WorldWideScience

Sample records for animal testing alternatives

  1. [Alternatives to animal testing].

    Science.gov (United States)

    Fabre, Isabelle

    2009-11-01

    The use of alternative methods to animal testing are an integral part of the 3Rs concept (refine, reduce, replace) defined by Russel & Burch in 1959. These approaches include in silico methods (databases and computer models), in vitro physicochemical analysis, biological methods using bacteria or isolated cells, reconstructed enzyme systems, and reconstructed tissues. Emerging "omic" methods used in integrated approaches further help to reduce animal use, while stem cells offer promising approaches to toxicologic and pathophysiologic studies, along with organotypic cultures and bio-artificial organs. Only a few alternative methods can so far be used in stand-alone tests as substitutes for animal testing. The best way to use these methods is to integrate them in tiered testing strategies (ITS), in which animals are only used as a last resort.

  2. Alternatives to ocular irritation testing in animals.

    Science.gov (United States)

    Atkinson, K A; Fentem, J H; Clothier, R H; Balls, M

    1992-01-01

    The preliminary conclusions of a survey of possible non-animal alternatives to the Draize rabbit eye irritancy test, recently conducted for the Commission of the European Communities, are presented. The various types of alternatives to animal tests are reviewed in terms of their current state of development and validation, and also their potential in relation to the type of exposure, level of testing, type of testing, type of effect, location of effect, and type of test material. Various problems concerning the availability and quality of in vivo eye irritation data, and the use of this data in in vitro/in vivo comparisons, are highlighted. Finally, the use of step-wise and integrated animal/non-animal and non-animal/non-animal test systems and strategies are discussed.

  3. Alternatives to animal testing: A review.

    Science.gov (United States)

    Doke, Sonali K; Dhawale, Shashikant C

    2015-07-01

    The number of animals used in research has increased with the advancement of research and development in medical technology. Every year, millions of experimental animals are used all over the world. The pain, distress and death experienced by the animals during scientific experiments have been a debating issue for a long time. Besides the major concern of ethics, there are few more disadvantages of animal experimentation like requirement of skilled manpower, time consuming protocols and high cost. Various alternatives to animal testing were proposed to overcome the drawbacks associated with animal experiments and avoid the unethical procedures. A strategy of 3 Rs (i.e. reduction, refinement and replacement) is being applied for laboratory use of animals. Different methods and alternative organisms are applied to implement this strategy. These methods provide an alternative means for the drug and chemical testing, up to some levels. A brief account of these alternatives and advantages associated is discussed in this review with examples. An integrated application of these approaches would give an insight into minimum use of animals in scientific experiments.

  4. Harmonisation of animal testing alternatives in China.

    Science.gov (United States)

    Cheng, Shujun; Qu, Xiaoting; Qin, Yao

    2017-12-01

    More and more countries are lining up to follow the EU's approach and implement a full ban on the sale of cosmetics that have been tested on animals, which has been the case in the EU since 2013. Besides animal welfare considerations, the need for mutual acceptance of data (MAD) and harmonisation of the global market have made the move toward non-animal testing a desirable general trend for countries worldwide. Over the last 10 years, the concept of alternative methods has been gradually developing in China. This has seen the harmonisation of relevant legislation, the organisation of various theoretical and hands-on training sessions, the exploration of method validation, the adoption of internationally recognised methods, the propagation of alternative testing standards, and an in-depth investigation into the potential use of in vitro methods in the biosciences. There are barriers to this progress, including the demand for a completely new infrastructure, the need to build technology capability, the requirement for a national standardisation system formed through international co-operation, and the lack of technical assistance to facilitate self-innovation. China is now increasing speed in harmonising its approach to the use of non-animal alternatives, accelerating technological development and attempting to incorporate non-animal, in vitro, testing methods into the national regulatory system.

  5. Animal alternatives for whole effluent toxicity testing ...

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicity based effluent assessments and subsequent discharge controls became globally important, when it was recognized that physical and chemical measurements alone did not protect the environment from potential impacts. Consequently, various strategies using different toxicity tests, whole effluent assessment techniques (incorporating bioaccumulation potential and persistence) plus supporting analytical tools have been developed over 30 years of practice. Numerous workshops and meetings have focused on effluent risk assessment through ASTM, SETAC, OSPAR, UK competent authorities, and EU specific country rules. Concurrent with this drive to improve effluent quality using toxicity tests, interest in reducing animal use has risen. The Health and Environmental Sciences Institute (HESI) organized and facilitated an international workshop in March 2016 to evaluate strategies for concepts, tools, and effluent assessments and update the toolbox of for effluent testing methods. The workshop objectives were to identify opportunities to use a suite of strategies for effluents, and to identify opportunities to reduce the reliance on animal tests and to determine barriers to implementation of new methodologie

  6. Alternatives to animal testing: A review

    OpenAIRE

    Doke, Sonali K.; Dhawale, Shashikant C.

    2013-01-01

    The number of animals used in research has increased with the advancement of research and development in medical technology. Every year, millions of experimental animals are used all over the world. The pain, distress and death experienced by the animals during scientific experiments have been a debating issue for a long time. Besides the major concern of ethics, there are few more disadvantages of animal experimentation like requirement of skilled manpower, time consuming protocols and high ...

  7. European Union Reference Laboratory for Alternatives to Animal Testing

    OpenAIRE

    HOLLEY TRACEY; BOWE GERARD; CAMPIA IVANA; BELZ SUSANNE; BERGGREN ELISABET; JANUSCH ROI ANNETT; WITTWEHR CLEMENS; WHELAN MAURICE

    2017-01-01

    The European Union is strongly committed to the Replacement, Reduction and Refinement of testing on animals (the 'Three Rs') as reflected in Directive 2010/63/EU on the protection of animals used for scientific purposes. As mandated by the Directive, the Joint Research Centre (JRC) runs the European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) which has the following duties: coordination and promotion of the development and use of alternative methods, including ...

  8. Testing Alternative Hypotheses about Animal Behavior.

    Science.gov (United States)

    Baker, William P.; Lang, Michael; Lawson, Anton E.

    Research indicates that the effectiveness of instruction in the elementary classroom is enhanced when it incorporates materials that actively engage students in the generation of scientific explanations. To this end, this document describes an exercise that allows Kindergarten students to explore the basic principles of animal behavior in an…

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

    Science.gov (United States)

    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.

  10. Alternatives to animal testing: current status and future perspectives.

    Science.gov (United States)

    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.

  11. Alternatives to Animal Use in Research, Testing, and Education. Summary.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Office of Technology Assessment.

    With an estimated 17-22 million animals used in laboratories annually in the United States, public interest in animal welfare has sparked an often emotional debate over such uses of animals. Concerns focus on balancing societal needs for continued progress in biomedical and behavioral research, for toxicity testing to safeguard the public, and for…

  12. Phototoxicity: Its Mechanism and Animal Alternative Test Methods

    Science.gov (United States)

    Park, Hyeonji; Lim, Kyung-Min

    2015-01-01

    The skin exposure to solar irradiation and photoreactive xenobiotics may produce abnormal skin reaction, phototoxicity. Phototoxicity is an acute light-induced response, which occurs when photoreacive chemicals are activated by solar lights and transformed into products cytotoxic against the skin cells. Multifarious symptoms of phototoxicity are identified, skin irritation, erythema, pruritis, and edema that are similar to those of the exaggerated sunburn. Diverse organic chemicals, especially drugs, are known to induce phototoxicity, which is probably from the common possession of UV-absorbing benzene or heterocyclic rings in their molecular structures. Both UVB (290~320 nm) and UVA (320~400 nm) are responsible for the manifestation of phototoxicity. Absorption of photons and absorbed energy (hv) by photoactive chemicals results in molecular changes or generates reactive oxygen species and depending on the way how endogenous molecules are affected by phototoxicants, mechanisms of phototoxcity is categorized into two modes of action: Direct when unstable species from excited state directly react with the endogenous molecules, and indirect when endogeneous molecules react with secondary photoproducts. In order to identify phototoxic potential of a chemical, various test methods have been introduced. Focus is given to animal alternative test methods, i.e., in vitro, and in chemico assays as well as in vivo. 3T3 neutral red uptake assay, erythrocyte photohemolysis test, and phototoxicity test using human 3-dimensional (3D) epidermis model are examples of in vitro assays. In chemico methods evaluate the generation of reactive oxygen species or DNA strand break activity employing plasmid for chemicals, or drugs with phototoxic potential. PMID:26191378

  13. The European Partnership for Alternative Approaches to Animal Testing (EPAA): Promoting Alternative Methods in Europe and Beyond

    OpenAIRE

    Cozigou, Gwenole; Crozier, Jonathan; Hendriksen, Coenraad; Manou, Irene; Ramirez-Hernandez, Tzutzuy; Weissenhorn, Renate

    2015-01-01

    Here in we introduce the European Partnership for Alternative Approaches to Animal Testing (EPAA) and its activities, which are focused on international cooperation toward alternative methods. The EPAA is one of the leading organizations in Europe for the promotion of alternative approaches to animal testing. Its innovative public–private partnership structure enables a consensus-driven dialogue across 7 industry sectors to facilitate interaction between regulators and regulated stakeholders....

  14. Alternatives to animal testing: information resources via the Internet and World Wide Web.

    Science.gov (United States)

    Hakkinen, P J Bert; Green, Dianne K

    2002-04-25

    Many countries, including the United States, Canada, European Union member states, and others, require that a comprehensive search for possible alternatives be completed before beginning some or all research involving animals. Completing comprehensive alternatives searches and keeping current with information associated with alternatives to animal testing is a challenge that will be made easier as people throughout the world gain access to the Internet and World Wide Web. Numerous Internet and World Wide Web resources are available to provide guidance and other information on in vitro and other alternatives to animal testing. A comprehensive Web site is Alternatives to Animal Testing on the Web (Altweb), which serves as an online clearinghouse for resources, information, and news about alternatives to animal testing. Examples of other important Web sites include the joint one for the (US) Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Norwegian Reference Centre for Laboratory Animal Science and Alternatives (The NORINA database). Internet mailing lists and online access to bulletin boards, discussion areas, newsletters, and journals are other ways to access and share information to stay current with alternatives to animal testing.

  15. Opportunities for animal alternatives implementation in the evolving OECD fish testing framework

    Science.gov (United States)

    This presentation reviews opportunities for animal alternative approaches in the FTF. These will be placed in the context of in vivo tests required in many regulatory situations for the registration of industrial chemicals, pharmaceuticals, and agrochemicals. The Framework inte...

  16. Critical Evaluation of Animal Alternative Tests for the Identification of Endocrine Active Substances

    Science.gov (United States)

    A significant amount of research is currently targeted to evaluate alternative test methods that may reduce, refine, or replace the use of animals, while ensuring human and environmental health and safety. It is important that the information gained from the alternative tests pr...

  17. The European Partnership for Alternative Approaches to Animal Testing (EPAA): promoting alternative methods in Europe and beyond.

    Science.gov (United States)

    Cozigou, Gwenole; Crozier, Jonathan; Hendriksen, Coenraad; Manou, Irene; Ramirez-Hernandez, Tzutzuy; Weissenhorn, Renate

    2015-03-01

    Here in we introduce the European Partnership for Alternative Approaches to Animal Testing (EPAA) and its activities, which are focused on international cooperation toward alternative methods. The EPAA is one of the leading organizations in Europe for the promotion of alternative approaches to animal testing. Its innovative public-private partnership structure enables a consensus-driven dialogue across 7 industry sectors to facilitate interaction between regulators and regulated stakeholders. Through a brief description of EPAA's activities and organizational structure, we first articulate the value of this collaboration; we then focus on 2 key projects driven by EPAA. The first project aims to address research gaps on stem cells for safety testing, whereas the second project strives for an approach toward demonstration of consistency in vaccine batch release testing. We highlight the growing need for harmonization of international acceptance and implementation of alternative approaches and for increased international collaboration to foster progress on nonanimal alternatives.

  18. Critical Evaluation of Animal Alternative Tests for the Identification of Endocrine Active Substances, oral presentation

    Science.gov (United States)

    In the past 20 years, considerable progress in animal alternatives accompanied by advances in the toxicological sciences and new emphases on aquatic vertebrates has appeared. A significant amount of current research is targeted to evaluate alternative test methods that may reduce...

  19. A European perspective on alternatives to animal testing for environmental hazard identification and risk assessment.

    Science.gov (United States)

    Scholz, Stefan; Sela, Erika; Blaha, Ludek; Braunbeck, Thomas; Galay-Burgos, Malyka; García-Franco, Mauricio; Guinea, Joaquin; Klüver, Nils; Schirmer, Kristin; Tanneberger, Katrin; Tobor-Kapłon, Marysia; Witters, Hilda; Belanger, Scott; Benfenati, Emilio; Creton, Stuart; Cronin, Mark T D; Eggen, Rik I L; Embry, Michelle; Ekman, Drew; Gourmelon, Anne; Halder, Marlies; Hardy, Barry; Hartung, Thomas; Hubesch, Bruno; Jungmann, Dirk; Lampi, Mark A; Lee, Lucy; Léonard, Marc; Küster, Eberhard; Lillicrap, Adam; Luckenbach, Till; Murk, Albertinka J; Navas, José M; Peijnenburg, Willie; Repetto, Guillermo; Salinas, Edward; Schüürmann, Gerrit; Spielmann, Horst; Tollefsen, Knut Erik; Walter-Rohde, Susanne; Whale, Graham; Wheeler, James R; Winter, Matthew J

    2013-12-01

    Tests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These tests raise ethical and economic concerns and are considered as inappropriate for assessing all of the substances and effluents that require regulatory testing. Hence, there is a strong demand for replacement, reduction and refinement strategies and methods. However, until now alternative approaches have only rarely been used in regulatory settings. This review provides an overview on current regulations of chemicals and the requirements for animal tests in environmental hazard and risk assessment. It aims to highlight the potential areas for alternative approaches in environmental hazard identification and risk assessment. Perspectives and limitations of alternative approaches to animal tests using vertebrates in environmental toxicology, i.e. mainly fish and amphibians, are discussed. Free access to existing (proprietary) animal test data, availability of validated alternative methods and a practical implementation of conceptual approaches such as the Adverse Outcome Pathways and Integrated Testing Strategies were identified as major requirements towards the successful development and implementation of alternative approaches. Although this article focusses on European regulations, its considerations and conclusions are of global relevance. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Recommendation for a non-animal alternative to rat caries testing.

    Science.gov (United States)

    Featherstone, John D B; Stookey, George K; Kaminski, Michael A; Faller, Robert V

    2011-10-01

    As a requirement of the Food & Drug Administration's final monograph on "Anticaries drug products for over-the-counter human use", the toothpaste industry has been conducting animal caries tests on every fluoride-containing toothpaste introduced into the U.S. market since 1996. The practice of testing in animals, although required by law, is in stark conflict with the corporate policy of many U.S. and global toothpaste manufacturers, in which, if possible, alternatives to animal testing are utilized. A provision does exist within the regulation which allows the use of an alternative method to demonstrate efficacy. However, to take advantage of this provision, a petition must be submitted to the FDA and in this petition data demonstrating the alternative provides results of "equivalent accuracy" must be included. After many years of research, model development and model comparisons, we have identified one particular laboratory model that demonstrated excellent correlation with the currently accepted animal caries models. This model, known as the Featherstone pH cycling model, is discussed in this paper. The Featherstone pH cycling model has been shown to produce results of equivalent accuracy to the animal caries model by: (1) demonstrating a clinically relevant fluoride dose response similar to that shown in the animal caries model (including 1100 ppm F, 250 ppm F and placebo); (2) demonstrating similar results to the animal caries model for clinically proven dentifrice formulations relative to positive and negative controls; (3) demonstrating discriminating ability in strong agreement with the animal caries model for differentiating between a dentifrice formulation with attenuated fluoride activity and a USP standard; and (4) providing a clinically relevant representation of the caries process, as demonstrated by orthodontic banding studies. In addition, the model sufficiently addresses both salivary and abrasive/anticalculus agent interference concerns. For more

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

    DEFF Research Database (Denmark)

    Adler, Sarah; Basketter, David; Creton, Stuart

    2011-01-01

    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......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...

  2. EU sales ban on new cosmetics tested on animals: impact on alternative methods, WTO implications and animal welfare aspects.

    Science.gov (United States)

    Ruhdel, Irmela W

    2004-06-01

    In 1993, the European Union (EU) adopted Directive 93/35/EEC, calling for a sales ban on new cosmetic products containing ingredients tested on animals after 1 January, 1998, provided that alternative methods had been developed by then. In May 2000, for the second time, the European Commission postponed that ban. The Commission justified the repeated postponement of the sales ban by saying that no animal-free methods were available, although three in vitro methods were scientifically approved in 1997. With three years delay, these methods have been published and therefore "made available" in the EU. OECD acceptance is still awaited. Another reason for the postponement was the fear of possible World Trade Organisation (WTO) conflicts. However, according to WTO rules, the protection of public morality or animal health could justify a restriction of the free trade principle. From the animal welfare point of view, an unqualified EU sales ban, combined with an animal testing ban, would provide the incentive to further promote the development and acceptance of alternative methods and to prove that ethical standards are legitimate concerns under WTO rules.

  3. Safety testing of acellular pertussis vaccines: Use of animals and 3Rs alternatives.

    Science.gov (United States)

    Hoonakker, Marieke; Arciniega, Juan; Hendriksen, Coenraad

    2017-11-02

    The current test of acellular Bordetella pertussis (aP) vaccines for residual pertussis toxin (PTx) is the Histamine Sensitization test (HIST), based on the empirical finding that PTx sensitizes mice to histamine. Although HIST has ensured the safety of aP vaccines for years, it is criticized for the limited understanding of how it works, its technical difficulty, and for animal welfare reasons. To estimate the number of mice used worldwide for HIST, we surveyed major aP manufacturers and organizations performing, requiring, or recommending the test. The survey revealed marked regional differences in regulatory guidelines, including the number of animals used for a single test. Based on information provided by the parties surveyed, we estimated the worldwide number of mice used for testing to be 65,000 per year: ∼48,000 by manufacturers and ∼17,000 by national control laboratories, although the latter number is more affected by uncertainty, due to confidentiality policies. These animals covered the release of approximately 850 final lots and 250 in-process lots of aP vaccines yearly. Although there are several approaches for HIST refinement and reduction, we discuss why the efforts needed for validation and implementation of these interim alternatives may not be worthwhile, when there are several in vitro alternatives in various stages of development, some already fairly advanced. Upon implementation, one or more of these replacement alternatives can substantially reduce the number of animals currently used for the HIST, although careful evaluation of each alternative's mechanism and its suitable validation will be necessary in the path to implementation.

  4. Validation of Alternative In Vitro Methods to Animal Testing: Concepts, Challenges, Processes and Tools.

    Science.gov (United States)

    Griesinger, Claudius; Desprez, Bertrand; Coecke, Sandra; Casey, Warren; Zuang, Valérie

    This chapter explores the concepts, processes, tools and challenges relating to the validation of alternative methods for toxicity and safety testing. In general terms, validation is the process of assessing the appropriateness and usefulness of a tool for its intended purpose. Validation is routinely used in various contexts in science, technology, the manufacturing and services sectors. It serves to assess the fitness-for-purpose of devices, systems, software up to entire methodologies. In the area of toxicity testing, validation plays an indispensable role: "alternative approaches" are increasingly replacing animal models as predictive tools and it needs to be demonstrated that these novel methods are fit for purpose. Alternative approaches include in vitro test methods, non-testing approaches such as predictive computer models up to entire testing and assessment strategies composed of method suites, data sources and decision-aiding tools. Data generated with alternative approaches are ultimately used for decision-making on public health and the protection of the environment. It is therefore essential that the underlying methods and methodologies are thoroughly characterised, assessed and transparently documented through validation studies involving impartial actors. Importantly, validation serves as a filter to ensure that only test methods able to produce data that help to address legislative requirements (e.g. EU's REACH legislation) are accepted as official testing tools and, owing to the globalisation of markets, recognised on international level (e.g. through inclusion in OECD test guidelines). Since validation creates a credible and transparent evidence base on test methods, it provides a quality stamp, supporting companies developing and marketing alternative methods and creating considerable business opportunities. Validation of alternative methods is conducted through scientific studies assessing two key hypotheses, reliability and relevance of the

  5. In vitro alternatives to the use of animals in ocular toxicology testing.

    Science.gov (United States)

    Ubels, John L; Clousing, Daniel P

    2005-07-01

    Chemical substances, including household products, industrial chemicals, and cosmetics, must be tested for ocular toxicity or irritancy so that the public can be assured of their safety or warned of dangers associated with their use. The in vivo Draize test is the standard method used to meet this requirement; however, this test is coming under increasing criticism on scientific and ethical grounds. This has led to the development of a large number of proposed in vitro tests, some of which are routinely used to screen chemicals in toxicology laboratories. This review addresses regulations governing ocular irritancy testing and the current status of the movement toward use of alternative methods. Such methods include the use of cultured cells, hen's eggs, isolated animal eyes and corneas, human corneal epithelial cell lines, and the recently developed in vitro corneal equivalent models. The protocols for these methods are outlined, and their endpoints are described with respect to prediction of in vivo responses. The tests are evaluated in the context of the outcomes of validation studies and acceptance by regulatory agencies. While several of these tests yield useful information concerning ocular irritancy, to date, no in vitro alternative test has been validated as a replacement for the Draize test. If the goal of replacing the in vivo test while protecting the public from chemical eye injury is to be achieved, further development and improvement of alternative tests, as well as establishment of a human ocular toxicity data base, are required.

