrum, P.F.; Mac, M.J.; Murphy, T.J.; Rathbun, J. E.; Smith, V. E.; Tatem, H. E.; Taylor, R.W.

1992-01-01

In response to a mandate in Section 118(c)(3) of the Water Quality Act of 1987, a program called Assessment and Remediation of Contaminated Sediments (ARCS) was established. Four technical work groups were formed. This paper details the research strategy of the Toxicity-Chemistry Work Group.The Work Group's general objectives are to develop survey methods and to map the degree of contamination and toxicity in bottom sediments at three study areas, which will serve as guidance for future surveys at other locations. A related objective is to use the data base that will be generated to calculate sediment quality concentrations by several methods. The information needed to achieve these goals will be collected in a series of field surveys at three areas: Saginaw Bay (MI), Grand Calumet River (IN), and Buffalo River (NY). Assessments of the extent of contamination and potential adverse effects of contaminants in sediment at each of these locations will be conducted by collecting samples for physical characterization, toxicity testing, mutagenicity testing, chemical analyses, and fish bioaccumulation assays. Fish populations will be assessed for tumors and external abnormalities, and benthic community structure will be analyzed. A mapping approach will use low-cost indicator parameters at a large number of stations, and will extrapolate by correlation from traditional chemical and biological studies at a smaller number of locations. Sediment toxicity testing includes elutriate, pore water and whole sediment bioassays in a three-tiered framework. In addition to the regular series of toxicity tests at primary mater stations, some stations are selected for a more extensive suite of tests.

Workshop Introduction: Systems Biology and Biological Models

EPA Science Inventory

As we consider the future of toxicity testing, the importance of applying biological models to this problem is clear. Modeling efforts exist along a continuum with respect to the level of organization (e.g. cell, tissue, organism) linked to the resolution of the model. Generally,...

Large Dataset of Acute Oral Toxicity Data Created for Testing ...

EPA Pesticide Factsheets

Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are being developed due to animal welfare and resource considerations. We compiled a large dataset of oral rat LD50 values to assess the predictive performance currently available in silico models. Our dataset combines LD50 values from five different sources: literature data provided by The Dow Chemical Company, REACH data from eChemportal, HSDB (Hazardous Substances Data Bank), RTECS data from Leadscope, and the training set underpinning TEST (Toxicity Estimation Software Tool). Combined these data sources yield 33848 chemical-LD50 pairs (data points), with 23475 unique data points covering 16439 compounds. The entire dataset was loaded into a chemical properties database. All of the compounds were registered in DSSTox and 59.5% have publically available structures. Compounds without a structure in DSSTox are currently having their structures registered. The structural data will be used to evaluate the predictive performance and applicable chemical domains of three QSAR models (TIMES, PROTOX, and TEST). Future work will combine the dataset with information from ToxCast assays, and using random forest modeling, assess whether ToxCast assays are useful in predicting acute oral toxicity. Pre

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

PubMed

Lafon, D

2006-10-01

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

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

PubMed Central

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

2015-01-01

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

Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

PubMed

Kerns, Sarah L; Dorling, Leila; Fachal, Laura; Bentzen, Søren; Pharoah, Paul D P; Barnes, Daniel R; Gómez-Caamaño, Antonio; Carballo, Ana M; Dearnaley, David P; Peleteiro, Paula; Gulliford, Sarah L; Hall, Emma; Michailidou, Kyriaki; Carracedo, Ángel; Sia, Michael; Stock, Richard; Stone, Nelson N; Sydes, Matthew R; Tyrer, Jonathan P; Ahmed, Shahana; Parliament, Matthew; Ostrer, Harry; Rosenstein, Barry S; Vega, Ana; Burnet, Neil G; Dunning, Alison M; Barnett, Gillian C; West, Catharine M L

2016-08-01

Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling. Copyright © 2016 The Ohio State University Wexner Medical Center. Published by Elsevier B.V. All rights reserved.

Acute toxicity and effects analysis of endosulfan sulfate to freshwater fish species.

PubMed

Carriger, John F; Hoang, Tham C; Rand, Gary M; Gardinali, Piero R; Castro, Joffre

2011-02-01

Endosulfan sulfate is a persistent environmental metabolite of endosulfan, an organochlorine insecticide-acaricide presently registered by the United States Environmental Protection Agency. There is, however, limited acute fish toxicity data for endosulfan sulfate. This study determines the acute toxicity (LC₅₀s and LC₁₀s) of endosulfan sulfate to three inland Florida native fish species (mosquitofish [Gambusia affinis]; least killifish [Heterandria formosa]; and sailfin mollies [Poecilia latipinna]) as well as fathead minnows (Pimephales promelas). Ninety-six-h acute toxicity tests were conducted with each fish species under flow-through conditions. For all of the above-mentioned fish species, 96-h LC₅₀ estimates ranged from 2.1 to 3.5 μg/L endosulfan sulfate. The 96-h LC₁₀ estimates ranged from 0.8 to 2.1 μg/L endosulfan sulfate. Of all of the fish tested, the least killifish appeared to be the most sensitive to endosulfan sulfate exposure. The above-mentioned data were combined with previous acute toxicity data for endosulfan sulfate and freshwater fish for an effects analysis. The effects analysis estimated hazardous concentrations expected to exceed 5, 10, and 50% of the fish species' acute LC₅₀ or LC₁₀ values (HC₅, HC₁₀, and HC₅₀). The endosulfan sulfate freshwater-fish acute tests were also compared with the available freshwater-fish acute toxicity data for technical endosulfan. Technical endosulfan is a mixture of α- and β-endosulfan. The LC₅₀s had a wider range for technical endosulfan, and their distribution produced a lower HC₁₀ than for endosulfan sulfate. The number of freshwater-fish LC₅₀s for endosulfan sulfate is much smaller than the number available for technical endosulfan, reflecting priorities in examining the toxicity of the parent compounds of pesticides. The toxicity test results and effects analyses provided acute effect values for endosulfan sulfate and freshwater fish that might be applied in future screening level ecologic risk assessments. The effects analyses also discussed several deficiencies in conventional methods for setting water-quality criteria and determining ecologic effects from acute toxicity tests.

The toxicity study of functionalized CNT from fermented tapioca on neuroblastoma cell

NASA Astrophysics Data System (ADS)

Nurulhuda, I.; Mazatulikhma, M. Z.; Alrokayan, S.; Khan, H.; Rusop, M.

2018-05-01

Carbon nanotubes known as one of the most interesting types of nanomaterials, especially use in application directly to cells. Somehow the use should take into consideration regarding the potential adverse impact on human health. Current study, the carbon nanotube was synthesized from fermented tapioca and functionalized with polyethylene glycol and directly test on the neuroblastoma cells in vitro. The toxicity effect on cells was assessed by 3(4, 5-dimethylthiazol-2-yl)-2, 5-tetrazolium bromide assays. It showed a dose-and time-dependent less toxic effect on functionalized carbon nanotube compared to non-functionalized. This leads us to the conclusion that functionalized carbon nanotube can be use for drug delivery in future.

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

PubMed

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

2015-05-01

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

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

PubMed

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

2016-09-01

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

COMPUTER SUPPORT SYSTEMS FOR ESTIMATING CHEMICAL TOXICITY: PRESENT CAPABILITIES AND FUTURE TRENDS

EPA Science Inventory

Computer Support Systems for Estimating Chemical Toxicity: Present Capabilities and Future Trends

A wide variety of computer-based artificial intelligence (AI) and decision support systems exist currently to aid in the assessment of toxicity for environmental chemicals. T...

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

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

Joseph Bidwell; Jonathan Fisher; Naomi Cooper

2008-03-31

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

An investigation of new toxicity test method performance in validation studies: 1. Toxicity test methods that have predictive capacity no greater than chance.

PubMed

Bruner, L H; Carr, G J; Harbell, J W; Curren, R D

2002-06-01

An approach commonly used to measure new toxicity test method (NTM) performance in validation studies is to divide toxicity results into positive and negative classifications, and the identify true positive (TP), true negative (TN), false positive (FP) and false negative (FN) results. After this step is completed, the contingent probability statistics (CPS), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) are calculated. Although these statistics are widely used and often the only statistics used to assess the performance of toxicity test methods, there is little specific guidance in the validation literature on what values for these statistics indicate adequate performance. The purpose of this study was to begin developing data-based answers to this question by characterizing the CPS obtained from an NTM whose data have a completely random association with a reference test method (RTM). Determining the CPS of this worst-case scenario is useful because it provides a lower baseline from which the performance of an NTM can be judged in future validation studies. It also provides an indication of relationships in the CPS that help identify random or near-random relationships in the data. The results from this study of randomly associated tests show that the values obtained for the statistics vary significantly depending on the cut-offs chosen, that high values can be obtained for individual statistics, and that the different measures cannot be considered independently when evaluating the performance of an NTM. When the association between results of an NTM and RTM is random the sum of the complementary pairs of statistics (sensitivity + specificity, NPV + PPV) is approximately 1, and the prevalence (i.e., the proportion of toxic chemicals in the population of chemicals) and PPV are equal. Given that combinations of high sensitivity-low specificity or low specificity-high sensitivity (i.e., the sum of the sensitivity and specificity equal to approximately 1) indicate lack of predictive capacity, an NTM having these performance characteristics should be considered no better for predicting toxicity than by chance alone.

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.

A hypothetical model for predicting the toxicity of high aspect ratio nanoparticles (HARN)

NASA Astrophysics Data System (ADS)

Tran, C. L.; Tantra, R.; Donaldson, K.; Stone, V.; Hankin, S. M.; Ross, B.; Aitken, R. J.; Jones, A. D.

2011-12-01

The ability to predict nanoparticle (dimensional structures which are less than 100 nm in size) toxicity through the use of a suitable model is an important goal if nanoparticles are to be regulated in terms of exposures and toxicological effects. Recently, a model to predict toxicity of nanoparticles with high aspect ratio has been put forward by a consortium of scientists. The High aspect ratio nanoparticles (HARN) model is a platform that relates the physical dimensions of HARN (specifically length and diameter ratio) and biopersistence to their toxicity in biological environments. Potentially, this model is of great public health and economic importance, as it can be used as a tool to not only predict toxicological activity but can be used to classify the toxicity of various fibrous nanoparticles, without the need to carry out time-consuming and expensive toxicology studies. However, this model of toxicity is currently hypothetical in nature and is based solely on drawing similarities in its dimensional geometry with that of asbestos and synthetic vitreous fibres. The aim of this review is two-fold: (a) to present findings from past literature, on the physicochemical property and pathogenicity bioassay testing of HARN (b) to identify some of the challenges and future research steps crucial before the HARN model can be accepted as a predictive model. By presenting what has been done, we are able to identify scientific challenges and research directions that are needed for the HARN model to gain public acceptance. Our recommendations for future research includes the need to: (a) accurately link physicochemical data with corresponding pathogenicity assay data, through the use of suitable reference standards and standardised protocols, (b) develop better tools/techniques for physicochemical characterisation, (c) to develop better ways of monitoring HARN in the workplace, (d) to reliably measure dose exposure levels, in order to support future epidemiological studies.

Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera) through a k-nearest neighbor model.

PubMed

Como, F; Carnesecchi, E; Volani, S; Dorne, J L; Richardson, J; Bassan, A; Pavan, M; Benfenati, E

2017-01-01

Ecological risk assessment of plant protection products (PPPs) requires an understanding of both the toxicity and the extent of exposure to assess risks for a range of taxa of ecological importance including target and non-target species. Non-target species such as honey bees (Apis mellifera), solitary bees and bumble bees are of utmost importance because of their vital ecological services as pollinators of wild plants and crops. To improve risk assessment of PPPs in bee species, computational models predicting the acute and chronic toxicity of a range of PPPs and contaminants can play a major role in providing structural and physico-chemical properties for the prioritisation of compounds of concern and future risk assessments. Over the last three decades, scientific advisory bodies and the research community have developed toxicological databases and quantitative structure-activity relationship (QSAR) models that are proving invaluable to predict toxicity using historical data and reduce animal testing. This paper describes the development and validation of a k-Nearest Neighbor (k-NN) model using in-house software for the prediction of acute contact toxicity of pesticides on honey bees. Acute contact toxicity data were collected from different sources for 256 pesticides, which were divided into training and test sets. The k-NN models were validated with good prediction, with an accuracy of 70% for all compounds and of 65% for highly toxic compounds, suggesting that they might reliably predict the toxicity of structurally diverse pesticides and could be used to screen and prioritise new pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-04-01

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

THE FUTURE OF COMPUTER-BASED TOXICITY PREDICTION: MECHANISM-BASED MODELS VS. INFORMATION MINING APPROACHES

EPA Science Inventory

The Future of Computer-Based Toxicity Prediction:
Mechanism-Based Models vs. Information Mining Approaches

When we speak of computer-based toxicity prediction, we are generally referring to a broad array of approaches which rely primarily upon chemical structure ...

A soil bioassay using the nematode Caenorhabditis elegans

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

Freeman, M.N.; Peredney, C.L.; Williams, P.L.

1999-07-01

Caenorhabditis elegans is a free-livings soil nematode that is commonly used as a biological model. Recently, much work has been done using the nematode as a toxicological model as well. Much of the work involving C. elegans has been performed in aquatic media, since it lives in the interstitial water of soil. However, testing in soil would be expected to more accurately reproduce the organism's normal environment and may take into consideration other factors not available in an aquatic test, i.e., toxicant availability effects due to sorption, various chemical interactions, etc. This study used a modification of a previous experimentalmore » protocol to determine 24h LC{sub 50} values for Cu in a Cecil series soil mixture, and examined the use of CuCl{sub 2} as a reference toxicant for soil toxicity testing with C. elegans. Three different methods of determining percent lethality were used, each dependent on how the number of worms missing after the recovery process was used in the lethality calculations. Only tests having {ge}80% worm recovery and {ge}90% control survival were used in determining the LC{sub 50}s, by Probit analysis. The replicate LC{sub 50} values generated a control chart for each method of calculating percent lethality. The coefficient of variation (CV) for each of the three methods was {le}14%. The control charts and the protocol outlined in this study are intended to be used to assess test organism health and monitor precision of future soil toxicity tests with C. elegans.« less

Consensus report on the future of animal-free systemic toxicity testing

EPA Science Inventory

This is a multi-authored consensus report from conferences held in 2011-2012. Complete author listing is as follows: Marcel Leist1,2, Nina Hasiwa1, Costanza Rovida1, Mardas Daneshian1, David Basketter3, Ian Kimber4, Harvey Clewell5, Tilman Gocht6, Alan Goldberg7, Derek Knight8, G...

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

Race, deprivation, and immigrant isolation: The spatial demography of air-toxic clusters in the continental United States.

PubMed

Liévanos, Raoul S

2015-11-01

This article contributes to environmental inequality outcomes research on the spatial and demographic factors associated with cumulative air-toxic health risks at multiple geographic scales across the United States. It employs a rigorous spatial cluster analysis of census tract-level 2005 estimated lifetime cancer risk (LCR) of ambient air-toxic emissions from stationary (e.g., facility) and mobile (e.g., vehicular) sources to locate spatial clusters of air-toxic LCR risk in the continental United States. It then tests intersectional environmental inequality hypotheses on the predictors of tract presence in air-toxic LCR clusters with tract-level principal component factor measures of economic deprivation by race and immigrant status. Logistic regression analyses show that net of controls, isolated Latino immigrant-economic deprivation is the strongest positive demographic predictor of tract presence in air-toxic LCR clusters, followed by black-economic deprivation and isolated Asian/Pacific Islander immigrant-economic deprivation. Findings suggest scholarly and practical implications for future research, advocacy, and policy. Copyright © 2015 Elsevier Inc. All rights reserved.

Simulated climate change conditions unveil the toxic potential of the fungicide pyrimethanil on the midge Chironomus riparius: a multigeneration experiment

PubMed Central

Müller, Ruth; Seeland, Anne; Jagodzinski, Lucas S; Diogo, Joao B; Nowak, Carsten; Oehlmann, Jörg

2012-01-01

Although it has been suggested that temperature increase may alter the toxic potential of environmental pollutants, few studies have investigated the potential risk of chemical stressors for wildlife under Global Climate Change (GCC) impact. We applied a bifactorial multigeneration study in order to test if GCC conditions alter the effects of low pesticide concentrations on life history and genetic diversity of the aquatic model organism Chironomus riparius. Experimental populations of the species were chronically exposed to a low concentration of the fungicide pyrimethanil (half of the no-observed-adverse-effect concentration: NOAEC/2) under two dynamic present-day temperature simulations (11.0–22.7°C; 14.0–25.2°C) and one future scenario (16.5–28.1°C). During the 140-day multigeneration study, survival, emergence, reproduction, population growth, and genetic diversity of C. riparius were analyzed. Our results reveal that high temperature and pyrimethanil act synergistically on the midge C. riparius. In simulated present-day scenarios, a NOAEC/2 of pyrimethanil as derived from a life-cycle toxicity test provoked only slight-to-moderate beneficial or adverse effects on C. riparius. In contrast, exposure to a NOAEC/2 concentration of pyrimethanil at a thermal situation likely for a summer under GCC conditions uncovered adverse effects on mortality and population growth rate. In addition, genetic diversity was considerably reduced by pyrimethanil in the future scenario, but only slightly under current climatic conditions. Our multigeneration study under near-natural (climatic) conditions indicates that not only the impact of climate change, but also low concentrations of pesticides may pose a reasonable risk for aquatic insects in future. PMID:22408736

Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH).

PubMed

Sobanska, Marta; Scholz, Stefan; Nyman, Anna-Maija; Cesnaitis, Romanas; Gutierrez Alonso, Simon; Klüver, Nils; Kühne, Ralph; Tyle, Henrik; de Knecht, Joop; Dang, Zhichao; Lundbergh, Ivar; Carlon, Claudio; De Coen, Wim

2018-03-01

In 2013 the Organisation for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity (FET) was adopted. It determines the acute toxicity of chemicals to embryonic fish. Previous studies show a good correlation of FET with the standard acute fish toxicity (AFT) test; however, the potential of the FET test to predict AFT, which is required by the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation (EC 1907/2006) and the Classification, Labelling and Packaging (CLP) Regulation (EC 1272/2008), has not yet been fully clarified. In 2015 the European Chemicals Agency (ECHA) requested that a consultant perform a scientific analysis of the applicability of FET to predict AFT. The purpose was to compare the toxicity of substances to fish embryos and to adult fish, and to investigate whether certain factors (e.g., physicochemical properties, modes of action, or chemical structures) could be used to define the applicability boundaries of the FET test. Given the limited data availability, the analysis focused on organic substances. The present critical review summarizes the main findings and discusses regulatory application of the FET test under REACH. Given some limitations (e.g., neurotoxic mode of action) and/or remaining uncertainties (e.g., deviation of some narcotic substances), it has been found that the FET test alone is currently not sufficient to meet the essential information on AFT as required by the REACH regulation. However, the test may be used within weight-of-evidence approaches together with other independent, relevant, and reliable sources of information. The present review also discusses further research needs that may overcome the remaining uncertainties and help to increase acceptance of FET as a replacement for AFT in the future. For example, an increase in the availability of data generated according to OECD test guideline 236 may provide evidence of a higher predictive power of the test. Environ Toxicol Chem 2018;37:657-670. © 2017 SETAC. © 2017 SETAC.

Toxicity of ZnO nanoparticles to Escherichia coli: mechanism and the influence of medium components.

PubMed

Li, Mei; Zhu, Lizhong; Lin, Daohui

2011-03-01

Water chemistry can be a major factor regulating the toxicity mechanism of ZnO nanoparticles (nano-ZnO) in water. The effect of five commonly used aqueous media with various chemical properties on the toxicity of nano-ZnO to Escherichia coli O111 (E. coli) was investigated, including ultrapure water, 0.85% NaCl, phosphate-buffered saline (PBS), minimal Davis (MD), and Luria-Bertani (LB). Combined results of physicochemical characterization and antibacterial tests of nano-ZnO in the five media suggest that the toxicity of nano-ZnO is mainly due to the free zinc ions and labile zinc complexes. The toxicity of nano-ZnO in the five media deceased as follows: ultrapure water > NaCl > MD > LB > PBS. The generation of precipitates (Zn(3)(PO(4))(2) in PBS) and zinc complexes (of zinc with citrate and amino acids in MD and LB, respectively) dramatically decreased the concentration of Zn(2+) ions, resulting in the lower toxicity in these media. Additionally, the isotonic and rich nutrient conditions improved the tolerance of E. coli to toxicants. Considering the dramatic difference of the toxicity of nano-ZnO in various aqueous media, the effect of water chemistry on the physicochemical properties of nanoparticles should be paid more attention in future nanotoxicity evaluations.

Incorporation of absorption and metabolism into liver toxicity prediction for phytochemicals: A tiered in silico QSAR approach.

PubMed

Liu, Yitong

2018-05-18

An increased use of herbal dietary supplements has been associated with adverse liver effects such as elevated serum enzymes and liver failure. The safety assessment for herbal dietary supplements is challenging since they often contain complex mixtures of phytochemicals, most of which have unknown pharmacokinetic and toxicological properties. Rapid tools are needed to evaluate large numbers of phytochemicals for potential liver toxicity. The current study demonstrates a tiered approach combining identification of phytochemicals in liver toxic botanicals, followed by in silico quantitative structure-activity relationship (QSAR) evaluation of these phytochemicals for absorption (e.g. permeability), metabolism (cytochromes P450) and liver toxicity (e.g. elevated transaminases). First, 255 phytochemicals from 20 botanicals associated with clinical liver injury were identified, and the phytochemical structures were subsequently used for QSAR evaluation. Among these identified phytochemicals, 193 were predicted to be absorbed and then used to generate metabolites, which were both used to predict liver toxicity. Forty-eight phytochemicals were predicted as liver toxic, either due to parent phytochemicals or metabolites. Among them, nineteen phytochemicals have previous evidence of liver toxicity (e.g. pyrrolizidine alkaloids), while the majority were newly discovered (e.g. sesquiterpenoids). These findings help reveal new toxic phytochemicals in herbal dietary supplements and prioritize future toxicological testing. Published by Elsevier Ltd.

SEURAT: Safety Evaluation Ultimately Replacing Animal Testing – Recommendations for future research in the field of predictive toxicology

EPA Science Inventory

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 ...

Past, present and emerging toxicity issues for jet fuel

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

Mattie, David R., E-mail: david.mattie@wpafb.af.mil; Sterner, Teresa R.

2011-07-15

The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8more » and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels.« less

Past, present and emerging toxicity issues for jet fuel.

PubMed

Mattie, David R; Sterner, Teresa R

2011-07-15

The US Air Force wrote the specification for the first official hydrocarbon-based jet fuel, JP-4, in 1951. This paper will briefly review the toxicity of the current fuel, JP-8, as compared to JP-4. JP-8 has been found to have low acute toxicity with the adverse effects being slight dermal irritation and weak dermal sensitization in animals. JP-4 also has low acute toxicity with slight dermal irritation as the adverse effect. Respiratory tract sensory irritation was greater in JP-8 than in JP-4. Recent data suggest exposure to jet fuel may contribute to hearing loss. Subchronic studies for 90 days with JP-8 and JP-4 showed little toxicity with the primary effect being male rat specific hydrocarbon nephropathy. A 1-year study was conducted for JP-4. The only tumors seen were associated with the male rat specific hydrocarbon nephropathy. A number of immunosuppressive effects have been seen after exposure to JP-8. Limited neurobehavioral effects have been associated with JP-8. JP-8 is not a developmental toxicant and has little reproductive toxicity. JP-4 has not been tested for immune, neurobehavioral or reproductive endpoints. JP-8 and JP-4 were negative in mutagenicity tests but JP-4 showed an increase in unscheduled DNA synthesis. Currently, JP-8 is being used as the standard for comparison of future fuels, including alternative fuels. Emerging issues of concern with jet fuels include naphthalene content, immunotoxicity and inhalation exposure characterization and modeling of complex mixtures such as jet fuels. Copyright © 2011 Elsevier Inc. All rights reserved.

Single-nucleotide polymorphisms studied for associations with urinary toxicity from (125)I prostate brachytherapy implants.

PubMed

Usmani, Nawaid; Leong, Nelson; Martell, Kevin; Lan, Lanna; Ghosh, Sunita; Pervez, Nadeem; Pedersen, John; Yee, Don; Murtha, Albert; Amanie, John; Sloboda, Ron; Murray, David; Parliament, Matthew

2014-01-01

To identify clinical, dosimetric, and genetic factors that are associated with late urinary toxicity after a (125)I prostate brachytherapy implant. Genomic DNA from 296 men treated with (125)I prostate brachytherapy monotherapy was extracted from saliva samples for this study. A retrospective database was compiled including clinical, dosimetric, and toxicity data for this cohort of patients. Fourteen candidate single-nucleotide polymorphism (SNPs) from 13 genes (TP53, ERCC2, GSTP1, NOS, TGFβ1, MSH6, RAD51, ATM, LIG4, XRCC1, XRCC3, GSTA1, and SOD2) were tested in this cohort for correlations with toxicity. This study identified 217 men with at least 2 years of followup. Of these, 39 patients developed Grade ≥2 late urinary complications with a transurethral resection of prostate, urethral stricture, gross hematuria, or a sustained increase in their International Prostate Symptom Score. The only clinical or dosimetric factor that was associated with late urinary toxicity was age (p = 0.02). None of the 14 SNPs tested in this study were associated with late urinary toxicity in the univariate analysis. This study identified age as the only variable being associated with late urinary toxicity. However, the small sample size and the candidate gene approach used in this study mean that further investigations are essential. Genome-wide association studies are emerging as the preferred approach for future radiogenomic studies to overcome the limitations from a candidate gene approach. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

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.

Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

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

Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher

2014-07-01

Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% ofmore » patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.« less

Comparative toxicities of selected rare earth elements: Sea urchin embryogenesis and fertilization damage with redox and cytogenetic effects.

PubMed

Pagano, Giovanni; Guida, Marco; Siciliano, Antonietta; Oral, Rahime; Koçbaş, Fatma; Palumbo, Anna; Castellano, Immacolata; Migliaccio, Oriana; Thomas, Philippe J; Trifuoggi, Marco

2016-05-01

Broad-ranging adverse effects are known for rare earth elements (REE), yet only a few studies tested the toxicity of several REE, prompting studies focusing on multi-parameter REE toxicity. Trichloride salts of Y, La, Ce, Nd, Sm, Eu and Gd were tested in Paracentrotus lividus sea urchin embryos and sperm for: (1) developmental defects in either REE-exposed larvae or in the offspring of REE-exposed sperm; (2) fertilization success; (3) mitotic anomalies in REE-exposed embryos and in the offspring of REE-exposed sperm, and (4) reactive oxygen species (ROS) formation, and malondialdehyde (MDA) and nitric oxide (NO) levels. REEs affected P. lividus larvae with concentration-related increase in developmental defects, 10(-6) to 10(-4)M, ranking as: Gd(III)>Y(III)>La(III)>Nd(III)≅Eu(III)>Ce(III)≅Sm(III). Nominal concentrations of REE salts were confirmed by inductively coupled plasma mass spectrometry (ICP-MS). Significant increases in MDA levels, ROS formation, and NO levels were found in REE-exposed embryos. Sperm exposure to REEs (10(-5) to 10(-4)M) resulted in concentration-related decrease in fertilization success along with increase in offspring damage. Decreased mitotic activity and increased aberration rates were detected in REE-exposed embryos and in the offspring of REE-exposed sperm. REE-associated toxicity affecting embryogenesis, fertilization, cytogenetic and redox endpoints showed different activities of tested REEs. Damage to early life stages, along with redox and cytogenetic anomalies should be the focus of future REE toxicity studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolism and toxicity of hydrochlorofluorocarbons: current knowledge and needs for the future.

PubMed Central

Anders, M W

1991-01-01

Hydrochlorofluorocarbons (HCFCs) are being developed as replacements for chlorofluorocarbons (CFCs) that deplete stratospheric ozone. The depletion of stratospheric ozone may increase the intensity of ultraviolet radiation at the earth's surface, which may be associated with global, adverse human health effects. The greater tropospheric lability of HCFCs, which is due to the presence of C-H bonds, reduces HCFC migration to the stratosphere; HCFCs should, therefore, cause less depletion of stratospheric ozone than CFCs. HCFCs under development include HCFC-22 (chlorodifluoromethane), HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane), HCFC-132b (1,2-dichloro-1,1-difluoroethane), HCFC-134a (1,1,1,2-tetrafluoroethane), HCFC-141b (1,1-dichloro-1-fluoroethane, and HCFC-142b (1-chloro-1,1-difluoroethane). With the exception of HCFC-22, which is already in use, the metabolism and toxicity of HCFCs have not been studied in detail. By analogy to chlorinated ethanes, predictions can be made about the possible metabolism of HCFCs, but there are insufficient data available to predict rates of metabolism. Although most HCFCs appear to show low acute toxicity, some HCFCs are mutagenic in the Ames test. Hence, future research on HCFCs should include studies on the in vivo and in vitro metabolism of HCFCs as well as on their toxicity in in vivo and in vitro systems. PMID:1820265

Metabolism and toxicity of hydrochlorofluorocarbons: current knowledge and needs for the future.

PubMed

Anders, M W

1991-12-01

Hydrochlorofluorocarbons (HCFCs) are being developed as replacements for chlorofluorocarbons (CFCs) that deplete stratospheric ozone. The depletion of stratospheric ozone may increase the intensity of ultraviolet radiation at the earth's surface, which may be associated with global, adverse human health effects. The greater tropospheric lability of HCFCs, which is due to the presence of C-H bonds, reduces HCFC migration to the stratosphere; HCFCs should, therefore, cause less depletion of stratospheric ozone than CFCs. HCFCs under development include HCFC-22 (chlorodifluoromethane), HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane), HCFC-132b (1,2-dichloro-1,1-difluoroethane), HCFC-134a (1,1,1,2-tetrafluoroethane), HCFC-141b (1,1-dichloro-1-fluoroethane, and HCFC-142b (1-chloro-1,1-difluoroethane). With the exception of HCFC-22, which is already in use, the metabolism and toxicity of HCFCs have not been studied in detail. By analogy to chlorinated ethanes, predictions can be made about the possible metabolism of HCFCs, but there are insufficient data available to predict rates of metabolism. Although most HCFCs appear to show low acute toxicity, some HCFCs are mutagenic in the Ames test. Hence, future research on HCFCs should include studies on the in vivo and in vitro metabolism of HCFCs as well as on their toxicity in in vivo and in vitro systems.