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

    Science.gov (United States)

    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.

  7. Practical application of non-whole animal alternatives: summary of IRAG workshop on eye irritation testing. Interagency Regulatory Alternatives Group.

    Science.gov (United States)

    Bradlaw, J; Gupta, K; Green, S; Hill, R; Wilcox, N

    1997-01-01

    In November 1993, the Interagency Regulatory Alternatives Group (IRAG) sponsored a workshop to examine the current scientific status of alternatives to the Draize eye irritation test by assessing the current practical application of methods used to predict in vivo eye irritation. Laboratories from around the world were invited to submit detailed in vitro and in vivo data in parallel according to a specific set of guidelines in a consistent format. In vitro scores were compared with individual tissue scores. Over 60 data sets from 41 laboratories were received for 29 different test methods. Methods were grouped into five categories: organotypic models, chorioallantoic membrane-based assays, cell function-based assays, cytotoxicity assays and other systems. Data submissions and correlation analyses have been used to demonstrate the application of guidelines in method evaluations. Findings are summarized and future directions are indicated. A significant outcome of the workshop was the co-operation demonstrated among representatives of industry, academia and government in sharing test data on more than 2000 chemicals, products and product formulations for evaluation by their peers. Information obtained from this workshop will add to the weight of scientific evidence and scientific consensus about in vitro test methods and will establish credibility for regulatory acceptance of non-whole animal alternatives for ocular irritation.

  8. Toxicity testing: the search for an in vitro alternative to animal testing.

    Science.gov (United States)

    May, J E; Xu, J; Morse, H R; Avent, N D; Donaldson, C

    2009-01-01

    Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

  9. State of the art on alternative methods to animal testing from an industrial point of view: ready for regulation?

    Science.gov (United States)

    Ashton, Rachel; De Wever, Bart; Fuchs, Horst W; Gaca, Marianna; Hill, Erin; Krul, Cyrille; Poth, Albrecht; Roggen, Erwin L

    2014-01-01

    Despite changing attitudes towards animal testing and current legislation to protect experimental animals, the rate of animal experiments seems to have changed little in recent years. On May 15-16, 2013, the In Vitro Testing Industrial Platform (IVTIP) held an open meeting to discuss the state of the art in alternative methods, how companies have, can, and will need to adapt and what drives and hinders regulatory acceptance and use. Several key messages arose from the meeting. First, industry and regulatory bodies should not wait for complete suites of alternative tests to become available, but should begin working with methods available right now (e.g., mining of existing animal data to direct future studies, implementation of alternative tests wherever scientifically valid rather than continuing to rely on animal tests) in non-animal and animal integrated strategies to reduce the numbers of animals tested. Sharing of information (communication), harmonization and standardization (coordination), commitment and collaboration are all required to improve the quality and speed of validation, acceptance, and implementation of tests. Finally, we consider how alternative methods can be used in research and development before formal implementation in regulations. Here we present the conclusions on what can be done already and suggest some solutions and strategies for the future.

  10. State of the art on alternative methods to animal testing from an industrial point of view: ready for regulation?

    OpenAIRE

    Gaca, Marianna; Wever, De, Bart; Fuchs, Horst; Poth, Albrecht; Ashton, Rachel; Hill, Erin; Roggen, Erwin; Krul, Cyrille

    2014-01-01

    Despite changing attitudes towards animal testing and current legislation to protect experimental animals, the rate of animal experiments seems to have changed little in recent years. On May 15–16, 2013, the In Vitro Testing Industrial Platform (IVTIP) held an open meeting to discuss the state of the art in alternative methods, how companies have, can, and will need to adapt and what drives and hinders regulatory acceptance and use. Several key messages arose from the meeting. First, industry...

  11. An alternative to animal testing in the quality control of erythropoietin.

    Science.gov (United States)

    Zimmermann, H; Gerhard, D; Hothorn, L A; Dingermann, T

    2011-06-01

    A physico-chemical method has been developed as an alternative to the current bioassay in normocythaemic mice for estimating the biological activity of erythropoietin batches. Capillary zone electrophoresis was used for quantification of the isoforms and their substructures were further elucidated by N-glycan mapping techniques. The analytical study was carried out on a total of 40 batches of epoetin beta which were selected to cover an adequate range of precisely established potency values. The relationship between the biological and chemical parameters was evaluated statistically in order to identify suitable covariates for the prediction of the biological activity. Out of several alternatives, a prediction model which is based on the percentages of isoforms per batch and the degree of sialidation was selected and tested. This model is comparable in terms of accuracy to the established in vivo bioassay, but is far superior in terms of precision. Further advantages of the method are improved animal welfare and savings in time and effort. The question whether the prediction model already meets the requirements for replacing the bioassay according to the ICH guideline Q6B is discussed.

  12. Go3R - semantic Internet search engine for alternative methods to animal testing.

    Science.gov (United States)

    Sauer, Ursula G; Wächter, Thomas; Grune, Barbara; Doms, Andreas; Alvers, Michael R; Spielmann, Horst; Schroeder, Michael

    2009-01-01

    Consideration and incorporation of all available scientific information is an important part of the planning of any scientific project. As regards research with sentient animals, EU Directive 86/609/EEC for the protection of laboratory animals requires scientists to consider whether any planned animal experiment can be substituted by other scientifically satisfactory methods not entailing the use of animals or entailing less animals or less animal suffering, before performing the experiment. Thus, collection of relevant information is indispensable in order to meet this legal obligation. However, no standard procedures or services exist to provide convenient access to the information required to reliably determine whether it is possible to replace, reduce or refine a planned animal experiment in accordance with the 3Rs principle. The search engine Go3R, which is available free of charge under http://Go3R.org, runs up to become such a standard service. Go3R is the world-wide first search engine on alternative methods building on new semantic technologies that use an expert-knowledge based ontology to identify relevant documents. Due to Go3R's concept and design, the search engine can be used without lengthy instructions. It enables all those involved in the planning, authorisation and performance of animal experiments to determine the availability of non-animal methodologies in a fast, comprehensive and transparent manner. Thereby, Go3R strives to significantly contribute to the avoidance and replacement of animal experiments.

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

    Science.gov (United States)

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

  14. Knowledge sharing to facilitate regulatory decision-making in regard to alternatives to animal testing: Report of an EPAA workshop.

    Science.gov (United States)

    Ramirez, Tzutzuy; Beken, Sonja; Chlebus, Magda; Ellis, Graham; Griesinger, Claudius; De Jonghe, Sandra; Manou, Irene; Mehling, Annette; Reisinger, Kerstin; Rossi, Laura H; van Benthem, Jan; van der Laan, Jan Willem; Weissenhorn, Renate; Sauer, Ursula G

    2015-10-01

    The European Partnership for Alternative Approaches to Animal Testing (EPAA) convened a workshop Knowledge sharing to facilitate regulatory decision-making. Fifty invited participants from the European Commission, national and European agencies and bodies, different industry sectors (chemicals, cosmetics, fragrances, pharmaceuticals, vaccines), and animal protection organizations attended the workshop. Four case studies exemplarily revealed which procedures are in place to obtain regulatory acceptance of new test methods in different sectors. Breakout groups discussed the status quo identifying the following facilitators for regulatory acceptance of alternatives to animal testing: Networking and communication (including cross-sector collaboration, international cooperation and harmonization); involvement of regulatory agencies from the initial stages of test method development on; certainty on prerequisites for test method acceptance including the establishment of specific criteria for regulatory acceptance. Data sharing and intellectual property issues affect many aspects of test method development, validation and regulatory acceptance. In principle, all activities should address replacement, reduction and refinement methods (albeit animal testing is generally prohibited in the cosmetics sector). Provision of financial resources and education support all activities aiming at facilitating the acceptance and use of alternatives to animal testing. Overall, workshop participants recommended building confidence in new methodologies by applying and gaining experience with them. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. E-cigarettes and the need and opportunities for alternatives to animal testing.

    Science.gov (United States)

    Hartung, Thomas

    2016-01-01

    E-cigarettes have become within only one decade an important commodity, changing the market of the most mass-killing commercial product. While a few years ago estimates suggested that in the course of the 21st century one billion people would die prematurely from tobacco consumption, e-cigarettes continuously gaining popularity promise 10-30fold lower health effects, possibly strongly changing this equation. However, they still are not a harmless life-style drug. Acceptability simply depends on whether we compare their use to smoking or to not-smoking. In the absence of long-term follow-up health data of users, additional uncertainty comes from the lack of safety data, though this uncertainty likely only is whether they represent 3 or 10% of the risk of their combustible counterpart. This means that there is little doubt that they represent a prime opportunity for smokers to switch, but also that their use by non-smokers should be avoided where possible. The real safety concerns, however, are that e-cigarettes expose their users to many compounds, contaminants and especially flavors (more than 7,000 according to recent counts), which have mostly not been tested, especially not for long-term inhalation exposure. Neither the precautionary traditional animal testing nor post-marketing surveillance will offer us data of sufficient quality or sufficiently fast to support product development and regulatory decisions. Thus, alternative methods lend themselves to fill this gap, making this new product category a possible engine for new method development and its implementation and validation.

  16. Alternatives to the use of animals in safety testing as required by the EU-Cosmetics Directive 2009.

    Science.gov (United States)

    Vogel, Richard

    2009-01-01

    Ingredients of cosmetic products are no longer allowed to be tested by animal experimentation (EU-Cosmetics Directive 76/768 EEC). For several toxicological endpoints this testing ban applies since March 11, 2009, while repeated dose toxicity tests and the test on skin sensitisation will follow on March 11, 2013. All currently available alternatives meeting the requirements of the first deadline are compiled in the following.

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Alternatives to animal testing in basic and preclinical research of atopic dermatitis.

    Science.gov (United States)

    Löwa, Anna; Jevtić, Marijana; Gorreja, Frida; Hedtrich, Sarah

    2018-01-22

    Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing prevalence, especially in industrialized countries. Roughly 25% of the children and 1%-3% of adults are affected. Although significant progress has been made in the understanding of the pathogenesis of AD, many aspects remain poorly understood. Moreover, there is a pressing need for improved therapeutic options. Studies to elucidate the pathophysiological pathways of AD and to identify novel therapeutic targets over the last few decades have been conducted almost exclusively in animal models. However, in vitro approaches such as 3D skin disease models have recently emerged due to an increasing awareness of distinct interspecies-related differences that hamper the effective translation of results from animal models to humans. In addition, there is growing political and social pressure to develop alternatives to animal models according to the 3Rs principle (reduction, refinement and replacement of animal models). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Proceedings of the Symposium on Current Concepts and Approaches on Animal Test Alternatives

    Science.gov (United States)

    1993-09-01

    Johnson, Jr. The Development and Validation of the Miniature Swine, Mouse and Rabbit Models as Alternatives to the Use of the Dog in Drug Testing...University of Toronto, where I did my graduate research, that Banting and Best kept the depancreatized dog , Marjorie, alive with injections of pancreatic...functional) - Synthetic activity (protein, RNA, DNA) - Metabolic poisoning (02 utilization/consumption, glycolysis, gluconeogenesis ) COMPENSATORY

  20. [Alternative methods to animal experiments. What can they afford in the safety testing of chemical substances under REACH?].

    Science.gov (United States)

    Lilienblum, Werner

    2008-12-01

    Alternative methods to safety studies using laboratory animals have been accepted by the OECD in areas such as local toxicity and mutagenicity. In more complex important fields, such as systemic single and repeated dose toxicity, toxicokinetics, sensitisation, reproductive toxicity and carcinogenicity, it is expected that the development and validation of computerised methods, testing batteries (in vitro and in silico) and tiered testing systems will need many years and have to overcome many scientific and regulatory obstacles, which makes it extremely difficult to predict the outcome and the time needed. Therefore, the validated alternative methods available will only have a limited impact on reducing the numbers of animals required under REACH. In the midterm, the strategy should be more directed towards the refinement or reduction of in vivo testing because the replacement concerning complex toxicological endpoints is at present not in sight.

  1. Workshop on Animal free Detection of Pertussis Toxin in Vaccines--Alternatives to the Histamine Sensitisation Test.

    Science.gov (United States)

    Bache, Christina; Hoonakker, Marieke; Hendriksen, Coenraad; Buchheit, Karl-Heinz; Spreitzer, Ingo; Montag, Thomas

    2012-07-01

    The Paul-Ehrlich-Institut (PEI), the Nederlands Vaccin Instituut (NVI) and the European Directorate for the Quality of Medicines & HealthCare (EDQM) organised the international scientific workshop "Animal free Detection of Pertussis Toxin in Vaccines--Alternatives to the Histamine Sensitisation Test" at the PEI in Langen (Germany) on 09-10 June 2011. Twenty-seven experts (regulators, representatives from national control laboratories, vaccine manufacturers and academia) from 7 countries participated in this workshop. The meeting was triggered by the lack of satisfaction with the current safety testing for acellular pertussis vaccines, the "Histamine Sensitisation Test" (HIST) in mice, and the growing attention for the alternatives under development. The workshop objectives were: a) to review the current status of available alternative methods, b) to discuss the sensitivity that an alternative test needs, c) to plan experiments that allow for comparison of the alternative tests. The results of the workshop are summarised in this meeting report. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

  2. Testing alternative designs for a roadside animal detection system using a driving simulator

    Directory of Open Access Journals (Sweden)

    Molly K. Grace

    2015-07-01

    Full Text Available Objectives: A Roadside Animal Detection System (RADS was installed in January 2012 along Highway 41 through Big Cypress National Preserve in Florida, USA in an attempt to reduce wildlife-vehicle collisions. The system uses flashing warning signs to alert drivers when a large animal is near the road. However, we suspected that the RADS warning signs could be ignored by drivers because they resemble other conventional signs. We hypothesized that word-based warning signs (current design are less effective than picture-based signs at catching drivers’ attention. Methods: We used a driving simulator to test (1 the effects of the RADS on collision rate, driver speed, and latency to brake; and (2 whether the RADS would be more effective if warning signs were picture-based. Participants were randomly assigned to one of three treatments: no warning (control, word-based RADS signs (current design, and picture-based RADS signs (proposed design. During the simulations, a deer entered the road in front of the driver, and we recorded whether drivers “crashed” or not. Results: Both the picture-based and word-based RADS signs resulted in significantly lower crash probabilities. The picture-based RADS signs performed better than the word-based signs in reducing speed and latency to brake, although the effect varied between twilight and night. However, the word-based RADS signs still did produce significant reductions in speed and braking latency. Conclusions: We conclude that the word-based RADS in Big Cypress should help prevent dangerous wildlife-vehicle collisions, but that redesigning the warning signs to be picture-based could yield even greater benefits.

  3. A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: skin irritation.

    Science.gov (United States)

    Macfarlane, Martin; Jones, Penny; Goebel, Carsten; Dufour, Eric; Rowland, Joanna; Araki, Daisuke; Costabel-Farkas, Margit; Hewitt, Nicola J; Hibatallah, Jalila; Kirst, Annette; McNamee, Pauline; Schellauf, Florian; Scheel, Julia

    2009-07-01

    Evaluation of the skin irritancy and corrosivity potential of an ingredient is a necessity in the safety assessment of cosmetic ingredients. To date, there are two formally validated alternatives to the rabbit Draize test for skin corrosivity in place, namely the rat skin transcutaneous electrical resistance (TER) assay and the Human Skin Model Test using EpiSkin, EpiDerm and SkinEthic reconstructed human epidermal equivalents. For skin irritation, EpiSkin, EpiDerm and SkinEthic are validated as stand-alone test replacements for the rabbit Draize test. Data from these tests are rarely considered in isolation and are evaluated in combination with other factors to establish the overall irritating or corrosive potential of an ingredient. In light of the deadlines established in the Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. In conclusion, the safety assessments for skin irritation/corrosion of new chemicals for use in cosmetics can be confidently accomplished using exclusively alternative methods.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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

  6. A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

    Directory of Open Access Journals (Sweden)

    Albrekt Ann-Sofie

    2011-08-01

    Full Text Available Abstract Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.

  7. A European perspective on alternatives to animal testing for environmental hazard identification and risk assessment

    NARCIS (Netherlands)

    Scholz, S.; Sela, E.; Blaha, L.; Braunbeck, T.; Galay-Burgos, M.; Garcia-Franco, M.; Guinea, J.; Kluver, N.; Schirmer, K.; Tanneberger, K.; Tobor-Kaplon, M.; Witters, H.; Belanger, S.; Benfenati, E.; Creton, S.; Cronin, M.T.D.; Eggen, R.I.L.; Embry, M.; Ekman, D.; Gourmelon, A.; Halder, M.; Hardy, B.; Hartung, T.; Hubesch, B.; Jungmann, D.; Lampi, M.A.; Lee, van L.; Leonard, M.; Kuster, E.; Lillicrap, A.; Luckenbach, T.; Murk, A.J.; Navas, J.M.; Peijnenburg, W.; Repetto, G.; Salinas, E.; Schuurmann, G.; Spielmann, H.; Tollefsen, K.E.; Walter-Rohde, S.; Whale, G.; Wheeler, J.R.; Winter, M.J.

    2013-01-01

    Tests with vertebrates are an integral part of environmental hazard identification and risk assessment of chemicals, plant protection products, pharmaceuticals, biocides, feed additives and effluents. These tests raise ethical and economic concerns and are considered as inappropriate for assessing

  8. Validity study of Animal-City Alternating Form Fluency Test in the identification of mild cognitive impairment and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Yun-bo SHI

    2015-07-01

    Full Text Available Objective To identify the sensitivity and specificity of Animal-City Alternating Form Fluency Test (ACFT differentiating mild cognitive impairment (MCI and Alzheimer's disease (AD from normal controls.  Methods A total of 121 MCI patients, 104 AD patients and 104 healthy controls, who were matched in sex, age and education level, were enrolled in this study. They performed Animal Category Verbal Fluency Test (AFT, City Category Verbal Fluency Test (CFT and ACFT. A series of standard neuropsychological tests were also administered to reflect episodic memory, verbal ability, working memory, executive function and processing speed. The validity and related influencing factors of ACFT was evaluated.  Results Compared with control group, the ACFT correct number in MCI and AD groups reduced significantly (P = 0.000, 0.000. Receiver operating characteristic (ROC curve revealed the sensitivity and specificity of ACFT in discriminating MCI (P = 0.012, 0.030 and AD (P = 0.004, 0.003 from normal controls were higher than those of AFT and CFT. There was no correlation of correct number in ACFT with age and education (P > 0.05, for all. The correlations of ACFT with Stroop Color-Word Test (SCWT, Digital Symbol Substitution Test (DSST, Shape Trail Test (STT and Digit Span Test (DS, all of which reflected attention and executive function, were significantly closer than those of AFT and CFT (P < 0.05, for all. Conclusions ACFT is more efficient in early cognitive impairment identification than the other traditional category verbal fluency tests. It is a new variant form of category verbal fluency test that could assess cognitive function and could be broadly applied in clinical practice. DOI: 10.3969/j.issn.1672-6731.2015.07.010

  9. A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: eye irritation.

    Science.gov (United States)

    McNamee, Pauline; Hibatallah, Jalila; Costabel-Farkas, Margit; Goebel, Carsten; Araki, Daisuke; Dufour, Eric; Hewitt, Nicola J; Jones, Penny; Kirst, Annette; Le Varlet, Béatrice; Macfarlane, Martin; Marrec-Fairley, Monique; Rowland, Joanna; Schellauf, Florian; Scheel, Julia

    2009-07-01

    The need for alternative approaches to replace the in vivo rabbit Draize eye test for evaluation of eye irritation of cosmetic ingredients has been recognised by the cosmetics industry for many years. Extensive research has lead to the development of several assays, some of which have undergone formal validation. Even though, to date, no single in vitro assay has been validated as a full replacement for the rabbit Draize eye test, organotypic assays are accepted for specific and limited regulatory purposes. Although not formally validated, several other in vitro models have been used for over a decade by the cosmetics industry as valuable tools in a weight of evidence approach for the safety assessment of ingredients and finished products. In light of the deadlines established in the EU Cosmetics Directive for cessation of animal testing for cosmetic ingredients, a COLIPA scientific meeting was held in Brussels on 30th January, 2008 to review the use of alternative approaches and to set up a decision-tree approach for their integration into tiered testing strategies for hazard and safety assessment of cosmetic ingredients and their use in products. Furthermore, recommendations are given on how remaining data gaps and research needs can be addressed.

  10. In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing.

    Science.gov (United States)

    Jomaa, Barae; Aarts, Jac M M J G; de Haan, Laura H J; Peijnenburg, Ad A C M; Bovee, Toine F H; Murk, Albertinka J; Rietjens, Ivonne M C M

    2013-01-01

    This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.

  11. State of the art on alternative methods to animal testing from an industrial point of view: ready for regulation?

    NARCIS (Netherlands)

    Ashton, R.; Wever, B. de; Fuchs, H.W.; Gaca, M.; Hill, E.; Krul, C.A.M.; Poth, A.; Roggen, E.L.

    2014-01-01

    Despite changing attitudes towards animal testing and current legislation to protect experimental animals, the rate of animal experiments seems to have changed little in recent years. On May 15–16, 2013, the In Vitro Testing Industrial Platform (IVTIP) held an open meeting to discuss the state of

  12. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop (presentation)

    Science.gov (United States)

    Since the 1940s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that toxicit...

  13. Animal alternatives for whole effluent toxicity testing: Perspectives from a global workshop

    Science.gov (United States)

    Since the 1940’s, effluent toxicity testing has been utilized to varying degrees in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only in the early 1980’s that ...

  14. Justification of the enucleated eye test with eyes of slaughterhouse animals as an alternative to the Draize eye irritation test with rabbits.

    Science.gov (United States)

    Prinsen, M K; Koëter, H B

    1993-01-01

    The enucleated eye test (EET) with the isolated eye of rabbits has been recognized as a valuable alternative to the Draize test, because it represents a test system nearest to the in vivo test, without the need to use live animals. In this ex vivo bioassay, three parameters are measured to detect possible adverse eye effects, namely corneal swelling, corneal opacity and fluorescein retention. The measurement of corneal swelling in this assay guarantees a highly objective and discriminative parameter. In combination with the detailed observation of corneal opacity and fluorescein retention, a reliable evaluation of the eye irritation potential of test materials is achieved. However, laboratory animals are still necessary as eye donors. The use of slaughter animals, such as the cow, the pig and the chicken, as possible as eye donors for the EET was therefore examined. From these candidates, the chicken appeared to be the most practicable. 21 reference compounds, ranging from non-irritant to severe irritant, which had been tested previously in a validation study on alternative test methods for eye irritation testing, sponsored by the Commission of the European Communities, were examined in the Chicken Enucleated Eye Test (CEET). When compared with the in vivo EC classification, the CEET correctly classified each of the compounds that must be labelled in the EC as irritant (R36) or severely irritant (R41). In addition, since the CEET recognizes three levels of irritancy rather than two (as in the case of the EC classification) a small number of the compounds were recognized as slightly irritant, which according to the EC classification need not be labelled. It was concluded that this ex vivo test system is highly accurate in the assessment of eye irritation potential without the use of laboratory animals.

  15. Alternatives to animal experimentation: The regulatory background

    International Nuclear Information System (INIS)

    Garthoff, Bernward

    2005-01-01

    The framework, in which alternatives to animal experiments can be developed, standardized, respectively formally validated, has to be seen in a global context. The ever increasing demand of testing for hazard and risk assessment in health and environment, exemplified by the EU REACH program, subsequently triggers laboratory animal testing. This holds especially true, if no valid alternative methods agreed to by the regulatory authorities and the scientific community are available. At least for regulatory toxicity testing, the global frame and network are given by institutions such as OECD, ICH, and alike. However, due to the necessity of global consent of states, organizations, and stakeholders, the time gap between availability of a novel alternative test method and its final acceptance by authorities and implementation thereafter is widening. The lack of new technologies or opportunities for alternative method application such as, for example, the broad use of transgenic animals for refinement of existing tests, adds to the problem. The bare existence of certain in vivo tests increases also the gap between public demands for testing versus availability of alternative tests. Industries operating on a worldwide basis support the alternative test development in their respective area of research and operational business. However, a more coordinating approach such as that of the ecopa-organization (European Consensus Platform on Alternatives) is needed to exploit the existing possibilities within the current regulatory framework. This will speed up the process of acceptance and challenge the political worldto feel responsible for the sequels of their demanding more testing, that is, by funding alternative method development in academia and industry

  16. The Center for Alternatives to Animal Testing - Europe (CAAT-EU): a transatlantic bridge for the paradigm shift in toxicology.

    Science.gov (United States)

    Daneshian, Mardas; Leist, Marcel; Hartung, Thomas

    2010-01-01

    The Center for Alternatives to Animal Testing - Europe (CAAT-EU) was founded based collaboration between the Johns Hopkins Bloomberg School of Public Health and the University of Konstanz. CAAT-EU, housed at the University of Konstanz, will coordinate transatlantic activities to promote humane science in research and education, and participate, as partner or coordinator, in publicly and privately funded European projects. Thomas Hartung will serve as program liaison representing Johns Hopkins University and Marcel Leist as the University of Konstanz liaison. CAAT-EU aims to: 1) Set up transatlantic consortia for international research projects on alternative methods. 2) Establish a CAAT Europe faculty and advisory board composed of sponsor representatives and prominent academics from Europe . 3) Participate in the Transatlantic Think Tank for Toxicology (t4) devoted to conceptual work for the paradigm shift in toxicology. 4) Coordinate a series of information days in Europe on relevant developments in the US, similar to the 2009 series CAAT held in the US on EU issues (one on the 7th Amendment to the EU Cosmetics Directive and one on EU and US chemical regulation). 5) Support ALTEX as the official journal of CAAT and CAAT-EU. 6) Develop strategic projects with sponsors to promote humane science and new toxicology, especially with CAAT faculty members. 7) Develop a joint education program between Johns Hopkins and the University of Konstanz, such as e-courses and the existing Humane Science Certificate program developed by CAAT, a student exchange program, and collaboration with the International Graduate School "Cell-based Characterization of De- and Regeneration" in Konstanz.

  17. Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation.

    Science.gov (United States)

    Höfer, Thomas; Gerner, Ingrid; Gundert-Remy, Ursula; Liebsch, Manfred; Schulte, Agnes; Spielmann, Horst; Vogel, Richard; Wettig, Klaus

    2004-10-01

    During the past 20 years the EU legislation for the notification of chemicals has focussed on new chemicals and at the same time failed to cover the evaluation of existing chemicals in Europe. Therefore, in a new EU chemicals policy (REACH, Registration, Evaluation and Authorization of Chemicals) the European Commission proposes to evaluate 30,000 chemicals within a period of 15 years. We are providing estimates of the testing requirements based on our personal experiences during the past 20 years. A realistic scenario based on an in-depth discussion of potential toxicological developments and an optimised "tailor-made" testing strategy shows that to meet the goals of the REACH policy, animal numbers may be significantly reduced below 10 million if industry would use in-house data from toxicity testing, which are confidential, if non-animal tests would be used, and if information from quantitative structure activity relationships (QSARs) would be applied in substance-tailored testing schemes. The procedures for evaluating the reproductive toxicity of chemicals have the strongest impact on the total number of animals bred for testing under REACH. We are assuming both an active collaboration with our colleagues in industry and substantial funding of the development and validation of advanced non-animal methods by the EU Commission, specifically in reproductive and developmental toxicity.

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

    NARCIS (Netherlands)

    Basketter, D.A.; Clewell, H.; Kimber, I.; Rossi, A.; Blaauboer, B.J.; Burrier, R.; Daneshian, M.; Eskes, C.; Goldberg, A.; Hasiwa, N.

    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

  19. The contributions of the European cosmetics industry to the development of alternatives to animal testing: dialogue with ECVAM and future challenges.

    Science.gov (United States)

    de Silva, Odile

    2002-12-01

    COLIPA (the European Federation of the Cosmetics Industry) represents 24 international companies and 2000 small and medium-sized enterprises. Together with ECVAM, COLIPA has been involved in the development and validation of alternative methods since the beginning of the validation efforts. The work of the Steering Committee on Alternatives to Animal Testing (SCAAT) is based on collaboration between companies, but also with academia, trade associations, the Scientific Committee on Cosmetics and Non-Food Products (SCCNFP), European Commission Directorates General, and ECVAM. Some success has been achieved, but some validation efforts have failed. One lesson is that the search for alternatives requires a lot of humility.

  20. Alternatives to animal experimentation in basic research.

    Science.gov (United States)

    Gruber, Franz P; Hartung, Thomas

    2004-01-01

    In contrast to animal testing required by law to guarantee minimum safety standards for the licensing of drugs and chemicals, there are no regulations in basic research forcing scientists to perform animal tests. By (usually) free choice, questions are posed and hypotheses are examined which, in many cases, can only be answered by means of animal tests. Just as easily, different questions could be asked or different hypotheses could be examined which do not require animal tests. The only criterion for the choice of a topic is its relevance which cannot necessarily be judged in the short-term. Thus, it is up to the individual scientist to judge what is worth studying and therefore worth animal consumption. The educated mind will consider ethical aspects of this choice. However, on the other hand, this decision is largely influenced by questions of efficacy or (in a negative sense) by the obstacles posed to an animal consuming approach. Here, peer review and general attitude will strongly influence the methodology chosen. Availability and awareness of adequate in vitro techniques represent the prerequisites for the use of alternative methods. The least one can do in basic research is to avoid tests which cause severe suffering to animals, as is required in Switzerland and other European countries by binding ethical principles and guidelines. The increasing standard of approval and control procedures has improved the situation over the years. There are many examples of successful alternative methods in basic research. But, the application of such methods is in most cases limited to the laboratories in which they were developed, calling for technology transfer. Exceptions are procedures that are used worldwide, like the production of monoclonal antibodies, which instead of using the ascites mouse can also be performed in vitro with some good will. In these cases, commercialisation of the techniques has aided their spread within the scientific community. Sadly, many

  1. Estimation of bisphenol A-Human toxicity by 3D cell culture arrays, high throughput alternatives to animal tests.

    Science.gov (United States)

    Lee, Dong Woo; Oh, Woo-Yeon; Yi, Sang Hyun; Ku, Bosung; Lee, Moo-Yeal; Cho, Yoon Hee; Yang, Mihi

    2016-09-30

    Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics and epoxy resins and has been extensively tested in animals to predict human toxicity. In order to reduce the use of animals for toxicity assessment and provide further accurate information on BPA toxicity in humans, we encapsulated Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D) on a micropillar chip coupled to a panel of metabolic enzymes on a microwell chip. As a result, we were able to assess the toxicity of BPA under various metabolic enzyme conditions using a high-throughput and micro assay; sample volumes were nearly 2,000 times less than that required for a 96-well plate. We applied a total of 28 different enzymes to each chip, including 10 cytochrome P450s (CYP450s), 10 UDP-glycosyltransferases (UGTs), 3 sulfotransferases (SULTs), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase 2 (ALDH2). Phase I enzyme mixtures, phase II enzyme mixtures, and a combination of phase I and phase II enzymes were also applied to the chip. BPA toxicity was higher in samples containing CYP2E1 than controls, which contained no enzymes (IC50, 184±16μM and 270±25.8μM, respectively, palternative to animal testing for estimating BPA toxicity via human metabolic systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Testing the biocompatibility of a glutathione-containing intra-ocular irrigation solution by using an isolated perfused bovine retina organ culture model - an alternative to animal testing.

    Science.gov (United States)

    Januschowski, Kai; Zhour, Ahmad; Lee, Albert; Maddani, Ramin; Mueller, Sebastien; Spitzer, Martin S; Schnichels, Sven; Schultheiss, Maximilian; Doycheva, Deshka; Bartz-Schmidt, Karl-Ulrich; Szurman, Peter

    2012-03-01

    The effects of a glutathione-containing intra-ocular irrigation solution, BSS Plus©, on retinal function and on the survival of ganglion cells in whole-mount retinal explants were studied. Evidence is provided that the perfused ex vivo bovine retina can serve as an alternative to in vivo animal testing. Isolated bovine retinas were prepared and perfused with an oxygen-saturated standard irrigation solution, and an electroretinogram was recorded to assess retinal function. After stable b-waves were detected, the isolated retinas were perfused with BSS Plus for 45 minutes. To investigate the effects of BSS Plus on photoreceptor function, 1mM aspartate was added to the irrigation solution in order to obtain a-waves, and the ERG trace was monitored for 75 minutes. For histological analysis, isolated whole retinal mounts were stored for 24 hours at 4°C, in the dark. The percentages of cell death in the retinal ganglion cell layer and in the outer and inner nuclear layers were estimated by using an ethidium homodimer-1 stain and the TUNEL assay. General swelling of the retina was examined with high-resolution optical coherence tomography. During perfusion with BSS Plus, no significant changes in a-wave and b-wave amplitudes were recorded. Retinas stored for 24 hours in BSS Plus showed a statistically significant smaller percentage (52.6%, standard deviation [SD] = 16.1%) of cell death in the retinal ganglion cell layer compared to the control group (69.6%, SD = 3.9, p = 0.0031). BSS Plus did not seem to affect short-term retinal function, and had a beneficial effect on the survival of retinal ganglion cells. This method for analysing the isolated perfused retina represents a valuable alternative for testing substances for their retinal biocompatibility and toxicity. 2012 FRAME.

  3. Alternatives to Use of Animals in Research,

    Science.gov (United States)

    1980-03-28

    prevent unnecessary cruelty to animals . (I’ As discussed with your office, we fou --iU-ifrma-- ___ tion availab)e to enable us to adequately respond to...use of labora- tory animals . In that study, alternatives were defined as systems or procedures that could reduce the (1) number of animals used or (2...information is needed on the advantages and limitations of alternative methods and the extent of inappropriate animal experimentation before decid- ing

  4. Differential Reinforcement of Alternative Behavior Increases Resistance to Extinction: Clinical Demonstration, Animal Modeling, and Clinical Test of One Solution

    Science.gov (United States)

    Mace, F. Charles; McComas, Jennifer J.; Mauro, Benjamin C.; Progar, Patrick R.; Taylor, Bridget; Ervin, Ruth; Zangrillo, Amanda N.

    2010-01-01

    Basic research with pigeons on behavioral momentum suggests that differential reinforcement of alternative behavior (DRA) can increase the resistance of target behavior to change. This finding suggests that clinical applications of DRA may inadvertently increase the persistence of target behavior even as it decreases its frequency. We conducted…

  5. Electrochemistry of Canis familiaris cytochrome P450 2D15 with gold nanoparticles: An alternative to animal testing in drug discovery.

    Science.gov (United States)

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Valetti, Francesca; Gilardi, Gianfranco

    2015-10-01

    This work reports for the first time the direct electron transfer of the Canis familiaris cytochrome P450 2D15 on glassy carbon electrodes to provide an analytical tool as an alternative to P450 animal testing in the drug discovery process. Cytochrome P450 2D15, that corresponds to the human homologue P450 2D6, was recombinantly expressed in Escherichia coli and entrapped on glassy carbon electrodes (GC) either with the cationic polymer polydiallyldimethylammonium chloride (PDDA) or in the presence of gold nanoparticles (AuNPs). Reversible electrochemical signals of P450 2D15 were observed with calculated midpoint potentials (E1/2) of −191 ± 5 and −233 ± 4 mV vs. Ag/AgCl for GC/PDDA/2D15 and GC/AuNPs/2D15, respectively. These experiments were then followed by the electro-catalytic activity of the immobilized enzyme in the presence of metoprolol. The latter drug is a beta-blocker used for the treatment of hypertension and is a specific marker of the human P450 2D6 activity. Electrocatalysis data showed that only in the presence of AuNps the expected α-hydroxy-metoprolol product was present as shown by HPLC. The successful immobilization of the electroactive C. familiaris cytochrome P450 2D15 on electrode surfaces addresses the ever increasing demand of developing alternative in vitromethods for amore detailed study of animal P450 enzymes' metabolism, reducing the number of animals sacrificed in preclinical tests.

  6. In vitro detection of cardiotoxins or neurotoxins affecting ion channels or pumps using beating cardiomyocytes as alternative for animal testing

    NARCIS (Netherlands)

    Nicolas, J.A.Y.; Hendriksen, P.J.M.; Haan, de L.H.J.; Koning, R.; Rietjens, I.M.C.M.; Bovee, T.F.H.

    2015-01-01

    The present study investigated if and to what extent murine stem cell-derived beating cardiomyocytes within embryoid bodies can be used as a broad screening in vitro assay for neurotoxicity testing, replacing for example in vivo tests for marine neurotoxins. Effect of nine model compounds, acting on

  7. The classification of motor neuron defects in the zebrafish embryo toxicity test (ZFET) as an animal alternative approach to assess developmental neurotoxicity.

    Science.gov (United States)

    Muth-Köhne, Elke; Wichmann, Arne; Delov, Vera; Fenske, Martina

    2012-07-01

    Rodents are widely used to test the developmental neurotoxicity potential of chemical substances. The regulatory test procedures are elaborate and the requirement of numerous animals is ethically disputable. Therefore, non-animal alternatives are highly desirable, but appropriate test systems that meet regulatory demands are not yet available. Hence, we have developed a new developmental neurotoxicity assay based on specific whole-mount immunostainings of primary and secondary motor neurons (using the monoclonal antibodies znp1 and zn8) in zebrafish embryos. By classifying the motor neuron defects, we evaluated the severity of the neurotoxic damage to individual primary and secondary motor neurons caused by chemical exposure and determined the corresponding effect concentration values (EC₅₀). In a proof-of-principle study, we investigated the effects of three model compounds thiocyclam, cartap and disulfiram, which show some neurotoxicity-indicating effects in vertebrates, and the positive controls ethanol and nicotine and the negative controls 3,4-dichloroaniline (3,4-DCA) and triclosan. As a quantitative measure of the neurotoxic potential of the test compounds, we calculated the ratios of the EC₅₀ values for motor neuron defects and the cumulative malformations, as determined in a zebrafish embryo toxicity test (zFET). Based on this index, disulfiram was classified as the most potent and thiocyclam as the least potent developmental neurotoxin. The index also confirmed the control compounds as positive and negative neurotoxicants. Our findings demonstrate that this index can be used to reliably distinguish between neurotoxic and non-neurotoxic chemicals and provide a sound estimate for the neurodevelopmental hazard potential of a chemical. The demonstrated method can be a feasible approach to reduce the number of animals used in developmental neurotoxicity evaluation procedures. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. [Alternatives to animal experimentation v.s. animal rights terrorism].