Metabolism and toxicity of hydrochlorofluorocarbons: Current knowledge and needs for the future

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

Anders, M.W.

1991-12-01

Hydrochlorofluorocarbons (HCFCs) are being developed as replacements for chlorofluorocarbons (CFCs) that deplete stratospheric ozone. The depletion of stratospheric ozone may increase in intensity of ultraviolet radiation at the earth's surface, which may be associated with global, adverse human health effects. The greater tropospheric lability of HCFCs, which is due to the presence of C-H bonds, reduces HCFC migration to the stratosphere; HCFCs should, therefore, cause less depletion of stratospheric ozone than CFCs. HCFCs under development include HCFC-22 (chlorodifluoromethane), HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane), HCFC-132b (1,2-dichloro-1,1-difluoroethane), HCFC-134a (1,1,1,2-tetrafluoroethane), HCFC-141b (1,1-dichloro-1-fluoroethane), and HCFC-142b (1-chloro-1,1-difluoroethane). With the exception of HCFC-22, which is already in use, themore » metabolism and toxicity of HCFCs have not been studied in detail. By analogy to chlorinated ethanes, predictions can be made about the possible metabolism of HCFCs, but there are insufficient data available to predict rates of metabolism. Although most HCFCs appear to show low acute toxicity, some HCFCs are mutagenic in the Ames test. Hence, future research on HCFCs should include studies on the in vivo and in vitro metabolism of HCFCs as well as on their toxicity in in vivo and in vitro systems. 63 refs., 4 figs., 1 tab.« less

From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century.

PubMed

Choudhuri, Supratim; Patton, Geoffrey W; Chanderbhan, Ronald F; Mattia, Antonia; Klaassen, Curtis D

2018-01-01

Toxicology has made steady advances over the last 60+ years in understanding the mechanisms of toxicity at an increasingly finer level of cellular organization. Traditionally, toxicological studies have used animal models. However, the general adoption of the principles of 3R (Replace, Reduce, Refine) provided the impetus for the development of in vitro models in toxicity testing. The present commentary is an attempt to briefly discuss the transformation in toxicology that began around 1980. Many genes important in cellular protection and metabolism of toxicants were cloned and characterized in the 80s, and gene expression studies became feasible, too. The development of transgenic and knockout mice provided valuable animal models to investigate the role of specific genes in producing toxic effects of chemicals or protecting the organism from the toxic effects of chemicals. Further developments in toxicology came from the incorporation of the tools of "omics" (genomics, proteomics, metabolomics, interactomics), epigenetics, systems biology, computational biology, and in vitro biology. Collectively, the advances in toxicology made during the last 30-40 years are expected to provide more innovative and efficient approaches to risk assessment. A goal of experimental toxicology going forward is to reduce animal use and yet be able to conduct appropriate risk assessments and make sound regulatory decisions using alternative methods of toxicity testing. In that respect, Tox21 has provided a big picture framework for the future. Currently, regulatory decisions involving drugs, biologics, food additives, and similar compounds still utilize data from animal testing and human clinical trials. In contrast, the prioritization of environmental chemicals for further study can be made using in vitro screening and computational tools. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.

Antibiotic toxicity and absorption in zebrafish using liquid chromatography-tandem mass spectrometry.

PubMed

Zhang, Fan; Qin, Wei; Zhang, Jing-Pu; Hu, Chang-Qin

2015-01-01

Evaluation of drug toxicity is necessary for drug safety, but in vivo drug absorption is varied; therefore, a rapid, sensitive and reliable method for measuring drugs is needed. Zebrafish are acceptable drug toxicity screening models; we used these animals with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in a multiple reaction monitoring mode to quantify drug uptake in zebrafish to better estimate drug toxicity. Analytes were recovered from zebrafish homogenate by collecting supernatant. Measurements were confirmed for drugs in the range of 10-1,000 ng/mL. Four antibiotics with different polarities were tested to explore any correlation of drug polarity, absorption, and toxicity. Zebrafish at 3 days post-fertilization (dpf) absorbed more drug than those at 6 h post-fertilization (hpf), and different developmental periods appeared to be differentially sensitive to the same compound. By observing abnormal embryos and LD50 values, zebrafish embryos at 6 hpf were considered to be suitable for evaluating embryotoxicity. Also, larvae at 3 dpf were adapted to measure acute drug toxicity in adult mammals. Thus, we can exploit zebrafish to study drug toxicity and can reliably quantify drug uptake with LC-MS/MS. This approach will be helpful for future studies of toxicology in zebrafish.

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

PubMed Central

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

2008-01-01

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

Alternatives to animal testing: research, trends, validation, regulatory acceptance.

PubMed

Huggins, Jane

2003-01-01

Current trends and issues in the development of alternatives to the use of animals in biomedical experimentation are discussed in this position paper. Eight topics are considered and include refinement of acute toxicity assays; eye corrosion/irritation alternatives; skin corrosion/irritation alternatives; contact sensitization alternatives; developmental/reproductive testing alternatives; genetic engineering (transgenic) assays; toxicogenomics; and validation of alternative methods. The discussion of refinement of acute toxicity assays is focused primarily on developments with regard to reduction of the number of animals used in the LD(50) assay. However, the substitution of humane endpoints such as clinical signs of toxicity for lethality in these assays is also evaluated. Alternative assays for eye corrosion/irritation as well as those for skin corrosion/irritation are described with particular attention paid to the outcomes, both successful and unsuccessful, of several validation efforts. Alternative assays for contact sensitization and developmental/reproductive toxicity are presented as examples of methods designed for the examination of interactions between toxins and somewhat more complex physiological systems. Moreover, genetic engineering and toxicogenomics are discussed with an eye toward the future of biological experimentation in general. The implications of gene manipulation for research animals, specifically, are also examined. Finally, validation methods are investigated as to their effectiveness, or lack thereof, and suggestions for their standardization and improvement, as well as implementation are reviewed.

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

PubMed

Wills, Lauren P

2017-11-01

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

Inhalation toxicity studies: OECD guidelines in relation to REACH and scientific developments.

PubMed

Arts, Josje H E; Muijser, H; Jonker, D; van de Sandt, J J M; Bos, P M J; Feron, V J

2008-06-01

The OECD Health Effects Test Guidelines (TGs) provide guidance concerning the use of methods for the identification and characterization of hazards from chemical substances. These TGs are largely based on tests in routine use for many years and are known to yield information relevant to various types of toxicity. They have proven their value in practice and will remain of paramount importance for decades to come. However, the TGs describe mostly animal assays, and there is an increasingly strong urge to reduce animal testing on ethical grounds. In addition, assessment procedures are generally considered too slow and too rigid, which has resulted in elaborate testing of a relatively small number of chemicals, while virtually nothing is known about the vast majority of compounds. The major objectives of Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) are to improve the knowledge about the properties and use of chemicals and to speed up the procedure of risk assessment. The REACH text contains information requirements that can be met by OECD TGs but REACH also provides rules for adaptation of the standard testing regime. Also, various components of "Intelligent Testing Strategies" are described in order to limit animal testing. This paper briefly describes the OECD TGs for inhalation toxicity studies, including those in preparation, and their role in future hazard identification. This will be discussed in relation to the evaluation of the safety of thousands of chemicals in a relatively short period of time and scientific developments, including the use of alternatives to animal testing.

A risk-based classification scheme for genetically modified foods. II: Graded testing.

PubMed

Chao, Eunice; Krewski, Daniel

2008-12-01

This paper presents a graded approach to the testing of crop-derived genetically modified (GM) foods based on concern levels in a proposed risk-based classification scheme (RBCS) and currently available testing methods. A graded approach offers the potential for more efficient use of testing resources by focusing less on lower concern GM foods, and more on higher concern foods. In this proposed approach to graded testing, products that are classified as Level I would have met baseline testing requirements that are comparable to what is widely applied to premarket assessment of GM foods at present. In most cases, Level I products would require no further testing, or very limited confirmatory analyses. For products classified as Level II or higher, additional testing would be required, depending on the type of the substance, prior dietary history, estimated exposure level, prior knowledge of toxicity of the substance, and the nature of the concern related to unintended changes in the modified food. Level III testing applies only to the assessment of toxic and antinutritional effects from intended changes and is tailored to the nature of the substance in question. Since appropriate test methods are not currently available for all effects of concern, future research to strengthen the testing of GM foods is discussed.

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.

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.

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

Assuring safety without animal testing: the case for the human testis in vitro.

PubMed

Chapin, Robert E; Boekelheide, Kim; Cortvrindt, Rita; van Duursen, Majorie B M; Gant, Tim; Jegou, Bernard; Marczylo, Emma; van Pelt, Ans M M; Post, Janine N; Roelofs, Maarke J E; Schlatt, Stefan; Teerds, Katja J; Toppari, Jorma; Piersma, Aldert H

2013-08-01

From 15 to 17 June 2011, a dedicated workshop was held on the subject of in vitro models for mammalian spermatogenesis and their applications in toxicological hazard and risk assessment. The workshop was sponsored by the Dutch ASAT initiative (Assuring Safety without Animal Testing), which aims at promoting innovative approaches toward toxicological hazard and risk assessment on the basis of human and in vitro data, and replacement of animal studies. Participants addressed the state of the art regarding human and animal evidence for compound mediated testicular toxicity, reviewed existing alternative assay models, and brainstormed about future approaches, specifically considering tissue engineering. The workshop recognized the specific complexity of testicular function exemplified by dedicated cell types with distinct functionalities, as well as different cell compartments in terms of microenvironment and extracellular matrix components. This complexity hampers quick results in the realm of alternative models. Nevertheless, progress has been achieved in recent years, and innovative approaches in tissue engineering may open new avenues for mimicking testicular function in vitro. Although feasible, significant investment is deemed essential to be able to bring new ideas into practice in the laboratory. For the advancement of in vitro testicular toxicity testing, one of the most sensitive end points in regulatory reproductive toxicity testing, such an investment is highly desirable. Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Assessment of acute toxicity tests and rhizotron experiments to characterize lethal and sublethal control of soil-based pests.

PubMed

Agatz, Annika; Schumann, Mario M; French, Bryan W; Brown, Colin D; Vidal, Stefan

2018-03-24

Characterizing lethal and sublethal control of soil-based pests with plant protection products is particularly challenging due to the complex and dynamic interplay of the system components. Here, we present two types of studies: acute toxcity experiments (homogenous exposure of individuals in soil) and rhizotron experiments (heterogeneous exposure of individuals in soil) to investigate their ability to strengthen our understanding of mechanisms driving the effectivness of the plant protection product. Experiments were conducted using larvae of the western corn rootworm Diabrotica virgifera LeConte and three pesticide active ingredients: clothianidin (neonicotinoid), chlorpyrifos (organophosphate) and tefluthrin (pyrethroid). The order of compound concentrations needed to invoke a specific effect intensity (EC 50 values) within the acute toxicity tests was chlorpyrifos > tefluthrin > clothianidin. This order changed for the rhizotron experiments because application type, fate and transport of the compounds in the soil profile, and sublethal effects on larvae also influence their effectiveness in controlling larval feeding on corn roots. Beyond the pure measurement of efficacy through observing relative changes in plant injury to control plants, the tests generate mechanistic understanding for drivers of efficacy apart from acute toxicity. The experiments have the potential to enhance efficacy testing and product development, and might be useful tools for assessing resistance development in the future. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Behavioral toxicology in the 21st century: challenges and opportunities for behavioral scientists. Summary of a symposium presented at the annual meeting of the neurobehavioral teratology society, June, 2009.

PubMed

Bushnell, Philip J; Kavlock, Robert J; Crofton, Kevin M; Weiss, Bernard; Rice, Deborah C

2010-01-01

The National Research Council (NRC) of the National Academies of Science recently published a report of its vision of toxicity testing in the 21st century. The report proposes that the current toxicity testing paradigm that depends upon whole-animal tests be replaced with a strategy based upon in vitro tests, in silico models and evaluations of toxicity at the human population level. These goals are intended to set in motion changes that will transform risk assessment into a process in which adverse effects on public health are predicted by quantitative structure-activity relationship (QSAR) models and data from suites of high-throughput in vitro tests. The potential roles for whole-animal testing in this futuristic vision are both various and undefined. A symposium was convened at the annual meeting of the Neurobehavioral Teratology Society in Rio Grande, Puerto Rico in June, 2009 to discuss the potential challenges and opportunities for behavioral scientists in developing and/or altering this strategy toward the ultimate goal of protecting public health from hazardous chemicals. R. Kavlock described the NRC vision, introduced the concept of the 'toxicity pathway' (a central guiding principle of the NRC vision), and described the current status of an initial implementation this approach with the EPA's ToxCast(R) program. K. Crofton described a pathway based upon disruption of thyroid hormone metabolism during development, including agents, targets, and outcomes linked by this mode of action. P. Bushnell proposed a pathway linking the neural targets and cellular to behavioral effects of acute exposure to organic solvents, whose predictive power is limited by our incomplete understanding of the complex CNS circuitry that mediates the behavioral responses to solvents. B. Weiss cautioned the audience regarding a pathway approach to toxicity testing, using the example of the developmental toxicity of phthalates, whose effects on mammalian sexual differentiation would be difficult to identify based on screening tests in vitro. Finally, D. Rice raised concerns regarding the use of data derived from toxicity screening tests to human health risk assessments. Discussion centered around opportunities and challenges for behavioral toxicologists regarding this impending paradigm shift. Opportunities include: identifying and characterizing toxicity pathways; informing the conditions and limits of extrapolation; addressing issues of susceptibility and variability; providing reality-checks on selected positives and negatives from screens; and performing targeted testing and dose-response assessments of chemicals flagged during screening. Challenges include: predicting behavior using models of complex neurobiological pathways; standardizing study designs and dependent variables to facilitate creation of databases; and managing the cost and efficiency of behavioral assessments. Thus, while progress is being made in approaching the vision of 21st century toxicology, we remain a long way from replacing whole-animal tests; indeed, some animal testing will be essential for the foreseeable future at least. Initial advances will likely provide better prioritization tools so that animal resources are used more efficiently and effectively.

The future trajectory of adverse outcome pathways: a commentary.

PubMed

Sewell, Fiona; Gellatly, Nichola; Beaumont, Maria; Burden, Natalie; Currie, Richard; de Haan, Lolke; Hutchinson, Thomas H; Jacobs, Miriam; Mahony, Catherine; Malcomber, Ian; Mehta, Jyotigna; Whale, Graham; Kimber, Ian

2018-04-01

The advent of adverse outcome pathways (AOPs) has provided a new lexicon for description of mechanistic toxicology, and a renewed enthusiasm for exploring modes of action resulting in adverse health and environmental effects. In addition, AOPs have been used successfully as a framework for the design and development of non-animal approaches to toxicity testing. Although the value of AOPs is widely recognised, there remain challenges and opportunities associated with their use in practise. The purpose of this article is to consider specifically how the future trajectory of AOPs may provide a basis for addressing some of those challenges and opportunities.

Amphipod bioassay of selected sediments from Sequim Bay, Washington

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

Ramsdell, K.A.; Strand, J.A.; Cullinan, V. I.

1989-06-01

Amphipod bioassays performed during reconnaissance surveys of Sequim Bay in 1983--1984 for the US Environmental Protection Agency suggested possible sediment toxicity at three sites. These findings were not supported by other biological analyses and tests (dominant infauna, oyster larvae test) nor by the finding of relatively low levels of priority pollutants. In 1988, a re-examination of the 1983--1984 sites demonstrated that the Sequim Bay sediments were clearly nontoxic. Mean survivorship ranged from 89 to 100%. It was hypothesized that earlier indications of toxicity may have been due to a relatively high percentage of fines ({ge}80%) and/or a relatively low interstitialmore » salinity (24%) encountered at one or more of the 1983--1984 sites. The continued use of Sequim Bay as both a reference bay and a source of control sediment in future marine research is recommended. 13 refs., 5 figs., 3 tabs.« less

Current approaches and future role of high content imaging in safety sciences and drug discovery.

PubMed

van Vliet, Erwin; Daneshian, Mardas; Beilmann, Mario; Davies, Anthony; Fava, Eugenio; Fleck, Roland; Julé, Yvon; Kansy, Manfred; Kustermann, Stefan; Macko, Peter; Mundy, William R; Roth, Adrian; Shah, Imran; Uteng, Marianne; van de Water, Bob; Hartung, Thomas; Leist, Marcel

2014-01-01

High content imaging combines automated microscopy with image analysis approaches to simultaneously quantify multiple phenotypic and/or functional parameters in biological systems. The technology has become an important tool in the fields of safety sciences and drug discovery, because it can be used for mode-of-action identification, determination of hazard potency and the discovery of toxicity targets and biomarkers. In contrast to conventional biochemical endpoints, high content imaging provides insight into the spatial distribution and dynamics of responses in biological systems. This allows the identification of signaling pathways underlying cell defense, adaptation, toxicity and death. Therefore, high content imaging is considered a promising technology to address the challenges for the "Toxicity testing in the 21st century" approach. Currently, high content imaging technologies are frequently applied in academia for mechanistic toxicity studies and in pharmaceutical industry for the ranking and selection of lead drug compounds or to identify/confirm mechanisms underlying effects observed in vivo. A recent workshop gathered scientists working on high content imaging in academia, pharmaceutical industry and regulatory bodies with the objective to compile the state-of-the-art of the technology in the different institutions. Together they defined technical and methodological gaps, proposed quality control measures and performance standards, highlighted cell sources and new readouts and discussed future requirements for regulatory implementation. This review summarizes the discussion, proposed solutions and recommendations of the specialists contributing to the workshop.

Interactions of metal-based engineered nanoparticles with aquatic higher plants: A review of the state of current knowledge.

PubMed

Thwala, Melusi; Klaine, Stephen J; Musee, Ndeke

2016-07-01

The rising potential for the release of engineered nanoparticles (ENPs) into aquatic environments requires evaluation of risks to protect ecological health. The present review examines knowledge pertaining to the interactions of metal-based ENPs with aquatic higher plants, identifies information gaps, and raises considerations for future research to advance knowledge on the subject. The discussion focuses on ENPs' bioaccessibility; uptake, adsorption, translocation, and bioaccumulation; and toxicity effects on aquatic higher plants. An information deficit surrounds the uptake of ENPs and associated dynamics, because the influence of ENP characteristics and water quality conditions has not been well documented. Dissolution appears to be a key mechanism driving bioaccumulation of ENPs, whereas nanoparticulates often adsorb to plant surfaces with minimal internalization. However, few reports document the internalization of ENPs by plants; thus, the role of nanoparticulates' internalization in bioaccumulation and toxicity remains unclear, requiring further investigation. The toxicities of metal-based ENPs mainly have been associated with dissolution as a predominant mechanism, although nano toxicity has also been reported. To advance knowledge in this domain, future investigations need to integrate the influence of ENP characteristics and water physicochemical parameters, as their interplay determines ENP bioaccessibility and influences their risk to health of aquatic higher plants. Furthermore, harmonization of test protocols is recommended for fast tracking the generation of comparable data. Environ Toxicol Chem 2016;35:1677-1694. © 2016 SETAC. © 2016 SETAC.

Current and future needs for developmental toxicity testing.

PubMed

Makris, Susan L; Kim, James H; Ellis, Amy; Faber, Willem; Harrouk, Wafa; Lewis, Joseph M; Paule, Merle G; Seed, Jennifer; Tassinari, Melissa; Tyl, Rochelle

2011-10-01

A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well. Now there are opportunities to incorporate new technologies and approaches to testing into the existing assessment paradigm, or to apply innovative approaches to various aspects of risk assessment. Developmental toxicology testing can be enhanced by the refinement or replacement of traditional in vivo protocols, including through the use of in vitro assays, studies conducted in alternative nonmammalian species, the application of new technologies, and the use of in silico models. Potential benefits to the current regulatory process include the ability to screen large numbers of chemicals quickly, with the commitment of fewer resources than traditional toxicology studies, and to refine the risk assessment process through an enhanced understanding of the mechanisms of developmental toxicity and their relevance to potential human risk. As the testing paradigm evolves, the ability to use developmental toxicology data to meet diverse critical regulatory needs must be retained. © 2011 Wiley Periodicals, Inc.

Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future.

PubMed

Orr, Michael S

2014-05-01

To review the available evidence evaluating the toxicological profiles of electronic cigarettes (e-cigarettes) in order to understand the potential impact of e-cigarettes on individual users and the public health. Systematic literature searches were conducted between October 2012 and October 2013 using five electronic databases. Search terms such as 'e-cigarettes' and 'electronic delivery devices' were used to identify the toxicology information for e-cigarettes. As of October 2013, the scientific literature contains very limited information regarding the toxicity of e-cigarettes commercially available in the USA. While some preliminary toxicology data suggests that e-cigarette users are exposed to lower levels of toxicants relative to cigarette smokers, the data available is extremely limited at this time. At present, there is insufficient toxicological data available to perform thorough risk assessment analyses for e-cigarettes; few toxicology studies evaluating e-cigarettes have been conducted to date, and standard toxicological testing paradigms have not been developed for comparing disparate types of tobacco products such as e-cigarettes and traditional cigarettes. Overall, the limited toxicology data on e-cigarettes in the public domain is insufficient to allow a thorough toxicological evaluation of this new type of tobacco product. In the future, the acquisition of scientific datasets that are derived from scientifically robust standard testing paradigms, include comprehensive chemical characterisation of the aerosol, provide information on users' toxicant exposure levels, and from studies replicated by independent researchers will improve the scientific community's ability to perform robust toxicological evaluations of e-cigarettes.

Electronic cigarettes in the USA: a summary of available toxicology data and suggestions for the future

PubMed Central

Orr, Michael S

2014-01-01

Objective To review the available evidence evaluating the toxicological profiles of electronic cigarettes (e-cigarettes) in order to understand the potential impact of e-cigarettes on individual users and the public health. Methods Systematic literature searches were conducted between October 2012 and October 2013 using five electronic databases. Search terms such as ‘e-cigarettes’ and ‘electronic delivery devices’ were used to identify the toxicology information for e-cigarettes. Results As of October 2013, the scientific literature contains very limited information regarding the toxicity of e-cigarettes commercially available in the USA. While some preliminary toxicology data suggests that e-cigarette users are exposed to lower levels of toxicants relative to cigarette smokers, the data available is extremely limited at this time. At present, there is insufficient toxicological data available to perform thorough risk assessment analyses for e-cigarettes; few toxicology studies evaluating e-cigarettes have been conducted to date, and standard toxicological testing paradigms have not been developed for comparing disparate types of tobacco products such as e-cigarettes and traditional cigarettes. Conclusions Overall, the limited toxicology data on e-cigarettes in the public domain is insufficient to allow a thorough toxicological evaluation of this new type of tobacco product. In the future, the acquisition of scientific datasets that are derived from scientifically robust standard testing paradigms, include comprehensive chemical characterisation of the aerosol, provide information on users’ toxicant exposure levels, and from studies replicated by independent researchers will improve the scientific community's ability to perform robust toxicological evaluations of e-cigarettes. PMID:24732158

The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and scientific research.

PubMed

Embry, Michelle R; Belanger, Scott E; Braunbeck, Thomas A; Galay-Burgos, Malyka; Halder, Marlies; Hinton, David E; Léonard, Marc A; Lillicrap, Adam; Norberg-King, Teresa; Whale, Graham

2010-04-15

Animal alternatives research has historically focused on human safety assessments and has only recently been extended to environmental testing. This is particularly for those assays that involve the use of fish. A number of alternatives are being pursued by the scientific community including the fish embryo toxicity (FET) test, a proposed replacement alternative to the acute fish test. Discussion of the FET methodology and its application in environmental assessments on a global level was needed. With this emerging issue in mind, the ILSI Health and Environmental Sciences Institute (HESI) and the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) held an International Workshop on the Application of the Fish Embryo Test as an Animal Alternative Method in Hazard and Risk Assessment and Scientific Research in March, 2008. The workshop included approximately 40 scientists and regulators representing government, industry, academia, and non-governmental organizations from North America, Europe, and Asia. The goal was to review the state of the science regarding the investigation of fish embryonic tests, pain and distress in fish, emerging approaches utilizing fish embryos, and the use of fish embryo toxicity test data in various types of environmental assessments (e.g., hazard, risk, effluent, and classification and labeling of chemicals). Some specific key outcomes included agreement that risk assessors need fish data for decision-making, that extending the FET to include eluethereombryos was desirable, that relevant endpoints are being used, and that additional endpoints could facilitate additional uses beyond acute toxicity testing. The FET was, however, not yet considered validated sensu OECD. An important action step will be to provide guidance on how all fish tests can be used to assess chemical hazard and to harmonize the diverse terminology used in test guidelines adopted over the past decades. Use of the FET in context of effluent assessments was considered and it is not known if fish embryos are sufficiently sensitive for consideration as a surrogate to the sub-chronic 7-day larval fish growth and survival test used in the United States, for example. Addressing these needs by via workshops, research, and additional data reviews were identified for future action by scientists and regulators.

Comparative toxicities of selected rare earth elements: Sea urchin embryogenesis and fertilization damage with redox and cytogenetic effects

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

Pagano, Giovanni, E-mail: gbpagano@tin.it; Guida, Marco; Siciliano, Antonietta

Background: Broad-ranging adverse effects are known for rare earth elements (REE), yet only a few studies tested the toxicity of several REE, prompting studies focusing on multi-parameter REE toxicity. Methods: Trichloride salts of Y, La, Ce, Nd, Sm, Eu and Gd were tested in Paracentrotus lividus sea urchin embryos and sperm for: (1) developmental defects in either REE-exposed larvae or in the offspring of REE-exposed sperm; (2) fertilization success; (3) mitotic anomalies in REE-exposed embryos and in the offspring of REE-exposed sperm, and (4) reactive oxygen species (ROS) formation, and malondialdehyde (MDA) and nitric oxide (NO) levels. Results: REEs affectedmore » P. lividus larvae with concentration-related increase in developmental defects, 10{sup −6} to 10{sup −4} M, ranking as: Gd(III)>Y(III)>La(III)>Nd(III)≅Eu(III)>Ce(III)≅Sm(III). Nominal concentrations of REE salts were confirmed by inductively coupled plasma mass spectrometry (ICP-MS). Significant increases in MDA levels, ROS formation, and NO levels were found in REE-exposed embryos. Sperm exposure to REEs (10{sup −5} to 10{sup −4} M) resulted in concentration-related decrease in fertilization success along with increase in offspring damage. Decreased mitotic activity and increased aberration rates were detected in REE-exposed embryos and in the offspring of REE-exposed sperm. Conclusion: REE-associated toxicity affecting embryogenesis, fertilization, cytogenetic and redox endpoints showed different activities of tested REEs. Damage to early life stages, along with redox and cytogenetic anomalies should be the focus of future REE toxicity studies. - Highlights: • Seven rare earth elements exerted different effects on sea urchin early life stages. • Embryo-, spermio- and mitotoxicity, and oxidative/ nitrosative stress were found. • Nominal vs. analytical REE concentrations were checked. • Comparative toxicities were evaluated for the different REE.« less

Multivariate analysis of toxicity experimental results of environmental endpoints. (FutureToxII)

EPA Science Inventory

The toxicity of hundreds of chemicals have been assessed in laboratory animal studies through EPA chemical regulation and toxicological research. Currently, over 5000 laboratory animal toxicity studies have been collected in the Toxicity Reference Database (ToxRefDB). In addition...

Toxic behavior of silver and zinc oxide nanoparticles on environmental microorganisms.

PubMed

Dhas, Sindhu Priya; Shiny, Punalur John; Khan, Sudheer; Mukherjee, Amitava; Chandrasekaran, Natrajan

2014-09-01

Silver and zinc oxide nanoparticles (Ag and ZnO NPs) are widely used as antimicrobial agents. However, their potential toxicological impact on environmental microorganisms is largely unexplored. The aim of this work was to investigate the sensitivity and adaptability of five bacterial species isolated from sewage towards Ag and ZnO NPs. The bacterial species were exposed to increasing concentration of nanoparticles and the growth inhibitory effect, exopolysaccharides (EPSs) and extracellular proteins (ECPs) productions were determined. The involvement of surface charge in nanoparticles toxicity was also determined. The bacterial species were constantly exposed to nanoparticles to determine the adaptation behavior toward nanoparticles. The nanoparticles exhibited remarkable growth inhibitory effect on tested bacterial species. The toxicity of nanoparticles was found to be strongly dependent on surface charge effects. Though, these organisms are highly sensitive to Ag and ZnO NPs, the continuous exposure to these nanoparticles leads to moderate adaptation of bacterial species and the adapted bacterial species convert the highly toxic nano form to less toxic microform. Finally we predict that the continuing applications of nanoparticles in consumer products may lead to the development of nanoparticles resistant bacterial strains in future. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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

Boron-containing acids: preliminary evaluation of acute toxicity and access to the brain determined by Raman scattering spectroscopy.