    Science.gov (United States)

    Kurosawa, Tsutomu Miki

    2008-05-01

    Systematic modern animal experimentation was established by Bernard Claude who wrote "An Introduction to the Study of Experimental Medicine" in 1865. At this point, the public was already asking that the pain and distress of experimental animals be reduced. For this, scientists, William Russell and Rex Burch in 1959 proposed the principles of alternatives to animal experimentation, the "3Rs". Since that time, animal welfare advocates have promoted the 3Rs concept in biomedical research communities. However, cruel animal experiments have continued and there are reports of radical extremists showing their opposition by invasion, arson, theft and even bombing of institutions involved, resulting in killing of the animals. SHAC, one extremist group believed to be animal welfare activitists was recognized as a terrorist group after the 9.11 tragedy in USA and the government viewed their activities very seriously. In 2001, British animal extremists invaded Japanese universities and stole laboratory resources; one individual was arrested and sentenced to prison for three years; Japanese who assisted in the incident were arrested and one was sentenced for one year. In 2006, SHAC USA members were prosecuted and sentenced for up to 6 years for their terrorism activities including arson. We need to consider the background of these activities which are financially supported by animal welfare advocates. The way we, as scientists who conduct such experiments can respond is by promoting alternatives to this experimentation. In Japan, the animal welfare law was revised in 2005 stressing the importance of 3Rs in scientific activities with animals. The promotion of 3Rs should be strengthened in the pharmaceutical community.

  9. Alternative fat sources to animal fat for pigs

    DEFF Research Database (Denmark)

    Lauridsen, Charlotte; Christensen, Thomas Bruun; Halekoh, Ulrich

    2007-01-01

    % of either animal fat, palm oil mix, palm oil, vegetable oil mix, coconut oil, or rapeseed oil were tested in weaned and growing pigs. It was concluded that several vegetable fat sources (palm oil mix, palm oil, coconut oil, rapeseed oil) could be used as alternatives to animal fat in pig feed, whereas fat......The use of fats and oils in diets for pigs is of great importance due to their high energy value. As a consequence of the BSE-crisis in the European Union, the amount of animal fat available for animal feeds has been reduced, and alternative fat sources are of increasing importance. In this paper...

  10. A FRAME response to the Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects--2010.

    Science.gov (United States)

    Balls, Michael; Clothier, Richard

    2010-10-01

    This response on behalf of FRAME to the European Commission's consultation on the five chapters of the Draft Report on Alternative (Non-animal) Methods for Cosmetics Testing: Current Status and Future Prospects--2010, is via a Comment in ATLA, rather than via the template supplied by the Commission. This is principally so that a number of general points about cosmetic ingredient testing can be made. It is concluded that the five draft chapters do not provide a credible basis for the Commission's forthcoming report to the European Parliament and the European Council on the five cosmetic ingredient safety issues for which the 7th Amendment to the Cosmetic Directive's ban on animal testing was postponed until 2013. This is mainly because there is insufficient focus in the draft chapters on the specific nature of cosmetic ingredients, their uses, their local effects and metabolism at their sites of application, and, in particular, on whether their possible absorption into the body would be likely to lead to their accumulation in target sites at levels approaching Thresholds of Toxicological Concern. Meanwhile, there continues to be uncertainty about how the provisions of the Cosmetics Directive should be applied, given the requirements of the REACH system and directives concerned with the safety of other chemicals and products. © 2010 FRAME.

  11. A critical review of anaesthetised animal models and alternatives for military research, testing and training, with a focus on blast damage, haemorrhage and resuscitation.

    Science.gov (United States)

    Combes, Robert D

    2013-11-01

    Military research, testing, and surgical and resuscitation training, are aimed at mitigating the consequences of warfare and terrorism to armed forces and civilians. Traumatisation and tissue damage due to explosions, and acute loss of blood due to haemorrhage, remain crucial, potentially preventable, causes of battlefield casualties and mortalities. There is also the additional threat from inhalation of chemical and aerosolised biological weapons. The use of anaesthetised animal models, and their respective replacement alternatives, for military purposes -- particularly for blast injury, haemorrhaging and resuscitation training -- is critically reviewed. Scientific problems with the animal models include the use of crude, uncontrolled and non-standardised methods for traumatisation, an inability to model all key trauma mechanisms, and complex modulating effects of general anaesthesia on target organ physiology. Such effects depend on the anaesthetic and influence the cardiovascular system, respiration, breathing, cerebral haemodynamics, neuroprotection, and the integrity of the blood-brain barrier. Some anaesthetics also bind to the NMDA brain receptor with possible differential consequences in control and anaesthetised animals. There is also some evidence for gender-specific effects. Despite the fact that these issues are widely known, there is little published information on their potential, at best, to complicate data interpretation and, at worst, to invalidate animal models. There is also a paucity of detail on the anaesthesiology used in studies, and this can hinder correct data evaluation. Welfare issues relate mainly to the possibility of acute pain as a side-effect of traumatisation in recovered animals. Moreover, there is the increased potential for animals to suffer when anaesthesia is temporary, and the procedures invasive. These dilemmas can be addressed, however, as a diverse range of replacement approaches exist, including computer and mathematical

  12. In vitro detection of cardiotoxins or neurotoxins affecting ion channels or pumps using beating cardiomyocytes as alternative for animal testing.

    Science.gov (United States)

    Nicolas, Jonathan; Hendriksen, Peter J M; de Haan, Laura H J; Koning, Rosella; Rietjens, Ivonne M C M; Bovee, Toine F H

    2015-03-01

    The present study investigated if and to what extent murine stem cell-derived beating cardiomyocytes within embryoid bodies can be used as a broad screening in vitro assay for neurotoxicity testing, replacing for example in vivo tests for marine neurotoxins. Effect of nine model compounds, acting on either the Na(+), K(+), or Ca(2+) channels or the Na(+)/K(+) ATP-ase pump, on the beating was assessed. Diphenhydramine, veratridine, isradipine, verapamil and ouabain induced specific beating arrests that were reversible and none of the concentrations tested induced cytotoxicity. Three K(+) channel blockers, amiodarone, clofilium and sematilide, and the Na(+)/K(+) ATPase pump inhibitor digoxin had no specific effect on the beating. In addition, two marine neurotoxins i.e. saxitoxin and tetrodotoxin elicited specific beating arrests in cardiomyocytes. Comparison of the results obtained with cardiomyocytes to those obtained with the neuroblastoma neuro-2a assay revealed that the cardiomyocytes were generally somewhat more sensitive for the model compounds affecting Na(+) and Ca(2+) channels, but less sensitive for the compounds affecting K(+) channels. The stem cell-derived cardiomyocytes were not as sensitive as the neuroblastoma neuro-2a assay for saxitoxin and tetrodotoxin. It is concluded that the murine stem cell-derived beating cardiomyocytes provide a sensitive model for detection of specific neurotoxins and that the neuroblastoma neuro-2a assay may be a more promising cell-based assay for the screening of marine biotoxins. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Metabolic activation capacity by primary hepatocytes expands the applicability of the embryonic stem cell test as alternative to experimental animal testing.

    Science.gov (United States)

    Hettwer, Michael; Reis-Fernandes, Marcos A; Iken, Marcus; Ott, Michael; Steinberg, Pablo; Nau, Heinz

    2010-08-01

    The murine embryonic stem cell test (EST) represents a validated alternative method for in vivo embryotoxicity testing. In the present study, primary hepatocytes were combined with the EST by a preincubation approach to improve its predictivity on bioactivation caused teratogenicity. As substances the well-known proteratogens cyclophosphamide (CPA) and valpromide (VPD) were used. The embryotoxic potential of CPA was detected by a strong decrease of the resulting ID(50)-concentration (50% inhibition of ES cell differentiation) after incubation with murine hepatocytes. Interspecies variation in metabolism was detected by testing VPD. After incubation of VPD with murine hepatocytes no inhibition of ES cell differentiation was observed, since hardly any teratogenic VPD metabolites were formed. In contrast, with human hepatocytes a significant conversion of VPD into the teratogen valproic acid (VPA) was observed. In summary we developed a co-culture approach for embryotoxicity testing, whereby the test compounds were incubated with hepatocytes and the supernatant was added to the ES cell culture to obtain a dose dependency of the preincubated test substances. Copyright 2010 Elsevier Inc. All rights reserved.

  14. [Alternative methods to animal experimentation. Scientific and ethical problems].

    Science.gov (United States)

    Adolphe, M

    1995-06-01

    The alternative methods include all the technologies able to replace animal experimentation. This denomination has been much debated and several researchers prefer the term of complementary methods. Alternative methods consist mainly of methods based on organ and cell culture but also includes cell organelles. These methods have been introduced gradually over the years particularly in toxicology but also in biology, physiology, pathology and pharmacology. The reasons for this development are from technological and ethical sources. This last point was due to the consciousness of industrial countries on the animal suffering which is at the origin of groups for animal welfare, able to influence european governments. The results of the development of the alternative methods are an increase in fundamental and applied research under the influence of various organisations such as in England: FRAME (Fund for the Replacement of Animals in Medical Experimentals), in USA: John Hopkins Center and in ECC: ECVAM (European Center for the Validation of Alternative Methods). This last Center is particularly devoted to validation which are defined as "the process whereby the reliability and relevance of a procedure are established for a particular purpose". This involves several stages. Some validations procedures are now in progress mainly in the aim of evaluating potential alternative methods to the Draize eye irritation test. Alternative methods are able to decrease the use of animal experiments and consequently improve animal ethics although they could not replace totally animal experiments. However they are complementary and very useful for the screening of drugs and mechanistic areas.

  15. A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: genotoxicity. A COLIPA analysis.

    Science.gov (United States)

    Pfuhler, Stefan; Kirst, Annette; Aardema, Marilyn; Banduhn, Norbert; Goebel, Carsten; Araki, Daisuke; Costabel-Farkas, Margit; Dufour, Eric; Fautz, Rolf; Harvey, James; Hewitt, Nicola J; Hibatallah, Jalila; Carmichael, Paul; Macfarlane, Martin; Reisinger, Kerstin; Rowland, Joanna; Schellauf, Florian; Schepky, Andreas; Scheel, Julia

    2010-01-01

    For the assessment of genotoxic effects of cosmetic ingredients, a number of well-established and regulatory accepted in vitro assays are in place. A caveat to the use of these assays is their relatively low specificity and high rate of false or misleading positive results. Due to the 7th amendment to the EU Cosmetics Directive ban on in vivo genotoxicity testing for cosmetics that was enacted March 2009, it is no longer possible to conduct follow-up in vivo genotoxicity tests for cosmetic ingredients positive in in vitro genotoxicity tests to further assess the relevance of the in vitro findings. COLIPA, the European Cosmetics Association, has initiated a research programme to improve existing and develop new in vitro methods. A COLIPA workshop was held in Brussels in April 2008 to analyse the best possible use of available methods and approaches to enable a sound assessment of the genotoxic hazard of cosmetic ingredients. Common approaches of cosmetic companies are described, with recommendations for evaluating in vitro genotoxins using non-animal approaches. A weight of evidence approach was employed to set up a decision-tree for the integration of alternative methods into tiered testing strategies. Copyright 2010 Elsevier Inc. All rights reserved.

  16. Alternative test models for skin aging research.

    Science.gov (United States)

    Nakamura, Motoki; Haarmann-Stemmann, Thomas; Krutmann, Jean; Morita, Akimichi

    2018-02-25

    Increasing ethical concerns regarding animal experimentation have led to the development of various alternative methods based on the 3Rs (Refinement, Reduction, and Replacement), first described by Russell and Burch in 1959. Cosmetic and skin aging research are particularly susceptible to concerns related to animal testing. In addition to animal welfare reasons, there are scientific and economic reasons to reduce and avoid animal experiments. Importantly, animal experiments may not reflect findings in humans mainly because of the differences of architectures and immune responses between animal skin and human skin. Here we review the shift from animal testing to the development and application of alternative non-animal based methods and the necessity and benefits of this shift. Some specific alternatives to animal models are discussed, including biochemical approaches, two-dimensional and three-dimensional cell cultures, and volunteer studies, as well as future directions, including genome-based research and the development of in silico computer simulations of skin models. Among the in vitro methods, three-dimensional reconstructed skin models are highly popular and useful alternatives to animal models however still have many limitations. With careful selection and skillful handling, these alternative methods will become indispensable for modern dermatology and skin aging research. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Progress Toward Replacing Animals in Toxicity Testing for Cosmetics

    OpenAIRE

    Nye, Marisa B.

    2006-01-01

    In the 1980’s, animal rights activists successfully motivated the cosmetic industry to begin researching alternatives to animal tests. The European Union has taken action to stimulate development and validation of alternatives to animal testing through the Sixth and Seventh Amendments to the Cosmetics Directive. In this paper, I will briefly describe the history of the search for alternatives to animal testing for cosmetics. I will then discuss the progress that has been ma...

  18. Alternative Raw Materials for Animal Feed

    OpenAIRE

    A R Alimon

    2009-01-01

    The increase in world fuel prices in the last few years has charged the global animal feedstuffs. In Malaysia, the feed industry is dependent on the importation of corn and soybean meal as the poultry and swine industries are almost totally based on corn soya bean meal diets. However, there are many byproducts and coproducts available in Malaysia as alternatives to corn or soy bean. Since Malaysia has more than 4 million hectares of oil palm plantation and after processing for the oil, large ...

  19. Alternative Raw Materials for Animal Feed

    Directory of Open Access Journals (Sweden)

    A R Alimon

    2009-06-01

    Full Text Available The increase in world fuel prices in the last few years has charged the global animal feedstuffs. In Malaysia, the feed industry is dependent on the importation of corn and soybean meal as the poultry and swine industries are almost totally based on corn soya bean meal diets. However, there are many byproducts and coproducts available in Malaysia as alternatives to corn or soy bean. Since Malaysia has more than 4 million hectares of oil palm plantation and after processing for the oil, large quantities of several byproducts are produced. This paper describes several available byproducts and co products in Malaysia, their nutritive value and their problems.

  20. Reporter cell lines for detection of pertussis toxin in acellular pertussis vaccines as a functional animal-free alternative to the in vivo histamine sensitization test.

    Science.gov (United States)

    Hoonakker, Marieke E; Verhagen, Lisa M; van der Maas, Larissa; Sloots, Arjen; Hendriksen, Coenraad F M

    2017-02-22

    Detoxified pertussis toxin (pertussis toxoid) is a major antigen in acellular pertussis vaccines. Testing these vaccines on the presence of residual pertussis toxin (PTx) and reversion to toxicity is performed by the regulatory required in vivo Histamine Sensitization test (HIST). Lack of mechanistic understanding of the HIST, technical handicaps and animal welfare concerns, have promoted the development of alternative methods. As the majority of the cellular effects of PTx depend on its ability to activate intracellular pathways involving cAMP, the in vitro cAMP-PTx assay was developed. Although this assay could be used to detect PTx activity, it lacked sensitivity and robustness for use in a quality control setting. In the present study, novel reporter cell lines (CHO-CRE and A10-CRE) were generated that stably express a reporter construct responsive to changes in intracellular cAMP levels. These reporter cell lines were able to detect PTx in a concentration-dependent manner when combined with fixed amounts of forskolin. The CHO-CRE cell line enabled detection of PTx in the context of a multivalent vaccine containing aP, with a sensitivity equal to the HIST. However, the sensitivity of the A10-CRE cells was insufficient for this purpose. The experiments also suggest that the CHO-CRE reporter cell line might be suitable for assessment of cellular effects of PTd reverted to PTx. The CHO-CRE reporter cell line provides a platform that meets the criteria for specificity and sensitivity and is a promising in vitro model with potential to replace the HIST. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. T4 report. An expert consortium review of the EC-commissioned report "Alternative (non-animal) methods for cosmetics testing: Current status and future prospects - 2010"

    NARCIS (Netherlands)

    Hartung, T.; Blaauboer, B.J.; Bosgra, S.; Carney, E.; Coenen, J.; Conolly, R.B.; Corsini, E.; Green, S.; Faustman, E.M.; Gaspari, A.; Hayashi, M.; Hayes, A.W.; Hengstler, J.G.; Knudsen, L.E.; Knudsen, T.B.; McKim, J.M.; Pfaller, W.; Roggen, E.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

  2. Alternatives to Animal Use in Research and Testing. Hearing before the Subcommittee on Science, Research and Technology of the Committee on Science and Technology. House of Representatives, Ninety-Ninth Congress, Second Session.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. House Committee on Science and Technology.

    Perspectives, policy issues, and options for Congressional action that relate most directly to the development and implementation of alternatives to animal use in research and testing are addressed in this report. Testimonies and reports include those from the Office of Technology Assessment, the National Institute of Health, and the Food and Drug…

  3. Patients' attitudes towards animal testing

    DEFF Research Database (Denmark)

    Masterton, Malin; Renberg, Tobias; Kälvemark Sporrong, Sofia

    2014-01-01

    A strong argument for the practice of animal testing in medical research is the potential benefit to patients in getting improved pain relief, minimising morbidity and mortality. However, patients’ opinions on the ethics of animal testing are seldom sought, despite their role as principal...... stakeholders. This study compared the attitudes of patients and researchers on animal testing. Focus-group interviews were held with patients suffering from chronic inflammatory diseases, resulting in a questionnaire that was distributed January–May 2011. The questionnaire was posted to patient members...... of the Swedish Rheumatism Association (n=1195) and to all scientific experts serving on Ethical Review Boards in Sweden (n=364), with response rates of 65 per cent and 60 per cent, respectively. Results show that patients hold a positive stance towards animal testing, but with many caveats, and the level...

  4. Alternative methods and strategies to reduce, refine, and replace animal use for veterinary vaccine post-licensing safety testing: state of the science and future directions

    OpenAIRE

    KULPA-EDDY Jodie; SRINIVAS Geetha; HALDER Maria; BROWN Karen; DRAAYER Hans; GALVIN Jeffrey; CLAASEN Ivo; WOODLAND Ralph; DOELLING Vivian; JONES Brett; STOKES William

    2011-01-01

    NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the last in the series, addresses methods and strategies for veterinary vacci...

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

    DEFF Research Database (Denmark)

    Hartung, Thomas; Blaauboer, Bas J; Bosgra, Sieto

    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...

  6. Animal Exposure During Burn Tests

    Science.gov (United States)

    Gaume, J. G.

    1978-01-01

    An animal exposure test system (AETS) was designed and fabricated for the purpose of collecting physiological and environmental (temperature) data from animal subjects exposed to combustion gases in large scale fire tests. The AETS consisted of an open wire mesh, two-compartment cage, one containing an exercise wheel for small rodents, and the other containing one rat instrumented externally for electrocardiogram (ECG) and respiration. Cage temperature is measured by a thermistor located in the upper portion of the rat compartment. Animal activity is monitored by the ECG and the records indicate an increase in EMG (electromyograph) noise super-imposed by the increased activity of the torso musculature. Examples of the recordings are presented and discussed as to their significance regarding toxicity of fire gases and specific events occurring during the test. The AETS was shown to be a useful tool in screening materials for the relative toxicity of their outgassing products during pyrolysis and combustion.

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

    Science.gov (United States)

    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.

  8. Prediction of skin sensitizers using alternative methods to animal experimentation.

    Science.gov (United States)

    Johansson, Henrik; Lindstedt, Malin

    2014-07-01

    Regulatory frameworks within the European Union demand that chemical substances are investigated for their ability to induce sensitization, an adverse health effect caused by the human immune system in response to chemical exposure. A recent ban on the use of animal tests within the cosmetics industry has led to an urgent need for alternative animal-free test methods that can be used for assessment of chemical sensitizers. To date, no such alternative assay has yet completed formal validation. However, a number of assays are in development and the understanding of the biological mechanisms of chemical sensitization has greatly increased during the last decade. In this MiniReview, we aim to summarize and give our view on the recent progress of method development for alternative assessment of chemical sensitizers. We propose that integrated testing strategies should comprise complementary assays, providing measurements of a wide range of mechanistic events, to perform well-educated risk assessments based on weight of evidence. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  9. 9 CFR 117.4 - Test animals.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Test animals. 117.4 Section 117.4 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS ANIMALS AT LICENSED ESTABLISHMENTS § 117.4...

  10. Freshwater Planarians as an Alternative Animal Model for Neurotoxicology.

    Science.gov (United States)

    Hagstrom, Danielle; Cochet-Escartin, Olivier; Zhang, Siqi; Khuu, Cindy; Collins, Eva-Maria S

    2015-09-01

    Traditional toxicology testing has relied on low-throughput, expensive mammalian studies; however, timely testing of the large number of environmental toxicants requires new in vitro and in vivo platforms for inexpensive medium- to high-throughput screening. Herein, we describe the suitability of the asexual freshwater planarian Dugesia japonica as a new animal model for the study of developmental neurotoxicology. As these asexual animals reproduce by binary fission, followed by regeneration of missing body structures within approximately 1 week, development and regeneration occur through similar processes allowing us to induce neurodevelopment "at will" through amputation. This short time scale and the comparable sizes of full and regenerating animals enable parallel experiments in adults and developing worms to determine development-specific aspects of toxicity. Because the planarian brain, despite its simplicity, is structurally and molecularly similar to the mammalian brain, we are able to ascertain neurodevelopmental toxicity that is relevant to humans. As a proof of concept, we developed a 5-step semiautomatic screening platform to characterize the toxicity of 9 known neurotoxicants (consisting of common solvents, pesticides, and detergents) and a neutral agent, glucose, and quantified effects on viability, stimulated and unstimulated behavior, regeneration, and brain structure. Comparisons of our findings with other alternative toxicology animal models, such as zebrafish larvae and nematodes, demonstrated that planarians are comparably sensitive to the tested chemicals. In addition, we found that certain compounds induced adverse effects specifically in developing animals. We thus conclude that planarians offer new complementary opportunities for developmental neurotoxicology animal models. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    OpenAIRE

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really ...

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

    Science.gov (United States)

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

    2011-10-01

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

  13. [Reduction of animal experiments in experimental drug testing].

    Science.gov (United States)

    Behrensdorf-Nicol, H; Krämer, B

    2014-10-01

    In order to ensure the quality of biomedical products, an experimental test for every single manufactured batch is required for many products. Especially in vaccine testing, animal experiments are traditionally used for this purpose. For example, efficacy is often determined via challenge experiments in laboratory animals. Safety tests of vaccine batches are also mostly performed using laboratory animals. However, many animal experiments have clear inherent disadvantages (low accuracy, questionable transferability to humans, unclear significance). Furthermore, for ethical reasons and animal welfare aspects animal experiments are also seen very critical by the public. Therefore, there is a strong trend towards replacing animal experiments with methods in which no animals are used ("replacement"). If a replacement is not possible, the required animal experiments should be improved in order to minimize the number of animals necessary ("reduction") and to reduce pain and suffering caused by the experiment to a minimum ("refinement"). This "3R concept" is meanwhile firmly established in legislature. In recent years many mandatory animal experiments have been replaced by alternative in vitro methods or improved according to the 3R principles; numerous alternative methods are currently under development. Nevertheless, the process from the development of a new method to its legal implementation takes a long time. Therefore, supplementary regulatory measures to facilitate validation and acceptance of new alternative methods could contribute to a faster and more consequent implementation of the 3R concept in the testing of biomedical products.

  14. Alternative Therapy of Animals – Homeopathy and Other Alternative Methods of Therapy

    Directory of Open Access Journals (Sweden)

    Løken Torleiv

    2002-03-01

    Full Text Available Alternative therapy of animals is described, in the meaning of alternatives to veterinary therapy traditionally accepted by veterinary faculties and schools and included in their curricula. Alternative therapy composes of different disciplines, of which homeopathy is emphasised in this presentation. Information is given on the use and interest of such therapy among veterinarians and animal owners. Homeopathy as other alternative therapies, may offer great advances, if they induce any effect. Some of the disciplines are based on a scientifically accepted documentation. Others, and homeopathy in particular, are missing such a documentation of effect. The justification of including alternative therapy in treating animals is discussed. Research in alternative therapy of animals is greatly needed, in particular to evaluate therapeutic methods which are in extensive use without any documented effect. An ongoing research project in Norway on the effect of homeopathic treatment of mastitis in cows is shortly presented.

  15. EPA Releases Draft Policy to Reduce Animal Testing for Skin Sensitization

    Science.gov (United States)

    The document, Draft Interim Science Policy: Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing, describes the science behind the non-animal alternatives that can now be used to identify skin sensitization.

  16. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    Science.gov (United States)

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.

  17. Antibiotic Alternatives: The Substitution of Antibiotics in Animal Husbandry?

    Directory of Open Access Journals (Sweden)

    Guyue eCheng

    2014-05-01

    Full Text Available It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could relly replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre- and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm and virulence, and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.

  18. Alternative Water Processor Test Development

    Science.gov (United States)

    Pickering, Karen D.; Mitchell, Julie L.; Adam, Niklas M.; Barta, Daniel; Meyer, Caitlin E.; Pensinger, Stuart; Vega, Leticia M.; Callahan, Michael R.; Flynn, Michael; Wheeler, Ray; hide

    2013-01-01

    The Next Generation Life Support Project is developing an Alternative Water Processor (AWP) as a candidate water recovery system for long duration exploration missions. The AWP consists of biological water processor (BWP) integrated with a forward osmosis secondary treatment system (FOST). The basis of the BWP is a membrane aerated biological reactor (MABR), developed in concert with Texas Tech University. Bacteria located within the MABR metabolize organic material in wastewater, converting approximately 90% of the total organic carbon to carbon dioxide. In addition, bacteria convert a portion of the ammonia-nitrogen present in the wastewater to nitrogen gas, through a combination of nitrification and denitrification. The effluent from the BWP system is low in organic contaminants, but high in total dissolved solids. The FOST system, integrated downstream of the BWP, removes dissolved solids through a combination of concentration-driven forward osmosis and pressure driven reverse osmosis. The integrated system is expected to produce water with a total organic carbon less than 50 mg/l and dissolved solids that meet potable water requirements for spaceflight. This paper describes the test definition, the design of the BWP and FOST subsystems, and plans for integrated testing.

  19. Alternative Water Processor Test Development

    Science.gov (United States)

    Pickering, Karen D.; Mitchell, Julie; Vega, Leticia; Adam, Niklas; Flynn, Michael; Wjee (er. Rau); Lunn, Griffin; Jackson, Andrew

    2012-01-01

    The Next Generation Life Support Project is developing an Alternative Water Processor (AWP) as a candidate water recovery system for long duration exploration missions. The AWP consists of biological water processor (BWP) integrated with a forward osmosis secondary treatment system (FOST). The basis of the BWP is a membrane aerated biological reactor (MABR), developed in concert with Texas Tech University. Bacteria located within the MABR metabolize organic material in wastewater, converting approximately 90% of the total organic carbon to carbon dioxide. In addition, bacteria convert a portion of the ammonia-nitrogen present in the wastewater to nitrogen gas, through a combination of nitrogen and denitrification. The effluent from the BWP system is low in organic contaminants, but high in total dissolved solids. The FOST system, integrated downstream of the BWP, removes dissolved solids through a combination of concentration-driven forward osmosis and pressure driven reverse osmosis. The integrated system is expected to produce water with a total organic carbon less than 50 mg/l and dissolved solids that meet potable water requirements for spaceflight. This paper describes the test definition, the design of the BWP and FOST subsystems, and plans for integrated testing.

  20. Simulation of physiology experiments--an alternative to animal use.

    Science.gov (United States)

    Nageswari, K Sri; Devi, M Syamala; Sharma, Rajeev

    2007-01-01

    Amphibian experiments on nerve-muscle preparation and heart are essential as per first year MBBS practical syllabus, for learning basic concepts in Physiology. Need was felt to design and develop computer based simulation software as an alternative to animal use, due to growing concern and stringent laws imposed by animal ethical bodies. Computer algorithms were developed for 13 amphibian experiments, by manually tracing the graphs obtained through mechanical experimentation and storing the X, Y coordinates for the end points of each line segment as data base tables. By retrieving the data base tables, one for each experiment, the computer simulated graphs were drawn using Visual Basic 6 with timer control and Macromedia Flash for animation effects. A CD-ROM consisting of the software for computer simulation of all the amphibian experiments, as an alternative to the conventional animal experiments, has been developed for the benefit of medical students across the country, as a useful active learning tool.

  1. Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation.

    Science.gov (United States)

    Cheluvappa, Rajkumar; Scowen, Paul; Eri, Rajaraman

    2017-08-01

    Animals have been used in research and teaching for a long time. However, clear ethical guidelines and pertinent legislation were instated only in the past few decades, even in developed countries with Judeo-Christian ethical roots. We compactly cover the basics of animal research ethics, ethical reviewing and compliance guidelines for animal experimentation across the developed world, "our" fundamentals of institutional animal research ethics teaching, and emerging alternatives to animal research. This treatise was meticulously constructed for scientists interested/involved in animal research. Herein, we discuss key animal ethics principles - Replacement/Reduction/Refinement. Despite similar undergirding principles across developed countries, ethical reviewing and compliance guidelines for animal experimentation vary. The chronology and evolution of mandatory institutional ethical reviewing of animal experimentation (in its pioneering nations) are summarised. This is followed by a concise rendition of the fundamentals of teaching animal research ethics in institutions. With the advent of newer methodologies in human cell-culturing, novel/emerging methods aim to minimise, if not avoid the usage of animals in experimentation. Relevant to this, we discuss key extant/emerging alternatives to animal use in research; including organs on chips, human-derived three-dimensional tissue models, human blood derivates, microdosing, and computer modelling of various hues. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

  2. Alternative Test Methods for Developmental Neurotoxicity: A ...

    Science.gov (United States)

    Exposure to environmental contaminants is well documented to adversely impact the development of the nervous system. However, the time, animal and resource intensive EPA and OECD testing guideline methods for developmental neurotoxicity (DNT) are not a viable solution to characterizing potential chemical hazards for the thousands of untested chemicals currently in commerce. Thus, research efforts over the past decade have endeavored to develop cost-effective alternative DNT testing methods. These efforts have begun to generate data that can inform regulatory decisions. Yet there are major challenges to both the acceptance and use of this data. Major scientific challenges for DNT include development of new methods and models that are “fit for purpose”, development of a decision-use framework, and regulatory acceptance of the methods. It is critical to understand that use of data from these methods will be driven mainly by the regulatory problems being addressed. Some problems may be addressed with limited datasets, while others may require data for large numbers of chemicals, or require the development and use of new biological and computational models. For example mechanistic information derived from in vitro DNT assays can be used to inform weight of evidence (WoE) or integrated approaches to testing and assessment (IATA) approaches for chemical-specific assessments. Alternatively, in vitro data can be used to prioritize (for further testing) the thousands

  3. An animal welfare perspective on animal testing of GMO crops.

    Science.gov (United States)

    Kolar, Roman; Rusche, Brigitte

    2008-01-01

    The public discussion on the introduction of agro-genetic engineering focuses mainly on economical, ecological and human health aspects. The fact is neglected that laboratory animals must suffer before either humans or the environment are affected. However, numerous animal experiments are conducted for toxicity testing and authorisation of genetically modified plants in the European Union. These are ethically questionable, because death and suffering of the animals for purely commercial purposes are accepted. Therefore, recent political initiatives to further increase animal testing for GMO crops must be regarded highly critically. Based on concrete examples this article demonstrates that animal experiments, on principle, cannot provide the expected protection of users and consumers despite all efforts to standardise, optimise or extend them.

  4. Assessment of the potential irritation and photoirritation of novel amino acid-based surfactants by in vitro methods as alternative to the animal tests

    International Nuclear Information System (INIS)

    Benavides, Tomas; Martinez, Veronica; Mitjans, Montserrat; Infante, Maria Rosa; Moran, Carmen; Clapes, Pere; Clothier, Richard; Vinardell, Maria Pilar

    2004-01-01

    The ultraviolet-A radiation damage effects on skin and eyes will be increased by phototoxic compounds which could be present in pharmaceutical or cosmetic formulations. Great efforts have been made in the last years to find surfactants to replace those with phototoxic potential in commercial use. Series of different in vitro models for phototoxicity, included to validated neutral red uptake (NRU) 3T3 phototoxicity assay are useful screening tools. The phototoxic effects of a novel family of glycerol amino acid-based surfactant compounds were examined via these assays. Human red blood cells and two immortalised cell lines, murine fibroblast cell line 3T3, and one human keratinocyte cell line, HaCaT, were the in vitro models employed to predict potential photoirritation. The phototoxic end-points assessed were hemolysis (human red blood cell test) and resazurin transformation to resorufin and NRU in cell culture methods. The results suggest that no phototoxic effects by any new amino acid derived-surfactants, could be identified

  5. Towards an alternative testing strategy for nanomaterials used in nanomedicine

    DEFF Research Database (Denmark)

    Dusinska, M; Boland, S; Saunders, M

    2015-01-01

    TEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach...

  6. A review of the status of alternative approaches to animal testing and the development of integrated testing strategies for assessing the toxicity of chemicals under REACH--a summary of a DEFRA-funded project conducted by Liverpool John Moores University and FRAME.

    Science.gov (United States)

    Grindon, Christina; Combes, Robert; Cronin, Mark T D; Roberts, David W; Garrod, John

    2006-03-01

    Liverpool John Moores University and FRAME were recently awarded a DEFRA tender to conduct a review of the status of alternative approaches to animal testing, and to recommend further research with regard to the forthcoming European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The outcome of the project is summarised, including the prospects for in vitro and in silico testing, areas where reduction and refinement could be applied, and how decision-tree integrated testing strategies could be used to reduce the number of animals needed to fulfil the testing requirements of the REACH system. This paper is a prelude to a series of individual papers on detailed suggestions for applying non-animal methods to each of the major toxicity endpoints in REACH.

  7. Implications of Animal Welfare on Toxicity Testing

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    1993-01-01

    The testing strategy for chemical substances is discussed with regard to obtaining improved quality of data for health assessment while respecting the ethical responsibility for consideration of the welfare of the animals involved. Ensuring animal welfare without indulging too much in anthropomor...... in anthropomorphism leads to better research/testing. Current trends in toxicity testing will result in tests involving more sophisticated techniques, better quality of laboratory animals, and eventually the use of fewer animals.......The testing strategy for chemical substances is discussed with regard to obtaining improved quality of data for health assessment while respecting the ethical responsibility for consideration of the welfare of the animals involved. Ensuring animal welfare without indulging too much...

  8. Alternative animal model for studies of total skin thickness burns.

    Science.gov (United States)

    Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio

    2017-10-01

    To present an alternative experimental model of third degree burn of easy reproducibility. Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with exposure time of 10 seconds and group 15 (G15) the animals were burned at 150°C with exposure time of 15 seconds. Histopathological analyzes showed that all three groups had similar morphological characteristics, with total thickness involvement. The technique is effective to reproduce a third degree burn and suggests the temperature of 150ºC with 5 seconds of exposure in order to minimize the risks to the animals.

  9. [In vitro alternatives to Draize eye irritation test].

    Science.gov (United States)

    Zhou, Jianchang; Yang, Mingjie; Yang, Xingfen; He, Xiwen

    2004-07-01

    For reasons of animal welfare and better science, a series of in vitro methods, including assays based isolated eye or cornea, Chorioallantoic membrane, cultured tissue or cell, had been established and evaluated to replace the Draize eye irritation test. This paper provides a brief review of the recent progress in the in vitro alternatives to Draize eye irritation test, and the principles of scientific validation of these alternatives were also discussed.

  10. Alternative animal model for studies of total skin thickness burns

    OpenAIRE

    Andrade, Ana Laura Martins de; Parisi, Julia Risso; Brassolatti, Patrícia; Parizotto, Nivaldo Antonio

    2017-01-01

    Abstract Purpose: To present an alternative experimental model of third degree burn of easy reproducibility. Methods: Eighteen male Wister rats were randomly divided into three groups, 6 of which were allocated to each group. A soldering iron coupled to an aluminum plate was used to produce burn, at a temperature of 150ºC, with different exposure times per group. Group 5 (G5) animals were burned at 150°C with exposure time of 5 seconds; Group 10 (G10) the animals were burned at 150°C with e...

  11. Animal experimentation in snake venom research and in vitro alternatives.

    Science.gov (United States)

    Sells, Paula G

    2003-08-01

    Current experimental techniques used in snake venom research (with and without the use of animals) are reviewed. The emphasis is on the reduction of the use of animals in the development of antivenoms for the clinical treatment of snakebite. Diagnostic and research techniques for the major pathologies of envenoming are described and those using animals are contrasted with non-sentient methods where possible. In particular, LD50 and ED50 assays using animals (in vivo) and fertilised eggs (in vivo, non-sentient) are compared as well as in vitro procedures (ELISA and haemolytic test) for ED50 estimations. The social context of antivenom production, supply and demand is outlined together with the consequent tension between the benefits derived and the increase in opposition to experiments on animals. Stringent regulations governing the use of animals, limited research funds and public pressure all focus the need for progress towards non-animal, or non-sentient, research methods. Some achievements are noted but success is hampered by lack of detailed knowledge of the many constituents of venom which have to be assessed as a whole rather than individually. The only way to evaluate the net pathological effect of venom is to use a living system, usually a rodent, and similarly, the efficacy of antivenoms is also measured in vivo. The pre-clinical testing of antivenoms in animals is therefore a legal requirement in many countries and is strictly monitored by government authorities. New technologies applied to the characterisation of individual venom proteins should enable novel in vitro assays to be designed thus reducing the number of animals required. In the meantime, the principles of Reduce, Refine and Replace relating to animals in research are increasingly endorsed by those working in the field and the many agencies regulating ethical and research policy.

  12. Using Role Play to Debate Animal Testing

    Science.gov (United States)

    Agell, Laia; Soria, Vanessa; Carrió, Mar

    2015-01-01

    The use of animals in biomedical research is a socio-scientific issue in which decision-making is complicated. In this article, we describe an experience involving a role play activity performed during school visits to the Barcelona Biomedical Research Park (PRBB) to debate animal testing. Role playing games require students to defend different…

  13. The current status of animal use and alternatives in Korean veterinary medical schools.

    Science.gov (United States)

    Lee, Gwi Hyang; Choe, Byung In; Kim, Jin Suk; Hart, Lynette A; Han, Jin Soo

    2010-06-01

    Two new Korean laws regulating animal welfare and the humane use of animals in science came into effect in 2008 and 2009. Both these laws impose ethical committee review prior to the performance of animal experiments in research, testing and education. This study briefly summarises the new Korean laws, and investigates the current status regarding the numbers of animals used, the alternatives to animals which are used, the curricula relating to the humane use of animals, and ethical review practices in Korean veterinary education. Approximately 4,845 animals, representing 20 different species, were used in veterinary medical education in Korea in 2007. Korea has begun to introduce formal courses on animal welfare for the humane treatment of animals used in experiments, and an ethical protocol review system prior to animal use in education. Korea is moving toward better animal welfare, by incorporating practices consistent with international standards. The information presented represents the first such data gathered in Korea, which should prove useful for monitoring the implementation of replacement, reduction, and refinement measures in animal use for education purposes.