PubMed

Soriano-Ursúa, Marvin A; Farfán-García, Eunice D; López-Cabrera, Yessica; Querejeta, Enrique; Trujillo-Ferrara, José G

2014-01-01

Boron-containing compounds (BCCs), particularly boron containing acids (BCAs), have become attractive moieties or molecules in drug development. It has been suggested that when functional groups with boron atoms are added to well-known drugs, the latter are conferred with greater potency and efficacy in relation to their target receptors. However, the use of BCAs in drug development is limited due to the lack of a toxicological profile. Consequently, the aim of the present study was to evaluate the acute toxicity of boric and boronic acids. Thus, a determination was made of the lethal dose (LD50) of test compounds in male CD1 mice, as well as the effective dose required to negatively affect spontaneous motor activity and to produce notable behavioral abnormalities. After treatment of animals at different doses, macroscopic observations were made from a necropsy, and Raman scattering spectroscopic studies were carried out on brain tissue samples. In general, the results show that most of the tested BCAs have very low toxicity, evidenced by the high doses required to induce notable toxic effects (greater than 100 mg/kg of body weight for all compounds, except for 3-thyenilboronic acid). Such toxic effects, presumably mediated by action on the CNS, include eye damage, gastrointestinal effects (e.g., gastric-gut dilatation and fecal retention), sedation, hypnosis and/or trembling. This preliminary toxicological profile suggests that BCAs can be considered potential therapeutic agents or moieties to be added to other compounds in the development of new drugs. Future studies are required to explore possible chronic toxicity of BCCs. Copyright © 2013 Elsevier Inc. All rights reserved.

Airborne Dust in Space Vehicles and Habitats

NASA Technical Reports Server (NTRS)

James, John

2006-01-01

Airborne dust, suspended inside a space vehicle or in future celestial habitats, can present a serious threat to crew health if it is not controlled. During the Apollo missions to the moon, lunar dust brought inside the capsule caused eye irritation and breathing difficulty to the crew when they launched from the moon and re-acquired "microgravity." During Shuttle flights reactive and toxic dusts such as lithium hydroxide have created a risk to crew health, and fine particles from combustion events can be especially worrisome. Under nominal spaceflight conditions, airborne dusts and particles tend to be larger than on earth because of the absence of gravity settling. Aboard the ISS, dusts are effectively managed by HEPA filters, although floating dust in newly-arrived modules can be a nuisance. Future missions to the moon and to Mars will present additional challenges because of the possibility that external dust will enter the breathing atmosphere of the habitat and reach the crew's respiratory system. Testing with simulated lunar and Martian dust has shown that these materials are toxic when placed into the lungs of test animals. Defining and evaluating the physical and chemical properties of Martian dusts through robotic missions will challenge our ability to prepare better dust simulants and to determine the risk to crew health from exposure to such dusts.

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.

Intrinsic toxicity of hemoglobin: how to counteract it.

PubMed

Simoni, Jan; Simoni, Grace; Moeller, John F

2009-02-01

The development of safe and effective blood substitutes is of great importance in both civilian and military medicine. The currently tested hemoglobin (Hb)-based oxygen carriers, however, have toxicity and efficacy problems. A number of unwanted effects have been observed in human trials, creating doubts about their clinical usefulness. In some subjects, vasoconstriction and decreased blood flow to the vital organs, heart attack, stroke, systemic inflammation, organ damage, and even death, have been attributed to the transfusion of these experimental products. Hb is a well-known pressor agent and strong oxidant, although the full understanding of its intrinsic toxicity is yet to be uncovered. In particular, the complete mechanism of Hb-induced vasoconstriction needs full elucidation. Knowledge of the biological events that trigger the induction of genes upon treatment with redox-active Hb, as well as its catabolism, is still incomplete. It seems that our limited knowledge of free Hb effects in vivo is the main reason for not yet having a viable substitute of human blood. The future for universal red cell substitutes is in the new-generation products that address all of Hb's intrinsic toxicity issues.

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

Non-Toxic, Low-Freezing, Drop-In Replacement Heat Transfer Fluids

NASA Technical Reports Server (NTRS)

Cutbirth, J. Michael

2012-01-01

A non-toxic, non-flammable, low-freezing heat transfer fluid is being developed for drop-in replacement within current and future heat transfer loops currently using water or alcohol-based coolants. Numerous water-soluble compounds were down-selected and screened for toxicological, physical, chemical, compatibility, thermodynamic, and heat transfer properties. Two fluids were developed, one with a freezing point near 0 C, and one with a suppressed freezing point. Both fluids contain an additive package to improve material compatibility and microbial resistance. The optimized sub-zero solution had a freezing point of 30 C, and a freezing volume expansion of 10-percent of water. The toxicity of the solutions was experimentally determined as LD(50) greater than 5g/kg. The solutions were found to produce minimal corrosion with materials identified by NASA as potentially existing in secondary cooling loops. Thermal/hydrodynamic performance exceeded that of glycol-based fluids with comparable freezing points for temperatures Tf greater than 20 C. The additive package was demonstrated as a buffering agent to compensate for CO2 absorption, and to prevent microbial growth. The optimized solutions were determined to have physically/chemically stable shelf lives for freeze/thaw cycles and longterm test loop tests.

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

EPA Pesticide Factsheets

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

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.

Multilevel eEmpirical Bayes modeling for improved estimation of toxicant formulations tosuppress parasitic sea lamprey in the Upper Great Lakes

USGS Publications Warehouse

Hatfield, Laura A.; Gutreuter, Steve; Boogaard, Michael A.; Carlin, Bradley P.

2011-01-01

Estimation of extreme quantal-response statistics, such as the concentration required to kill 99.9% of test subjects (LC99.9), remains a challenge in the presence of multiple covariates and complex study designs. Accurate and precise estimates of the LC99.9 for mixtures of toxicants are critical to ongoing control of a parasitic invasive species, the sea lamprey, in the Laurentian Great Lakes of North America. The toxicity of those chemicals is affected by local and temporal variations in water chemistry, which must be incorporated into the modeling. We develop multilevel empirical Bayes models for data from multiple laboratory studies. Our approach yields more accurate and precise estimation of the LC99.9 compared to alternative models considered. This study demonstrates that properly incorporating hierarchical structure in laboratory data yields better estimates of LC99.9 stream treatment values that are critical to larvae control in the field. In addition, out-of-sample prediction of the results of in situ tests reveals the presence of a latent seasonal effect not manifest in the laboratory studies, suggesting avenues for future study and illustrating the importance of dual consideration of both experimental and observational data.

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

Personalizing health care: feasibility and future implications.

PubMed

Godman, Brian; Finlayson, Alexander E; Cheema, Parneet K; Zebedin-Brandl, Eva; Gutiérrez-Ibarluzea, Inaki; Jones, Jan; Malmström, Rickard E; Asola, Elina; Baumgärtel, Christoph; Bennie, Marion; Bishop, Iain; Bucsics, Anna; Campbell, Stephen; Diogene, Eduardo; Ferrario, Alessandra; Fürst, Jurij; Garuoliene, Kristina; Gomes, Miguel; Harris, Katharine; Haycox, Alan; Herholz, Harald; Hviding, Krystyna; Jan, Saira; Kalaba, Marija; Kvalheim, Christina; Laius, Ott; Lööv, Sven-Ake; Malinowska, Kamila; Martin, Andrew; McCullagh, Laura; Nilsson, Fredrik; Paterson, Ken; Schwabe, Ulrich; Selke, Gisbert; Sermet, Catherine; Simoens, Steven; Tomek, Dominik; Vlahovic-Palcevski, Vera; Voncina, Luka; Wladysiuk, Magdalena; van Woerkom, Menno; Wong-Rieger, Durhane; Zara, Corrine; Ali, Raghib; Gustafsson, Lars L

2013-08-13

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer's perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

Personalizing health care: feasibility and future implications

PubMed Central

2013-01-01

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer’s perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients. PMID:23941275

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

Testing Chemical Safety: What Is Needed to Ensure the Widespread Application of Non-animal Approaches?

PubMed Central

Burden, Natalie; Sewell, Fiona; Chapman, Kathryn

2015-01-01

Scientists face growing pressure to move away from using traditional animal toxicity tests to determine whether manufactured chemicals are safe. Numerous ethical, scientific, business, and legislative incentives will help to drive this shift. However, a number of hurdles must be overcome in the coming years before non-animal methods are adopted into widespread practice, particularly from regulatory, scientific, and global perspectives. Several initiatives are nevertheless underway that promise to increase the confidence in newer alternative methods, which will support the move towards a future in which less data from animal tests is required in the assessment of chemical safety. PMID:26018957

[Application of chemical ecology in controlling marine fouling organisms].

PubMed

Fang, Fang; Yan, Tao; Liu, Qing

2005-10-01

Many marine organisms can produce secondary metabolites beneficial to the protection of marine environments against fouling, and thus, applying chemo-ecological methods to extract the natural antifoulants from marine organisms to resolve the problems relevant to marine fouling is a new thinking in resent years. Its aim is to search for high efficient and non-toxic antifoulants to replace the existing chemically synthetic ones which are unfortunately found to have widespread toxic effects on marine environment. Although we know few about the antifouling mechanisms of secondary metabolites, many natural products have been proved to have antifouling activity. Therefore, basic and applied researches on the ecological roles of these natural compounds, their action mechanisms, coating compatibility, controlled release, and field test are required in the future.

Effects of Salinity on Oil Spill Dispersant Toxicity in Estuarine Organisms

NASA Astrophysics Data System (ADS)

Eckmann, C. A.

2016-02-01

Chemical dispersants can be a useful tool to mitigate oil spills, but the potential risks to sensitive estuarine species should be carefully considered. To improve the decision making process, more information is needed regarding the effects of oil spill dispersants on the health of coastal ecosystems under variable environmental conditions such as salinity. The two oil dispersants used in this study were Corexit ® 9500 and Finasol ® OSR 52. Corexit ® 9500 was the primary dispersant used during the 2010 Deepwater Horizon oil spill event, while Finasol® OSR 52 is another dispersant approved for oil spill response in the U.S., yet considerably less is known regarding its toxicity to estuarine species. The grass shrimp, Palaemonetes pugio, was used as a model estuarine species. It is a euryhaline species that tolerates salinities from brackish to full strength seawater. Adult and larval life stages were tested with each dispersant at three salinities, 5ppt, 20ppt, and 30ppt. Median acute lethal toxicity thresholds were calculated. Lipid peroxidation assays were conducted on surviving shrimp to investigate sublethal effects. The toxicity of both dispersants was significantly influenced by salinity, with greatest toxicity observed at the lowest salinity tested. Larval shrimp were significantly more sensitive than adult shrimp to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Furthermore, significant sublethal effects were seen at higher concentrations of both dispersants compared to the control. These data will enable environmental managers to make informed decisions regarding dispersant use in future oil spills.

Effects of Salinity on Oil Spill Dispersant Toxicity in Estuarine Organisms

NASA Astrophysics Data System (ADS)

Eckmann, C. A.

2015-12-01

Chemical dispersants can be a useful tool to mitigate oil spills, but the potential risks to sensitive estuarine species should be carefully considered. To improve the decision making process, more information is needed regarding the effects of oil spill dispersants on the health of coastal ecosystems under variable environmental conditions such as salinity. The two oil dispersants used in this study were Corexit ® 9500 and Finasol ® OSR 52. Corexit ® 9500 was the primary dispersant used during the 2010 Deepwater Horizon oil spill event, while Finasol® OSR 52 is another dispersant approved for oil spill response in the U.S., yet considerably less is known regarding its toxicity to estuarine species. The grass shrimp, Palaemonetes pugio, was used as a model estuarine species. It is a euryhaline species that tolerates salinities from brackish to full strength seawater. Adult and larval life stages were tested with each dispersant at three salinities, 5ppt, 20ppt, and 30ppt. Median acute lethal toxicity thresholds were calculated. Lipid peroxidation assays were conducted on surviving shrimp to investigate sublethal effects. The toxicity of both dispersants was significantly influenced by salinity, with greatest toxicity observed at the lowest salinity tested. Larval shrimp were significantly more sensitive than adult shrimp to both dispersants, and both life stages were significantly more sensitive to Finasol than to Corexit. Furthermore, significant sublethal effects were seen at higher concentrations of both dispersants compared to the control. These data will enable environmental managers to make informed decisions regarding dispersant use in future oil spills.

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

Organotypic liver culture models: Meeting current challenges in toxicity testing

PubMed Central

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

2012-01-01

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

Piperonyl butoxide enhances the bioconcentration and photoinduced toxicity of fluoranthene and benzo[a]pyrene to larvae of the grass shrimp (Palaemonetes pugio).

PubMed

Weinstein, John E; Garner, Thomas R

2008-04-08

Piperonyl butoxide (PBO) is a commonly used synergist in many pyrethroid formulations due to its ability to interfere with cytochrome P450 (CYP) monooxygenases. Because PBO can co-occur in the estuarine environment with polycyclic aromatic hydrocarbons (PAHs), a class of compounds metabolized by CYP isozymes, the overall objective of this study was to investigate the influence of PBO on the bioconcentration and photoinduced toxicity of two common PAH contaminants, fluoranthene (FLU) and benzo[a]pyrene (BaP), on the larvae of the grass shrimp (Palaemonetes pugio). PBO alone was not particularly toxic to grass shrimp larvae. In dark exposures and under simulated sunlight (UV-A=211.0+/-7.0 microW/cm(2), UV-B=9.8+/-2.4microW/cm(2)), 96-h LC(50) values were similar (814.4 and 888.6 microg/L, respectively), suggesting that PBO toxicity is not enhanced in the presence of sunlight. The presence of sublethal concentrations of PBO in single PAH toxicity tests increased the bioconcentration of the two tested PAHs, and these increases were greatest at the lowest tested PAH concentrations. Mean bioconcentration factors (BCF) at the three lowest FLU and BaP treatments increased 14.3- and 7.1-fold, respectively, in the low PBO (127 microg/L) exposure compared to that of the no PBO exposure. Under simulated sunlight, PBO exposure also increased the photoinduced toxicity of the two tested PAHs, and this increase occurred in a PBO concentration-dependent fashion. For FLU, 96-h LC(50) values decreased from 2.35 microg/L in the absence of PBO to 0.76 microg/L in the high PBO (256 microg/L) exposure. For BaP, 96-h LC(50) values similarly decreased from 1.02 microg/L in the absence of PBO to 0.30microg/L in the high PBO exposure. The presence of PBO also influenced the PAH tissue residue-response relationship, but in different ways for FLU and BaP. For FLU, slopes of the tissue residue-response relationship decreased in the presence of PBO, and for BaP, there was a trend towards increased slopes in the presence of PBO. These results demonstrate that sublethal levels of PBO increase the bioconcentration and photoinduced toxicity of certain PAH in grass shrimp larvae, and underscore the need to consider the potential for PBO to synergize the toxicity of co-occurring environmental contaminants in future risk assessments.

Health effects of metoprolol in epibenthic and endobenthic invertebrates-A basis to validate future in vitro biotests for effect-based biomonitoring.

PubMed

Jungmann, Dirk; Berg, Kristin; Dieterich, Andreas; Frank, Martin; Gräf, Tonya; Scheurer, Marco; Schwarz, Simon; Siewert, Carmen; Oetken, Matthias

2017-02-23

The aim of this study was to determine the effect data for metoprolol as a model substance for beta-blockers in aquatic invertebrates. The results will be used as a basis for the validation of future mode of action-based in vitro test systems targeting this class of pharmaceuticals. Effects of metoprolol were investigated in two autochthonous species with high relevance in stream ecology: the amphipod Gammarus fossarum and the oligochaete Lumbriculus variegatus. Mortality in G. fossarum was not observed in acute toxicity testing (48 h), and a significant increase of mortality at 45 mg/L was found when amphipods were exposed chronically (40 days). The most sensitive population-relevant endpoints were the juvenile-adult ratio and number of egg-bearing females with NOEC/LOEC-values of 5/15 mg/L. No proteotoxic effects were identified in G. fossarum. The sediment toxicity test with L. variegatus according to the OECD Guideline 225 with an exposure time of 28 days resulted in EC 10 -values of 92.5 and 126.1 mg/kg dw for the endpoints reproduction and biomass, respectively. In L. variegatus the response kinetics of Hsp70 showed no significant difference between the treatments. A tendency for rising lipid peroxide concentrations was found between 0.03 and 10 mg/kg dw , which were significant between the treatments, but not to the control.

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.

The evolution of juvenile animal testing for small and large molecules.

PubMed

Baldrick, Paul

2013-11-01

Recent formalised regulatory requirements for ensuring safe use of new drugs in children has increased the requirement, when considered relevant, to perform juvenile animal testing before commencing paediatric clinical trials. A key goal of this work is to identify or examine for a developmental or toxicity finding not seen in other toxicology testing. With our current knowledge, this paper examines what types of testing are occurring, what novel findings are being seen and their relevance in the safety evaluation process. Furthermore, trends for now and the future in the type of juvenile animal testing will be described including a need for more focused study designs and more published data on modern cross-species postnatal development. Copyright © 2013 Elsevier Inc. All rights reserved.

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

USGS Publications Warehouse

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

1999-01-01

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

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 fish embryo test (FET): origin, applications, and future.

PubMed

Braunbeck, Thomas; Kais, Britta; Lammer, Eva; Otte, Jens; Schneider, Katharina; Stengel, Daniel; Strecker, Ruben

2015-11-01

Originally designed as an alternative for the acute fish toxicity test according to, e.g., OECD TG 203, the fish embryo test (FET) with the zebrafish (Danio rerio) has been optimized, standardized, and validated during an OECD validation study and adopted as OECD TG 236 as a test to assess toxicity of embryonic forms of fish. Given its excellent correlation with the acute fish toxicity test and the fact that non-feeding developmental stages of fish are not categorized as protected stages according to the new European Directive 2010/63/EU on the protection of animals used for scientific purposes, the FET is ready for use not only for range-finding but also as a true alternative for the acute fish toxicity test, as required for a multitude of national and international regulations. If-for ethical reasons-not accepted as a full alternative, the FET represents at least a refinement in the sense of the 3Rs principle. Objections to the use of the FET have mainly been based on the putative lack of biotransformation capacity and the assumption that highly lipophilic and/or high molecular weight substances might not have access to the embryo due to the protective role of the chorion. With respect to bioactivation, the only substance identified so far as not being activated in the zebrafish embryo is allyl alcohol; all other biotransformation processes that have been studied in more detail so far were found to be present, albeit, in some cases, at lower levels than in adult fish. With respect to larger molecules, the extension of the test duration to 96 h (i.e., beyond hatch) has-at least for the substances tested so far-compensated for the reduced access to the embryo; however, more research is necessary to fully explore the applicability of the FET to substances with a molecular weight >3 kDa as well as substances with a neurotoxic mode of action. An extension of the endpoints to also cover sublethal endpoints makes the FET a powerful tool for the detection of teratogenicity, dioxin-like activity, genotoxicity and mutagenicity, neurotoxicity, as well as various forms of endocrine disruption.

Discovery and ramifications of incidental Magnéli phase generation and release from industrial coal-burning.

PubMed

Yang, Yi; Chen, Bo; Hower, James; Schindler, Michael; Winkler, Christopher; Brandt, Jessica; Di Giulio, Richard; Ge, Jianping; Liu, Min; Fu, Yuhao; Zhang, Lijun; Chen, Yuru; Priya, Shashank; Hochella, Michael F

2017-08-08

Coal, as one of the most economic and abundant energy sources, remains the leading fuel for producing electricity worldwide. Yet, burning coal produces more global warming CO 2 relative to all other fossil fuels, and it is a major contributor to atmospheric particulate matter known to have a deleterious respiratory and cardiovascular impact in humans, especially in China and India. Here we have discovered that burning coal also produces large quantities of otherwise rare Magnéli phases (Ti x O 2x-1 with 4 ≤ x ≤ 9) from TiO 2 minerals naturally present in coal. This provides a new tracer for tracking solid-state emissions worldwide from industrial coal-burning. In its first toxicity testing, we have also shown that nanoscale Magnéli phases have potential toxicity pathways that are not photoactive like TiO 2 phases, but instead seem to be biologically active without photostimulation. In the future, these phases should be thoroughly tested for their toxicity in the human lung.Solid-state emissions from coal burning remain an environmental concern. Here, the authors have found that TiO2 minerals present in coal are converted into titanium suboxides during burning, and initial biotoxicity screening suggests that further testing is needed to look into human lung consequences.

Preparation of near-infrared-labeled targeted contrast agents for clinical translation

NASA Astrophysics Data System (ADS)

Olive, D. Michael

2011-03-01

Targeted fluorophore-labeled contrast agents are moving toward translation to human surgical use. To prepare for future clinical use, we examined the performance of potential ligands targeting the epidermal growth factor receptor, α5β3 integrins, and GLUT transporters for their suitability as directed contrast agents. Each agent was labeled with IRDye 800CW, and near-infrared dye with excitation/emission wavelengths of 789/805 nm, which we determined had favorable toxicity characteristics. The probe molecules examined consisted of Affibodies, nanobodies, peptides, and the sugar 2-deoxy-D-glucose. Each probe was tested for specific and non-specific binding in cell based assays. All probe types showed good performance in mouse models for detecting either spontaneous tumors or tumor xenografts in vivo. Each of the probes tested show promise for future human clinical studies.

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

PubMed Central

Vandooren, Jennifer; Berghmans, Nele; Dillen, Chris; Van Aelst, Ilse; Ronsse, Isabelle; Israel, Liron Limor; Rosenberger, Ina; Kreuter, Jörg; Lellouche, Jean-Paul; Michaeli, Shulamit; Locatelli, Erica; Franchini, Mauro Comes; Aiertza, Miren K; Sánchez-Abella, Laura; Loinaz, Iraida; Edwards, Dylan R; Shenkman, Louis; Opdenakker, Ghislain

2013-01-01

The need for test systems for nanoparticle biocompatibility, toxicity, and inflammatory or adaptive immunological responses is paramount. Nanoparticles should be free of microbiological and chemical contaminants, and devoid of toxicity. Nevertheless, in the absence of contamination, these particles may still induce undesired immunological effects in vivo, such as enhanced autoimmunity, hypersensitivity reactions, and fibrosis. Here we show that artificial particles of specific sizes affect immune cell recruitment as tested in a dermal air pouch model in mice. In addition, we demonstrate that the composition of nanoparticles may influence immune cell recruitment in vivo. Aside from biophysical characterizations in terms of hydrodynamic diameter, zeta potential, concentration, and atomic concentration of metals, we show that – after first-line in vitro assays – characterization of cellular and molecular effects by dermal air pouch analysis is straightforward and should be included in the quality control of nanoparticles. We demonstrate this for innate immunological effects such as neutrophil recruitment and the production of immune-modulating matrix metalloproteases such as MMP-9; we propose the use of air pouch leukocytosis analysis as a future standard assay. PMID:24379662

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System.

PubMed

Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Masarudin, Mas Jaffri; Ahmad Saad, Fathinul Fikri

2017-08-31

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO₃)₃ as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment.

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

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.

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 ...

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...

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.

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

PubMed

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

2018-05-01

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

Environmental transformations and ecological effects of iron-based nanoparticles.

PubMed

Lei, Cheng; Sun, Yuqing; Tsang, Daniel C W; Lin, Daohui

2018-01-01

The increasing application of iron-based nanoparticles (NPs), especially high concentrations of zero-valent iron nanoparticles (nZVI), has raised concerns regarding their environmental behavior and potential ecological effects. In the environment, iron-based NPs undergo physical, chemical, and/or biological transformations as influenced by environmental factors such as pH, ions, dissolved oxygen, natural organic matter (NOM), and biotas. This review presents recent research advances on environmental transformations of iron-based NPs, and articulates their relationships with the observed toxicities. The type and extent of physical, chemical, and biological transformations, including aggregation, oxidation, and bio-reduction, depend on the properties of NPs and the receiving environment. Toxicities of iron-based NPs to bacteria, algae, fish, and plants are increasingly observed, which are evaluated with a particular focus on the underlying mechanisms. The toxicity of iron-based NPs is a function of their properties, tolerance of test organisms, and environmental conditions. Oxidative stress induced by reactive oxygen species is considered as the primary toxic mechanism of iron-based NPs. Factors influencing the toxicity of iron-based NPs are addressed and environmental transformations play a significant role, for example, surface oxidation or coating by NOM generally lowers the toxicity of nZVI. Research gaps and future directions are suggested with an aim to boost concerted research efforts on environmental transformations and toxicity of iron-based NPs, e.g., toxicity studies of transformed NPs in field, expansion of toxicity endpoints, and roles of laden contaminants and surface coating. This review will enhance our understanding of potential risks of iron-based NPs and proper uses of environmentally benign NPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of the Insecticidal Characteristics of Commercially Available Plant Essential Oils Against Aedes aegypti and Anopheles gambiae (Diptera: Culicidae).

PubMed

Norris, Edmund J; Gross, Aaron D; Dunphy, Brendan M; Bessette, Steven; Bartholomay, Lyric; Coats, Joel R

2015-09-01

Aedes aegypti and Anopheles gambiae are two mosquito species that represent significant threats to global public health as vectors of Dengue virus and malaria parasites, respectively. Although mosquito populations have been effectively controlled through the use of synthetic insecticides, the emergence of widespread insecticide-resistance in wild mosquito populations is a strong motivation to explore new insecticidal chemistries. For these studies, Ae. aegypti and An. gambiae were treated with commercially available plant essential oils via topical application. The relative toxicity of each essential oil was determined, as measured by the 24-h LD(50) and percentage knockdown at 1 h, as compared with a variety of synthetic pyrethroids. For Ae. aegypti, the most toxic essential oil (patchouli oil) was ∼1,700-times less toxic than the least toxic synthetic pyrethroid, bifenthrin. For An. gambiae, the most toxic essential oil (patchouli oil) was ∼685-times less toxic than the least toxic synthetic pyrethroid. A wide variety of toxicities were observed among the essential oils screened. Also, plant essential oils were analyzed via gas chromatography/mass spectrometry (GC/MS) to identify the major components in each of the samples screened in this study. While the toxicities of these plant essential oils were demonstrated to be lower than those of the synthetic pyrethroids tested, the large amount of GC/MS data and bioactivity data for each essential oil presented in this study will serve as a valuable resource for future studies exploring the insecticidal quality of plant essential oils. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence of increasing temperature and salinity on herbicide toxicity in estuarine phytoplankton.

PubMed

DeLorenzo, Marie E; Danese, Loren E; Baird, Thomas D

2013-07-01

Ecological risk assessments are, in part, based on results of toxicity tests conducted under standard exposure conditions. Global climate change will have a wide range of effects on estuarine habitats, including potentially increasing water temperature and salinity, which may alter the risk assessment of estuarine pollutants. We examined the effects of increasing temperature and salinity on the toxicity of common herbicides (irgarol, diuron, atrazine, and ametryn) to the phytoplankton species Dunaliella tertiolecta. Static 96-h algal bioassays were conducted for each herbicide under four exposure scenarios: standard temperature and salinity (25°C, 20 ppt), standard temperature and elevated salinity (25°C, 40 ppt), elevated temperature and standard salinity (35°C, 20 ppt), and elevated temperature and elevated salinity (35°C, 40 ppt). The endpoints assessed were algal cell density at 96 h, growth rate, chlorophyll a content, lipid content, and starch content. Increasing exposure temperature reduced growth rate and 96-h cell density but increased the cellular chlorophyll and lipid concentrations of the control algae. Exposure condition did not alter starch content of control algae. Herbicides were found to decrease growth rate, 96 h cell density, and cellular chlorophyll and lipid concentrations, while starch concentrations increased with herbicide exposure. Herbicide effects under standard test conditions were then compared with those observed under elevated temperature and salinity. Herbicide effects on growth rate, cell density, and starch content were more pronounced under elevated salinity and temperature conditions. To encompass the natural variability in estuarine temperature and salinity, and to account for future changes in climate, toxicity tests should be conducted under a wider range of environmental conditions. Copyright © 2011 Wiley Periodicals, Inc.

Biological activity of Xanthium strumarium seed extracts on different cancer cell lines and Aedes caspius, Culex pipiens (Diptera: Culicidae).

PubMed

Al-Mekhlafi, Fahd A; Abutaha, Nael; Mashaly, Ashraf M A; Nasr, Fahd A; Ibrahim, Khalid E; Wadaan, Mohamed A

2017-05-01

Effects of methanol extracts of Xanthium strumarium on different cancer cell lines and on the mortality rates of Aedes caspius, Culex pipiens (Diptera: Culicidae) were investigated. Among the cell lines tested, the Jurkat cell line was the most sensitive to the methanol extract and ethyl acetate fraction, with reported LC 50 values of 50.18 and 48.73 μg/ml respectively. Conversely, methanol extracts were not that toxic to the A549 cell line though the toxicity increased on further purification. The percentage of growth inhibition was dose dependent for the methanol extract and ethyl acetate fraction. The ethyl acetate fraction showed higher toxicity to all cell lines tested when compared to the methanol extract. The results showed that methanol extracts of plant seeds caused 100% mortality of mosquito larvae at a concentration of 1000 μg/ml after 24 h of treatment. The LC 50 and LC 90 values of X. strumarium were found to be 531.07 and 905.95 μg/ml against Ae. caspius and 502.32 and 867.63 μg/ml against Cx. Pipiens, respectively. From the investigations, it was concluded that the crude extract of X. strumarium showed a weak potential for controlling the larval instars of Ae. caspius and Cx. pipiens . However, on further purification the extract lost the larvicidal activity. The ethyl acetate fraction showed higher toxicity to all cell lines tested when compared to the methanol extract. The ethyl acetate fraction investigated in this study appears to have a weak larvicidal activity but a promising cytotoxic activity. Future studies will include purification and investigation in further detail of the action of X. strumarium on Cancer Cell Lines and mosquitoes.

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.

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.

Analysis and toxicity of 59 PAH in petrogenic and pyrogenic environmental samples including dibenzopyrenes, 7H-benzo[c]fluorene, 5-methylchrysene and 1-methylpyrene.

PubMed

Richter-Brockmann, Sigrid; Achten, Christine

2018-06-01

In this study 59 PAH were analyzed in samples of petrogenic and pyrogenic sources as well as mixed environmental matrices. Among the analytes, PAH of molecular weights from 128 Da to 302 Da in alkylated and in native form were included. Results show that non-EPA PAH make up 69.3–95.1% of the overall toxic equivalents (TEQ) as based on the toxic equivalent factors (TEF) of 24 PAH. Particularly 7H-benzo[c]fluorene, dibenzopyrene isomers and alkylated PAH (in particular 5-methylchrysene and 1-methylpyrene) turned out to have a huge impact on the toxicity and must not be neglected in future risk assessment. In detail, dibenzopyrenes have a high impact on toxicity predominantly in pyrogenic materials (21% to 84%; mean: 59%) whereas 7H-benzo[c]fluorene dominates toxicity of petrogenic materials (up to 80%; mean: 26%). However, in the studied mixed environmental samples the toxic impact of both groups together is as high as about 80%. Many non-EPA PAH are not considered in risk assessment and amongst them there are some very toxic ones. This needs to be carefully evaluated in future studies.

Alternatives to animal testing: current status and future perspectives.

PubMed

Liebsch, Manfred; Grune, Barbara; Seiler, Andrea; Butzke, Daniel; Oelgeschläger, Michael; Pirow, Ralph; Adler, Sarah; Riebeling, Christian; Luch, Andreas

2011-08-01

On the occasion of the 20th anniversary of the Center for Alternative Methods to Animal Experiments (ZEBET), an international symposium was held at the German Federal Institute for Risk Assessment (BfR) in Berlin. At the same time, this symposium was meant to celebrate the 50th anniversary of the publication of the book "The Principles of Humane Experimental Technique" by Russell and Burch in 1959 in which the 3Rs principle (that is, Replacement, Reduction, and Refinement) has been coined and introduced to foster the development of alternative methods to animal testing. Another topic addressed by the symposium was the new vision on "Toxicology in the twenty-first Century", as proposed by the US-National Research Council, which aims at using human cells and tissues for toxicity testing in vitro rather than live animals. An overview of the achievements and current tasks, as well as a vision of the future to be addressed by ZEBET@BfR in the years to come is outlined in the present paper.

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective.

PubMed

Chen, Guoli; Yang, Zhaohai; Eshleman, James R; Netto, George J; Lin, Ming-Tseh

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional "one test-one drug" assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

In vitro toxicity of nanoparticles in BRL 3A rat liver cells.

PubMed

Hussain, S M; Hess, K L; Gearhart, J M; Geiss, K T; Schlager, J J

2005-10-01

This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100 nm), molybdenum (MoO(3); 30, 150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe(3)O(4); 30, 47 nm), and titanium dioxide (TiO(2); 40 nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1 microm), manganese oxide (MnO(2); 1-2 microm), and tungsten (W; 27 microm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5-50 microg/ml. However, Fe(3)O(4), Al, MoO(3) and TiO(2) had no measurable effect at lower doses (10-50 microg/ml), while there was a significant effect at higher levels (100-250 microg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10-50 microg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100-250 microg/ml). In summary the Ag was highly toxic whereas, MoO(3) moderately toxic and Fe(3)O(4), Al, MnO(2) and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PubMed

Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

2015-04-01

Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

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.

Earthworm Comet Assay for Assessing the Risk of Weathered Petroleum Hydrocarbon Contaminated Soils: Need to Look Further than Target Contaminants.

PubMed

Ramadass, Kavitha; Palanisami, Thavamani; Smith, Euan; Mayilswami, Srinithi; Megharaj, Mallavarapu; Naidu, Ravi

2016-11-01

Earthworm toxicity assays contribute to ecological risk assessment and consequently standard toxicological endpoints, such as mortality and reproduction, are regularly estimated. These endpoints are not enough to better understand the mechanism of toxic pollutants. We employed an additional endpoint in the earthworm Eisenia andrei to estimate the pollutant-induced stress. In this study, comet assay was used as an additional endpoint to evaluate the genotoxicity of weathered hydrocarbon contaminated soils containing 520 to 1450 mg hydrocarbons kg -1 soil. Results showed that significantly higher DNA damage levels (two to sixfold higher) in earthworms exposed to hydrocarbon impacted soils. Interestingly, hydrocarbons levels in the tested soils were well below site-specific screening guideline values. In order to explore the reasons for observed toxicity, the contaminated soils were leached with rainwater and subjected to earthworm tests, including the comet assay, which showed no DNA damage. Soluble hydrocarbon fractions were not found originally in the soils and hence no hydrocarbons leached out during soil leaching. The soil leachate's Electrical Conductivity (EC) decreased from an average of 1665 ± 147 to 204 ± 20 µS cm -1 . Decreased EC is due to the loss of sodium, magnesium, calcium, and sulphate. The leachate experiment demonstrated that elevated salinity might cause the toxicity and not the weathered hydrocarbons. Soil leaching removed the toxicity, which is substantiated by the comet assay and soil leachate analysis data. The implication is that earthworm comet assay can be included in future eco (geno) toxicology studies to assess accurately the risk of contaminated soils.

Comparative study to evaluate the anti-viral efficacy of Glycyrrhiza glabra extract and ribavirin against the Newcastle disease virus

PubMed Central

Omer, Muhammad Ovais; AlMalki, Waleed Hassan; Shahid, Imran; Khuram, Shahzada; Altaf, Imran; Imran, Saeed

2014-01-01

Background: The Newcastle disease represents as one of the most infectious viral disease, which afflicts almost every species of the birds. The causative agent of the disease is a single-stranded RNA virus with rapid replication capability. Objective: This study was performed to evaluate the comparative anti-viral efficacy and toxicity of Glycyrrhiza glabra aqueous extract and ribavirin against the Newcastle disease virus. Materials and Methods: The embryonated eggs were divided into six groups (A, B, C, D, E and F). Groups A, B, C, and D were further subdivided into three subgroups. The virus was identified by hemagglutination inhibition test. Spot hemagglutination test and viability of embryos were also evaluated. Three different concentrations i-e., 30 mg/100 ml, 60 mg/100 ml, and 120 mg/100 ml of the Glycyrrhiza aqueous extract and 10 μg/ml, 20 μg/ml, and 40 μg/ml ribavirin in deionized water were evaluated for their toxicity and anti-viral activity in the embryonated eggs. Results: 60 mg/100 ml concentration of Glycyrrhiza extract did not produce any toxicity in the embryonated eggs and showed anti-viral activity against the virus. Similarly, 20 μg/ml ribavirin was non-toxic in the embryonated eggs and contained anti-viral activity. Conclusion: It may conclude from the presented study that 60 mg/100 ml Glycyrrhiza extract inhibits replication of Newcastle disease virus and is non-toxic in the embryonated eggs. So, Glycyrrhiza glabra extract may be further evaluated in future to determine the potentially active compounds for their anti-viral activity against Newcastle disease virus. Furthermore, the mechanism of action of these active phytochemicals as an antiviral agent would be helpful to elucidate the pathogenesis of the disease. PMID:24497736

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

Multilevel Empirical Bayes Modeling for Improved Estimation of Toxicant Formulations to Suppress Parasitic Sea Lamprey in the Upper Great Lakes

USGS Publications Warehouse

Hatfield, L.A.; Gutreuter, S.; Boogaard, M.A.; Carlin, B.P.

2011-01-01

Estimation of extreme quantal-response statistics, such as the concentration required to kill 99.9% of test subjects (LC99.9), remains a challenge in the presence of multiple covariates and complex study designs. Accurate and precise estimates of the LC99.9 for mixtures of toxicants are critical to ongoing control of a parasitic invasive species, the sea lamprey, in the Laurentian Great Lakes of North America. The toxicity of those chemicals is affected by local and temporal variations in water chemistry, which must be incorporated into the modeling. We develop multilevel empirical Bayes models for data from multiple laboratory studies. Our approach yields more accurate and precise estimation of the LC99.9 compared to alternative models considered. This study demonstrates that properly incorporating hierarchical structure in laboratory data yields better estimates of LC99.9 stream treatment values that are critical to larvae control in the field. In addition, out-of-sample prediction of the results of in situ tests reveals the presence of a latent seasonal effect not manifest in the laboratory studies, suggesting avenues for future study and illustrating the importance of dual consideration of both experimental and observational data. ?? 2011, The International Biometric Society.

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.

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

PubMed

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

2018-04-01

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

A 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).

FutureTox: building the road for 21st century toxicology and risk assessment practices.

PubMed

Rowlands, J Craig; Sander, Miriam; Bus, James S

2014-02-01

This article reports on the outcome of FutureTox, a Society of Toxicology (SOT) Contemporary Concepts in Toxicology (CCT) workshop, whose goal was to address the challenges and opportunities associated with implementing 21st century technologies for toxicity testing, hazard identification, and risk assessment. One goal of the workshop was to facilitate an interactive multisector and discipline dialog. To this end, workshop invitees and participants included stakeholders from governmental and regulatory agencies, research institutes, academia, and the chemical and pharmaceutical industry in Europe and the United States. The workshop agenda was constructed to collectively review and discuss the state-of-the-science in these fields, better define the problems and challenges, outline their collective goals for the future, and identify areas of common agreement key to advancing these technologies into practice.

FutureTox: Building the Road for 21st Century Toxicology and Risk Assessment Practices

PubMed Central

Rowlands, J. Craig; Bus, James S.

2014-01-01

This article reports on the outcome of FutureTox, a Society of Toxicology (SOT) Contemporary Concepts in Toxicology (CCT) workshop, whose goal was to address the challenges and opportunities associated with implementing 21st century technologies for toxicity testing, hazard identification, and risk assessment. One goal of the workshop was to facilitate an interactive multisector and discipline dialog. To this end, workshop invitees and participants included stakeholders from governmental and regulatory agencies, research institutes, academia, and the chemical and pharmaceutical industry in Europe and the United States. The workshop agenda was constructed to collectively review and discuss the state-of-the-science in these fields, better define the problems and challenges, outline their collective goals for the future, and identify areas of common agreement key to advancing these technologies into practice. PMID:24204016

In vitro antioxidant potential of medicinal plant extracts and their activities against oral bacteria based on Brazilian folk medicine.

PubMed

Alviano, Wagner S; Alviano, Daniela S; Diniz, Cláudio G; Antoniolli, Angelo R; Alviano, Celuta S; Farias, Luiz M; Carvalho, Maria Auxiliadora R; Souza, Margareth M G; Bolognese, Ana Maria

2008-06-01

This study aims to determine antibacterial activities of Cocos nucifera (husk fiber), Ziziphus joazeiro (inner bark), Caesalpinia pyramidalis (leaves), aqueous extracts and Aristolochia cymbifera (rhizomes) alcoholic extract against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans and Lactobacillus casei. The antioxidant activity and acute toxicity of these extracts were also evaluated. The plant extracts antibacterial activity was evaluated in vitro and the minimal inhibitory concentration (MIC) was determined by the broth micro-dilution assay. The bacterial killing kinetic was also evaluated for all extracts. In addition, the antibacterial effect of the extracts was tested in vitro on artificial oral biofilms. The acute toxicity of each extract was determined in according to Lorke [Lorke D. A new approach to practical acute toxicity testing. Arch Toxicol 1983;54:275-87] and the antioxidant activity was evaluated by DPPH photometric assay [Mensor LL, Menezes FS, Leitão GG, Reis AS, Santos TC, Coube CS, et al. Screening of Brazilian plants extract for antioxidant activity by the use of DPPH free radical method. Phytother Res 2001;15:127-30]. MIC and the bactericidal concentrations were identical, for each evaluated extract. However, microbes of artificial biofilms were less sensitive to the extracts than the planktonic strains. A. cymbifera extract induced the highest bactericidal effect against all tested bacteria, followed by C. nucifera, Z. joazeiro and C. pyramidalis extracts, respectively. All extracts showed good antioxidant potential, being C. nucifera and C. pyramidalis aqueous extracts the most active ones. In conclusion, all oral bacteria tested (planktonic or in artificial biofilms) were more susceptible to, and rapidly killed in presence of A. cymbifera, C. pyramidalis and C. nucifera than Z. joazeiro extracts, respectively. Thus, these extracts may be of great interest for future studies about treatment of oral diseases, considering their potent antioxidant activity and low toxicity.

Biocompatible Colloidal Suspensions Based on Magnetic Iron Oxide Nanoparticles: Synthesis, Characterization and Toxicological Profile

PubMed Central

Coricovac, Dorina-Elena; Moacă, Elena-Alina; Pinzaru, Iulia; Cîtu, Cosmin; Soica, Codruta; Mihali, Ciprian-Valentin; Păcurariu, Cornelia; Tutelyan, Victor A.; Tsatsakis, Aristidis; Dehelean, Cristina-Adriana

2017-01-01

The use of magnetic iron oxide nanoparticles in biomedicine has evolved intensely in the recent years due to the multiple applications of these nanomaterials, mainly in domains like cancer. The aim of the present study was: (i) to develop biocompatible colloidal suspensions based on magnetic iron oxide nanoparticles as future theranostic tools for skin pathology and (ii) to test their effects in vitro on human keratinocytes (HaCat cells) and in vivo by employing an animal model of acute dermal toxicity. Biocompatible colloidal suspensions were obtained by coating the magnetic iron oxide nanoparticles resulted during the solution combustion synthesis with a double layer of oleic acid, as innovative procedure in increasing bioavailability. The colloidal suspensions were characterized in terms of dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro effects of these suspensions were tested by means of Alamar blue assay and the noxious effects at skin level were measured using non-invasive methods. The in vitro results indicated a lack of toxicity on normal human cells induced by the iron oxide nanoparticles colloidal suspensions after an exposure of 24 h to different concentrations (5, 10, and 25 μg·mL−1). The dermal acute toxicity test showed that the topical applications of the colloidal suspensions on female and male SKH-1 hairless mice were not associated with significant changes in the quality of barrier skin function. PMID:28400730

3D in vitro technology for drug discovery.

PubMed

Hosseinkhani, Hossein

2012-02-01

Three-dimensional (3D) in vitro systems that can mimic organ and tissue structure and function in vivo, will be of great benefit for a variety of biological applications from basic biology to toxicity testing and drug discovery. There have been several attempts to generate 3D tissue models but most of these models require costly equipment, and the most serious disadvantage in them is that they are too far from the mature human organs in vivo. Because of these problems, research and development in drug discovery, toxicity testing and biotech industries are highly expensive, and involve sacrifice of countless animals and it takes several years to bring a single drug/product to the market or to find the toxicity or otherwise of chemical entities. Our group has been actively working on several alternative models by merging biomaterials science, nanotechnology and biological principles to generate 3D in vitro living organs, to be called "Human Organs-on-Chip", to mimic natural organ/tissues, in order to reduce animal testing and clinical trials. We have fabricated a novel type of mechanically and biologically bio-mimicking collagen-based hydrogel that would provide for interconnected mini-wells in which 3D cell/organ culture of human samples in a manner similar to human organs with extracellular matrix (ECM) molecules would be possible. These products mimic the physical, chemical, and biological properties of natural organs and tissues at different scales. This paper will review the outcome of our several experiments so far in this direction and the future perspectives.

Key physicochemical properties of nanomaterials in view of their toxicity: an exploratory systematic investigation for the example of carbon-based nanomaterial

NASA Astrophysics Data System (ADS)

Salieri, Beatrice; Pasteris, Andrea; Netkueakul, Woranan; Hischier, Roland

2017-03-01

Currently, a noncomprehensive understanding of the physicochemical properties of carbon-based nanomaterial (CBNs), which may affect toxic effects, is still observable. In this study, an exploratory systematic investigation into the key physicochemical properties of multiwall carbon nanotube (MWCNT), single-wall carbon nanotube (SWCNT), and C60-fullerene on their ecotoxicity has been undertaken. We undertook an extensive survey of the literature pertaining to the ecotoxicity of organism representative of the trophic level of algae, crustaceans, and fish. Based on this, a set of data reporting both the physicochemical properties of carbon-based nanomaterial and the observed toxic effect has been established. The relationship between physicochemical properties and observed toxic effect was investigated based on various statistical approaches. Specifically, analysis of variance by one-way ANOVA was used to assess the effect of categorical properties (use of a dispersant or treatments in the test medium, type of carbon-based nanomaterial, i.e., SWCNT, MWCNT, C60-fullerene, functionalization), while multiple regression analysis was used to assess the effect of quantitative properties (i.e., diameter length of nanotubes, secondary size) on the toxicity values. The here described investigations revealed significant relationships among the physicochemical properties and observed toxic effects. The research was mainly affected by the low availability of data and also by the low variability of the studies collected. Overall, our results demonstrate that the here proposed and applied approach could have a major role in identifying the physicochemical properties of relevance for the toxicity of nanomaterial. However, the future success of the approach would require that the ENMs and the experimental conditions used in the toxicity studies are fully characterized.

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.

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

Long-Term Management Strategy for Dredged Material Disposal for Naval Facilities at Pearl Harbor, Hawaii Phase III - Analysis of Alternatives and Development of an LTMS

DTIC Science & Technology

2000-03-01

are needed to restrict contaminants losses via the leachate and volatilization pathways. Plant uptake testing indicated a potential need to restrict...or control future use of the site, to amend the material with soil additives, to phytoremediate , or to provide a final surface cover of clean...initial release including toxicity and bioaccumulation, effluent, runoff, leachate , plant uptake, upland and aquatic animal uptake, and

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.

Structurally distinct toxicity inhibitors bind at common loci on β-amyloid fibril

PubMed Central

Keshet, Ben; Gray, Jeffrey J; Good, Theresa A

2010-01-01

The accumulation of aggregated β-Amyloid (Aβ) in the brain is a hallmark of Alzheimer's disease and is thought to play a role in the neurotoxicity associated with the disease. The mechanism by which Aβ aggregates induce toxicity is uncertain. Nonetheless, several small molecules have been found to interact with Aβ fibrils and to prevent their toxicity. In this paper we studied the binding of these known toxicity inhibitors to Aβ fibrils, as a means to explore surfaces or loci on Aβ aggregates that may be significant in the mechanism of action of these inhibitors. We believe knowledge of these binding loci will provide insight into surfaces on the Aβ fibrils important in Aβ biological activity. The program DOCK was used to computationally dock the inhibitors to an Aβ fibril. The inhibitors docked at two shared binding loci, near Lys28 and at the C-termini near Asn27 and Val39. The docking predictions were experimentally verified using lysine specific chemical modifications and Aβ fibrils mutated at Asn27. We found that both Congo red and Myricetin, despite being structurally different, bound at the same two sites. Additionally, our data suggests that three additional Aβ toxicity inhibitors may also bind in one of the sites. Identification of these common binding loci provides targets on the Aβ fibril surface that can be tested in the future for their role in Aβ biological activity. PMID:20882638

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

Histological Development of Male Reproductive Organs in Microminipigs.

PubMed

Kangawa, Akihisa; Otake, Masayoshi; Enya, Satoko; Yoshida, Toshinori; Shibata, Masatoshi

2016-12-01

Microminipigs are becoming increasingly attractive alternatives for various experimental applications, such as general toxicology studies, owing to their manageable size. However, there are limited studies on the male reproductive organs of microminipigs, particularly on the histological aspects of sexual maturity. To clarify the development of male reproductive organs, 35 male microminipigs, aged 0 to 12 months, were used in this study. Histological and histomorphological evaluation was performed based on spermatogenic development, measurement of tubular structure in testes and epididymides, and histological progress of accessory glands. In addition, spontaneous testicular changes were quantitatively assessed. Histologically, male microminipigs sexually matured around 4.5 months of age, when spermatogenesis in testes and structural development in genital organs were completed. Spontaneous testicular changes occurred in all the animals investigated. Multinucleated giant cell was most commonly observed, followed by hypospermatogenesis and tubular atrophy/hypoplasia. However, the number of affected tubules was less than 1% in testes after 4.5 months of age, suggesting that the influence of these changes on evaluation of toxicity studies may be minimal. It is preferable to use sexually mature animals in toxicology studies; therefore, the information obtained by the present study will be helpful for future toxicity evaluations in microminipigs.

Gadolinium-Doped Gallic Acid-Zinc/Aluminium-Layered Double Hydroxide/Gold Theranostic Nanoparticles for a Bimodal Magnetic Resonance Imaging and Drug Delivery System

PubMed Central

Sani Usman, Muhammad; Hussein, Mohd Zobir; Fakurazi, Sharida; Ahmad Saad, Fathinul Fikri

2017-01-01

We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO3)3 as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment. PMID:28858229

The chalcone derivative Chana 1 protects against amyloid β peptide-induced oxidative stress and cognitive impairment.

PubMed

Kwak, Jieun; Kim, Mi-Jeong; Choi, Kyung-Chul; Choi, Hyo-Kyung; Jun, Woojin; Park, Hyun-Jin; Lee, Yoo-Hyun; Yoon, Ho-Geun

2012-07-01

Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid β (Aβ)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aβ-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aβ-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aβ-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

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

USGS Publications Warehouse

Elder, J.F.

1989-01-01

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

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

USGS Publications Warehouse

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

2008-01-01

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

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

PubMed

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

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

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.

Use of big data in drug development for precision medicine

PubMed Central

Kim, Rosa S.; Goossens, Nicolas; Hoshida, Yujin

2016-01-01

Summary Drug development has been a costly and lengthy process with an extremely low success rate and lack of consideration of individual diversity in drug response and toxicity. Over the past decade, an alternative “big data” approach has been expanding at an unprecedented pace based on the development of electronic databases of chemical substances, disease gene/protein targets, functional readouts, and clinical information covering inter-individual genetic variations and toxicities. This paradigm shift has enabled systematic, high-throughput, and accelerated identification of novel drugs or repurposed indications of existing drugs for pathogenic molecular aberrations specifically present in each individual patient. The exploding interest from the information technology and direct-to-consumer genetic testing industries has been further facilitating the use of big data to achieve personalized Precision Medicine. Here we overview currently available resources and discuss future prospects. PMID:27430024

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.

Assessment of Chemical Impact of Invasive Bryozoan Pectinatella magnifica on the Environment: Cytotoxicity and Antimicrobial Activity of P. magnifica Extracts.

PubMed

Kollar, Peter; Šmejkal, Karel; Salmonová, Hana; Vlková, Eva; Lepšová-Skácelová, Olga; Balounová, Zuzana; Rajchard, Josef; Cvačka, Josef; Jaša, Libor; Babica, Pavel; Pazourek, Jiří

2016-11-04

Pectinatella magnifica , an invasive bryozoan, might significantly affect ecosystem balance due to its massive occurrence in many areas in Europe and other parts of the world. Biological and chemical analyses are needed to get complete information about the impact of the animal on the environment. In this paper, we aimed to evaluate in vitro cytotoxic effects of five extracts prepared from P. magnifica using LDH assay on THP-1 cell line. Antimicrobial activities of extracts against 22 different bacterial strains were tested by microdilution method. Our study showed that all extracts tested, except aqueous portion, demonstrated LD 50 values below 100 μg/mL, which indicates potential toxicity. The water extract of P. magnifica with LD 50 value of 250 μg/mL also shows potentially harmful effects. Also, an environmental risk resulting from the presence and increasing biomass of potentially toxic benthic cyanobacteria in old colonies should not be underestimated. Toxicity of Pectinatella extracts could be partially caused by presence of Aeromonas species in material, since we found members of these genera as most abundant bacteria associated with P. magnifica . Furthermore, P. magnifica seems to be a promising source of certain antimicrobial agents. Its methanolic extract, hexane, and chloroform fractions possessed selective inhibitory effect on some potential pathogens and food spoiling bacteria in the range of MIC 0.5-10 mg/mL. Future effort should be made to isolate and characterize the content compounds derived from P. magnifica , which could help to identify the substance(s) responsible for the toxic effects of P. magnifica extracts.

Toxicity characterization of urban stormwater with bioanalytical tools.

PubMed

Tang, Janet Y M; Aryal, Rupak; Deletic, Ana; Gernjak, Wolfgang; Glenn, Eva; McCarthy, David; Escher, Beate I

2013-10-01

Stormwater harvesting has become an attractive alternative strategy to address the rising demand for urban water supply due to limited water sources and population growth. Nevertheless, urban stormwater is also a major source of surface water pollution. Runoff from different urban catchments with source contributions from anthropogenic activities and various land uses causes variable contaminant profiles, thus posing a challenging task for environmental monitoring and risk assessment. A thorough understanding of raw stormwater quality is essential to develop appropriate treatment facilities for potential indirect potable reuse of stormwater. While some of the key chemical components have previously been characterized, only scarce data are available on stormwater toxicity. We benchmarked stormwater samples from urban, residential and industrial sites across various Australian capital cities against samples from the entire water cycle, from sewage to drinking water. Six biological endpoints, targeting groups of chemicals with modes of toxic action of particular relevance for human and environmental health, were investigated: non-specific toxicity (Microtox and combined algae test), the specific modes of action of phytotoxicity (combined algae test), dioxin-like activity (AhR-CAFLUX), and estrogenicity (E-SCREEN), as well as reactive toxicity encompassing genotoxicity (umuC) and oxidative stress (AREc32). Non-specific toxicity was highly variable across sites. The baseline toxicity equivalent concentrations of the most polluted samples were similar to secondary treated effluent from wastewater treatment plants. Phytotoxicity results correlated well with the measured herbicide concentrations at all sites. High estrogenicity was found in two sampling events and could be related to sewage overflow. Genotoxicity, dioxin-like activity, and oxidative stress response were evident in only three of the samples where the stormwater drain was beside a heavy traffic road, confirming that road runoff is the potential source of contaminants, while the bioanalytical equivalent concentrations (BEQ) of these samples were similar to those of raw sewage. This study demonstrates the benefit of bioanalytical tools for screening-level stormwater quality assessment, forming the basis for the evaluation of future stormwater treatment and reuse schemes. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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

Antinociceptive and anticonvulsant effects of the monoterpene linalool oxide.

PubMed

Souto-Maior, Flávia Negromonte; Fonsêca, Diogo Vilar da; Salgado, Paula Regina Rodrigues; Monte, Lucas de Oliveira; de Sousa, Damião Pergentino; de Almeida, Reinaldo Nóbrega

2017-12-01

Linalool oxide (OXL) (a monoterpene) is found in the essential oils of certain aromatic plants, or it is derived from linalool. The motivation for this work is the lack of psychopharmacological studies on this substance. To evaluate OXL's acute toxicity, along with its anticonvulsant and antinociceptive activities in male Swiss mice. OXL (50, 100 and 150 mg/kg, i.p.) was investigated for acute toxicity and in the Rota-rod test. Antinociceptive activity was evaluated by the acetic acid-induced writhing test, and by formalin testing. Anticonvulsant effects were demonstrated by testing for pentylenetetrazol (PTZ)-induced seizures and by Maximum Electroshock headset (MES) test. OXL was administered to the animals intraperitoneally 30 min before for pharmacological tests. OXL showed an LD 50 of ∼721 (681-765) mg/kg. In the Rota-rod test, it was observed that OXL caused no damage to the animal's motor coordination. OXL significantly reduced (p < .001) the number of writhings. OXL also significantly decreased (p < .05, p < .01 or p < .001) paw-licking time in the two phases of the formalin test. OXL significantly reduced (p < .01 or p < .001) the duration of tonic seizures in the MES test, and at the dose 150 mg/kg, significantly increased (p < .01) the latency to first seizure in the PTZ test. The tested doses of OXL were safe, with no motor impairment, and show clear antinociceptive and anticonvulsant potential. Future investigations with this monoterpene may lead to the development of a new molecule with even higher potency and selectivity.

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.

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.

Systematic Review of Radiation Therapy Toxicity Reporting in Randomized Controlled Trials of Rectal Cancer: A Comparison of Patient-Reported Outcomes and Clinician Toxicity Reporting

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

Gilbert, Alexandra, E-mail: a.gilbert@leeds.ac.uk; Ziegler, Lucy; Martland, Maisie

The use of multimodal treatments for rectal cancer has improved cancer-related outcomes but makes monitoring toxicity challenging. Optimizing future radiation therapy regimens requires collection and publication of detailed toxicity data. This review evaluated the quality of toxicity information provided in randomized controlled trials (RCTs) of radiation therapy in rectal cancer and focused on the difference between clinician-reported and patient-reported toxicity. Medline, EMBASE, and the Cochrane Library were searched (January 1995-July 2013) for RCTs reporting late toxicity in patients treated with regimens including preoperative (chemo)radiation therapy. Data on toxicity measures and information on toxicity reported were extracted using Quantitative Analyses ofmore » Normal Tissue Effects in the Clinic recommendations. International Society for Quality of Life Research standards on patient-reported outcomes (PROs) were used to evaluate the quality of patient-reported toxicity. Twenty-one RCT publications met inclusion criteria out of 4144 articles screened. All PRO studies reported higher rates of toxicity symptoms than clinician-reported studies and reported on a wider range and milder symptoms. No clinician-reported study published data on sexual dysfunction. Of the clinician-reported studies, 55% grouped toxicity data related to an organ system together (eg “Bowel”), and 45% presented data only on more-severe (grade ≥3) toxicity. In comparison, all toxicity grades were reported in 79% of PRO publications, and all studies (100%) presented individual symptom toxicity data (eg bowel urgency). However, PRO reporting quality was variable. Only 43% of PRO studies presented baseline data, 28% did not use any psychometrically validated instruments, and only 29% of studies described statistical methods for managing missing data. Analysis of these trials highlights the lack of reporting standards for adverse events and reveals the differences between clinician and patient reporting of toxicity. Recommendations for improving the quality of adverse event data collection are provided, with the aim of improving critical appraisal of outcomes for future studies.« less

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.

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.

Tier 3 Toxicity Value White Paper

EPA Pesticide Factsheets

The purpose of this white paper is to articulate the issues pertaining to Tier 3 toxicity values and provide recommendations on processes that will improve the transparency and consistency of identifying, evaluating, selecting, and documenting Tier 3 toxicity values for use in the Superfund and Resource Conservation and Recovery Act (RCRA) programs. This white paper will be used to assist regional risk assessors in selecting Tier 3 toxicity values as well as provide the foundation for future regional and national efforts to improve guidance and policy on Tier 3 toxicity values.

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.

Comparing terpenes from plant essential oils as pesticides for the poultry red mite (Dermanyssus gallinae).