  14. Laboratory animal science in China: current status and potential for adoption of Three R alternatives.

    Science.gov (United States)

    Kong, Qi; Qin, Chuan

    2010-03-01

    This paper aims to describe the development of laboratory animal science in China on the basis of historical evidence and recent national survey data, and to identify the problems facing the adoption of Three R alternatives. The authors undertook a national survey in 2006, by means of a questionnaire sent to 31 provinces, municipalities and autonomous regions, and also compared data from a variety of sources, including several national surveys and published papers. Laboratory animal science in China has developed rapidly over the past 30 years, as a result of a combination of economic, governmental and societal forces. More than 100,000 people work in the field of laboratory animal science, in 2,000 laboratory animal centres, institutes, universities, organisations, and companies. During the year of our survey, more than 19 million laboratory animals were produced from 320 licensed production facilities. Approximately 16 million laboratory animals were used in animal experiments, in 1530 facilities licensed for their use. The scale of the market for the supply and use of laboratory animals is huge, and thus it is very important to improve the level of adoption of these alternatives, in education, research and testing. For China, this presents a significant economic and technological opportunity in the field of biosciences research. The concept of the Three Rs first appeared in China in the 1980s, when the scale of laboratory animal sciences was starting to increase. In the 1990s, the Three Rs concept became commonly accepted among laboratory animal scientists, and began to appear in government documents. In the first decade of the 21st century, the Three Rs principles have become increasingly applied in our day-to-day work. But further time is still needed to achieve the full application of the Three Rs principles, especially the adoption of Three R alternatives. This paper describes the achievements in China relating to laboratory animal science, the use of Three

  15. Proposal for a Brazilian centre on alternative test methods.

    Science.gov (United States)

    Eskes, Chantra; Sá-Rocha, Vanessa de Moura; Nunes, Jadir; Presgrave, Octavio; de Carvalho, Dermeval; Masson, Philippe; Rivera, Ekaterina; Coecke, Sandra; Kreysa, Joachim; Hartung, Thomas

    2009-01-01

    Several initiatives have recently taken place in Brazil in order to foster the creation of centers dedicated to alternatives to animal testing. In 2008, Vanessa Sá-Rocha organized a meeting with Brazilian regulatory authorities and the major stakeholders in the field of testing to foster discussions on the process of funding, development, and validation of alternative methods in Brazil. Octavio Presgrave published a scientific article on "The Need for the Establishment of a Brazilian Centre for the Validation of Alternative Methods." Also in 2008, Jadir Nunes, together with Dermeval de Carvalho, prepared and presented a proposal to the Brazilian National Agency of Health Surveillance (ANVISA) for the creation of a Centre for the Validation of Alternative Methods. ECVAM and other European stakeholders have been involved in the initiatives. Furthermore, also in 2008, a new legislation has been adopted in Brazil regarding the use of animals for scientific purposes ("lei Arouca"). The legislation establishes, among other provisions, the task of monitoring and evaluating the introduction of alternative methods. However, the legislation does not provide for promotion of or information about, existing alternative methods to the larger Brazilian scientific community. In order to streamline the different activities, Chantra Eskes acted as a facilitator by establishing a new joint proposal with the current Brazilian stakeholders, aimed at setting up a Brazilian Center on Alternative Test Methods.

  16. Testing and assessment strategies, including alternative and new approaches

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    2003-01-01

    ethical concern. However, irrespective of animal welfare it is an important aspect of the discipline of toxicology that the primary object is human health. The ideal testing and assessment strategy is simple to use all the available test methods and preferably more in laboratory animal species from which...... there are more than 100000 chemicals which are potential for human exposure, so the development of alternative testing and assessment strategies has taken place in the recent years. The toxicological evaluation should enable the society to cope with the simultaneous requirement of many chemicals for different...... uses and of the absence of health problems involved with their use. Thus, the regulatory toxicology is a cocktail of science and pragmatism added a crucial concern for animal welfare. Test methods are most often used in a testing sequence as bricks in a testing strategy. The main key driving forces...

  17. New EPA Guidance for Testing Pesticides Will Reduce Animal Testing

    Science.gov (United States)

    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.

  18. Test report : alternative fuels propulsion durability evaluation

    Science.gov (United States)

    2012-08-28

    This document, prepared by Honeywell Aerospace, Phoenix, AZ (Honeywell), contains the final : test report (public version) for the U.S. Department of Transportation/Federal Aviation : Administration (USDOT/FAA) Alternative Fuels Propulsion Engine Dur...

  19. Ethical guidelines, animal profile, various animal models used in periodontal research with alternatives and future perspectives

    Directory of Open Access Journals (Sweden)

    Mohan Kumar Pasupuleti

    2016-01-01

    Full Text Available Laboratory animal models serve as a facilitator to investigate the etiopathogenesis of periodontal disease, are used to know the efficacy of reconstructive and regenerative procedures, and are also helpful in evaluation of newer therapeutic techniques including laser and implant therapies prior to application in the human beings. The aim of this review is to know the different animal models used in various specialties of dental research and to know the ethical guidelines prior to the usage of experimental models with main emphasis on how to refine, replace, and reduce the number of animal models usage in the laboratory. An online search for experimental animal models used in dental research was performed using MEDLINE/PubMed database. Publications from 2009 to May 2013 in the specialty of periodontics were included in writing this review. A total of 652 references were published in PubMed/MEDLINE databases based on the search terms used. Out of 245 studies, 241 were related to the periodontal research published in English from 2009 to 2013. Relevant papers were chosen according to the inclusion and exclusion criteria. After extensive electronic and hand search on animal models, it has been observed that various animal models were used in dental research. Search on animal models used for dental research purpose revealed that various animals such as rats, mice, guinea pigs, rabbit, beagle dogs, goats, and nonhuman primates were extensively used. However, with the new advancement of ex vivo animal models, it has become easy to investigate disease pathogenesis and to test the efficacy of newer therapeutic modalities with the reduced usage of animal models. This review summarized the large amount of literature on animal models used in periodontal research with main emphasis on ethical guidelines and on reducing the animal model usage in future perspective.

  20. 77 FR 52333 - International Workshop on Alternatives to the Murine Histamine Sensitization Test (HIST) for...

    Science.gov (United States)

    2012-08-29

    ... Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing... reducing or replacing the use of animals in vaccine safety testing. The goal is to address the path toward... testing expense and animal usage. An international workshop organized in 2010 \\1\\ by NICEATM, Interagency...

  1. The potential of tissue engineering for developing alternatives to animal experiments: a systematic review.

    Science.gov (United States)

    de Vries, Rob B M; Leenaars, Marlies; Tra, Joppe; Huijbregtse, Robbertjan; Bongers, Erik; Jansen, John A; Gordijn, Bert; Ritskes-Hoitinga, Merel

    2015-07-01

    An underexposed ethical issue raised by tissue engineering is the use of laboratory animals in tissue engineering research. Even though this research results in suffering and loss of life in animals, tissue engineering also has great potential for the development of alternatives to animal experiments. With the objective of promoting a joint effort of tissue engineers and alternative experts to fully realise this potential, this study provides the first comprehensive overview of the possibilities of using tissue-engineered constructs as a replacement of laboratory animals. Through searches in two large biomedical databases (PubMed, Embase) and several specialised 3R databases, 244 relevant primary scientific articles, published between 1991 and 2011, were identified. By far most articles reviewed related to the use of tissue-engineered skin/epidermis for toxicological applications such as testing for skin irritation. This review article demonstrates, however, that the potential for the development of alternatives also extends to other tissues such as other epithelia and the liver, as well as to other fields of application such as drug screening and basic physiology. This review discusses which impediments need to be overcome to maximise the contributions that the field of tissue engineering can make, through the development of alternative methods, to the reduction of the use and suffering of laboratory animals. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Alternative Dietary Fiber Sources in Companion Animal Nutrition

    Directory of Open Access Journals (Sweden)

    George C. Fahey, Jr.

    2013-08-01

    Full Text Available The US has a pet population of approximately 70 million dogs and 74 million cats. Humans have developed a strong emotional bond with companion animals. As a consequence, pet owners seek ways to improve health, quality of life and longevity of their pets. Advances in canine and feline nutrition have contributed to improved longevity and well-being. Dietary fibers have gained renewed interest in the pet food industry, due to their important role in affecting laxation and stool quality. More recently, because of increased awareness of the beneficial effects of dietary fibers in health, as well as the popularity of functional foods and holistic and natural diets, alternative and novel carbohydrates have become widespread in human and pet nutrition. Fiber sources from cereal grains, whole grains and fruits have received increasing attention by the pet food industry and pet owners. While limited scientific information is available on the nutritional and nutraceutical properties of alternative fiber sources, studies indicate that corn fiber is an efficacious fiber source for pets, showing no detrimental effects on palatability or nutrient digestibility, while lowering the glycemic response in adult dogs. Fruit fiber and pomaces have good water-binding properties, which may be advantageous in wet pet food production, where a greater water content is required, along with low water activity and a firm texture of the final product. Rice bran is a palatable fiber source for dogs and may be an economical alternative to prebiotic supplementation of pet foods. However, it increases the dietary requirement of taurine in cats. Barley up to 40% in a dry extruded diet is well tolerated by adult dogs. In addition, consumption of complex carbohydrates has shown a protective effect on cardiovascular disease and oxidative stress. Alternative fiber sources are suitable ingredients for pet foods. They have been shown to be nutritionally adequate and to have potential

  3. Alternative dietary fiber sources in companion animal nutrition.

    Science.gov (United States)

    de Godoy, Maria R C; Kerr, Katherine R; Fahey, George C

    2013-08-06

    The US has a pet population of approximately 70 million dogs and 74 million cats. Humans have developed a strong emotional bond with companion animals. As a consequence, pet owners seek ways to improve health, quality of life and longevity of their pets. Advances in canine and feline nutrition have contributed to improved longevity and well-being. Dietary fibers have gained renewed interest in the pet food industry, due to their important role in affecting laxation and stool quality. More recently, because of increased awareness of the beneficial effects of dietary fibers in health, as well as the popularity of functional foods and holistic and natural diets, alternative and novel carbohydrates have become widespread in human and pet nutrition. Fiber sources from cereal grains, whole grains and fruits have received increasing attention by the pet food industry and pet owners. While limited scientific information is available on the nutritional and nutraceutical properties of alternative fiber sources, studies indicate that corn fiber is an efficacious fiber source for pets, showing no detrimental effects on palatability or nutrient digestibility, while lowering the glycemic response in adult dogs. Fruit fiber and pomaces have good water-binding properties, which may be advantageous in wet pet food production, where a greater water content is required, along with low water activity and a firm texture of the final product. Rice bran is a palatable fiber source for dogs and may be an economical alternative to prebiotic supplementation of pet foods. However, it increases the dietary requirement of taurine in cats. Barley up to 40% in a dry extruded diet is well tolerated by adult dogs. In addition, consumption of complex carbohydrates has shown a protective effect on cardiovascular disease and oxidative stress. Alternative fiber sources are suitable ingredients for pet foods. They have been shown to be nutritionally adequate and to have potential nutraceutical

  4. Cancer screening tests for small animals.

    Science.gov (United States)

    Schleis, Stephanie E

    2014-09-01

    Cancer is increasingly more common. Several tests for the diagnosis and treatment of cancer in companion animals have been developed. Screening tests discussed include those for lymphoid neoplasia, hemangiosarcoma, and transitional cell carcinoma of the bladder. None of these tests should be used in isolation for diagnosis. Vincristine and doxorubicin are mainstays in the treatment of canine lymphoma. However, it is important and accepted practice to test individuals of predisposed breeds for this mutation before administering these drugs in a lymphoma protocol. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A Web-based Alternative Non-animal Method Database for Safety Cosmetic Evaluations.

    Science.gov (United States)

    Kim, Seung Won; Kim, Bae-Hwan

    2016-07-01

    Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a database of safety information on toxicological mechanisms and pathways collected through in vivo, in vitro, and in silico methods. We developed the CAMSEC database (named after the research team; the Consortium of Alternative Methods for Safety Evaluation of Cosmetics) to fulfill this purpose. On the same website, our aim is to provide updates on current alternative research methods in Korea. The database will not be used directly to conduct safety evaluations, but researchers or regulatory individuals can use it to facilitate their work in formulating safety evaluations for cosmetic materials. We hope this database will help establish new alternative research methods to conduct efficient safety evaluations of cosmetic materials.

  6. Research perspectives for pre-screening alternatives to animal experimentation

    International Nuclear Information System (INIS)

    Walum, Erik; Hedander, Jan; Garberg, Per

    2005-01-01

    The MEIC study revealed a high predictivity of in vitro cytotoxicity data for human acute systemic toxicity. The idea, put forward by several authors, that compounds that show high cytotoxicity should not need further testing for confirmation but could be assumed toxic also in vivo provides a convenient concept for the selection of the most relevant compounds for further studies in large sets of chemicals, as in the REACH program. The automated techniques applied in high throughput screening (HTS) by the pharmaceutical and biotech industries to select hits in extensive compound collections represent an opportunity to significantly increase the capacity of cytotoxicity testing. Furthermore, it has been suggested that a combination of cytotoxicity data and some basic biokinetic information would greatly improve the accuracy in the extrapolation from in vitro to in vivo and thus make it possible to identify additional toxic compounds that might have escaped in the initial screen. Such information, which can be obtained in a medium throughput screening mode (MTS), includes biotransformation, absorption and some aspects of distribution. The measurement of the net flux of a compound over a cellular barrier, as the one formed in culture by human Caco-2 cells, gives useful, but limited, information on both gut absorption and blood-brain barrier penetration. The test procedures discussed here, as well as other supplementary in vitro tests, cannot always easily be described in terms of animal-based test replacements. In those instances, the necessary test validation cannot be carried out using animal reference data, and prediction models may have to be adapted to new ideas. Consequently, concepts of prospective validation to supplement the now well-established retrospective validation have to be developed

  7. [Draize test and alternative methods for evaluating irritation from chemical substances].

    Science.gov (United States)

    Moskalewski, S; Mystkowska, E T; Kiss, E

    1995-01-01

    The eye irritancy test in rabbits (Draize test) is currently the method used to evaluate the hazard or safety of chemical substances. To reduce the need for animal testing some new procedures as alternative were elaborated. We present a review of method used as well as evaluation of sensitivity and repeatability of alternative tests applied in laboratories of European Economic Communities.

  8. Assuring safety without animal testing concept (ASAT). Integration of human disease data with in vitro data to improve toxicology testing

    NARCIS (Netherlands)

    Stierum, Rob; Aarts, Jac; Boorsma, Andre; Bosgra, Sieto; Caiment, Florian; Ezendam, Janine; Greupink, Rick; Hendriksen, Peter; Soeteman-Hernandez, Lya G.; Jennen, Danyel; Kleinjans, Jos; Kroese, Dinant; Kuper, Frieke; van Loveren, Henk; Monshouwer, Mario; Russel, Frans; van Someren, Eugene; Tsamou, Maria; Groothuis, Geny

    2014-01-01

    According to the Assuring Safety Without Animal Testing (ASAT) principle, risk assessment may ultimately become possible without the use of animals (Fentem et al., (2004). Altern. Lab. Anim. 32, 617-623). The ASAT concept takes human disease mechanisms as starting point and tries to define if

  9. Alternative methods for the replacement of eye irritation testing.

    Science.gov (United States)

    Lotz, Christian; Schmid, Freia F; Rossi, Angela; Kurdyn, Szymon; Kampik, Daniel; De Wever, Bart; Walles, Heike; Groeber, Florian K

    2016-01-01

    In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test has been criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation.This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and the current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed in regard of possible limitations and their status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be applicable to predict all GHS categories.

  10. Large animal models for vaccine development and testing.

    Science.gov (United States)

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-01-01

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. Animals and the 3Rs in toxicology research and testing: The way forward.

    Science.gov (United States)

    Stokes, W S

    2015-12-01

    Despite efforts to eliminate the use of animals in testing and the availability of many accepted alternative methods, animals are still widely used for toxicological research and testing. While research using in vitro and computational models has dramatically increased in recent years, such efforts have not yet measurably impacted animal use for regulatory testing and are not likely to do so for many years or even decades. Until regulatory authorities have accepted test methods that can totally replace animals and these are fully implemented, large numbers of animals will continue to be used and many will continue to experience significant pain and distress. In order to positively impact the welfare of these animals, accepted alternatives must be implemented, and efforts must be directed at eliminating pain and distress and reducing animal numbers. Animal pain and distress can be reduced by earlier predictive humane endpoints, pain-relieving medications, and supportive clinical care, while sequential testing and routine use of integrated testing and decision strategies can reduce animal numbers. Applying advances in science and technology to the development of scientifically sound alternative testing models and strategies can improve animal welfare and further reduce and replace animal use. © The Author(s) 2015.

  12. Test Results From a High Power Linear Alternator Test Rig

    Science.gov (United States)

    Birchenough, Arthur G.; Hervol, David S.; Gardner, Brent G.

    2010-01-01

    Stirling cycle power conversion is an enabling technology that provides high thermodynamic efficiency but also presents unique challenges with regard to electrical power generation, management, and distribution. The High Power Linear Alternator Test Rig (HPLATR) located at the NASA Glenn Research Center (GRC) in Cleveland, Ohio is a demonstration test bed that simulates electrical power generation from a Stirling engine driven alternator. It implements the high power electronics necessary to provide a well regulated DC user load bus. These power electronics use a novel design solution that includes active rectification and power factor control, active ripple suppression, along with a unique building block approach that permits the use of high voltage or high current alternator designs. This report describes the HPLATR, the test program, and the operational results.

  13. A framework program for the teaching of alternative methods (replacement, reduction, refinement) to animal experimentation.

    Science.gov (United States)

    Daneshian, Mardas; Akbarsha, Mohammad A; Blaauboer, Bas; Caloni, Francesca; Cosson, Pierre; Curren, Rodger; Goldberg, Alan; Gruber, Franz; Ohl, Frauke; Pfaller, Walter; van der Valk, Jan; Vinardell, Pilar; Zurlo, Joanne; Hartung, Thomas; Leist, Marcel

    2011-01-01

    Development of improved communication and education strategies is important to make alternatives to the use of animals, and the broad range of applications of the 3Rs concept better known and understood by different audiences. For this purpose, the Center for Alternatives to Animal Testing in Europe (CAAT-Europe) together with the Transatlantic Think Tank for Toxicology (t(4)) hosted a three-day workshop on "Teaching Alternative Methods to Animal Experimentation". A compilation of the recommendations by a group of international specialists in the field is summarized in this report. Initially, the workshop participants identified the different audience groups to be addressed and also the communication media that may be used. The main outcome of the workshop was a framework for a comprehensive educational program. The modular structure of the teaching program presented here allows adaptation to different audiences with their specific needs; different time schedules can be easily accommodated on this basis. The topics cover the 3Rs principle, basic research, toxicological applications, method development and validation, regulatory aspects, case studies and ethical aspects of 3Rs approaches. This expert consortium agreed to generating teaching materials covering all modules and providing them in an open access online repository.

  14. Free the animals? Investigating attitudes toward animal testing in Britain and the United States.

    Science.gov (United States)

    Swami, Viren; Furnham, Adrian; Christopher, Andrew N

    2008-06-01

    In this study, 185 British and 143 American undergraduates completed a battery of tests that measured attitudes toward animal testing and various individual difference variables. Attitudes toward animal testing factored into two interpretable factors: general attitudes toward animal testing, and animal welfare and conditions of testing. Overall, there was support for animal testing under the right conditions, although there was also concern for the welfare of animals and the conditions under which testing takes place. There were small but significant national difference on both factors (with Americans more positive about testing and less positive about animal welfare), and a significant sex difference on the first factor (women were more negative about testing). Correlation and regression analyses showed that there were few significant individual difference predictors of both factors. These results are discussed in relation to past and future work on attitudes toward animal testing.

  15. Non-animal sensitization testing: state-of-the-art.

    Science.gov (United States)

    Vandebriel, Rob J; van Loveren, Henk

    2010-05-01

    Predictive tests to identify the sensitizing properties of chemicals are carried out using animals. In the European Union timelines for phasing out many standard animal tests were established for cosmetics. Following this policy, the new European Chemicals Legislation (REACH) favors alternative methods, if validated and appropriate. In this review the authors aim to provide a state-of-the art overview of alternative methods (in silico, in chemico, and in vitro) to identify contact and respiratory sensitizing capacity and in some occasions give a measure of potency. The past few years have seen major advances in QSAR (quantitative structure-activity relationship) models where especially mechanism-based models have great potential, peptide reactivity assays where multiple parameters can be measured simultaneously, providing a more complete reactivity profile, and cell-based assays. Several cell-based assays are in development, not only using different cell types, but also several specifically developed assays such as three-dimenionally (3D)-reconstituted skin models, an antioxidant response reporter assay, determination of signaling pathways, and gene profiling. Some of these assays show relatively high sensitivity and specificity for a large number of sensitizers and should enter validation (or are indeed entering this process). Integrating multiple assays in a decision tree or integrated testing system is a next step, but has yet to be developed. Adequate risk assessment, however, is likely to require significantly more time and efforts.

  16. Refuge alternatives relief valve testing and design

    OpenAIRE

    Lutz, T.J.; Bissert, P.T.; Homce, G.T.; Yonkey, J.A.