PubMed

Sparagano, O; Khallaayoune, K; Duvallet, G; Nayak, S; George, D

2013-11-01

Resistance to conventional synthetic pesticides has been widely reported in ticks, parasitic mites and other pests of veterinary and medical significance. New and novel approaches to manage these pests are therefore needed to ensure efficient control programmes that can be implemented now and in the future. Recent research in this area has focused on the pesticidal potential of plant essential oils. These products are attractive as pesticide candidates on the grounds of low mammalian toxicity, short environmental persistence and complex chemistries (limiting the development of pest resistance against them). Although issues may exist concerning reliability in efficacy of essential oils, these may be overcome by identifying and developing bioactive oil components for use in pest management. In the current work, three such components (terpenes) found in essential oils (eugenol, geraniol and citral) were tested against the poultry red mite Dermanyssus gallinae. All provided 100% mortality in toxicity tests when undiluted. Even at 1% of this dose, eugenol was 20% effective against experimental pest populations, although the remaining terpenes were largely ineffective at this concentration. © 2013 Blackwell Verlag GmbH.

Chitosan doped with nanoparticles of copper, nickel and cobalt.

PubMed

Cárdenas-Triviño, Galo; Elgueta, Carolina; Vergara, Luis; Ojeda, Javier; Valenzuela, Ariel; Cruzat, Christian

2017-11-01

Metal colloids in 2 propanol using nanoparticles (NPs) of copper, nickel and cobalt were prepared by Chemical Liquid Deposition (CLD) method. The resulting colloidal dispersions were characterized by Transmission Electron Microscopy (TEM). The colloids were supported in chitosan. Then, microbiological assays were performed using E. coli and S. aureus in order to determine the bactericide/bacteriostatic activity of nanoparticles (NPs) trapped or chelated with chitosan. Finally, the toxicity of the metal colloids Cu, Ni and Co was tested. Bio-assays were conducted in three different animal species. First of all on earth warms (Eisenia foetida) to evaluate the toxicity and the biocompatibility of chitosan in lactic acid (1% and 0.5%). Secondly bio-assay done in fishes (rainbow trout), the liver toxicity of NPs in vivo was evaluated. Finally, a bio-assay was conducted in Sprange-Dawley rats of 100g weight, which were injected intraperitoneally with different solutions of chitosan metal colloids. Then, the minimum and maximum concentration were determined for copper, nickel and cobalt. The purpose of the use of chitosan was acting as a carrier for some magnetic NPs, which toxicity would allow to obtain new polymeric materials with potential applications as magnet future drugs carrier. Copyright © 2017 Elsevier B.V. All rights reserved.

Derivation of freshwater quality criteria for zinc using interspecies correlation estimation models to protect aquatic life in China.

PubMed

Feng, C L; Wu, F C; Dyer, S D; Chang, H; Zhao, X L

2013-01-01

Species sensitivity distributions (SSDs) are usually used in the development of water quality criteria and require a large number of toxicity values to define a hazard level to protect the majority of species. However, some toxicity data for certain chemicals are limited, especially for endangered and threatened species. Thus, it is important to predict the unknown species toxicity data using available toxicity data. To address this need, interspecies correlation estimation (ICE) models were developed by US EPA to predict acute toxicity of chemicals to diverse species based on a more limited data set of surrogate species toxicity data. Use of SSDs generated from ICE models allows for the prediction of protective water quality criteria, such as the HC5 (hazard concentration, 5th percentile). In the present study, we tested this concept using toxicity data collected for zinc. ICE-based-SSDs were generated using three surrogate species (common carp (Cyprinus carpio), rainbow trout (Oncorhynchus mykiss), and Daphnia magna) and compared with the measured-based SSD and corresponding HC5. The results showed that no significant differences were observed between the ICE- and the measured-based SSDs and HC5s. Furthermore, the examination of species placements within the SSDs indicated that the most sensitive species to zinc were invertebrates, especially crustaceans. Given the similarity of SSD and HC5s for zinc, the use of ICE to derive potential water quality criteria for diverse chemicals in China is proposed. Further, a combination of measured and ICE-derived data will prove useful for assessing water quality and chemical risks in the near future. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

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

2010-01-01

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

Insights into influencing factor, degradation mechanism and potential toxicity involved in aqueous ozonation of oxcarbazepine (CHEM46939R1).

PubMed

Wang, Tao; Huang, Zhen-Xing; Miao, Heng-Feng; Ruan, Wen-Quan; Ji, Xiao-Ping; Sun, Fu-Bao; Zhao, Ming-Xing; Ren, Hong-Yan

2018-06-01

Oxcarbazepine (OXC), as a potent antiepileptic drug, is widely used in recent years, but its residue is potentially harmful to the environment. Although ozonation is a high-efficient technology for chemical oxidation during water treatment, it cannot completely mineralize organic matters, but partially transforms them into some unidentified by-products. In order to provide more insight into OXC ozonation process, the influencing factor, transformation mechanism and potential toxicity were comprehensively investigated in this study. The results showed that the optimal ozonation temperature was 20 °C with a pseudo-first-order reaction rate constant of 0.161 min -1 . The increase of pH significantly enhanced OXC degradation, while the presence of bicarbonate caused a remarkable negative effect, manifesting that hydroxyl radical (OH) oxidation should play an important role in OXC ozonation. Moreover, transformation mechanism was further elucidated based on the identification of ten OXC-related by-products using UPLC-Q-TOF-MS n , which mainly consisted of electrophilic substitution, N-heterocyclic ring cleavage and re-arrangement, hydroxylation, carbonylation, demethoxylation and deamidation, etc. The toxicity evaluation, using US Environmental Protection Agency Toxicity Estimation Software Tool (US-EPA TEST), suggested that most identified by-products were probably more toxic than OXC itself. Besides, further experiments, by measuring inhibitory effect of ozonated mixture on Vibrio fischeri bioluminescence, demonstrated that by-products with higher toxicity tended to be accumulated under a short reaction time. Taken together, the present investigation provided valuable information for further understanding OXC ozonation process, and suggested that special attention should be paid to the control and elimination of toxic transformation by-products in future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Toxicity of silver and gold nanoparticles on marine microalgae.

PubMed

Moreno-Garrido, Ignacio; Pérez, Sara; Blasco, Julián

2015-10-01

The increased use of nanomaterials in several novel industrial applications during the last decade has led to a rise in concerns about the potential toxic effects of released engineered nanoparticles (NPs) into the environment, as their potential toxicity to aquatic organisms is just beginning to be recognised. Toxicity of metallic nanoparticles to aquatic organisms, including microalgae, seems to be related to their physical and chemical properties, as well as their behaviour in the aquatic media where processes of dissolution, aggregation and agglomeration can occur. Although the production of these particles has increased considerably in recent years, data on their toxicity on microalgae, especially those belonging to marine or estuarine environments remain scarce and scattered. The literature shows a wide variation of results on toxicity, mainly due to the different methodology used in bioassays involving microalgae. These can range for up to EC50 data, in the case of AgNPs, representing five orders of magnitude. The importance of initial cellular density is also addressed in the text, as well as the need for keeping test conditions as close as possible to environmental conditions, in order to increase their environmental relevance. This review focuses on the fate and toxicity of silver, gold, and gold-silver alloy nanoparticles on microalgae, as key organisms in aquatic ecosystems. It is prompted by their increased production and use, and taking into account that oceans and estuaries are the final sink for those NPs. The design of bioassays and further research in the field of microalgae nanoecotoxicology is discussed, with a brief survey on newly developed technology of green (algae mediated) production of Ag, Au and Ag-Au bimetallic NPs, as well as some final considerations about future research on this field. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells.

PubMed

Kogel, U; Gonzalez Suarez, I; Xiang, Y; Dossin, E; Guy, P A; Mathis, C; Marescotti, D; Goedertier, D; Martin, F; Peitsch, M C; Hoeng, J

2015-12-01

Cigarette smoking causes serious and fatal diseases. The best way for smokers to avoid health risks is to quit smoking. Using modified risk tobacco products (MRTPs) may be an alternative to reduce the harm caused for those who are unwilling to quit smoking, but little is known about the toxic effects of MRTPs, nor were the molecular mechanisms of toxicity investigated in detail. The toxicity of an MRTP and the potential molecular mechanisms involved were investigated in high-content screening tests and whole genome transcriptomics analyses using human bronchial epithelial cells. The prototypic (p)MRTP that was tested had less impact than reference cigarette 3R4F on the cellular oxidative stress response and cell death pathways. Higher pMRTP aerosol extract concentrations had impact on pathways associated with the detoxification of xenobiotics and the reduction of oxidative damage. A pMRTP aerosol concentration up to 18 times higher than the 3R4F caused similar perturbation effects in biological networks and led to the perturbation of networks related to cell stress, and proliferation biology. These results may further facilitate the development of a systems toxicology-based impact assessment for use in future risk assessments in line with the 21st century toxicology paradigm, as shown here for an MRTP. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Linking mode of action of the model respiratory and photosynthesis uncoupler 3,5-dichlorophenol to adverse outcomes in Lemna minor.

PubMed

Xie, Li; Gomes, Tânia; Solhaug, Knut Asbjørn; Song, You; Tollefsen, Knut Erik

2018-04-01

Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers. The results demonstrated that 3,5-DCP caused concentration-dependent effects in chloroplasts and mitochondria. Uncoupling of oxidative phosphorylation (OXPHOS), reduction in chlorophyll (Chlorophyll a and b) content, reproduction rate and frond size were the most sensitive endpoints, followed by formation of reactive oxygen species (ROS), lipid peroxidation (LPO), reduction of carotenoid content and impairment of photosynthesis efficiency. Suppression of photosystem II (PSII) efficiency, electron transport rate (ETR), chlorophyll (a and b) contents and oxidative phosphorylation (OXPHOS) were closely correlated while ROS production and LPO were negative correlated with ETR, carotenoid content and growth parameters. A network of conceptual Adverse Outcome Pathways (AOPs) was developed to decipher the causal relationships between molecular, cellular, and apical adverse effects occurring in L. minor to form a basis for future studies with similar compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

Preclinical Biosafety Evaluation of Genetically Modified Human Adipose Tissue-Derived Mesenchymal Stem Cells for Clinical Applications to Brainstem Glioma.

PubMed

Choi, Seung Ah; Yun, Jun-Won; Joo, Kyeung Min; Lee, Ji Yeoun; Kwak, Pil Ae; Lee, Young Eun; You, Ji-Ran; Kwon, Euna; Kim, Woo Ho; Wang, Kyu-Chang; Phi, Ji Hoon; Kang, Byeong-Cheol; Kim, Seung-Ki

2016-06-15

Stem-cell based gene therapy is a promising novel therapeutic approach for inoperable invasive tumors, including brainstem glioma. Previously, we demonstrated the therapeutic potential of human adipose tissue-derived mesenchymal stem cells (hAT-MSC) genetically engineered to express a secreted form of tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) against brainstem glioma. However, safety concerns should be comprehensively investigated before clinical applications of hAT-MSC.sTRAIL. At first, we injected stereotactically low (1.2 × 10(5) cells/18 μL), medium (2.4 × 10(5)/18 μL), or high dose (3.6 × 10(5)/18 μL) of hAT-MSC.sTRAIL into the brainstems of immunodeficient mice reflecting the plan of the future clinical trial. Local toxicity, systemic toxicity, secondary tumor formation, and biodistribution of hAT-MSC.sTRAIL were investigated. Next, presence of hAT-MSC.sTRAIL was confirmed in the brain and major organs at 4, 9, and 14 weeks in brainstem glioma-bearing mice. In the 15-week subchronic toxicity test, no serious adverse events in terms of body weight, food consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology were observed. In the 26-week tumorigenicity test, hAT-MSC.sTRAIL made no detectable tumors, whereas positive control U-87 MG cells made huge tumors in the brainstem. No remaining hAT-MSC.sTRAIL was observed in any organs examined, including the brainstem at 15 or 26 weeks. In brainstem glioma-bearing mice, injected hAT-MSC.sTRAIL was observed, but gradually decreased over time in the brain. The mRNA of human specific GAPDH and TRAIL was not detected in all major organs. These results indicate that the hAT-MSC.sTRAIL could be applicable to the future clinical trials in terms of biosafety.

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

The Dynamics of Microcystis Genotypes and Microcystin Production and Associations with Environmental Factors during Blooms in Lake Chaohu, China

PubMed Central

Yu, Li; Kong, Fanxiang; Zhang, Min; Yang, Zhen; Shi, Xiaoli; Du, Mingyong

2014-01-01

Lake Chaohu, which is a large, shallow, hypertrophic freshwater lake in southeastern China, has been experiencing lake-wide toxic Microcystis blooms in recent decades. To illuminate the relationships between microcystin (MC) production, the genotypic composition of the Microcystis community and environmental factors, water samples and associated environmental data were collected from June to October 2012 within Lake Chaohu. The Microcystis genotypes and MC concentrations were quantified using quantitative real-time PCR (qPCR) and HPLC, respectively. The results showed that the abundances of Microcystis genotypes and MC concentrations varied on spatial and temporal scales. Microcystis exists as a mixed population of toxic and non-toxic genotypes, and the proportion of toxic Microcystis genotypes ranged from 9.43% to 87.98%. Both Pearson correlation and stepwise multiple regressions demonstrated that throughout the entire lake, the abundances of total and toxic Microcystis and MC concentrations showed significant positive correlation with the total phosphorus and water temperature, suggesting that increases in temperature together with the phosphorus concentrations may promote more frequent toxic Microcystis blooms and higher concentrations of MC. Whereas, dissolved inorganic carbon (DIC) was negatively correlated with the abundances of total and toxic Microcystis and MC concentrations, indicating that rising DIC concentrations may suppress toxic Microcystis abundance and reduce the MC concentrations in the future. Therefore, our results highlight the fact that future eutrophication and global climate change can affect the dynamics of toxic Microcystis blooms and hence change the MC levels in freshwater. PMID:25474494

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective

PubMed Central

Chen, Guoli; Yang, Zhaohai; Eshleman, James R.; Netto, George J.

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional “one test-one drug” assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC. PMID:27699178

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

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.

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

Alternative models in developmental toxicology.

PubMed

Lee, Hyung-yul; Inselman, Amy L; Kanungo, Jyotshnabala; Hansen, Deborah K

2012-02-01

In light of various pressures, toxicologists have been searching for alternative methods for safety testing of chemicals. According to a recent policy in the European Union (Regulation, Evaluation Authorisation and Restriction of Chemicals, REACH), it has been estimated that over the next twelve to fifteen years, approximately 30,000 chemicals may need to be tested for safety, and under current guidelines such testing would require the use of approximately 7.2 million laboratory animals [ Hofer et al. 2004 ]. It has also been estimated that over 80% of all animals used for safety testing under REACH legislation would be used for examining reproductive and developmental toxicity [Hofer et al., 2004]. In addition to REACH initiatives, it has been estimated that out of 5,000 to 10,000 new drug entities that a pharmaceutical company may start with, only one is finally approved by the Food and Drug Administration at a cost of over one billion dollars [ Garg et al. 2011 ]. A large portion of this cost is due to animal testing. Therefore, both the pharmaceutical and chemical industries are interested in using alternative models and in vitro tests for safety testing. This review will examine the current state of three alternative models - whole embryo culture (WEC), the mouse embryonic stem cell test (mEST), and zebrafish. Each of these alternatives will be reviewed, and advantages and disadvantages of each model will be discussed. These models were chosen because they are the models most commonly used and would appear to have the greatest potential for future applications in developmental toxicity screening and testing.

In Vitro Developmental Toxicology Screens: A Report on the Progress of the Methodology and Future Applications.

PubMed

Zhang, Cindy; Ball, Jonathan; Panzica-Kelly, Julie; Augustine-Rauch, Karen

2016-04-18

There has been increasing focus on generation and assessment of in vitro developmental toxicology models for assessing teratogenic liability of chemicals. The driver for this focus has been to find reliable in vitro assays that will reduce or replace the use of in vivo tests for assessing teratogenicity. Such efforts may be eventually applied in testing pharmaceutical agents where a developmental toxicology assay or battery of assays may be incorporated into regulatory testing to replace one of the two species currently used in teratogenic assessment. Such assays may be eventually applied in testing a broader spectrum of chemicals, supporting efforts aligned with Tox21 strategies and responding to REACH legislation. This review describes the developmental toxicology assays that are of focus in these assessments: rodent whole embryo culture, zebrafish embryo assays, and embryonic stem cell assays. Progress on assay development as well as future directions of how these assays are envisioned to be applied for broader safety testing of chemicals are discussed. Altogether, the developmental model systems described in this review provide rich biological systems that can be utilized in better understanding teratogenic mechanisms of action of chemotypes and are promising in providing proactive safety assessment related to developmental toxicity. Continual advancements in refining/optimizing these in vitro assays are anticipated to provide a robust data set to provide thoughtful assessment of how whole animal teratogenicity evaluations can be reduced/refined in the future.

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.

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...

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.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

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 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.

Emerging approaches in predictive toxicology.

PubMed

Zhang, Luoping; McHale, Cliona M; Greene, Nigel; Snyder, Ronald D; Rich, Ivan N; Aardema, Marilyn J; Roy, Shambhu; Pfuhler, Stefan; Venkatactahalam, Sundaresan

2014-12-01

Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well-established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high-throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high-throughput analysis. The advantages of three-dimensional model systems and stem cells and their use in predictive toxicology testing are also described. © 2014 Wiley Periodicals, Inc.

Single-walled carbon nanotube, multi-walled carbon nanotube and Fe2O3 nanoparticles induced mitochondria mediated apoptosis in melanoma cells.

PubMed

Naserzadeh, Parvaneh; Ansari Esfeh, Fatemeh; Kaviani, Mahboubeh; Ashtari, Khadijeh; Kheirbakhsh, Raheleh; Salimi, Ahmad; Pourahmad, Jalal

2018-06-01

Nanomaterials (NM) exhibit novel anticancer properties. The toxicity of three nanoparticles that are currently being produced in high tonnage including single-walled carbon nanotube (SWCNT), multi-walled carbon nanotube (MWCNT) and Fe 2 O 3 nanoparticles, were compared with normal and melanoma cells. All tested nanoparticles induced selective toxicity and caspase 3 activation through mitochondria pathway in melanoma cells and mitochondria cause the generating of reactive oxygen species (ROS), mitochondrial membrane potential decline (MMP collapse), mitochondria swelling, and cytochrome c release. The pretreatment of butylated hydroxytoluene (BHT), a cell-permeable antioxidant and cyclosporine A (Cs. A), a mitochondrial permeability transition (MPT), pore sealing agent decreased cytotoxicity, caspase 3 activation, ROS generation, and mitochondrial damages induced by SWCNT, MWCNT, and IONPs. Our promising results provide a potential approach for the future therapeutic use of SWCNT, MWCNT, and IONPs in melanoma through mitochondrial targeting.

Emerging Approaches in Predictive Toxicology

PubMed Central

Zhang, Luoping; McHale, Cliona M.; Greene, Nigel; Snyder, Ronald D.; Rich, Ivan N.; Aardema, Marilyn J.; Roy, Shambhu; Pfuhler, Stefan; Venkatactahalam, Sundaresan

2016-01-01

Predictive toxicology plays an important role in the assessment of toxicity of chemicals and the drug development process. While there are several well-established in vitro and in vivo assays that are suitable for predictive toxicology, recent advances in high-throughput analytical technologies and model systems are expected to have a major impact on the field of predictive toxicology. This commentary provides an overview of the state of the current science and a brief discussion on future perspectives for the field of predictive toxicology for human toxicity. Computational models for predictive toxicology, needs for further refinement and obstacles to expand computational models to include additional classes of chemical compounds are highlighted. Functional and comparative genomics approaches in predictive toxicology are discussed with an emphasis on successful utilization of recently developed model systems for high-throughput analysis. The advantages of three-dimensional model systems and stem cells and their use in predictive toxicology testing are also described. PMID:25044351

Structurally distinct toxicity inhibitors bind at common loci on β-amyloid fibril.

PubMed

Keshet, Ben; Gray, Jeffrey J; Good, Theresa A

2010-12-01

The accumulation of aggregated β-Amyloid (Aβ) in the brain is a hallmark of Alzheimer's disease and is thought to play a role in the neurotoxicity associated with the disease. The mechanism by which Aβ aggregates induce toxicity is uncertain. Nonetheless, several small molecules have been found to interact with Aβ fibrils and to prevent their toxicity. In this paper we studied the binding of these known toxicity inhibitors to Aβ fibrils, as a means to explore surfaces or loci on Aβ aggregates that may be significant in the mechanism of action of these inhibitors. We believe knowledge of these binding loci will provide insight into surfaces on the Aβ fibrils important in Aβ biological activity. The program DOCK was used to computationally dock the inhibitors to an Aβ fibril. The inhibitors docked at two shared binding loci, near Lys28 and at the C-termini near Asn27 and Val39. The docking predictions were experimentally verified using lysine specific chemical modifications and Aβ fibrils mutated at Asn27. We found that both Congo red and Myricetin, despite being structurally different, bound at the same two sites. Additionally, our data suggests that three additional Aβ toxicity inhibitors may also bind in one of the sites. Identification of these common binding loci provides targets on the Aβ fibril surface that can be tested in the future for their role in Aβ biological activity. Copyright © 2010 The Protein Society.

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

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.

Benzo[a]pyrene exposure under future ocean acidification scenarios weakens the immune responses of blood clam, Tegillarca granosa.

PubMed

Su, Wenhao; Zha, Shanjie; Wang, Yichen; Shi, Wei; Xiao, Guoqiang; Chai, Xueliang; Wu, Hongxi; Liu, Guangxu

2017-04-01

Persistent organic pollutants (POPs) are known to converge into the ocean and accumulate in the sediment, posing great threats to marine organisms such as the sessile bottom burrowing bivalves. However, the immune toxicity of POPs, such as B[a]P, under future ocean acidification scenarios remains poorly understood to date. Therefore, in the present study, the impacts of B[a]P exposure on the immune responses of a bivalve species, Tegillarca granosa, under present and future ocean acidification scenarios were investigated. Results obtained revealed an increased immune toxicity of B[a]P under future ocean acidification scenarios in terms of reduced THC, altered haemocyte composition, and hampered phagocytosis, which may attribute to the synergetic effects of B[a]P and ocean acidification. In addition, the gene expressions of pathogen pattern recognition receptors (TLR1, TLR2, TLR4, TLR6), pathway mediators (TRAF6, TAK1, TAB2, IKKα and Myd88), and effectors (NF-ĸB) of the important immune related pathways were significantly down-regulated upon exposure to B[a]P under future ocean acidification scenarios. Results of the present study suggested an increased immune toxicity of B[a]P under future ocean acidification scenarios, which will significantly hamper the immune responses of T. granosa and subsequently render individuals more susceptible to pathogens challenges. Copyright © 2017 Elsevier Ltd. 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.

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 ...

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

Approaches to evaluating the toxicity and carcinogenicity of man-made fibers: summary of a workshop held November 11-13, 1991, Durham, North Carolina.

PubMed

McClellan, R O; Miller, F J; Hesterberg, T W; Warheit, D B; Bunn, W B; Kane, A B; Lippmann, M; Mast, R W; McConnell, E E; Reinhardt, C F

1992-12-01

The Workshop on Approaches to Evaluating the Toxicity and Carcinogenicity of Man-Made Fibers (MMF) was held in Durham, North Carolina, on November 11-13, 1991. The goal of the workshop was to reach a consensus, or to determine the extent to which a consensus existed, in two areas. Participants were asked to identify scientifically sound approaches for evaluating the toxicity and carcinogenicity of man-made fibers based on today's science and to determine research appropriate for study during the next 5 years that can provide an improved scientific basis for future revisions of approaches used to evaluate man-made fiber toxicity and carcinogenicity. During the first day, a series of "state of knowledge" presentations were made to provide all participants with a common data base from which to interact and discuss scientific issues. The workshop participants were assigned to one of four discussion groups, which met separately in three half-day sessions following the first day of presentations. All groups discussed the same topics: exposure assessment, hazard identification, and dose-response information needed to integrate to characterize risk in the first session; approaches to obtaining the needed information in the second session; and recommended approaches and guidelines for evaluating the toxicity and carcinogenicity of MMF and research needs in the third session. The workshop participants reconvened as a whole after each discussion session, and one member from each group reported the group's conclusions. A closure period was also included at the end of the workshop for review and discussion of items that had been considered during the workshop. The primary conclusions reached were the following: -All fiber types capable of depositing in the thorax are not alike in their pathogenic potential. -Only fiber samples with dimensions similar to those to which humans can inhale should be tested. -A complete characterization (i.e., dimensions, fiber number, mass, and aerodynamic diameter) of the fiber aerosol and retained dose is essential. -Appropriate aerosol generation methods must be used for inhalation studies in order to preserve fiber lengths. -A tiered approach to toxicity evaluation is recommended that includes: 1. In vitro screening for durability, surface properties, cytotoxicity, and similar properties, etc; 2. Short-term inhalation or other in vivo studies; 3. That chronic inhalation studies are the "gold standard" (i.e., provide most appropriate data for risk characterization). -The rat is the most appropriate species for inhalation studies. -In chronic inhalation studies, animals should be retained to at least 20% survival after 2-year exposure. -Serial lung burden analyses are an essential component of inhalation studies and are essential for understanding exposure-dose-response relationships. -Studies oriented to understanding mechanisms of toxicity and carcinogenicity are important adjuncts to traditional toxicity studies. -Histopathological analyses of tissues of the respiratory tract represent primary endpoints for evaluating effects of inhaled fibers. Major effects include pulmonary fibrosis, lung tumors, and mesotheliomas. Experimental tissues should be archived for future studies; wherever possible, handling and preservation of tissues should be done in a way that maximizes their future use in mechanistic studies. -Potential human exposures throughout the entire life-cycle of the fiber must be considered and fibrous material for toxicologic studies prepared accordingly. -Intracavity studies are inappropriate for risk characterization but can play a useful screening role in assessing fiber toxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

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

Impact of globalization under the ICH guidelines on the conduct of reproductive toxicity studies--report on current status in Japan, Europe and the U.S. by questionnaire survey.

PubMed

Mineshima, Hiroshi; Endo, Yoshihiko; Ogasawara, Hiroyuki; Nishigaki, Keiji; Numa, Toshiaki; Hirano, Fumiya; Matsuzawa, Toshiaki

2004-08-01

We surveyed interpretation of the ICH guidelines concerning reproductive toxicology. Valid responses were obtained from Japan (JPN), Europe (EUR) and the U.S. The results obtained were compared to those at the time of a previous survey targeted at JPN facilities in 1995-1996 as well as compared among all three regions. Compared to the previous survey in Japan, the number of facilities performing toxicokinetics (TK) in rats has slightly increased. This result was considered to represent changes of attitude toward TK in reproductive toxicity studies. Differences in interpretation of the guidelines between JPN, EUR and the US were widely seen. Clear differences were noted in sperm examinations, postnatal tests, fetal examinations, some examinations for F1 animals after culling and TK. Researchers in the West seemed to be interpreting the ICH guidelines more flexibly from the scientific point of view. JPN researchers appeared to interpret the guidelines, including notes, as rigid requirements. Most of the parts which produced different interpretations were the notes in the guidelines. The force of mention in the notes should be defined in the future. In addition, there were doubts about some parts, including notes, which had been found to have become unsuitable for the implementation of studies because of scientific progress or from long experience in using the guidelines. Therefore, updates of the guidelines may be needed in the future as well as the remedy of interpretation by JPN researchers. In JPN, the number of reproductive toxicity studies has decreased. The scanty experience in JPN therefore raises apprehension of appropriate selection and stagnating development of methodology, and might hinder the maintenance of the guidelines. In the future, the cooperation of CROs as well as global collaboration will be essential not only to scientific developments of reproductive toxicology but also updates of the guidelines.

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.

Candida lipolytica UCP0988 Biosurfactant: Potential as a Bioremediation Agent and in Formulating a Commercial Related Product

PubMed Central

Santos, Danyelle K. F.; Resende, Ana H. M.; de Almeida, Darne G.; Soares da Silva, Rita de Cássia F.; Rufino, Raquel D.; Luna, Juliana M.; Banat, Ibrahim M.; Sarubbo, Leonie A.

2017-01-01

The aim of the present study was to investigate the potential application of the biosurfactant from Candida lipolytica grown in low-cost substrates, which has previously been produced and characterized under optimized conditions as an adjunct material to enhance the remediation processes of hydrophobic pollutants and heavy metals generated by the oil industry and propose the formulation of a safe and stable remediation agent. In tests carried out with seawater, the crude biosurfactant demonstrated 80% oil spreading efficiency. The dispersion rate was 50% for the biosurfactant at a concentration twice that of the CMC. The biosurfactant removed 70% of motor oil from contaminated cotton cloth in detergency tests. The crude biosurfactant also removed 30–40% of Cu and Pb from standard sand, while the isolated biosurfactant removed ~30% of the heavy metals. The conductivity of solutions containing Cd and Pb was sharply reduced after biosurfactants' addition. A product was prepared through adding 0.2% potassium sorbate as preservative and tested over 120 days. The formulated biosurfactant was analyzed for emulsification and surface tension under different pH values, temperatures, and salt concentrations and tested for toxicity against the fish Poecilia vivipara. The results showed that the formulation had no toxicity and did not cause significant changes in the tensoactive capacity of the biomolecule while maintaining activity demonstrating suitability for potential future commercial product formulation. PMID:28507538

Toxic Emissions from a Military Test Site in the Territory of Sardinia, Italy

PubMed Central

Cristaldi, Mauro; Foschi, Cristiano; Szpunar, Germana; Brini, Carlo; Marinelli, Fiorenzo; Triolo, Lucio

2013-01-01

This work assesses the environmental impact from chemical emissions due to military tests and routine activities in the area occupied by the Italian Inter-force Test Range (PISQ), located at Salto di Quirra, Sardinia, Italy. After reviewing the military activities carried out at PISQ, such as rocket launching, blasting and armament destruction, projectile and mortar fire impact, the associated pollution is evaluated. Chemical analyses were performed by means of Scanning Electronic Microscopy and Energy Dispersion Spectrometry on biotic and abiotic matrices. Residues of Rb, Tl, W, Ti and Al were found in matrices collected in the PISQ areas and environs. A review of experimental data on air, water, soil, milk, forage and animal tissues obtained by various Public Agencies of Sardinia proved that toxic element residues often exceeded the legal limits. PM10 and PM2.5 air concentrations also exceeded the legal limits after military blasting. Cd and Pb contents in the liver and kidneys of sheep living in farms at PISQ and in control farms that were located more than 20 km away from PISQ were higher than the legal limits. This work was performed to investigate concentration of xenobiotics in ecosystems emitted from PISQ activities. This assessment could be useful to focus future epidemiological studies carried out in PISQ and its neighbouring areas. PMID:23603867

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

High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

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

Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus

Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracilmore » (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.« less

Cytotoxicity of Spent Pot Liner on Allium cepa root tip cells: A comparative analysis in meristematic cell type on toxicity bioassays.