    2016-01-01

    The U.S. National Institute for Occupational Safety and Health (NIOSH) has been researching refuge alternatives (RAs) since 2007. RAs typically have built-in pressure relief valves (PRVs) to prevent the unit from reaching unsafe pressures. The U.S. Mine Safety and Health Administration requires that these valves vent the chamber at a maximum pressure of 1.25 kPa (0.18 psi, 5.0 in. H2O), or as specified by the manufacturer, above mine atmospheric pressure in the RA. To facilitate PRV testing, ...

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

    NARCIS (Netherlands)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, B; 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

    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

  18. The Role of Alternative Testing Strategies in Environmental Risk Assessment of Engineered Nanomaterials

    OpenAIRE

    Hjorth, Rune; Holden, Patricia; Hansen, Steffen Foss; Colman, Ben; Grieger, Khara; Hendren, Christine

    2017-01-01

    Within toxicology there is a pressure to find new test systems and organisms to replace, reduce and refine animal testing. In nanoecotoxicology the need for alternative testing strategies (ATS) is further emphasized as the validity of tests and risk assessment practices developed for dissolved chemicals are challenged. Nonetheless, standardized whole organism animal testing is still considered the gold standard for environmental risk assessment. Advancing risk analysis of engineered nanomater...

  19. An alternative test battery in detecting ocular irritancy of agrochemicals.

    Science.gov (United States)

    Tavaszi, J; Budai, P; Pálovics, A; Kismányoki, A

    2008-01-01

    Using animals in toxicological screening is a controversial issue. To get knowledge about eye irritation, recently only the in vivo Draize-test is accepted, which is one of the most criticized methods because of the injuries inflicted on the test animals. In recent years various in vitro methods have been developed to replace the primary irritation test. Most of these tests are in process of validation. The Draize rabbit eye test, or some modification of this test is essentially the only method for determining ocular irritation that is accepted by authorities. Several in vitro methods have been used to investigate the toxicity of potential eye irritants with the aim of replacing in vitro eye irritation testing. This study reports the results of an alternative approach for predicting irritation potential of agrochemicals. The approach was a two-stage test battery in vitro. The first stage was a cytotoxicity test, the MTT assay. The second stage was the HET-CAM test. The chick chorioallantoic membrane (CAM), being a connective tissue sheet with a visible blood supply, has been proposed as a substrate to identify the eye irritation potential of chemicals. During the HET-CAM test the chemicals are placed directly onto the chorioallantoic membrane. The changes of the vascular injury (haemorrhage, lysis or coagulation) are indications of the potential of the chemical to damage mucous membranes in vivo. MTT assay is a simple method to determine the viability of cells in the presence of a chemical. Cells are cultured with several concentrations of a substance or product, then the ratio of cell destruction is determined. LCC50 (concentration lethal for the 50 % of the cells) is assessed. This is in correlation of the eye irrigative potential of the chemical. In our studies comparative screening was performed with 6 agrochemicals to establish parallel data on alternative test battery (HET-CAM, MTT) and in vivo (Draize) results. In most cases, this study showed a good

  20. High Power Alternator Test Unit (ATU) Electrical System Test

    Science.gov (United States)

    Birchenough, Arthur; Hervol, David

    2007-01-01

    The Alternator Test Unit (ATU) in the Lunar Power System Facility (LPSF) located at the NASA Glenn Research Center (GRC) in Cleveland, OH was used to simulate the operating conditions and evaluate the performance of the ATU and it s interaction with various LPSF components in accordance with the JIMO AC Power System Requirements. The testing was carried out at the breadboard development level. Results of these tests will be used for the development and validation of analytical models for performance and lifetime prediction.

  1. Refuge alternatives relief valve testing and design.

    Science.gov (United States)

    Lutz, T J; Bissert, P T; Homce, G T; Yonkey, J A

    2016-10-01

    The U.S. National Institute for Occupational Safety and Health (NIOSH) has been researching refuge alternatives (RAs) since 2007. RAs typically have built-in pressure relief valves (PRVs) to prevent the unit from reaching unsafe pressures. The U.S. Mine Safety and Health Administration requires that these valves vent the chamber at a maximum pressure of 1.25 kPa (0.18 psi, 5.0 in. H 2 O), or as specified by the manufacturer, above mine atmospheric pressure in the RA. To facilitate PRV testing, an instrumented benchtop test fixture was developed using an off-the-shelf centrifugal blower and ductwork. Relief pressures and flow characteristics were measured for three units: (1) a modified polyvinyl chloride check valve, (2) an off-the-shelf brass/cast-iron butterfly check valve and (3) a commercially available valve that was designed specifically for one manufacturer's steel prefabricated RAs and had been adapted for use in one mine operator's built-in-place RA. PRVs used in tent-style RAs were not investigated. The units were tested with different modifications and configurations in order to check compliance with Title 30 Code of Federal Regulations, or 30 CFR, regulations. The commercially available relief valve did not meet the 30 CFR relief pressure specification but may meet the manufacturer's specification. Alternative valve designs were modified to meet the 30 CFR relief pressure specification, but all valve designs will need further design research to examine survivability in the event of a 103 kPa (15.0 psi) impulse overpressure during a disaster.

  2. Testing Cosmetics on Animals: An Idea Who's Time Has Gone

    OpenAIRE

    Lewis, Noah

    2005-01-01

    Despite tremendous progress in reducing animal testing in the assessment the safety of cosmetic products, it persists and there is no definitive end in sight. The reasons for this are not entirely clear because the major constituents, consumers, animal rights activists, and the corporations engaged in the testing all seem to want it to end. While the government still requires animal testing for drugs and other consumer products, there is no explicit requirement for the animal testing of cosme...

  3. 77 FR 38751 - Codification of Animal Testing Policy

    Science.gov (United States)

    2012-06-29

    ... Animal Testing Policy AGENCY: Consumer Product Safety Commission. ACTION: Proposed Statement of Policy on Animal Testing SUMMARY: The Consumer Product Safety Commission (CPSC or Commission) proposes to codify its statement of policy on animal testing, as amended, which was previously published in the Federal...

  4. Effects of different simplified milk recording methods on genetic evaluation with test-day animal model

    NARCIS (Netherlands)

    Portolano, B.; Maizon, D.O.; Riggio, V.; Tolone, M.; Cacioppo, D.

    2007-01-01

    The aims of the present study were to compare estimated breeding values (EBV) for milk yield using different testing schemes with a test-day animal model and to evaluate the effect of different testing schemes on the ranking of top sheep. Alternative recording schemes that use less information than

  5. Recommendations for Developing Alternative Test Methods for Screening and Prioritization of Chemicals for Developmental Neurotoxicity

    Science.gov (United States)

    Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternative methods to current animal testing protocols and gUidelines. An immediate goal is to develop test methods that are capable of screening large numbers of chemic...

  6. Immune changes in test animals during spaceflight

    Science.gov (United States)

    Lesnyak, A. T.; Sonnenfeld, G.; Rykova, M. P.; Meshkov, D. O.; Mastro, A.; Konstantinova, I.

    1993-01-01

    Over the past two decades, it has become apparent that changes in immune parameters occur in cosmonauts and astronauts after spaceflight. Therefore, interest has been generated in the use of animal surrogates to better understand the nature and extent of these changes, the mechanism of these changes, and to allow the possible development of countermeasures. Among the changes noted in animals after spaceflight are alterations in lymphocytic blastogenesis, cytokine function, natural killer cell activity, and colony-stimulating factors. The nature and significance of spaceflight-induced changes in immune responses will be the focus of this review.

  7. Biogas : Animal Waste That Can be Alternative Energy Source

    Directory of Open Access Journals (Sweden)

    Tuti Haryati

    2006-09-01

    Full Text Available Biogas is a renewable energy which can be used as alternative fuel to replace fossil fuel such as oil and natural gas . Recently, diversification on the use of energy has increasingly become an important issue because the oil sources are depleting . Utilization of agricultural wastes for biogas production can minimize the consumption of commercial energy source such as kerosene as well as the use of firewood . Biogas is generated by the process of organic material digestion by certain anaerobe bacteria activity in aerobic digester . Anaerobic digestion process is basically carried out in three steps i.e. hydrolysis, acidogenic and metanogenic . Digestion process needs certain condition such as C : N ratio, temperature, acidity and also digester design . Most anaerobic digestions perform best at 32 - 35°C or at 50 - 55°C, and pH 6 .8 - 8 . At these temperatures, the digestion process essentially converts organic matter in the present of water into gaseous energy . Generally, biogas consists of methane about 60 - 70% and yield about 1,000 British Thermal Unit/ft 3 or 252 Kcal/0.028 m3 when burned . In several developing countries, as well as in Europe and the United States, biogas has been commonly used as a subtitute environmental friendly energy . Meanwhile, potentially Indonesia has abundant potential of biomass waste, however biogas has not been used maximally .

  8. Sound preference test in animal models of addicts and phobias.

    Science.gov (United States)

    Soga, Ryo; Shiramatsu, Tomoyo I; Kanzaki, Ryohei; Takahashi, Hirokazu

    2016-08-01

    Biased or too strong preference for a particular object is often problematic, resulting in addiction and phobia. In animal models, alternative forced-choice tasks have been routinely used, but such preference test is far from daily situations that addicts or phobic are facing. In the present study, we developed a behavioral assay to evaluate the preference of sounds in rodents. In the assay, several sounds were presented according to the position of free-moving rats, and quantified the sound preference based on the behavior. A particular tone was paired with microstimulation to the ventral tegmental area (VTA), which plays central roles in reward processing, to increase sound preference. The behaviors of rats were logged during the classical conditioning for six days. Consequently, some behavioral indices suggest that rats search for the conditioned sound. Thus, our data demonstrated that quantitative evaluation of preference in the behavioral assay is feasible.

  9. Transportable Emissions Testing Laboratory for Alternative Vehicles Emissions Testing

    Energy Technology Data Exchange (ETDEWEB)

    Clark, Nigel

    2012-01-31

    The overall objective of this project was to perform research to quantify and improve the energy efficiency and the exhaust emissions reduction from advanced technology vehicles using clean, renewable and alternative fuels. Advanced vehicle and alternative fuel fleets were to be identified, and selected vehicles characterized for emissions and efficiency. Target vehicles were to include transit buses, school buses, vocational trucks, delivery trucks, and tractor-trailers. Gaseous species measured were to include carbon monoxide, carbon dioxide, oxides of nitrogen, hydrocarbons, and particulate matter. An objective was to characterize particulate matter more deeply than by mass. Accurate characterization of efficiency and emissions was to be accomplished using a state-of-the-art portable emissions measurement system and an accompanying chassis dynamometer available at West Virginia University. These two units, combined, are termed the Transportable Laboratory. An objective was to load the vehicles in a real-world fashion, using coast down data to establish rolling resistance and wind drag, and to apply the coast down data to the dynamometer control. Test schedules created from actual vehicle operation were to be employed, and a specific objective of the research was to assess the effect of choosing a test schedule which the subject vehicle either cannot follow or can substantially outperform. In addition the vehicle loading objective was to be met better with an improved flywheel system.

  10. Risk-based testing of imported animals

    NARCIS (Netherlands)

    Vos-de Jong, de Clazien; Goot, van der J.A.; Zijderveld, van F.G.; Swanenburg, M.; Elbers, A.R.W.

    2015-01-01

    In intra-EU trade, the health status of animals is warranted by issuing a health certificate after clinical inspection in the exporting country. This certificate cannot provide guarantee of absence of infection, especially not for diseases with a long incubation period and no overt clinical signs

  11. Experiences of the REACH testing proposals system to reduce animal testing.

    Science.gov (United States)

    Taylor, Katy; Stengel, Wolfgang; Casalegno, Carlotta; Andrew, David

    2014-01-01

    In order to reduce animal testing, companies registering chemical substances under the EU REACH legislation must propose rather than conduct certain tests on animals. Third parties can submit 'scientifically valid information' relevant to these proposals to the Agency responsible, the European Chemicals Agency (ECHA), who are obliged to take the information into account. The European Coalition to End Animal Experiments (ECEAE) provided comments on nearly half of the 817 proposals for vertebrate tests on 480 substances published for comment for the first REACH deadline (between 1 August 2009 and 31 July 2012). The paper summarises the response by registrants and the Agency to third party comments and highlights issues with the use of read across, in vitro tests, QSAR and weight of evidence approaches. Use of existing data and evidence that testing is legally or scientifically unjustified remain the most successful comments for third parties to submit. There is a worrying conservatism within the Agency regarding the acceptance of alternative approaches and examples of where registrants have also failed to maximise opportunities to avoid testing.

  12. Animal Effects from Soviet Atmospheric Nuclear Tests

    Science.gov (United States)

    2008-03-01

    rem (the zero index indicates that the doses were measured in front of a protection barrier, i.e., for open ground). Because of uncertainties ...asthenia, listlessness, anorexia , vomiting, flux (diarrhea) and hemodynamic aberrations. The peripheral blood in the majority of cases 49 demonstrates...adynamia and anorexia (lack of appetite) prevailed. There was also an observable lowering of the animal’s body temperature, as well as paleness of the

  13. Alternatives Analysis for the Resumption of Transient Testing Program

    Energy Technology Data Exchange (ETDEWEB)

    Lee Nelson

    2013-11-01

    An alternatives analysis was performed for resumption of transient testing. The analysis considered eleven alternatives – including both US international facilities. A screening process was used to identify two viable alternatives from the original eleven. In addition, the alternatives analysis includes a no action alternative as required by the National Environmental Policy Act (NEPA). The alternatives considered in this analysis included: 1. Restart the Transient Reactor Test Facility (TREAT) 2. Modify the Annular Core Research Reactor (ACRR) which includes construction of a new hot cell and installation of a new hodoscope. 3. No Action

  14. Use of animals for toxicology testing is necessary to ensure patient safety in pharmaceutical development.

    Science.gov (United States)

    Mangipudy, Raja; Burkhardt, John; Kadambi, Vivek J

    2014-11-01

    There is an active debate in toxicology literature about the utility of animal testing vis-a-vis alternative in vitro paradigms. To provide a balanced perspective and add to this discourse it is important to review the current paradigms, explore pros and cons of alternatives, and provide a vision for the future. The fundamental goal of toxicity testing is to ensure safety in humans. In this article, IQ Consortium DruSafe, while submitting the view that nonclinical testing in animals is an important and critical component of the risk assessment paradigm in developing new drugs, also discusses its views on alternative approaches including a roadmap for what would be required to enhance the utilization of alternative approaches in the safety assessment process. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Testing Alternative Definitions of Chronic Homelessness.

    Science.gov (United States)

    Byrne, Thomas; Culhane, Dennis P

    2015-09-01

    This study examined the potential impact of a proposed change to the official federal definition of chronic homelessness. Using administrative data from the emergency shelters in a large U.S. city, this study estimated the number of persons identified as chronically homeless under the current definition of chronic homelessness, a proposed new federal definition, and two alternative definitions and examined shelter utilization for each group. Fewer than half as many people were considered chronically homeless under the proposed new federal definition compared with the current definition. Persons considered chronically homeless by the proposed new definition and, to a lesser extent, by the two alternative definitions, made heavier use of shelter compared with persons who met the current definition. A proposed new and two alternative definitions of chronic homelessness are better suited than the existing federal definition for identifying persons with the most protracted experiences of homelessness.

  16. [Voluntary testing procedures of farm animal housing equipment according to the Animal Welfare Act of 1998].

    Science.gov (United States)

    Hesse, D; Knierim, U; von Borell, E; Herrmann, H; Koch, L; Müller, C; Rauch, H W; Sachser, N; Schwabenbauer, K; Zerbe, F

    1999-04-01

    Before its broad application in practice, housing equipment should be tested, in particular with regard to animal welfare. The differing positions of the German Federal Council (Bundesrat) and the German Federal Parliament (Bundestag), whether such testing should be mandatory or voluntary, have been conciliated in the amended animal welfare act by empowering the Federal Ministry of Food, Agriculture and Fisheries (BML) to fix official standards for voluntary testing procedures by regulation. On request of the BML, a report as scientific basis for a draft regulation is currently prepared by the scientific animal welfare committee of the German Agricultural Society (DLG). The scientific animal welfare committee has been appointed by the DLG in order to provide support in the effort to strengthen animal welfare aspects in the DLG-utility testing procedure of housing equipment, which is in place since 1953. The committee elaborates standards concerning testing methods, assessment criteria and the necessary size of investigations. As required, the scientific animal welfare committee may support the DLG-testing bodies in the implementation of the animal welfare part of the testing procedure. It will, moreover, be involved in the welfare assessment based on the testing results. The amendments of the already established testing procedure will help to fulfill the general requirements on an acceptable animal welfare testing procedure. While keeping in mind that there are certain limits in what can be achieved by a voluntary testing procedure, the enhanced consideration of animal welfare aspects within the DLG-utility testing procedure has the advantage to be relatively unbureaucratic and in line with EU legislation, and is, therefore, an appropriate tool for a contibrution to improved animal welfare in livestock housing.

  17. Effects of different simplified milk recording methods on genetic evaluation with Test-Day animal model

    Directory of Open Access Journals (Sweden)

    D. Cacioppo

    2010-04-01

    Full Text Available The aims of the present study were to compare estimated breeding values (EBV for milk yield using different testing schemes with a test-day animal model and to evaluate the effect of different testing schemes on the ranking of top sheep. Alternative recording schemes that use less information than that currently obtained with a monthly test-day schedule were employed to estimate breeding values. A random regression animal mixed model that used a spline function of days in milk was fitted. EBVs obtained with alternative recording schemes showed different degrees of Spearman correlation with EBVs obtained using the monthly recording scheme. These correlations ranged from 0.77 to 0.92. A reduction in accuracy and intensity of selection could be anticipated if these alternative schemes are used; more research in this area is needed to reduce the costs of test-day recording.

  18. Constraints in animal health service delivery and sustainable improvement alternatives in North Gondar, Ethiopia

    Directory of Open Access Journals (Sweden)

    Hassen Kebede

    2014-02-01

    Full Text Available Poor livestock health services remain one of the main constraints to livestock production in many developing countries, including Ethiopia. A study was carried out in 11 districts of North Gondar, from December 2011 to September 2012, with the objective of identifying the existing status and constraints of animal health service delivery, and thus recommending possible alternatives for its sustainable improvement. Data were collected by using pre-tested questionnaires and focus group discussion. Findings revealed that 46.34% of the responding farmers had taken their animals to government veterinary clinics after initially trying treatments with local medication. More than 90.00% of the clinical cases were diagnosed solely on clinical signs or even history alone. The antibacterial drugs found in veterinary clinics were procaine penicillin (with or without streptomycin, oxytetracycline and sulphonamides, whilst albendazole, tetramisole and ivermectin were the only anthelmintics. A thermometer was the only clinical aid available in all clinics, whilst only nine (45.00% clinics had a refrigerator. In the private sector, almost 95.00% were retail veterinary pharmacies and only 41.20% fulfilled the requirement criteria set. Professionals working in the government indicated the following problems: lack of incentives (70.00%, poor management and lack of awareness (60.00% and inadequate budget (40.00%. For farmers, the most frequent problems were failure of private practitioners to adhere to ethical procedures (74.00% and lack of knowledge of animal diseases and physical distance from the service centre (50.00%. Of all responding farmers, 58.54% preferred the government service, 21.14% liked both services equally and 20.33% preferred the private service. Farmers’ indiscriminate use of drugs from the black market (23.00% was also mentioned as a problem by private practitioners. Sustainable improvement of animal health service delivery needs increased

  19. Constraints in animal health service delivery and sustainable improvement alternatives in North Gondar, Ethiopia

    Directory of Open Access Journals (Sweden)

    Hassen Kebede

    2014-11-01

    Full Text Available Poor livestock health services remain one of the main constraints to livestock production in many developing countries, including Ethiopia. A study was carried out in 11 districts of North Gondar, from December 2011 to September 2012, with the objective of identifying the existing status and constraints of animal health service delivery, and thus recommending possible alternatives for its sustainable improvement. Data were collected by using pre-tested questionnaires and focus group discussion. Findings revealed that 46.34% of the responding farmers had taken their animals to government veterinary clinics after initially trying treatments with local medication. More than 90.00% of the clinical cases were diagnosed solely on clinical signs or even history alone. The antibacterial drugs found in veterinary clinics were procaine penicillin (with or without streptomycin, oxytetracycline and sulphonamides, whilst albendazole, tetramisole and ivermectin were the only anthelmintics. A thermometer was the only clinical aid available in all clinics, whilst only nine (45.00% clinics had a refrigerator. In the private sector, almost 95.00% were retail veterinary pharmacies and only 41.20% fulfilled the requirement criteria set. Professionals working in the government indicated the following problems: lack of incentives (70.00%, poor management and lack of awareness (60.00% and inadequate budget (40.00%. For farmers, the most frequent problems were failure of private practitioners to adhere to ethical procedures (74.00% and lack of knowledge of animal diseases and physical distance from the service centre (50.00%. Of all responding farmers, 58.54% preferred the government service, 21.14% liked both services equally and 20.33% preferred the private service. Farmers’ indiscriminate use of drugs from the black market (23.00% was also mentioned as a problem by private practitioners. Sustainable improvement of animal health service delivery needs increased

  20. Alternative methods for skin irritation testing: the current status : ECVAM skin irritation task force report 1

    NARCIS (Netherlands)

    Botham, P.A.; Earl, L.K.; Fentem, J.H.; Roguet, R.; Sandt, J.J.M.