PubMed

Palmieri, Marcel José; Andrade-Vieira, Larissa Fonseca; Campos, José Marcello Salabert; Dos Santos Gedraite, Leonardo; Davide, Lisete Chamma

2016-11-01

Spent Pot Liner (SPL) is a waste generated during the production of aluminum. It is comprised of a mixture of substances most of which, like cyanide, aluminum and fluoride, are toxic. Previous studies indicate the highly toxic nature of SPL. However studies using cells of the differentiation/elongation zone of the root meristem (referred as M2 cells in this study) after a proper recovery period in water were never considered. Using these cells could be useful to further understanding the toxicity mechanisms of SPL. A comparative approach between the effects on M2 cells and meristematic cells of the proximal meristem zone (referred as M1 cells in this study) could lead to understanding how DNA damage caused by SPL behaves on successive generations of cells. Allium cepa cells were exposed to 4 different concentrations of SPL (2.5, 5, 7.5 and 10gL(-1)) mixed with soil and diluted in a CaCl2 0.01M to simulate the ionic forces naturally encountered on the environment. A solution containing only soil diluted on CaCl2 0.01M was used as control. M1 and M2 cells were evaluated separately, taking into account four different parameters: (1) mitotic alterations (MA); (2) presence of condensed nuclei (CN); (3) mitotic index (MI); (4) presence of micronucleus (MCN). Significant differences were observed between M1 and M2 roots tip cells for these four parameters accessed. M1 cells was more prompt to reveal citogenotoxicity through the higher frequency of MA observed. Meanwhile, for M2 cells higher frequencies of MCN and CN was noticed, followed by a reduction of MI. Also, it was possible to detect significant differences between the tested treatments and the control on every case. These results indicate SPL toxic effects carries on to future cells generations. This emphasizes the need to properly manage this waste. Joint evaluation of cells from both M1 and M2 regions was proven valuable for the evaluation of a series of parameters on all toxicity tests. Copyright © 2016. Published by Elsevier Inc.

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.

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY: AN EXPANDED VIEW OF CHEMICAL TOXICITY

EPA Science Inventory

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. T...

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.

Strategies for integrating transcriptional profiling into high throughput toxicity testing (SOT Symposium Workshop presentation)

EPA Science Inventory

Presentation Description: 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....

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

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.

Test for Non-Synergistic Interactions in Phytomedicine, Just as You Do for Isolated Compounds

PubMed Central

Patel, Areeba; Mondal, Amit

2018-01-01

Phytomedicine has often been used as “alternative therapy,” which in our opinion is unfortunate as it prevents its main actions being systematically studied, side effects explored, and toxicity tested, like all single-compound-based medicine. Our group is interested in finding which traditional or modern phytomedicines actually work and which are simply “working” through placebo, standardizing phytomedicine preparations, studying their toxicity, and finding active molecules in plants for modification and chemical synthesis as single compounds. Although fluctuation in efficacy due to seasonal and geographical variations in phytomedicine remains a concern, if well regulated, even plant extracts without isolated compounds can serve medicinal needs where single-compound options are currently not great. A potential concern with such phytomedicine is frequent mixing of ingredients in commercial formulations without test of synergism. Our study on the use of 2 traditional plants for Parkinson disease shows a clear lack of synergism, and to study nonsynergism better, we developed a new visualization approach. In this commentary, using our study on Parkinson disease as an example, we make a case for better evaluation of phytomedicines, especially testing for synergistic interactions. We also critique our own exploration of oxidative stress and few behavioral parameters alone to lay grounds for what we and hopefully others can do in future to extract more information from their phytomedicine studies. We hope this commentary acts as a good warning for anyone mixing 2 phytomedicines without testing. PMID:29706766

Test for Non-Synergistic Interactions in Phytomedicine, Just as You Do for Isolated Compounds.

PubMed

Patel, Areeba; Khan, Farooq Ali; Sikdar, Arindam; Mondal, Amit; Shukla, Sunil Dutt; Khurana, Sukant

2018-01-01

Phytomedicine has often been used as "alternative therapy," which in our opinion is unfortunate as it prevents its main actions being systematically studied, side effects explored, and toxicity tested, like all single-compound-based medicine. Our group is interested in finding which traditional or modern phytomedicines actually work and which are simply "working" through placebo, standardizing phytomedicine preparations, studying their toxicity, and finding active molecules in plants for modification and chemical synthesis as single compounds. Although fluctuation in efficacy due to seasonal and geographical variations in phytomedicine remains a concern, if well regulated, even plant extracts without isolated compounds can serve medicinal needs where single-compound options are currently not great. A potential concern with such phytomedicine is frequent mixing of ingredients in commercial formulations without test of synergism. Our study on the use of 2 traditional plants for Parkinson disease shows a clear lack of synergism, and to study nonsynergism better, we developed a new visualization approach. In this commentary, using our study on Parkinson disease as an example, we make a case for better evaluation of phytomedicines, especially testing for synergistic interactions. We also critique our own exploration of oxidative stress and few behavioral parameters alone to lay grounds for what we and hopefully others can do in future to extract more information from their phytomedicine studies. We hope this commentary acts as a good warning for anyone mixing 2 phytomedicines without testing.

Evaluation of Functional SiO₂ Nanoparticles Toxicity by a 3D Culture Model.

PubMed

Pellen-Mussi, Pascal; Tricot-Doleux, Sylvie; Neaime, Chrystelle; Nerambourg, Nicolas; Cabello-Hurtado, Francisco; Cordier, Stéphane; Grasset, Fabien; Jeanne, Sylvie

2018-05-01

as a kind of non-metal oxide SiO2 NPs have been extensively used in biomedicine, pharmaceuticals and other industrial manufacturing fields, such as DNA delivery, cancer therapy… Our group had developed a method based on microemulsion process to prepare SiO2 NPs incorporating photonic or magnetic nanocrystals and luminescent nanosized inorganic metal atom clusters. However, the toxicity of nanoparticles is known to be closely related to their physico-chemical characteristics and chemical composition. it is therefore of interest to investigate the toxicity of these novel SiO2 NPs to the cells that may come in contact. the potential toxic effect of the functional @SiO2 NPs containing Mo6 clusters with or without gold nanoparticles was investigated, at concentrations 1 μg/mL, 10 μg/mL and 100 μg/mL each, on three different cell lines. Cell viability was measured by the MTT test in monolayer's culture whereas the cytotoxicity in spheroid model was examined by the APH assay. In a second time, oxidative-stress-induced cytotoxicity was investigated through glutathione levels dosages. the results indicated that both A549 and L929 cell lines did not exhibit susceptibility to functional @SiO2 NPs-induced oxidative stress unlike KB cells. SiO2 NPs containing CMB may become toxic to cultured cells but only at a very high dosage level. Therefore, this toxicity depends on cell lines and more, on the model of cell cultures. The selection of appropriate cell line remains a critical component in nanotoxicology. these results are relevant to future applications of SiO2 gold-cluster NPs in controlled release applications.

The influence of predation on the chronic response of Artemia sp. populations to a toxicant

PubMed Central

BEKETOV, MIKHAIL A; LIESS, MATTHIAS

2006-01-01

Environmental risk assessment of contaminants is conventionally based on toxic effects assessed in organism-level test systems. We suggest that, for the prediction of toxicant effects, population- and community-level effects should be considered. The aim of this study was to investigate how predation could alter a prey population's response to a toxicant to reveal effects at population and community levels.Populations of the brine shrimp Artemia sp. were maintained in the laboratory with and without simulated predation. Individuals were exposed for 1 h to the pyrethroid insecticide esfenvalerate (0, 0·01, 0·04 and 0·08 µg L−1) and subsequently observed for 6 weeks.Unpredated exposed populations showed a reduced population density compared with the control. However, even at the highest concentration of insecticide, populations were sustained until the end of the experiment. The lower density in the exposed populations led to reduced competition and subsequently to enhanced development of surviving individuals and an increased proportion of young individuals. In contrast, the combination of predation and short-term toxicant exposure at concentrations of 0·04 and 0·08 µg L−1 produced extinction of the populations after 39 and 32 days of exposure, respectively.Synthesis and applications. The response of populations of brine shrimp to toxicants at the community level may be stronger when predation is present than the response of populations without predation pressure, as the regulation capacity of the population (measured as an increased production of offspring at reduced population densities) is exhausted when predation is present. Future ecotoxicological risk assessment schemes should consider relevant community characteristics such as predation as part of an environmental risk assessment. PMID:18784796

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.

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...

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.

Safety and Tolerability of Panax ginseng Root Extract: A Randomized, Placebo-Controlled, Clinical Trial in Healthy Korean Volunteers

PubMed Central

Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo

2012-01-01

Abstract Objectives Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. Methods This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Results Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. Conclusions P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product. PMID:22909282

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.

Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents

NASA Astrophysics Data System (ADS)

El-Helby, Abdel Ghany A.; Ayyad, Rezk R.; Sakr, Helmy M.; Abdelrahim, Adel S.; El-Adl, K.; Sherbiny, Farag S.; Eissa, Ibrahim H.; Khalifa, Mohamed M.

2017-02-01

In view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4-22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues.

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.

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.

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.

Combustion of liquid paint wastes in fluidized bed boiler as element of waste management system in the paint factory

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

Soko, W.A.; Biaecka, B.

1998-12-31

In this paper the solution to waste problems in the paint industry is presented by describing their combustion in a fluidized bed boiler as a part of the waste management system in the paint factory. Based on the Cleaner Production idea and concept of integration of design process with a future exploitation of equipment, some modifications of the waste management scheme in the factory are discussed to reduce the quantity of toxic wastes. To verify this concept combustion tests of paint production wastes and cocombustion of paint wastes with coal in an adopted industrial boiler were done. Results of thesemore » tests are presented in the paper.« less

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.

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...

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

Management of recurrent or metastatic thyroid cancer.

PubMed

Tahara, Makoto

2018-01-01

Recently, vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) have become available for the treatment of recurrent or metastatic thyroid cancer. However, a number of clinical challenges that impact the use of VEGFR-targeted TKI in daily clinical practice have arisen. Toxicity is considerable, to the extent that most physicians hesitate to start VEGFR-targeted TKI and prefer to continue a watch-and-wait approach until the patient's disease markedly worsens. This delayed use of VEGFR-targeted TKI leads to a higher incidence of serious adverse events than was reported in clinical trials. Moreover, the watch-and-wait approach has several demerits, including a worsening of quality of life, worsening of outcomes in patients of older age or with follicular thyroid cancer and increased risk of brain metastasis or bleeding. Thus, optimal timing for the start of VEGFR-targeted TKI requires careful consideration. Moreover, management of VEGFR-targeted TKI toxicities requires appropriate supportive care, well-organised infrastructure in the outpatient clinic and patient education. Future treatment will progress to precision medicine based on molecular testing. Promotion of precision medicine requires the establishment of a system of easy access to molecular testing and the promotion of translational research for the development of new drugs.

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

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.

Toxicity and biodegradability of high strength/toxic organic liquid industrial effluents and hazardous landfill leachates.

PubMed

Naidoo, V; du Preez, M; Rakgotho, T; Odhav, B; Buckley, C A

2002-01-01

Industrial effluents and leachates from hazardous landfill sites were tested for toxicity using the anaerobic toxicity assay. This test was done on several industrial effluents (brewery spent grain effluent, a chemical industry effluent, size effluent), and several hazardous landfill leachates giving vastly different toxicity results. The brewery effluent, spent grain effluent and size effluent were found to be less toxic than the chemical effluent and hazardous landfill leachate samples. The chemical industry effluent was found to be most toxic. Leachate samples from the H:h classified hazardous landfill site were found to be less toxic at high concentrations (40% (v/v)) while the H:H hazardous landfill leachate samples were found to be more toxic even at low concentrations of 4% (v/v). The 30 d biochemical methane potential tests revealed that the brewery effluent, organic spent grain effluent and size effluent were 89%, 63%, and 68% biodegradable, respectively. The leachate from Holfontein hazardous landfill site was least biodegradable (19%) while the chemical effluent and Aloes leachate were 29% and 32% biodegradable under anaerobic conditions.

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.

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. 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). Results from this test showed LC{sub 50}more » values of 0.97 and 0.84 mg Cu/L for phytoplankton and YCT-S, respectively. Previously obtained values for phytoplankton tests are 2.02 and 1.12 mg Cu/L. Too few tests have been conducted with copper as the toxicant to determine a normal range of values. Although significant reduction in growth, compared to 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.« less

Intra- and interlaboratory variability in acute toxicity tests with glochidia and juveniles of freshwater mussels (Unionidae)

USGS Publications Warehouse

Wang, N.; Augspurger, T.; Barnhart, M.C.; Bidwell, Joseph R.; Cope, W.G.; Dwyer, F.J.; Geis, S.; Greer, I.E.; Ingersoll, C.G.; Kane, C.M.; May, T.W.; Neves, R.J.; Newton, T.J.; Roberts, A.D.; Whites, D.W.

2007-01-01

The present study evaluated the performance and variability in acute toxicity tests with glochidia and newly transformed juvenile mussels using the standard methods outlined in American Society for Testing and Materials (ASTM). Multiple 48-h toxicity tests with glochidia and 96-h tests with juvenile mussels were conducted within a single laboratory and among five laboratories. All tests met the test acceptability requirements (e.g., ???90% control survival). Intralaboratory tests were conducted over two consecutive mussel-spawning seasons with mucket (Actinonaias ligamentina) or fatmucket (Lampsilis siliquoidea) using copper, ammonia, or chlorine as a toxicant. For the glochidia of both species, the variability of intralaboratory median effective concentrations (EC50s) for the three toxicants, expressed as the coefficient of variation (CV), ranged from 14 to 27% in 24-h exposures and from 13 to 36% in 48-h exposures. The intralaboratory CV of copper EC50s for juvenile fatmucket was 24% in 48-h exposures and 13% in 96-h exposures. Interlaboratory tests were conducted with fatmucket glochidia and juveniles by five laboratories using copper as a toxicant. The interlaboratory CV of copper EC50s for glochidia was 13% in 24-h exposures and 24% in 48-h exposures, and the interlaboratory CV for juveniles was 22% in 48-h exposures and 42% in 96-h exposures. The high completion success and the overall low variability in test results indicate that the test methods have acceptable precision and can be performed routinely. ?? 2007 SETAC.

Toxicity of benzotriazole and benzotriazole derivatives to three aquatic species.

PubMed

Pillard, D A; Cornell, J S; Dufresne, D L; Hernandez, M T

2001-02-01

Benzotriazole and its derivatives comprise an important class of corrosion inhibitors, typically used as trace additives in industrial chemical mixtures such as coolants, deicers, surface coatings, cutting fluids, and hydraulic fluids. Recent studies have shown that benzotriazole derivatives are a major component of aircraft deicing fluids (ADFs) responsible for toxicity to bacteria (Microtox). Our current research compared the toxicity of benzotriazole (BT), two methylbenzotriazole (MeBT) isomers, and butylbenzotriazole (BBT). Acute toxicity assays were used to model the response of three common test organisms: Microtox bacteria (Vibrio fischeri), fathead minnow (Pimephales promelas) and water flea (Ceriodaphnia dubia). The response of all the three organisms varied over two orders of magnitude among all compounds. Vibrio fischeri was more sensitive than either C. dubia or P. promelas to all the test materials, while C. dubia was less sensitive than P. promelas. The response of test organisms to unmethylated benzotriazole and 4-methylbenzotriazole was similar, whereas 5-methylbenzotriazole was more toxic than either of these two compounds. BBT was the most toxic benzotriazole derivative tested, inducing acute toxicity at a concentration of < or = 3.3 mg/l to all organisms.

Evaluation of new aquatic toxicity test methods for oil dispersants

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

Pace, C.B.; Clark, J.R.; Bragin, G.E.

1994-12-31

Current aquatic toxicity test methods used for dispersant registration do not address real world exposure scenarios. Current test methods require 48 or 96 hour constant exposure conditions. In contrast, environmentally realistic exposures can be described as a pulse in which the initial concentration declines over time. Recent research using a specially designed testing apparatus (the California system) has demonstrated that exposure to Corexit 9527{reg_sign} under pulsed exposure conditions may be 3 to 22 times less toxic compared to continuous exposure scenarios. The objectives of this study were to compare results of toxicity tests using the California test system to resultsmore » from standardized tests, evaluate sensitivity of regional (Holmesimysis cast and Atherinops affinis) vs. standard test species (Mysidopsis bahia and Menidia beryllina) and determine if tests using the California test system and method are reproducible. All tests were conducted using Corexit 9527{reg_sign} as the test material. Standard toxicity tests conducted with M. bahia and H. cast resulted in LC50s similar to those from tests using the California apparatus. LC50s from tests conducted in the authors` laboratory with the California system and standard test species were within a factor of 2 to 6 of data previously reported for west coast species. Results of tests conducted with H. cast in the laboratory compared favorably to data reported by Singer et al. 1991.« less

Use of estuarine water column tests for detecting toxic conditions in ambient areas of the Chesapeake Bay watershed

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

Hall, L.W. Jr.; Ziegenfuss, M.C.; Anderson, R.D.

1995-02-01

Various estuarine water column toxicity tests were conducted twice in nine different ambient stations in the Chesapeake Bay watershed over a 2-year period (1991 to 1993) to determine if toxic conditions existed. The following 8-d toxicity tests were conducted: larval sheepshead minnow (Cyprinodon variegatus) survival and growth test; larval grass shrimp (Palaemonetes pugio) survival and growth test; and a copepod (Eurytemora affinis) life-cycle test. During the second year of testing, two 48-h coot clam (Mulinia lateralis) tests were conducted at each station during each testing period. In 1991, the toxicity tests were conducted twice at stations in the Potomac Rivermore » at Morgantown and Dahlgren, and in the Patapsco River and the Wye River at the Manor House. All of the above tests were conducted during the fall of 1992 and spring of 1993 at two stations in the Wye River, Nanticoke River, and Middle River. Inorganic contaminants, organic contaminants, and water-quality conditions were measured concurrently during the toxicity testing of ambient water. In 1991, reduced growth of sheepshead minnow larvae was reported at both Potomac River stations during the first test. Significant mortality of either the copepod or sheepshead minnow larvae was also reported at the Wye River during both tests. Results from the 1992/93 testing generally showed minimal effects for three of the test species at all stations. Reduced normal shell development was reported for the coot clam at both Middle River stations during the fall and spring tests concurrently with concentrations of various trace metals that exceeded chronic marine water-quality criteria.« less

Draft Test Guideline: Aquatic Invetebrate Acute Toxicity, Test, Freshwater Daphnids

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 Acute Toxicity Test, Freshwater And Marine

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 Life Cycle Toxicity

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.

Thermal Stress and Toxicity

EPA Science Inventory

Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at subthermoneutral te...

Sediment toxicity identification evaluation (TIE) studies at marine sites suspected of ordnance contamination

USGS Publications Warehouse

Carr, R.S.; Nipper, M.; Biedenbach, J.M.; Hooten, R.L.; Miller, K.; Saepoff, S.

2001-01-01

A sediment quality assessment survey and subsequent toxicity identification evaluation (TIE) study was conducted at several sites in Puget Sound, Washington. The sites were previously suspected of contamination with ordnance compounds. The initial survey employed sea urchin porewater toxicity tests to locate the most toxic stations. Sediments from the most toxic stations were selected for comprehensive chemical analyses. Based on the combined information from the toxicity and chemical data, three adjacent stations in Ostrich Bay were selected for the TIE study. The results of the phase I TIE suggested that organics and metals were primarily responsible for the observed toxicity in the sea urchin fertilization test. In addition to these contaminants, ammonia was also contributing to the toxicity for the sea urchin embryological development test. The phase II TIE study isolated the majority of the toxicity in the fraction containing nonpolar organics with high log Kow, but chemical analyses failed to identify a compound present at a concentration high enough to be responsible for the observed toxicity. The data suggest that some organic or organometallic contaminant(s) that were not included in the comprehensive suite of chemical analyses caused the observed toxicological responses.

Sediment Toxicity Identification Evaluations (TIEs): Manipulating Bioavailability to Whole Organisms to Identify Environmental Toxins

EPA Science Inventory

Toxicity tests are a common method for determining whether sediment contaminants represent an environmental risk. Toxicity tests indicate if contaminants in sediments are bioavailable and capable of causing adverse biological effects to whole aquatic organisms. Several environmen...

An interlaboratory comparison of sediment elutriate preparation and toxicity test methods

EPA Science Inventory

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

Optimizing the performance of Hyalella azteca in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

EPA Science Inventory

The freshwater amphipod Hyalella azteca is a common organism used for sediment toxicity testing in the United States and elsewhere. Standard methods for 10-d and 42-d toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. Under the methods in the man...

Optimizing the performance of the amphipod, Hyalella azteca, in chronic toxicity tests: Results of feeding studies with various foods and feeding regimes

EPA Science Inventory

The freshwater amphipod, Hyalella azteca, is a common organism used for sediment toxicity testing. Standard methods for 10-d and 42-d sediment toxicity tests with H. azteca were last revised and published by USEPA/ASTM in 2000. While Hyalella azteca methods exist for sediment tox...

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing - t4 report*.

PubMed

Basketter, David A; Clewell, Harvey; Kimber, Ian; Rossi, Annamaria; Blaauboer, Bas; Burrier, Robert; Daneshian, Mardas; Eskes, Chantra; Goldberg, Alan; Hasiwa, Nina; Hoffmann, Sebastian; Jaworska, Joanna; Knudsen, Thomas B; Landsiedel, Robert; Leist, Marcel; Locke, Paul; Maxwell, Gavin; McKim, James; McVey, Emily A; Ouédraogo, Gladys; Patlewicz, Grace; Pelkonen, Olavi; Roggen, Erwin; Rovida, Costanza; Ruhdel, Irmela; Schwarz, Michael; Schepky, Andreas; Schoeters, Greet; Skinner, Nigel; Trentz, Kerstin; Turner, Marian; Vanparys, Philippe; Yager, James; Zurlo, Joanne; Hartung, Thomas

2012-01-01

Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.

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

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

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

1997-01-01

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

Acute toxic tests of rainwater samples using Daphnia magna.

PubMed

Sakai, Manabu

2006-06-01

Rainwater samples were collected at Isogo Ward of Yokohama City, Japan, from 23 June to 31 July 2003. The toxic potency of pollutants present in 13 rainwater samples was tested using Daphnia magna. Most test animals died within 48 h in five test solutions that were prepared from rainwater samples. On the other hand, when nonpolar compounds such as pesticides were removed from rainwater samples before the toxic tests, mortalities in all test solutions were less than 10%. Eight kinds of pesticides were detected in rainwater samples. The highest concentration was of dichlorvos, at 0.74 microg/L. Results indicated that insecticides in rainwater sometimes lethally affected D. magna and that toxic potency of insecticides that are present in rainwater constitutes an important problem for environmental protection.

Lethal Dietary Toxicities of Environmental Contaminants and Pesticides to Coturnix

USGS Publications Warehouse

Hill, E.F.; Camardese, M.B.

1986-01-01

Five-day subacute dietary toxicity tests of 193 potential environmental contaminants, pesticides, organic solvents, and various adjuvants are presented for young coturnix (Japanese quail, Coturnix japonica Temminck and Schlegel). The report provides the most comprehensive data base available for avian subacute dietary toxicity tests and is primarily intended for use in ranking toxicities by a standard method that has a reasonable degree of environmental relevance. Findings are presented in two parts: Part I is a critique of selected drugs that includes discussion of subacute toxicity in relation to chemical class and structure, pesticide formulation, and age of animals; Part II is a summary of toxicologic findings for each test substance and provides a statistically basis for comparing toxicities. Data presented include the median lethal concentration (LC50), slope of the probit regression curve (dose-response curve), response chronology, and food consumption. We observed that: 1) fewer than 15% of the compounds were classed 'very' or 'highly' toxic (i.e, LC50 < 200 ppm) and all of these were either chlorinated hydrocarbons, organophosphates, or organometallics; 2) subacute toxicity may vary widely among structurally similar chemicals and between different formulations of the same chemical; therefore, conclusions about lethal hazard must be made cautiously until the actual formulation of inset has been tested: 3) inclusion of a general standard in each battery of tests is useful for detection of atypical trials and monitoring population changes but should not be used indiscriminantly for adjusting LC50's for intertest differences unless the chemicals of concern and the standard elicit their toxicities through the same action; 4) although other species have been tested effectively under the subacute protocol, coturnix were ideal for the stated purpose of this research because they are inexpensive, well-adapted to the laboratory environment, and yield good intertest reproducibility of response.

Effects of five sulphonamides on duckweed (Lemna minor) after prolonged exposure time and their dependency on photoradiation.

PubMed

Białk-Bielińska, Anna; Matzke, Marianne; Caban, Magda; Stolte, Stefan; Kumirska, Jolanta; Stepnowski, Piotr

2018-03-15

Sulphonamides (SAs) are one of the most commonly used veterinary drugs and therefore their residues are regularly found in the environment. So far scientific attention has mostly been paid to the evaluation of their acute ecotoxicological effects with data on long-term effects for non-target organisms still largely missing. Therefore, the main aim of this study was to evaluate the potential toxicities of five sulphonamides to duckweed (Lemna minor) after prolonged exposure time (14days). To elucidate whether their phytotoxic effects result from potential photodegradation products, the toxicity of standard solutions of selected sulphonamides was also investigated in a standard 7-day test but after irradiation (by keeping them under the test conditions) for the selected time (after 7 and 14days). The ecotoxicological tests were accompanied by chemical analyses to be able to link the observed effects to the concentrations and nature of the exposed compounds. The results showed a shift in the toxicity of SAs: a strong decrease in toxicity for the two most toxic sulphonamides (sulphamethoxazole and sulphadimethoxine) and a slight increase in toxicity for three other SAs (sulphadimidine, sulphathiazole, sulphamerazine) in the prolonged test. However, a decrease in the toxicity and concentration of all the SAs was observed when stock solutions were irradiated prior to the toxicity experiment, which suggests that the observed effects towards L. minor of five SAs in the prolonged test cannot be directly associated with the degradation of these compounds under the test conditions but with their different mode of toxic action towards these organisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancing the fathead minnow fish embryo toxicity test: Optimizing embryo production and assessing the utility of additional test endpoints.

PubMed

Roush, Kyle S; Krzykwa, Julie C; Malmquist, Jacob A; Stephens, Dane A; Sellin Jeffries, Marlo K

2018-05-30

The fathead minnow fish embryo toxicity (FET) test has been identified as a potential alternative to toxicity test methods that utilize older fish. However, several challenges have been identified with the fathead minnow FET test, including: 1) difficulties in obtaining appropriately-staged embryos for FET test initiation, 2) a paucity of data comparing fathead minnow FET test performance to the fathead minnow larval growth and survival (LGS) test and 3) a lack of sublethal endpoints that could be used to estimate chronic toxicity and/or predict adverse effects. These challenges were addressed through three study objectives. The first objective was to optimize embryo production by assessing the effect of breeding group composition (number of males and females) on egg production. Results showed that groups containing one male and four females produced the largest clutches, enhancing the likelihood of procuring sufficient numbers of embryos for FET test initiation. The second study objective was to compare the performance of the FET test to that of the fathead minnow LGS test using three reference toxicants. The FET and LGS tests were similar in their ability to predict the acute toxicity of sodium chloride and ethanol, but the FET test was found to be more sensitive than the LGS test for sodium dodecyl sulfate. The last objective of the study was to evaluate the utility and practicality of several sublethal metrics (i.e., growth, developmental abnormalities and growth- and stress-related gene expression) as FET test endpoints. Developmental abnormalities, including pericardial edema and hatch success, were found to offer the most promise as additional FET test endpoints, given their responsiveness, potential for predicting adverse effects, ease of assessment and low cost of measurement. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of soil toxicity at Joliet Army Ammunition Plant

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

Simini, M.; Amos, J.C.; Wentsel, R.S.

1995-04-01

Environmental toxicity testing and chemical analyses of soil were performed as part of an ecological risk assessment at the Joliet Army Ammunition Plant (JAAP), Joliet, Illinois. Soils were collected from an area where munitions were loaded, assembled, and packed (area L7, group 1), and from an area where waste explosives were burned on unprotected soil (area L2). Control samples were collected from an adjacent field. Soil toxicity was determined using early seedling growth and vigor tests, earthworm survival and growth tests, and Microtox{reg_sign} assays. Relative toxicity of soils was determined within each area based on statistical significant (p = 0.05)more » of plant and earthworm growth and survival, and the effective concentration at which luminescence of the bacterium Photobacterium phosphoreum was reduced by 50% (EC50) in the Microtox assay. Samples were designated as having high, moderate, or no significant toxicity. Soil that had significant toxicity according to at least one test, and representative samples showing no toxicity, were analyzed for munitions via HPLC. Chemical residues found in soils were 2,4,6-trinitrotoluene (TNT); 1,3,5-trinitrobenzene (TNB); 2,4-dinitrotoluene (2,4-DNT); 2,6-dinitrotoluene; 2-amino-4,6-DNT; 4-amino-2,6-DNT; 1,3,5-trinitro-1,3,5-triazine (RDX); and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). All soils with no significant toxicity were void of these chemicals. However, some soils void of munitions still showed toxicity that may have been caused by elevated levels of heavy metals. Linear regressions of toxicity test results vs. chemical concentrations showed that TNT and TNB accounted for most off the soil toxicity. Lowest-observable-effect concentrations (LOEC) of TNT were determined from these data. This study presents a simple, relatively inexpensive methodology for assessing toxicity of soils containing TNT, RDX, and other contaminants related to munitions production.« less

Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

PubMed

Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

2017-06-01

Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing

PubMed Central

Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J.; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

2017-01-01

Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. PMID:28069485

A STUDY OF THE PHARMACOLOGY AND TOXICOLOGY OF VISION IN THE SOLDIER. 1. CHLOROQUINE AND HYDROXYCHLOROQUINE.

DTIC Science & Technology

A critical evaluation of reports on the toxic effects of chloroquine and hydroxychloroquine on vision has revealed a relationship between the dosage...revealed a possible explanation of the retinal toxicity of chloroquine and hydroxychloroquine . This phenomenon merits future study because reactions of

Framework for a Quantitative Systemic Toxicity Model (FutureToxII)

EPA Science Inventory

EPA’s ToxCast program profiles the bioactivity of chemicals in a diverse set of ~700 high throughput screening (HTS) assays. In collaboration with L’Oreal, a quantitative model of systemic toxicity was developed using no effect levels (NEL) from ToxRefDB for 633 chemicals with HT...

Draft Test Guideline: Whole Sediment Acute Toxicity Invertebrates, Freshwater

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: Whole Sediment Acute Toxicity Invertebrates, Marine

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.

Acute aquatic toxicity and biodegradation potential of biodiesel fuels

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

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

1995-12-31

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

Case Study Approaches for Implementing the 2007 NRC Report “Toxicity Testing in the 21st Century: A Vision and A Strategy”

PubMed Central

Andersen, Melvin E.; Clewell, Harvey J.; Carmichael, Paul L.; Boekelheide, Kim

2013-01-01

The 2007 report “Toxicity Testing in the 21st Century: A Vision and A Strategy” argued for a change in toxicity testing for environmental agents and discussed federal funding mechanisms that could be used to support this transformation within the USA. The new approach would test for in vitro perturbations of toxicity pathways using human cells with high throughput testing platforms. The NRC report proposed a deliberate timeline, spanning about 20 years, to implement a wholesale replacement of current in-life toxicity test approaches focused on apical responses with in vitro assays. One approach to accelerating implementation is to focus on well-studied prototype compounds with known toxicity pathway targets. Through a series of carefully executed case studies with four or five pathway prototypes, the various steps required for implementation of an in vitro toxicity pathway approach to risk assessment could be developed and refined. In this article, we discuss alternative approaches for implementation and also outline advantages of a case study approach and the manner in which the cases studies could be pursued using current methodologies. A case study approach would be complementary to recently proposed efforts to map the human toxome, while representing a significant extension toward more formal risk assessment compared to the profiling and prioritization approaches offered by programs such as the EPA’s ToxCast effort. PMID:21993955

Contrasting effects of chloride on growth, reproduction, and toxicant sensitivity in two genetically distinct strains of Hyalella azteca.

PubMed

Soucek, David J; Mount, David R; Dickinson, Amy; Hockett, J Russell; McEwen, Abigail R

2015-10-01

The strain of Hyalella azteca (Saussure: Amphipoda) commonly used for aquatic toxicity testing in the United States has been shown to perform poorly in some standardized reconstituted waters frequently used for other test species. In 10-d and 42-d experiments, the growth and reproduction of the US laboratory strain of H. azteca was shown to vary strongly with chloride concentration in the test water, with declining performance observed below 15 mg/L to 20 mg/L. In contrast to the chloride-dependent performance of the US laboratory strain of H. azteca, growth of a genetically distinct strain of H. azteca obtained from an Environment Canada laboratory in Burlington, Ontario, Canada, was not influenced by chloride concentration. In acute toxicity tests with the US laboratory strain of H. azteca, the acute toxicity of sodium nitrate increased with decreasing chloride in a pattern similar not only to that observed for control growth, but also to previous acute toxicity testing with sodium sulfate. Subsequent testing with the Burlington strain showed no significant relationship between chloride concentration and the acute toxicity of sodium nitrate or sodium sulfate. These findings suggest that the chloride-dependent toxicity shown for the US laboratory strain may be an unusual feature of that strain and perhaps not broadly representative of aquatic organisms as a whole. © 2015 SETAC.

Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

EPA Science Inventory

Quantitative Structure-Activity Relationship (QSAR) toxicity models have become popular tools for identifying potential toxic compounds and prioritizing candidates for animal toxicity tests. However, few QSAR studies have successfully modeled large, diverse mammalian toxicity end...

Integrated Approach of Agri-nanotechnology: Challenges and Future Trends

PubMed Central

Mishra, Sandhya; Keswani, Chetan; Abhilash, P. C.; Fraceto, Leonardo F.; Singh, Harikesh Bahadur

2017-01-01

Nanotechnology representing a new frontier in modern agriculture is anticipated to become a major thrust in near future by offering potential applications. This integrating approach, i.e., agri-nanotechnology has great potential to cope with global challenges of food production/security, sustainability and climate change. However, despite the potential benefits of nanotechnology in agriculture so far, their relevance has not reached up to the field conditions. The elevating concerns about fate, transport, bioavailability, nanoparticles toxicity and inappropriateness of regulatory framework limit the complete acceptance and inclination to adopt nanotechnologies in agricultural sector. Moreover, the current research trends lack realistic approach that fail to attain comprehensive knowledge of risk assessment factors and further toxicity of nanoparticles toward agroecosystem components viz. plant, soil, soil microbiomes after their release into the environment. Hence in the present review we attempt to suggest certain key points to be addressed in the current and future agri-nanotechnology researches on the basis of recognized knowledge gaps with strong recommendation of incorporating biosynthesized nanoparticles to carry out analogous functions. In this perspective, the major points are as follows: (i) Mitigating risk assessment factors (responsible for fate, transport, behavior, bioavailability and toxicity) for alleviating the subsequent toxicity of nanoparticles. (ii) Optimizing permissible level of nanoparticles dose within the safety limits by performing dose dependent studies. (iii) Adopting realistic approach by designing the experiments in natural habitat and avoiding in vitro assays for accurate interpretation. (iv) Most importantly, translating environmental friendly and non-toxic biosynthesized nanoparticles from laboratory to field conditions for agricultural benefits. PMID:28421100

Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

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

Rauscher, J.D.

1988-01-01

Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects ofmore » Se and Cu on planarians.« less

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

PubMed

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

2017-10-01

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

Adaptation of the fish juvenile growth test (OECD TG 215, 2000) to the marine species Dicentrarchus labrax.

PubMed

Tornambè, A; Manfra, L; Canepa, S; Oteri, F; Martuccio, G; Cicero, A M; Magaletti, E

2018-02-01

The OECD TG 215 method (2000) (C.14 method of EC Regulation 440/2008) was developed on the rainbow trout (Oncorynchus mykiss) to assess chronic toxicity (28d) of chemicals on fish juveniles. It contemplates to use other well documented species identifying suitable conditions to evaluate their growth. OECD proposes the European sea bass (Dicentrarchus labrax, L. 1758) as Mediterranean species among vertebrates recommended in the OECD guidelines for the toxicity testing of chemicals. In this context, our study is aimed to proposing the adaptation of the growth test (OECD TG 215, 2000) to D. labrax. For this purpose toxicity tests were performed with sodium dodecyl sulfate, a reference toxicant commonly used in fish toxicity assays. The main aspects of the testing procedure were reviewed: fish size (weight), environmental conditions, dilution water type, experimental design, loading rate and stocking density, feeding (food type and ration), test validity criteria. The experience gained from growth tests with the sea bass allows to promote its inclusion among the species to be used for the C.14 method. Copyright © 2016. Published by Elsevier Inc.

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

PubMed Central

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

2015-01-01

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

Incorporating New Technologies for 21st Century Toxicity ...

EPA Pesticide Factsheets

Presentation at the GlobalChem conference in Washington, DC on Incorporating New Technologies for 21st Century Toxicity Testing and Risk Assessment Presentation at the GlobalChem conference in Washington, DC on Incorporating New Technologies for 21st Century Toxicity Testing and Risk Assessment

Prediction of the developmental toxicity hazard potential of halogenated drinking water disinfection by-products tested by the in vitro hydra assay

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

Fu, L.J.; Johnson, E.M.; Newman, L.M.

A series of seven randomly selected potential halogenated water disinfection by-products were evaluated in vitro by the hydra assay to determine their developmental toxicity hazard potential. For six of the chemicals tested by this assay (dibromoacetonitrile; trichloroacetonitrile; 2-chlorophenol; 2,4,6-trichlorophenol; trichloroacetic acid; dichloroacetone) it was predicted that they would be generally equally toxic to both adult and embryonic mammals when studied by means of standard developmental toxicity teratology tests. However, the potential water disinfection by-product chloroacetic acid (CA) was determined to be over eight times more toxic to the embryonic developmental portion of the assay than it was to the adults.more » Because of this potential selectivity, CA is a high-priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential and/or to establish a NOAEL by the route of most likely human exposure.« less

Evaluation of an alternative in vitro test battery for detecting reproductive toxicants in a grouping context.

PubMed

Kroese, E Dinant; Bosgra, Sieto; Buist, Harrie E; Lewin, Geertje; van der Linden, Sander C; Man, Hai-yen; Piersma, Aldert H; Rorije, Emiel; Schulpen, Sjors H W; Schwarz, Michael; Uibel, Frederik; van Vugt-Lussenburg, Barbara M A; Wolterbeek, Andre P M; van der Burg, Bart

2015-08-01

Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as 'apical' tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negative [7]. Here we report on applying this battery within the context of grouping and read across, put forward as a potential tool to fill data gaps and avoid animal testing, to distinguish in vivo non- or weak developmental toxicants from potent developmental toxicants within groups of structural analogs. The battery correctly distinguished 2-methylhexanoic acid, monomethyl phthalate, and monobutyltin trichloride as non- or weak developmental toxicants from structurally related developmental toxicants valproic acid, mono-ethylhexyl phthalate, and tributyltin chloride, respectively, and, therefore, holds promise as a biological verification model in grouping and read across approaches. The relevance of toxicokinetic information is indicated. Copyright © 2014 Elsevier Inc. All rights reserved.

Development of novel in silico model for developmental toxicity assessment by using naïve Bayes classifier method.

PubMed

Zhang, Hui; Ren, Ji-Xia; Kang, Yan-Li; Bo, Peng; Liang, Jun-Yu; Ding, Lan; Kong, Wei-Bao; Zhang, Ji

2017-08-01

Toxicological testing associated with developmental toxicity endpoints are very expensive, time consuming and labor intensive. Thus, developing alternative approaches for developmental toxicity testing is an important and urgent task in the drug development filed. In this investigation, the naïve Bayes classifier was applied to develop a novel prediction model for developmental toxicity. The established prediction model was evaluated by the internal 5-fold cross validation and external test set. The overall prediction results for the internal 5-fold cross validation of the training set and external test set were 96.6% and 82.8%, respectively. In addition, four simple descriptors and some representative substructures of developmental toxicants were identified. Thus, we hope the established in silico prediction model could be used as alternative method for toxicological assessment. And these obtained molecular information could afford a deeper understanding on the developmental toxicants, and provide guidance for medicinal chemists working in drug discovery and lead optimization. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicity of seven foliar insecticides to four insect parasitoids attacking citrus and cotton pests.

PubMed

Prabhaker, Nilima; Morse, J G; Castle, S J; Naranjo, S E; Henneberry, T J; Toscano, N C

2007-08-01

Laboratory studies were carried out to compare the toxicity of seven foliar insecticides to four species of adult beneficial insects representing two families of Hymenoptera: Aphelinidae (Aphytis melinus Debach, Eretmocerus eremicus Rose & Zolnerowich, and Encarsiaformosa Gahan) and Mymaridae (Gonatocerus ashmeadi Girault) that attack California red scale, Aonidiella aurantii (Maskell); sweetpotato whitefly, Bemisia tabaci (Gennadius) (both E. eremicus and E. formosa); and glassy-winged sharpshooter, Homalodisca vitripennis (Germar), respectively. Insecticides from four pesticide classes were evaluated using a petri dish bioassay technique across a range of concentrations to develop dosage-mortality regressions. Insecticides tested included acetamiprid (neonicotinoid); chlorpyrifos (organophosphate); bifenthrin, cyfluthrin, and fenpropathrin (pyrethroids); and buprofezin and pyriproxyfen (insect growth regulators [IGRs]). Chlorpyrifos was consistently the most toxic pesticide to all four species of beneficial insects tested based on LC50 values recorded 24 h posttreatment compared with 48-h LC50 values with the neonicotinoid and pyrethroids or 96 h with the IGRs. Among the three pyrethroids, fenpropathrin was usually less toxic (except similar toxicity to A. melinus) than was cyfluthrin, and it was normally less toxic (except similar toxicity with E. formosa) than was bifenthrin. Acetamiprid was generally less toxic than bifenthrin (except similar toxicity with G. ashmeadi). The IGRs buprofezin and pyriproxyfen were usually less toxic than the contact pesticides, but we did not test for possible impacts on female fecundity. For all seven pesticides tested, A. melinus was the most susceptible parasitoid of the four test species. The data presented here will provide pest managers with specific information on the compatibility of select insecticides with natural enemies attacking citrus and cotton, Gossypium hirsutum L., pests.

Toxicities of triclosan, phenol, and copper sulfate in activated sludge.

PubMed

Neumegen, Rosalind A; Fernández-Alba, Amadeo R; Chisti, Yusuf

2005-04-01

The effect of toxicants on the BOD degradation rate constant was used to quantitatively establish the toxicity of triclosan, phenol, and copper (II) against activated sludge microorganisms. Toxicities were tested over the following ranges of concentrations: 0-450 mg/L for phenol, 0-2 mg/L for triclosan, and 0-35 mg/L for copper sulfate (pentahydrate). According to the EC(50) values, triclosan was the most toxic compound tested (EC(50) = 1.82 +/- 0.1 mg/L), copper (II) had intermediate toxicity (EC(50) = 18.3 +/- 0.37 mg/L), and phenol was the least toxic (EC(50) = 270 +/- 0.26 mg/L). The presence of 0.2% DMSO had no toxic effect on the activated sludge. The toxicity evaluation method used was simple, reproducible, and directly relevant to activated sludge wastewater treatment processes.

Effects of Lunar Dust Simulant (JSC-1A-vf) on WI-38 Human Embryonic Lung Cells

NASA Technical Reports Server (NTRS)

Currie, Stephen; Hammond, Dianne; Jeevarajan, Anthony

2007-01-01

In order to develop appropriate countermeasures for NASA's return mission to the moon, the potential toxicity of lunar dust needs to be examined. Due to its abrasiveness, reactivity, composition and small size, lunar dust may pose a serious health risk to astronauts who inhale it. This project focuses on the toxicity of lunar dust simulant (JSC-1A-vf) using WI-38 human embryonic lung cells. Past results show that the simulant has toxic effects on small animals using intratracheal instillation. Earlier studies in this lab suggest that the dust remaining in media after low speed centrifugation is toxic. In order to better assess its toxicity, the simulant has been diluted in media, filtered with a 5 micron filter before combining it with media. This filtered dust is compared with dust centrifuged in media. Whole dust toxicity is also tested. Toxicity is estimated using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) toxicity test which measures the activity of reducing enzymes in the mitochondria of viable cells. Preliminary results suggest that simulant which is diluted in media at different concentrations is slightly toxic. Interestingly, the cells appear to sweep up and collect the simulant. Whether this contributes to its toxicity is unclear. This project provides possible toxicity testing protocols for lunar dust and contributes to the knowledge of nanosize particle toxicity.

The Effects of Elevated Specific Conductivity on the Chronic Toxicity of Mining Influenced Streams Using Ceriodaphnia dubia

PubMed Central

Armstead, Mindy Yeager; Bitzer-Creathers, Leah; Wilson, Mandee

2016-01-01

Salinization of freshwater ecosystems as a result of human activities has markedly increased in recent years. Much attention is currently directed at evaluating the effects of increased salinity on freshwater biota. In the Central Appalachian region of the eastern United States, specific conductance from alkaline discharges associated with mountain top mining practices has been implicated in macroinvertebrate community declines in streams receiving coal mining discharges. Whole effluent toxicity testing of receiving stream water was used to test the hypothesis that mine discharges are toxic to laboratory test organisms and further, that toxicity is related to ionic concentrations as indicated by conductivity. Chronic toxicity testing using Ceriodaphnia dubia was conducted by contract laboratories at 72 sites with a total of 129 tests over a 3.5 year period. The database was evaluated to determine the ionic composition of mine effluent dominated streams and whether discharge constituents were related to toxicity in C. dubia. As expected, sulfate was found to be the dominant anion in streams receiving mining discharges with bicarbonate variable and sometimes a substantial component of the dissolved solids. Overall, the temporal variability in conductance was low at each site which would indicate fairly stable water quality conditions. Results of the toxicity tests show no relationship between conductance and survival of C. dubia in the mining influenced streams with the traditional toxicity test endpoints. However, consideration of the entire dataset revealed a significant inverse relationship between conductivity and neonate production. While conductivity explained very little of the high variability in the offspring production (r2 = 0.1304), the average numbers of offspring were consistently less than 20 neonates at the highest conductivities. PMID:27814378

Toxicity of sediments from lead-zinc mining areas to juvenile freshwater mussels (Lampsilis siliquoidea) compared to standard test organisms

USGS Publications Warehouse

Besser, John M.; Ingersoll, Christopher G.; Brumbaugh, William G.; Kemble, Nile E.; May, Thomas W.; Wang, Ning; MacDonald, Donald D.; Roberts, Andrew D.

2015-01-01

Sediment toxicity tests compared chronic effects on survival, growth, and biomass of juvenile freshwater mussels (28-d exposures with Lampsilis siliquoidea) to the responses of standard test organisms—amphipods (28-d exposures with Hyalella azteca) and midges (10-d exposures with Chironomus dilutus)—in sediments from 2 lead–zinc mining areas: the Tri-State Mining District and Southeast Missouri Mining District. Mussel tests were conducted in sediments sieved to <0.25 mm to facilitate recovery of juvenile mussels (2–4 mo old). Sediments were contaminated primarily with lead, zinc, and cadmium, with greater zinc and cadmium concentrations in Tri-State sediments and greater lead concentrations in southeast Missouri sediments. The frequency of highly toxic responses (reduced 10% or more relative to reference sites) in Tri-State sediments was greatest for amphipod survival (25% of samples), midge biomass (20%), and mussel survival (14%). In southeast Missouri sediments, the frequency of highly toxic samples was greatest for mussel biomass (25%) and amphipod biomass (13%). Thresholds for metal toxicity to mussels, expressed as hazard quotients based on probable effect concentrations, were lower for southeast Missouri sediments than for Tri-State sediments. Southeast Missouri sites with toxic sediments had 2 or fewer live mussel taxa in a concurrent mussel population survey, compared with 7 to 26 taxa at reference sites. These results demonstrate that sediment toxicity tests with juvenile mussels can be conducted reliably by modifying existing standard methods; that the sensitivity of mussels to metals can be similar to or greater than standard test organisms; and that responses of mussels in laboratory toxicity tests are consistent with effects on wild mussel populations.

Perovskite solar cells: must lead be replaced – and can it be done?

PubMed Central

Li, Jianbao; Zhou, Yangying; Wei, Yaxuan; Lin, Hong

2018-01-01

Abstract Perovskite solar cells have recently drawn significant attention for photovoltaic applications with a certified power conversion efficiency of more than 22%. Unfortunately, the toxicity of the dissolvable lead content in these materials presents a critical concern for future commercial development. This review outlines some criteria for the possible replacement of lead by less toxic elements, and highlights current research progress in the application of low-lead halide perovskites as optically active materials in solar cells. These criteria are discussed with the aim of developing a better understanding of the physio-chemical properties of perovskites and of realizing similar photovoltaic performance in perovskite materials either with or without lead. Some open questions and future development prospects are outlined for further advancing perovskite solar cells toward both low toxicity and high efficiency. PMID:29868147

Toxicity of carbon nanotubes to freshwater aquatic invertebrates

USGS Publications Warehouse

Mwangi, Joseph N.; Wang, Ning; Ingersoll, Christopher G.; Hardesty, Doug K.; Brunson, Eric L.; Li, Hao; Deng, Baolin

2012-01-01

Carbon nanotubes (CNTs) are hydrophobic in nature and thus tend to accumulate in sediments if released into aquatic environments. As part of our overall effort to examine the toxicity of carbon-based nanomaterials to sediment-dwelling invertebrates, we have evaluated the toxicity of different types of CNTs in 14-d water-only exposures to an amphipod (Hyalella azteca), a midge (Chironomus dilutus), an oligochaete (Lumbriculus variegatus), and a mussel (Villosa iris) in advance of conducting whole-sediment toxicity tests with CNTs. The results of these toxicity tests conducted with CNTs added to water showed that 1.00g/L (dry wt) of commercial sources of CNTs significantly reduced the survival or growth of the invertebrates. Toxicity was influenced by the type and source of the CNTs, by whether the materials were precleaned by acid, by whether sonication was used to disperse the materials, and by species of the test organisms. Light and electron microscope imaging of the surviving test organisms showed the presence of CNTs in the gut as well as on the outer surface of the test organisms, although no evidence was observed to show penetration of CNTs through cell membranes. The present study demonstrated that both the metals solubilized from CNTs such as nickel and the "metal-free" CNTs contributed to the toxicity.

Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

PubMed

Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

2011-01-01

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

Temporal pattern of toxicity in runoff from the Tijuana River Watershed.

PubMed

Gersberg, Richard M; Daft, Daniel; Yorkey, Darryl

2004-02-01

Samples were collected from the Tijuana River under both dry weather (baseflow) conditions and during wet weather, and tested for toxicity using Ceriodaphnia dubia tests. Toxicity of waters in the Tijuana River was generally low under baseflow conditions, but increased markedly during high flow runoff events. In order to determine the temporal pattern of toxicity during individual rain events, sequential grab samples were collected using an autosampler at 5-7 h intervals after the start of the rain event, and tested for acute toxicity. In all cases, peak toxicity values (ranging from 2.8 to 5.8TU) for each storm occurred within the first 1-2 h of initiation of the rain event, and were statistically higher (using the 95% CL) for each of the pre-storm base flow values. However, there was no statistically significant correlation (p<0.05) between flow rate and toxicity when all storm data was pooled. Additionally, we used toxicity identification evaluation (TIE) procedures to attempt to identify the classes of chemicals that account for this early storm toxicity. Solid phase extraction was the only treatment that showed consistent and significant (P<0.05) removal of toxicity. These TIEs, conducted on the most toxic sample of the river's flow during runoff events, suggest that non-polar organics may be responsible for such toxicity. The temporal pattern of toxicity, both during a given storm event and seasonally, indicates that wash-off from the watershed by rainfall may deplete the supply of toxicity available for wash-off in subsequent events, so that a clearly consistent relationship between flow and toxicity was not evident.

A REFORMULATED, RECONSTITUTED WATER FOR TESTING THE FRESHWATER AMPHIPOD, HYALELLA AZTECA

EPA Science Inventory

Toxicity testing with the freshwater amphipod, Hyalella azteca, has routinely been conducted using nonstandard waters. Four waters tested for acceptability for aqueous reference toxicant testing with H. azteca. These included three formulated (standardized) waters: moderately har...

Seasonal variation in sensitivity of larval sea lampreys to the lampricide 3-trifluoromethyl-4-nitrophenol

USGS Publications Warehouse

Scholefield, R.J.; Slaght, K.S.; Stephens, B.E.

2008-01-01

We evaluated the sensitivity of larval sea lampreys Petromyzon marinus to the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) in a series of toxicity tests in spring and summer. Although noted previously, the seasonal variation in sensitivity to TFM had never been tested as a means of reducing TFM usage in stream treatments. A preliminary study consisted of three spring and four summer static toxicity tests conducted at 12??C. A more comprehensive study consisted of 12 spring and summer paired flow-through toxicity tests conducted both at seasonal water temperatures and at 12??C. The sensitivity of larval sea lampreys to TFM was greater in spring than in summer. The preliminary static toxicity tests indicated that the concentration of TFM needed to kill larval sea lampreys in spring (May and June) was about one-half that required in summer (August); the concentrations lethal to 50% and 99.9% of the test animals (the LC50 and LC99.9 values) were less in spring than in summer. Analysis of variance of the flow-through toxicity data indicated that season significantly affected both the LC50 and LC99.9 values. For all 12 paired flow-through toxicity tests, the spring LC50 and LC99.9 values were less than the corresponding summer values. For 9 of the 12 paired flow-through toxicity tests, the dose-response toxicity lines were parallel and allowed statistical comparison of the LC50 values. The spring LC50 values were significantly lower than the summer values in eight of the nine tests. Verification of a seasonal variation in the sensitivity of larval sea lampreys to TFM will allow inclusion of this factor in the selection model currently used by both the U.S. Fish and Wildlife Service and the Department of Fisheries and Oceans-Canada to schedule lampricide stream treatments. ?? Copyright by the American Fisheries Society 2008.

Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

PubMed

Maynard, Samuel K; Edwards, Peter; Wheeler, James R

2014-07-01

Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single-stage designs. © 2014 The Authors.

Draft Test Guideline: Fish Acute Toxicity Mitigated By Humic Acid

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.

Toxicity of manganese to Ceriodaphnia dubia and Hyalella azteca

USGS Publications Warehouse

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

2000-01-01

Manganese is a toxic element frequently overlooked when assessing toxicity of effluents, sediments and pore waters. Manganese can be present at toxic levels in anoxic solutions due to its increased solubility under chemically-reducing conditions, and it can remain at those levels for days in aerated test waters due to slow precipitation kinetics. Ceriodaphnia dubia and Hyalella azteca are freshwater organisms often used for toxicity testing and recommended for assessments of effluents and pore waters. Lethal and reproductive-inhibition concentrations of Mn were determined for C. dubia in acute 48h tests and chronic 3-brood tests using animals <24 h old and between 24 and 48 h old. Sensitivity of H. azteca was determined with 7d old animals in acute 96h tests. Tests were run at three levels of water hardness to assess the amelioratory effect, which was often significant. Manganese concentrations were measured analytically at test initiation and after 96 h for calculations of toxicity endpoints and determinations of Mn precipitation during the tests. Minimal amounts of Mn (below 3%) precipitated within 96 h. LC50s determined for H. azteca progressively increased from 3.0 to 8.6 to 13.7 mg Mn/L in soft, moderately-hard and hard waters, respectively. The tolerance of C. dubia to Mn was not significantly different between moderately-hard and hard waters, but was significantly lower in soft water. There was no significant difference in Mn sensitivity between the ages of C. dubia tested. Acute LC50 values for C. dubia averaged 6.2, 14.5 and 15.2 mg Mn/L and chronic IC50 values averaged 3.9, 8.5 and 11.5 mg Mn/L for soft, moderately-hard and hard waters, respectively. Manganese toxicity should be considered when assessing solutions with concentrations near these levels.

AN ENVIRONMENTAL TECHNOLOGY VERIFICATION (ETV) TESTING OF SEVEN TECHNOLOGIES DETECTING TOXICITY IN DRINKING WATER (R2)

EPA Science Inventory

Rapid toxicity technologies can detect certain toxins and with testing it can be determined their susceptibility to interfering chemical in controlled experimental matrix. Rapid toxicity technologies do not identify or determine the concentrations of specific contaminants, but s...

An overview of the refinements and improvements to the USEPA’s sediment toxicity methods for freshwater sediment

EPA Science Inventory

Sediment toxicity tests are used for contaminated sediments, chemical registration, and water quality criteria evaluations and can be a core component of ecological risk assessments at contaminated sediments sites. Standard methods for conducting sediment toxicity tests have been...

Sediment quality assessment using survival and embryo malformation tests in amphipod crustaceans: The Gulf of Riga, Baltic Sea AS case study

NASA Astrophysics Data System (ADS)

Strode, Evita; Jansons, Mintauts; Purina, Ingrida; Balode, Maija; Berezina, Nadezhda A.

2017-08-01

The aim of this study was to assess the toxicity of bottom sediment and to estimate the potential effects of contaminated sediment on health of benthic organisms in the Gulf of Riga (eastern Baltic Sea). Two endpoints were used: survival rate (acute toxicity test) of five crustacean amphipod species and frequency of embryo malformation (samples were collected from the field) in the two species. Toxic resistance of living animals to sediment quality was measured as survival rate (%) at 25 study sites from 2010-2012. Significant differences in the toxic resistance between species were found: 80-100% for Monoporeia affinis, 70-95% for Corophium volutator, 38-88% for Pontogammarus robustoides, 38-100% for Bathyporeia pilosa and 60-100% for Hyalella azteca. Reproductive disorders, measured as percentage (%) of malformed embryos per female, varied in the ranges of 0.0-9.5% in deep water species M. affinis and 0.3-7.5% in littoral species P. robustoides. Both the acute toxicity test and embryo malformation test (only M. affinis was used) indicated moderate and poor sediment quality at 20% and 12% accordingly in the study sites, low toxicity of sediment was estimated in 64% of cases, and no toxicity was recorded in the rest of the cases (4%). Additionally, sediment toxicity test using aquatic organisms was combined with sediment chemical analysis (trace metals) and the Benthic Quality Index (macrozoobenthos) was based on data collected from 13 sites in the Gulf of Riga in 2010 and used for triad sediment quality assessment. According to this combined approach, 23% of the bottom sediments were classified as likely impacted and 23% as possibly impacted (central and southern part of the Gulf). However, the remaining 54% was identified as likely un-impacted. The sediment quality assessment with single survival test or chemical analyses showed better sediment quality in the Gulf than the triad method. The embryo malformation test appeared to be more sensitive to pollution than acute toxicity survival test, that allow us to recommend the inclusion of this novel biomarker in environmental monitoring, while combining it with other tests. In general, our results indicate good or moderate states of sediments and minimal effects of the toxic contamination in them on the Gulf of Riga ecosystem.

Toxicity of trifluoroacetate to aquatic organisms

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

Berends, A.G.; Rooij, C.G. de; Boutonnet, J.C.

1999-05-01

As a result of the atmospheric degradation of several hydrofluorocarbons and hydrochlorofluorocarbons, trifluoroacetate (TFA) will be formed. Through precipitation, TFA will enter aquatic ecosystems. To evaluate the impact on the aquatic environment, an aquatic toxicity testing program was carried out with sodium trifluoroacetate (NaTFA). During acute toxicity tests, no effects of NaTFA on water fleas (Daphnia magna) and zebra fish (Danio retrio) were found at a concentration of 1,200 mg/L. A 7-d study with duckweed (Lemna gibba Ge) revealed a NOEC of 300 mg/L. On the basis of the results of five toxicity tests with Selenastrum capricornutum, they determined amore » NOEC of 0.12 mg/L. However, algal toxicity tests with NaTFA and Chlorella vulgaris, Scenedesmus subspicatus, Chlamydomonas reinhardtii, Dunaliella tertiolecta, Eugelan gracilis, Phaeodactylum tricornutum, Navicula pelliculosa, Skeletonema costatum, Anabaena flos-aquae, and Microcystis aeruginosa resulted in EC50 values that were all higher than 100 mg/L. The toxicity of TFA to S. capricornutum could be due to metabolic defluorination to monofluoroacetate (MFA), which is known to inhibit the citric acid cycle. A toxicity test with MFA and S. capricornutum revealed it to be about three orders of magnitude more toxic than TFA. However, a bioactivation study revealed that defluorination of TFA was less than 4%. On the other hand, S. capricornutum exposed to a toxic concentration of NaTFA showed a recovery of growth when citric acid was added, suggesting that TFA (or a metabolite of TFA) interferes with the citric acid cycle. A recovery of the growth of S. capricornutum was also found when TFA was removed from the test solutions. Therefore, TFA should be considered algistatic and not algicidic for S. capricornutum. On the basis of the combined results of the laboratory tests and a previously reported semi-field study, they can consider a TFA concentration of 0.10 mg/L as safe for the aquatic ecosystem.« 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)

Russell, C.L.

1993-12-31

Clinch River-Environmental Restoration Program (CR-ERP) personnel and Tennessee Valley Authority (TVA) personnel conducted a study during the week of July 22--29, 1993. The organisms specified for testing were larval fathead minnows, Pimephales promelas, and the daphnid, Ceriodaphnia dubia. Surface water samples were collected by TVA Field engineering personnel from Clinch River Mile 19.0 and Mile 22.0 on July 21, 23, and 26. Samples were split and provided to the CR-ERP and TVA toxicology laboratories for testing. Exposure of test organisms to these samples resulted in no toxicity (survival, growth, or reproduction) to either species in testing conducted by TVA. Attachmentsmore » to this report include: Chain of custody forms -- originals; Toxicity test bench sheets and statistical analyses; and Reference toxicant test information.« less

Using Toxicity Tests in Ecological Risk Assessment

EPA Pesticide Factsheets

Toxicity tests are used to expose test organisms to a medium-water, sediment, or soil-and evaluate the effects of contamination on the survival, growth, reproduction, behavior and or other attributes of these organisms.

Toxic Substances; Mesityl Oxide; Final Test Rule

EPA Pesticide Factsheets

EPA is issuing a final test rule establishing testing requirements under section 4(a) of the Toxic Substances Control Act (TSCA) for manufacturers and processors of mesityl oxide (MO; CAS No. 141-97-7).

Comparisons of Sediment Test Volumes for Freshwater Solid Phase Sediment Toxicity Tests

EPA Science Inventory

Laboratory tests with benthic macroinvertebrates are commonly used to assess the potential toxicity of contaminated sediments, and detailed standard test procedures have been developed for various species. For freshwater, two benthic organisms, Hyalella azteca and Chironomus dil...

FETAX assay for evaluation of developmental toxicity.

PubMed

Mouche, Isabelle; Malesic, Laure; Gillardeaux, Olivier

2011-01-01

The Frog Embryo Teratogenesis Assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larva. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.

FETAX Assay for Evaluation of Developmental Toxicity.

PubMed

Mouche, Isabelle; Malésic, Laure; Gillardeaux, Olivier

2017-01-01

The frog embryo teratogenesis assay Xenopus (FETAX) test is a development toxicity screening test. Due to the small amount of compound needed and the capability to study organogenesis in a short period of time (96 h), FETAX test constitutes an efficient development toxicity alert test when performed early in drug safety development. The test is conducted on fertilized Xenopus laevis mid-blastula-stage eggs over the organogenesis period. Compound teratogenic potential is determined after analysis of the mortality and malformation observations on larvae. In parallel, FETAX test provides also information concerning embryotoxic effect based on larva length.

Evaluation of p,p'-DDT as a reference toxicant in bioassays

USGS Publications Warehouse

Marking, Leif L.

1966-01-01

p,p'-DDT was tested as a reference standard toxicant against 19 species of freshwater fish, including 39 lots from 10 sources. In particular, the rapidity, nonselectivity, and consistency of its toxicity to fish were evaluated in 96-hour static bioassays. The chemical was rapidly and consistently toxic to lake trout, carp, green sunfish, bluegill, and yellow perch. It lacked either rapid or consistent toxicity to rainbow trout, brook trout, goldfish, fathead minnows, and longear sunfish in 96-hour tests. Thus, p,p'-DDT is of limited usefulness as a reference standard toxicant in large bioassays with many species of fish.

TOXICITY TESTS FOR SEDIMENT QUALITY ASSESSMENTS

EPA Science Inventory

Toxic sediments have contributed to a wide-variety of environmental problems around the world. The observed effects include direct toxic effects to aquatic life, bio-magnification of toxicants in the food chain, and economic impacts. This chapter discusses the use of toxicity...

Integration of biological responses from a suite of bioassays for the Venice Lagoon (Italy) through sediment toxicity index - part A: development and comparison of two methodological approaches.

PubMed

Losso, Chiara; Novelli, Alessandra Arizzi; De Salvador, Davide; Ghetti, Pier Francesco; Ghirardini, Annamaria Volpi

2010-12-01

Marine and coastal quality assessment, based on test batteries involving a wide array of endpoints, organisms and test matrices, needs for setting up toxicity indices that integrate multiple toxicological measures for decision-making processes and that classify the continuous toxicity response into discrete categories according to the European Water Framework Directive. Two toxicity indices were developed for the lagoon environment such as the Venice Lagoon. Stepwise procedure included: the construction of a database that identified test-matrix pairs (indicators); the selection of a minimum number of ecotoxicological indicators, called toxicological core metrics (CMs-tox) on the basis of specific criteria; the development of toxicity scores for each CM-tox; the integration of the CMs-tox into two indices, the Toxicity Effect Index (TEI), based on the transformation of Toxic Unit (TU) data that were integrated as logarithmic sum, and the Weighted Average Toxicity Index (WATI), starting from toxicity classes integrated as weighted mean. Results from the indices are compared; advantages and drawbacks of both approaches are discussed. Copyright © 2010. Published by Elsevier Ltd.

Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

EPA Science Inventory

Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

Toxicity of Cold Lake Blend and Western Canadian Select dilbits to standard aquatic test species

EPA Science Inventory

Dilbits are blends of bitumen and natural gas condensates or crude oils with only limited toxicity data. Two dilbits, Cold Lake Blend and Western Canadian Select, were tested as either unweathered or weathered oils for acute and chronic toxicity to standard freshwater and estuari...

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

EPA Science Inventory

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

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

EPA Science Inventory

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

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

EPA Science Inventory

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

The Influence of Test Conditions on the Performance of Chironomus dilutus and Hyalella azteca in Sediment Toxicity Tests

EPA Science Inventory

In most all sediment toxicity assessments, the performance of organisms in control sediments is a key parameter in defining sediment toxicity, whether through direct statistical comparison to control or by normalizing to control performance to compare results across sites or batc...

A NEW APPROACH FOR CULTURING LEMNA MINOR (DUCKWEED) AND STANDARDIZED METHOD FOR USING ATRAZINE AS A REFERENCE TOXICANT

EPA Science Inventory

Lemna minor (Duckweed) is commonly used in aquatic toxicity investigations. Methods for culturing and testing with reference toxicants, such as atrazine, are somewhat variable among researchers. Our goal was to develop standardized methods of culturing and testing for use with L....

Toxicity of selected insecticides applied to western spruce budworm

Treesearch

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

1976-01-01

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

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

Human interleukin-10 delivered intrathecally by self-complementary adeno-associated virus 8 induces xenogeneic transgene immunity without clinical neurotoxicity in swine.

PubMed

Unger, Mark D; Pleticha, Josef; Heilmann, Lukas F; Newman, Laura K; Maus, Timothy P; Beutler, Andreas S

2018-05-25

Intrathecal interleukin-10 delivered by plasmid or viral gene vectors has been proposed for clinical testing because it is effective for chronic pain in rodents, a potential therapeutic for various human diseases, and was found to be non-toxic in dogs, when the human interleukin-10 ortholog was tested. However, recent studies in swine testing porcine interleukin-10 demonstrated fatal neurotoxicity. To deliver vector-encoded human interleukin-10 in swine, measure expression of the transgene in cerebrospinal fluid, and monitor animals for signs of neurotoxicity. Human interleukin-10 levels peaked 2 weeks after vector administration followed by a rapid decline that occurred concomitant with the emergence of anti-human interleukin-10 antibodies in the cerebrospinal fluid and serum. Animals remained neurologically healthy throughout the study period. This study suggests that swine are not idiosyncratically sensitive to intrathecal interleukin-10 because, recapitulating previous reports in dogs, they suffered no clinical neurotoxicity from the human ortholog. These results strongly infer that toxicity of intrathecal interleukin-10 in large animal models was previously overlooked because of a species mismatch between transgene and host. The present study further suggests that swine were protected from interleukin-10 by a humoral immune response against the xenogeneic cytokine. Future safety studies of interleukin-10 or related therapeutics may require syngeneic large animal models. This article is protected by copyright. All rights reserved.

Literature review on duckweed toxicity testing

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

Wang, W.

1990-06-01

Duckweed commonly refers to a group of floating, flowering plants of the family Lemnaceae. Duckweed plants are fast growing and widely distributed. They are easy to culture and to test. Some reports suggest that duckweed plants are tolerant to environmental toxicity. Other studies, however, indicate that duckweed plants are as sensitive to toxicity as other aquatic species. Duckweed plants are especially suitable for use in complex effluent bioassays, and for testing herbicide pollution in the aquatic environment, lake and river pollution, sediment toxicity, and the like. Duckweed and algae represent different levels of complexity in the plant kingdom. They complementmore » each other as phytotoxicity test organisms, instead of mutually excluding each other. Many duckweed species have been studied, primarily of the Lemna and Spirodela genera. Lemna minor and L. gibba have been recommended as standard test species. Differences in duckweed test methodology occur with regard to test types, test vessels, control tests, nutrient media, end points, and applications. 76 references.« less

Anodonta imbecillis QA Test 1, Clinch River - Environmental Restoration Program (CR-ERP)

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

Simbeck, D.J.

1997-06-01

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.« less

Estimating aquatic toxicity as determined through laboratory tests of great lakes sediments containing complex mixtures of environmental contaminants

USGS Publications Warehouse

1996-01-01

We developed and evaluated a total toxic units modeling approach for predicting mean toxicity as measured in laboratory tests for Great Lakes sediments containing complex mixtures of environmental contaminants (e.g., polychlorinated biphenyls, polycyclic aromatic hydrocarbons, pesticides, chlorinated dioxins, and metals). The approach incorporates equilibrium partitioning and organic carbon control of bioavailability for organic contaminants and acid volatile sulfide (AVS) control for metals, and includes toxic equivalency for planar organic chemicals. A toxic unit is defined as the ratio of the estimated pore-water concentration of a contaminant to the chronic toxicity of that contaminant, as estimated by U.S. Environmental Protection Agency Ambient Water Quality Criteria (AWQC). The toxic unit models we developed assume complete additivity of contaminant effects, are completely mechanistic in form, and were evaluated without any a posteriori modification of either the models or the data from which the models were developed and against which they were tested. A linear relationship between total toxic units, which included toxicity attributable to both iron and un-ionized ammonia, accounted for about 88% of observed variability in mean toxicity; a quadratic relationship accounted for almost 94%. Exclusion of either bioavailability components (i.e., equilibrium partitioning control of organic contaminants and AVS control of metals) or iron from the model substantially decreased its ability to predict mean toxicity. A model based solely on un-ionized ammonia accounted for about 47% of the variability in mean toxicity. We found the toxic unit approach to be a viable method for assessing and ranking the relative potential toxicity of contaminated sediments.

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

PubMed

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

2005-12-01

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

Predicting adult fish acute lethality with the zebrafish embryo: relevance of test duration, endpoints, compound properties, and exposure concentration analysis.

PubMed

Knöbel, Melanie; Busser, Frans J M; Rico-Rico, Angeles; Kramer, Nynke I; Hermens, Joop L M; Hafner, Christoph; Tanneberger, Katrin; Schirmer, Kristin; Scholz, Stefan

2012-09-04

The zebrafish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, which is required by various regulations for environmental risk assessment of chemicals. We investigated the reliability of the embryo test by probing organic industrial chemicals with a wide range of physicochemical properties, toxicities, and modes of toxic action. Moreover, the relevance of using measured versus nominal (intended) exposure concentrations, inclusion of sublethal endpoints, and different exposure durations for the comparability with reported fish acute toxicity was explored. Our results confirm a very strong correlation of zebrafish embryo to fish acute toxicity. When toxicity values were calculated based on measured exposure concentrations, the slope of the type II regression line was 1 and nearly passed through the origin (1 to 1 correlation). Measured concentrations also explained several apparent outliers. Neither prolonged exposure (up to 120 h) nor consideration of sublethal effects led to a reduced number of outliers. Yet, two types of compounds were less lethal to embryos than to adult fish: a neurotoxic compound acting via sodium channels (permethrin) and a compound requiring metabolic activation (allyl alcohol).

An evaluation of the toxicity of contaminated sediments from Waukegan Harbor, Illinois, following remediation

USGS Publications Warehouse

Kemble, N.E.; Hardesty, D.G.; Ingersoll, C.G.; Johnson, B. Thomas; Dwyer, F.J.; MacDonald, D.D.

2000-01-01

Waukegan Harbor in Illinois was designated as a Great Lakes Area of Concern due to high concentrations of sediment-associated polychlorinated biphenyls (PCBs). The objective of this study was to evaluate the toxicity of 20 sediment samples collected after remediation (primarily dredging) of Waukegan Harbor for PCBs. A 42-day whole sediment toxicity test with the amphipod Hyalella azteca (28-day sediment exposure followed by a 14-day reproductive phase) and sediment toxicity tests with Microtox® were conducted to evaluate sediments from Waukegan Harbor. Endpoints measured were survival, growth, and reproduction (amphipods) and luminescent light emission (bacteria). Survival of amphipods was significantly reduced in 6 of the 20 sediment samples relative to the control. Growth of amphipods (either length or weight) was significantly reduced relative to the control in all samples. However, reproduction of amphipods identified only two samples as toxic relative to the control. The Microtox basic test, conducted with organic extracts of sediments identified only one site as toxic. In contrast, the Microtox solid-phase test identified about 50% of the samples as toxic. A significant negative correlation was observed between reproduction and the concentration of three polynuclear aromatic hydrocarbons (PAHs) normalized to total organic carbon. Sediment chemistry and toxicity data were evaluated using sediment quality guidelines (consensus-based probable effect concentrations, PECs). Results of these analyses indicate that sediment samples from Waukegan Harbor were toxic to H. azteca contaminated at similar contaminant concentrations as sediment samples that were toxic to H. azteca from other areas of the United States. The relationship between PECs and the observed toxicity was not as strong for the Microtox test. The results of this study indicate that the first phase of sediment remediation in Waukegan Harbor successfully lowered concentrations of PCBs at the site. Though the sediments were generally not lethal, there were still sublethal effects of contaminants in sediments at this site observed on amphipods in long-term exposures (associated with elevated concentrations of metals, PCBs, and PAHs).

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 method for rapidly determining chemical toxicity was evaluated. 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 device, called the Motility Assay Apparatus (MAA) is tested for 30 second determination of 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, in addition to agreeing for all chemicals with previous manual evaluations of single cell motility.

Relative toxicity of pyrolysis products of some foams and fabrics

NASA Technical Reports Server (NTRS)

Hilado, C. J.

1976-01-01

A limited number of foams and fabrics was evaluated in the course of developing test procedures for determining the relative toxicity of materials. The principal variable studied, heating rate, did not affect the relative ranking of the materials tested. Two pyrolysis test procedures using the same basic approach but employing different sample weights, chamber volumes, laboratory animals, heating rates, and upper temperature limits, resulted in identical rankings of relative toxicity. The data obtained show that modification of conventional flexible polyurethane foams with flame retardants to comply with California upholstered furniture flammability regulations seems to consistently reduce toxicity under pyrolysis conditions.

Toxicity of pyrolysis gases from synthetic polymers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Soriano, J. A.; Kosola, K. L.; Kourtides, D. A.; Parker, J. A.

1977-01-01

The screening test method was used to investigate toxicity in polyethylene, polystyrene, polymethyl methacrylate, polyaryl sulfone, polyether sulfone, polyphenyl sulfone, and polyphenylene sulfide. Changing from a rising temperature program to a fixed temperature program resulted on shorter times to animal responses. This effect was attributed in part to more rapid generation of toxicants. The toxicants from the sulfur containing polymers appeared to act more rapidly than the toxicants from the other polymers. It was not known whether this effect was due primarily to difference in concentration or in the nature of the toxicants. The carbon monoxide concentration found did not account for the results observed with the sulfur containing polymers. Polyphenyl sulfone appeared to exhibit the least toxicity among the sulfur containing polymers evaluated under these test conditions.

Efficacy and Safety of Leucine Supplementation in the Elderly.

PubMed

Borack, Michael S; Volpi, Elena

2016-12-01

Leucine supplementation has grown in popularity due to the discovery of its anabolic effects on cell signaling and protein synthesis in muscle. The current recommendation is a minimum intake of 55 mg ⋅ kg -1 . d -1 Leucine acutely stimulates skeletal muscle anabolism and can overcome the anabolic resistance of aging. The value of chronic leucine ingestion for muscle growth is still unclear. Most of the research into leucine consumption has focused on efficacy. To our knowledge, very few studies have sought to determine the maximum safe level of intake. Limited evidence suggests that intakes of ≤1250 mg ⋅ kg -1 . d -1 do not appear to have any health consequences other than short-term elevated plasma ammonia concentrations. Similarly, no adverse events have been reported for the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), although no studies have tested HMB toxicity in humans. Therefore, future research is needed to evaluate leucine and HMB toxicity in the elderly and in specific health conditions. © 2016 American Society for Nutrition.

A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity.

PubMed

Rabanal, Francesc; Grau-Campistany, Ariadna; Vila-Farrés, Xavier; Gonzalez-Linares, Javier; Borràs, Miquel; Vila, Jordi; Manresa, Angeles; Cajal, Yolanda

2015-05-29

Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

Subchronic (13-week) oral toxicity study of dihomo-gamma-linolenic acid (DGLA) oil in rats.

PubMed

Kawashima, Hiroshi; Toyoda-Ono, Yoshiko; Suwa, Yoshihide; Kiso, Yoshinobu

2009-06-01

Dihomo-gamma-linolenic acid (DGLA) is one of the essential fatty acids, and has anti-inflammatory and anti-allergic effects. To assess the toxicity of a novel DGLA oil produced by the fungus Mortierella alpina, we examined it in the Ames test and in acute and subchronic oral toxicity tests in rats. In the Ames test, no mutagenicity was found up to 5000 microg/plate. The acute toxicity test revealed no toxicity related to DGLA oil at 10 g/kg. In the subchronic toxicity test, DGLA oil (500, 1000, and 2000 mg/kg) was orally administered. Water and soybean oil (2000 mg/kg) were used for the no-oil control and soybean oil control groups, respectively. There was no death in either sex. Because of administration of large amounts of oil, food consumption was low in the soybean oil control and the three test groups, which appeared to mildly decrease urinary excretion of Na, K, and Cl, as well as total serum protein, albumin, and blood urea nitrogen levels. There were no toxicological changes in body weight, food consumption, ophthalmological examination, urinalysis, hematological examination, blood biochemical examination, necropsy, organ weight, or histopathological examination. These findings show that the no-observed-adverse-effect level of the DGLA oil was 2000 mg/kg.

Toxicity of used drilling fluids to mysids (Mysidopsis bahia)

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

Gaetz, C.T.; Montgomery, R.; Duke, T.W.

1986-01-01

Static, acute toxicity tests were conducted with mysids (Mysidopsis bahia) and 11 used drilling fluids (also called drilling muds) obtained from active drilling platforms in the Gulf of Mexico, U.S.A. Each whole mud was tested, along with three phases of each mud: a liquid phase with all particulate materials removed; a suspended particulate phase composed of soluble and lighter particulate fractions; and a solid phase composed mainly of drill cuttings and rapidly settling particulates. These muds represented seven of the eight generic mud types described by the U.S. Environmental Protection Agency for use on the U.S. Outer Continental Shelf. Themore » toxicity of the 11 muds tested was apparently enhanced by the presence of aromatics. Furthermore, one mud tested repeatedly showed loss of toxicity with time, possibly from volatilization of aromatic fractions. The data demonstrated that aromatics in the drilling fluids affected their toxicity to M. bahia.« less

78 FR 66700 - Toxic Substances Control Act Chemical Testing; Receipt of Test Data

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... Chemical Testing; Receipt of Test Data AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: This notice announces EPA's receipt of test data on 21 chemicals. These data were submitted pursuant to 3 test rules issued by EPA under section 4 of the Toxic Substance Control Act (TSCA). The...

The test ability of fish Tawes to leachate garbage dump (TPA) Benowo

NASA Astrophysics Data System (ADS)

Juliardi AR, N. R.; Wiyanti, R. I.

2018-01-01

Leachate is a liquid from waste containing elements of dissolved and suspended elements. Garbage collected at the landfill site contains organic, inorganic and heavy metal substances. If the rains will produce leachate with mineral content, organic and heavy metals. When the condition or leachate flow in let to the soil surface can cause negative effects to the surrounding environment including for humans. Toxicity test it was conducted to determine the level of leachate toxicity of the test animals living in surface water located around of the “TPA Benowo”. In this study using Tawes fish with length between 4-6 cm. In this toxicity test is done in 2 stages, namely: range finding test, the search for this range is obtained 0% concentrations (as control) 0,3%; 0,6%; 0,9%; 0,12% and 0,15%. The next stage of toxicity acute test, at this stage of toxicity concentration do smaller again that is: 0,18%; 0,36%; 0,54%; 0,72% and 0,9%. The results obtained LC50 value of 0,385%, while eyes, brown stomach skin.

Chances only 50-50 for "Superfund" Legislation.

ERIC Educational Resources Information Center

Ember, Lois

1980-01-01

Discussed is the Surgeon General Julius B. Richmond, report, "Health Effects of Toxic Pollution: A Report from the Surgeon General," which considers toxic chemicals as "adding to the disease burden of the U.S. in a significant, although ill-defined, way." The reports ramifications are deliberated in view of future funding and legislation. (DS)

Sediment Toxicity Identification Evaluation

EPA Science Inventory

Approach combining chemical manipulations and aquatic toxicity testing, generally with whole organisms, to systematically characterize, identify and confirm toxic substances causing toxicity in whole sediments and sediment interstitial waters. The approach is divided into thre...

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

USGS Publications Warehouse

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

2016-01-01

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

40 CFR 797.1930 - Mysid shrimp acute toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Mysid shrimp acute toxicity test. 797... acclimated in accordance with the test design into the test chambers. Mysids in the test chambers are... individuals are of similar age and experimental history. Mysids used for establishing laboratory cultures may...

Effect of Simulated Weathering and Aging of TNT in Amended Sandy Loam Soil on Toxicity to the Enchytraeid Worm, Enchytreaeus Crypticus

DTIC Science & Technology

2006-05-01

high bioavailability of organic compounds. However, amended SSL soil was analyzed for presence of metabolic transformation products from nitroaromatic...Phillips, C.; Checkai, R. 1999. Comparison of malathion toxicity using enchytraeid reproduction test and earthworm toxicity test in different soil ...OF TNT IN AMENDED SANDY LOAM SOIL ON TOXICITY TO THE ENCHYTRAEID WORM, ENCHYTRAEUS CRYPTICUS Roman G. Kuperman Ronald T. Checkai Michael Simini

Comparative evaluation of cytotoxicity of a glucosamine-TBA conjugate and a chitosan-TBA conjugate.

PubMed

Guggi, Davide; Langoth, Nina; Hoffer, Martin H; Wirth, Michael; Bernkop-Schnürch, Andreas

2004-07-08

D-glucosamine and chitosan were modified by the immobilization of thiol groups utilizing 2-iminothiolane. The toxicity profile of the resulting D-glucosamine-TBA (4-thiobutylamidine) conjugate, of chitosan-TBA conjugate and of the corresponding unmodified controls was evaluated in vitro. On the one hand, the cell membrane damaging effect of 0.025% solutions of the test compounds was investigated via red blood cell lysis test. On the other hand, the cytotoxity of 0.025, 0.25 and 0.5% solutions of the test compounds was evaluated on L-929 mouse fibroblast cells utilizing two different bioassays: the MTT assay (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide), which assess the mitochondrial metabolic activity of the cells, and the BrdU-based enzyme-linked immunosorbent assay, which measures the incorporation in the DNA of 5-bromo-2'-deoxyuridine and consequently the cell proliferation. Results of the red blood cell lysis test showed that both thiolated compounds displayed a lower membrane damaging effect causing a significantly lower haemoglobine release than the unmodified compounds. Data obtained by the MTT assay and the BrdU assay revealed a concentration dependent relative cytotoxicity for all tested compounds. The covalent linkage of the TBA-substructure to D-glucosamine did not cause a significant increase in cytotoxicity, whereas at higher concentrations a slightly enhanced cytotoxic effect was caused by the derivatisation of chitosan. In conclusion, the -TBA derivatives show a comparable toxicity profile to the corresponding unmodified compounds, which should not compromise their future use as save pharmaceutical excipients.

An assessment of the potential toxicity of runoff from an urban roadscape during rain events.

PubMed

Waara, Sylvia; Färm, Carina

2008-05-01

The potential negative impact of urban storm water on aquatic freshwater ecosystems has been demonstrated in various studies with different types of biological methods. There are a number of factors that influence the amount and bioavailability of contaminants in storm water even if it is derived from an area with a fairly homogenous land use such as a roadscape where a variation in toxicity during rain events might be expected. There are only a few previous investigations on the toxicity of highway runoff and they have not explored these issues extensively. The main objective of this study is therefore to characterize the potential toxicity of highway runoff during several rain events before it enters a detention pond in Västerås, Sweden, using laboratory bioassays with test organisms representing various functional groups in an aquatic ecosystem. The results are to be used for developing a monitoring program, including biological methods. The storm water was sampled before the entrance to a detention pond, which receives run-off from a highway with approximately 20,000 vehicles a day. The drainage area, including the roadscape and vegetated areas, is 4.3 ha in size. Samples for toxicity tests were taken with an automatic sampler or manually during storm events. In total, the potential toxicity of 65 samples representing 15 different storm events was determined. The toxicity was assessed with 4 different test organisms; Vibrio fischeri using the Microtox comparison test, Daphnia magna using Daphtoxkit-F agna, Thamnocephalus platyurus using the ThamnotoxkitF and Lemna minor, duckweed using SS 028313. Of the 65 samples, 58 samples were tested with DaphniatoxkitF agna, 57 samples with the Microtox comparison test, 48 samples with ThamnotoxkitF and 20 samples with Lemna minor, duckweed. None of the storm water samples were toxic. No toxicity was detected with the Lemna minor test, but in 5 of the 23 samples tested in comparison to the control a growth stimulation of 22-46% was observed. This is in accordance with the chemical analysis of the storm water, which indicated rather large concentrations of tot-N and tot-P. In addition to the growth stimulation, morphological changes were observed in all the 5 samples from the winter event that was sampled. The lack of toxicity observed in our study might be due to a lower traffic intensity (20,000 vehicles/day) at the site and the trapping of pollutants in the vegetated areas of the roadscape, resulting in much smaller loads of pollutants in the storm water than in some previous studies. Ecotoxicological evaluations of storm water including run off from rain events from urban roadscape studies clearly reveal that toxicity may or may not be detected depending upon site, storm condition and the test organism chosen. However, storm water might not be as polluted as previously reported nor may the first flush be such a widespread phenomenon as we originally expected. In this study, there was also a good correlation between pollutant load measured and the lack of toxicity. The test organisms chosen in this study are commonly used in effluent control programs in Sweden and other countries, which makes it possible to compare the results with those from other effluents. In this study, only acute toxicity tests were used and further studies using chronic toxicity tests, assays for genotoxic compounds or in situ bioassays might reveal biological effects at this site. Furthermore, most of the samples were taken in spring, summer or fall and it is possible that winter conditions might alter the constituents in the storm water and, thus, the toxicity of the samples. Considering the complex nature of run off from urban roadscapes, it will be virtually impossible to evaluate properly the potential hazard of particular storm water and the efficiency of a particular treatment strategy from only physical and chemical characterizations of the effluent. Therefore, despite the lack of toxicity detected in this study, it is recommended that toxicity tests or other biological methods should be included in evaluations of the effects of runoff from roadscapes.

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.