    1998-01-01

    The ECVAM Skin Irritation Task Force was established in November 1996, primarily to prepare a report on the current status of the development and validation of alternative tests for skin irritation and corrosion and, in particular, to identify any appropriate non-animal tests for predicting human

  1. Combined in vitro tests as an alternative to in vivo eye irritation tests.

    Science.gov (United States)

    Ying, Yang; Xingfen, Yang; Wengai, Zhang; Jinheng, Cai; Jinyu, Xue; Guangyu, Yang; Xiaohua, Tan; Xiaoping, Xie; Xikun, Xiong; Junming, Huang; Xiang, Guo

    2010-08-01

    Accurate methods that test the eye irritation potential of chemicals, which do not involve the use of animals, are needed to meet new regulatory standards. We evaluated the applicability and predictive capacity of five in vitro tests for eye irritation: the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) assay; the Chorioallantoic Membrane-Trypan Blue Staining (CAM-TBS) assay; the Fluorescein Leakage Test (FLT); the 3T3-Neutral Red Uptake (3T3-NRU) cytotoxicity assay; and the red blood cell (RBC) haemolysis assay. A panel of 16 chemicals (some at multiple concentrations) was assessed by using the five tests, and the results were compared with historical in vivo Draize test data. The results showed rank correlation and class concordance between the five alternative methods and the Draize test for the 16 chemicals. These in vitro assays had good predictive capacity, reproducibility and reliability when compared to the Draize test. The best relationship was between the HET-CAM, CAM-TBS and FLT results, and the modified maximum average score(s) (MMAS). A prediction model (PM) was developed, based on the maximum possible correlation between the MMAS and the HET-CAM, CAM-TBS and FLT results. The PM had a good predictive capacity when compared to the results of animal tests, indicating its potential value for the in vitro screening of chemicals for eye irritation effects. 2010 FRAME.

  2. Alternative methods for eye and skin irritation tests: an overview.

    Science.gov (United States)

    Vinardell, M P; Mitjans, M

    2008-01-01

    The evaluation of eye and skin irritation potential is essential to ensuring the safety of individuals in contact with a wide variety of substances designed for industrial, pharmaceutical or cosmetic use. The Draize rabbit eye and skin irritancy tests have been used for 60 years to attempt to predict the human ocular and dermal irritation of such products. The Draize test has been the standard for ocular and dermal safety assessments for decades. However, several aspects of the test have been criticised. These include: the subjectivity of the method; the overestimation of human responses; and the method's cruelty. The inadequacies of the Draize test have led to several laboratories over the last 20 years making efforts to develop in vitro assays to replace it. Protocols that use different types of cell cultures and other methods have been devised to study eye and skin irritation. Different commercial kits have also been developed to study eye and skin irritation, based on the action of chemicals on these tissues. This article presents a review of the main alternatives developed to replace the use of animals in the study of chemical irritation. Particular attention is paid to the reproducibility of each method. (c) 2007 Wiley-Liss, Inc.

  3. Tests of Alternative Theories of Firm Growth.

    OpenAIRE

    Evans, David S

    1987-01-01

    This study examines the relationships among firm growth, firm size, and firm age for a sample of manufacturing firms between 1976 and 1982. Firm growth is found to decrease with firm age and firm size. These findings are robust to alternative assumptions concerning the effects of sample censoring and the functional form of the growth relationship. The inverse growth-age relationship is consistent with a theory of firm learning proposed by Boyan Jovanovic while the inverse growth-size relation...

  4. Local tolerance testing under REACH: Accepted non-animal methods are not on equal footing with animal tests.

    Science.gov (United States)

    Sauer, Ursula G; Hill, Erin H; Curren, Rodger D; Raabe, Hans A; Kolle, Susanne N; Teubner, Wera; Mehling, Annette; Landsiedel, Robert

    2016-07-01

    In general, no single non-animal method can cover the complexity of any given animal test. Therefore, fixed sets of in vitro (and in chemico) methods have been combined into testing strategies for skin and eye irritation and skin sensitisation testing, with pre-defined prediction models for substance classification. Many of these methods have been adopted as OECD test guidelines. Various testing strategies have been successfully validated in extensive in-house and inter-laboratory studies, but they have not yet received formal acceptance for substance classification. Therefore, under the European REACH Regulation, data from testing strategies can, in general, only be used in so-called weight-of-evidence approaches. While animal testing data generated under the specific REACH information requirements are per se sufficient, the sufficiency of weight-of-evidence approaches can be questioned under the REACH system, and further animal testing can be required. This constitutes an imbalance between the regulatory acceptance of data from approved non-animal methods and animal tests that is not justified on scientific grounds. To ensure that testing strategies for local tolerance testing truly serve to replace animal testing for the REACH registration 2018 deadline (when the majority of existing chemicals have to be registered), clarity on their regulatory acceptance as complete replacements is urgently required. 2016 FRAME.

  5. Strategy for Alternative Occupant Volume Testing

    Science.gov (United States)

    2009-10-20

    This paper describes plans for a series of quasi-static : compression tests of rail passenger equipment. These tests are : designed to evaluate the strength of the occupant volume under : static loading conditions. The research plan includes a detail...

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

    Directory of Open Access Journals (Sweden)

    Natalie Burden

    2015-05-01

    Full Text Available 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.

  7. In chemico evaluation of prohapten skin sensitizers: behavior of 2-methoxy-4-(¹³C)methylphenol in the peroxidase peptide reactivity assay (PPRA) as an alternative to animal testing.

    Science.gov (United States)

    Merckel, Fabien; Giménez-Arnau, Elena; Gerberick, G Frank; Lepoittevin, Jean-Pierre

    2013-04-26

    In chemico methods, based on the assessment of a hapten's reactivity toward peptides, have been proposed as alternative methods for the assessment of the skin sensitizing potential of chemicals. However, even with these approaches showing promise, a major drawback is the activation of prohaptens, i.e. molecules needing a metabolic activation to become reactive and therefore sensitizing. Recently, it has been proposed to couple an enzymatic activation step based on horseradish peroxidase (HRP)/hydrogen peroxide to such peptide reactivity assays. To evaluate this approach, the behavior of 2-methoxy-4-methylphenol (2M4MP), reported as a moderate sensitizer according to the Local Lymph Node Assay (LLNA), has been investigated in this assay. To follow the reaction with the peptides and characterize more easily intermediates and adducts, the molecule was first (13)C isotopically substituted at the most probable reactive position. When 2M4MP was incubated with HRP/H2O2 in a mixture PBS (pH 7.4, 0.1M)/acetonitrile 2:1, two main products were formed deriving from the formation of a quinone methide 2M4MQ subsequently trapped by either H2O2 or H2O to form a benzylic hydroperoxide or alcohol, respectively. When nucleophiles such as GSH or a peptide containing a cysteine residue (Pep-Cys) were present in the reaction medium, the quinone methide 2M4MQ was trapped by the more nucleophilic thiol function to form thio-adducts. No modifications of 2M4MP were observed when the same reactions were carried out without HRP confirming that the activation of the molecule was enzyme related. Amino nucleophiles were shown to be far less reactive towards the quinone methide 2M4MQ with only tiny formation of adducts with lysine or arginine side chains. In addition we demonstrated that the same enzymatic activation could also take place in a microemulsion based on sodium dodecyl sulfate/tert-butanol/chloroform/buffer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Developmental neurotoxicity testing: recommendations for developing alternative methods for the screening and prioritization of chemicals.

    Science.gov (United States)

    Crofton, Kevin M; Mundy, William R; Lein, Pamela J; Bal-Price, Anna; Coecke, Sandra; Seiler, Andrea E M; Knaut, Holger; Buzanska, Leonora; Goldberg, Alan

    2011-01-01

    Developmental neurotoxicity testing (DNT) is perceived by many stakeholders to be an area in critical need of alternative methods to current animal testing protocols and guidelines. An immediate goal is to develop test methods that are capable of screening large numbers of chemicals. This document provides recommendations for developing alternative DNT approaches that will generate the type of data required for evaluating and comparing predictive capacity and efficiency across test methods and laboratories. These recommendations were originally drafted to stimulate and focus discussions of alternative testing methods and models for DNT at the TestSmart DNT II meeting (http://caat.jhsph.edu/programs/workshops/dnt2.html) and this document reflects critical feedback from all stakeholders that participated in this meeting. The intent of this document is to serve as a catalyst for engaging the research community in the development of DNT alternatives and it is expected that these recommendations will continue to evolve with the science.

  9. Effects of different simplified milk recording methods on genetic evaluation with test-day animal model

    OpenAIRE

    Portolano, B.; Maizon, D. O.; Riggio, V.; Tolone, M.; Cacioppo, D.

    2007-01-01

    The aims of the present study were to compare estimated breeding values (EBV) for milk yield using different testing schemes with a test-day animal model and to evaluate the effect of different testing schemes on the ranking of top sheep. Alternative recording schemes that use less information than that currently obtained with a monthly test-day schedule were employed to estimate breeding values. A random regression animal mixed model that used a spline function of days in milk was fitted. EB...

  10. Alternative Testing Methods for Predicting Health Risk from Environmental Exposures

    Directory of Open Access Journals (Sweden)

    Annamaria Colacci

    2014-08-01

    Full Text Available Alternative methods to animal testing are considered as promising tools to support the prediction of toxicological risks from environmental exposure. Among the alternative testing methods, the cell transformation assay (CTA appears to be one of the most appropriate approaches to predict the carcinogenic properties of single chemicals, complex mixtures and environmental pollutants. The BALB/c 3T3 CTA shows a good degree of concordance with the in vivo rodent carcinogenesis tests. Whole-genome transcriptomic profiling is performed to identify genes that are transcriptionally regulated by different kinds of exposures. Its use in cell models representative of target organs may help in understanding the mode of action and predicting the risk for human health. Aiming at associating the environmental exposure to health-adverse outcomes, we used an integrated approach including the 3T3 CTA and transcriptomics on target cells, in order to evaluate the effects of airborne particulate matter (PM on toxicological complex endpoints. Organic extracts obtained from PM2.5 and PM1 samples were evaluated in the 3T3 CTA in order to identify effects possibly associated with different aerodynamic diameters or airborne chemical components. The effects of the PM2.5 extracts on human health were assessed by using whole-genome 44 K oligo-microarray slides. Statistical analysis by GeneSpring GX identified genes whose expression was modulated in response to the cell treatment. Then, modulated genes were associated with pathways, biological processes and diseases through an extensive biological analysis. Data derived from in vitro methods and omics techniques could be valuable for monitoring the exposure to toxicants, understanding the modes of action via exposure-associated gene expression patterns and to highlight the role of genes in key events related to adversity.

  11. Florida alternative NTCIP testing software (ANTS) for actuated signal controllers.

    Science.gov (United States)

    2009-01-01

    The scope of this research project did include the development of a software tool to test devices for NTCIP compliance. Development of the Florida Alternative NTCIP Testing Software (ANTS) was developed by the research team due to limitations found w...

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

    Science.gov (United States)

    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.

  13. Future improvements and implementation of animal care practices within the animal testing regulatory environment.

    Science.gov (United States)

    Guittin, Pierre; Decelle, Thierry

    2002-01-01

    Animal welfare is an increasingly important concern when considering biomedical experimentation. Many of the emerging regulations and guidelines specifically address animal welfare in laboratory animal care and use. The current revision of the appendix of the European Convention, ETS123 (Council of Europe), updates and improves on the current animal care standardization in Europe. New guidelines from the Organisation for Economic Co-operation and Development and the European Federation of Pharmaceutical Industries Association focus specifically on safety testing. These guidelines will affect the way toxicity studies are conducted and therefore the global drug development process. With the 3Rs principles taken into account, consideration regarding animal welfare will demand changes in animal care practices in regulatory safety testing. The most significant future improvements in animal care and use practices are likely to be environmental enrichment, management of animal pain and distress, and improved application of the humane endpoints. Our challenge is to implement respective guidelines based on scientific data and animal welfare, through a complex interplay of regulatory objective and public opinion. The current goal is to work toward solutions that continue to provide relevant animal models for risk assessment in drug development and that are science based. In this way, future improvements in animal care and use practices can be founded on facts, scientific results, and analysis. Some of these improvements become common practice in some countries. International harmonization can facilitate the development and practical application of "best scientific practices" by the consensus development process that harmonization requires. Since the implementation of good laboratory practices (GLP) standards in safety testing, these new regulations and recommendations represent a new way forward for animal safety studies.

  14. Conceptual Approaches to Alternate Methods in Toxicological Testing

    OpenAIRE

    Alan M. Goldberg; Andrew N. Rowan

    1987-01-01

    Due to public pressure, in vivo methods of toxicity testing is being attempted to be replaced by in vitro methods, such as cell and organ culture, computer modelling and modified LD50 tests using lesser number of animals. Specifically in the case of Draize eye irritancy test using rabbits, a number of refinements have been incorporated by different workers, mainly use of a local anaesthetic which will reduce animal distress without vitiating the test results. The author recommends exploration...

  15. Systems for animal exposure in full-scale fire tests

    Science.gov (United States)

    Hilado, C. J.; Cumming, H. J.; Kourtides, D. A.; Parker, J. A.

    1977-01-01

    Two systems for exposing animals in full-scale fire tests are described. Both systems involve the simultaneous exposure of two animal species, mice and rats, in modular units; determination of mortality, morbidity, and behavioral response; and analysis of the blood for carboxyhemoglobin. The systems described represent two of many possible options for obtaining bioassay data from full-scale fire tests. In situations where the temperatures to which the test animals are exposed can not be controlled, analytical techniques may be more appropriate than bioassay techniques.

  16. Developing a list of reference chemicals for testing alternatives to whole fish toxicity tests.

    Science.gov (United States)

    Schirmer, Kristin; Tanneberger, Katrin; Kramer, Nynke I; Völker, Doris; Scholz, Stefan; Hafner, Christoph; Lee, Lucy E J; Bols, Niels C; Hermens, Joop L M

    2008-11-11

    This paper details the derivation of a list of 60 reference chemicals for the development of alternatives to animal testing in ecotoxicology with a particular focus on fish. The chemicals were selected as a prerequisite to gather mechanistic information on the performance of alternative testing systems, namely vertebrate cell lines and fish embryos, in comparison to the fish acute lethality test. To avoid the need for additional experiments with fish, the U.S. EPA fathead minnow database was consulted as reference for whole organism responses. This database was compared to the Halle Registry of Cytotoxicity and a collation of data by the German EPA (UBA) on acute toxicity data derived from zebrafish embryos. Chemicals that were present in the fathead minnow database and in at least one of the other two databases were subject to selection. Criteria included the coverage of a wide range of toxicity and physico-chemical parameters as well as the determination of outliers of the in vivo/in vitro correlations. While the reference list of chemicals now guides our research for improving cell line and fish embryo assays to make them widely applicable, the list could be of benefit to search for alternatives in ecotoxicology in general. One example would be the use of this list to validate structure-activity prediction models, which in turn would benefit from a continuous extension of this list with regard to physico-chemical and toxicological data.

  17. An Alternative to the Use of Animals to Teach Diabetes Mellitus

    Science.gov (United States)

    Basso, Paulo José; Tazinafo, Lucas Favaretto; Silva, Mauro Ferreira; Rocha, Maria José Alves

    2014-01-01

    We developed an alternative approach to teach diabetes mellitus in our practical classes, replacing laboratory animals. We used custom rats made of cloth, which have a ventral zipper that allows stuffing with glass marbles to reach different weights. Three mock rats per group were placed into metabolic cages with real food and water and with test…

  18. Insights Gained from Testing Alternate Cell Designs

    International Nuclear Information System (INIS)

    O'Brien, J.E.; Stoots, C.M.; Herring, J.S.; Housley, G.K.; Sohal, M.S.; Milobar, D.G.; Cable, Thomas

    2009-01-01

    The Idaho National Laboratory (INL) has been researching the application of solid-oxide electrolysis cell for large-scale hydrogen production from steam over a temperature range of 800 to 900 C. The INL has been testing various solid oxide cell designs to characterize their electrolytic performance operating in the electrolysis mode for hydrogen production. Some results presented in this report were obtained from cells, initially developed by the Forschungszentrum Juelich and now manufactured by the French ceramics firm St. Gobain. These cells have an active area of 16 cm2 per cell. They were initially developed as fuel cells, but are being tested as electrolytic cells in the INL test stands. The electrolysis cells are electrode-supported, with ∼10 (micro)m thick yttria-stabilized zirconia (YSZ) electrolytes, ∼1400 (micro)m thick nickel-YSZ steam-hydrogen electrodes, and manganite (LSM) air-oxygen electrodes. The experiments were performed over a range of steam inlet mole fractions (0.1 to 0.6), gas flow rates, and current densities (0 to 0.6 A/cm2). Steam consumption rates associated with electrolysis were measured directly using inlet and outlet dewpoint instrumentation. On a molar basis, the steam consumption rate is equal to the hydrogen production rate. Cell performance was evaluated by performing DC potential sweeps at 800, 850, and 900 C. The voltage-current characteristics are presented, along with values of area-specific resistance as a function of current density. Long-term cell performance is also assessed to evaluate cell degradation. Details of the custom single-cell test apparatus developed for these experiments are also presented. NASA, in conjunction with the University of Toledo, has developed another fuel cell concept with the goals of reduced weight and high power density. The NASA cell is structurally symmetrical, with both electrodes supporting the thin electrolyte and containing micro-channels for gas diffusion. This configuration is

  19. PREPARE: guidelines for planning animal research and testing.

    Science.gov (United States)

    Smith, Adrian J; Clutton, R Eddie; Lilley, Elliot; Hansen, Kristine E Aa; Brattelid, Trond

    2018-04-01

    There is widespread concern about the quality, reproducibility and translatability of studies involving research animals. Although there are a number of reporting guidelines available, there is very little overarching guidance on how to plan animal experiments, despite the fact that this is the logical place to start ensuring quality. In this paper we present the PREPARE guidelines: Planning Research and Experimental Procedures on Animals: Recommendations for Excellence. PREPARE covers the three broad areas which determine the quality of the preparation for animal studies: formulation, dialogue between scientists and the animal facility, and quality control of the various components in the study. Some topics overlap and the PREPARE checklist should be adapted to suit specific needs, for example in field research. Advice on use of the checklist is available on the Norecopa website, with links to guidelines for animal research and testing, at https://norecopa.no/PREPARE .

  20. Humane Society International's global campaign to end animal testing.

    Science.gov (United States)

    Seidle, Troy

    2013-12-01

    The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 European sales ban for newly animal-tested cosmetics, in achieving the June 2013 cosmetics animal testing ban in India as well as major cosmetics regulatory policy shifts in China and South Korea, and in securing precedent-setting reductions in in vivo data requirements for pesticides in the EU through the revision of biocides and plant protection product regulations, among others. HSI is currently working to export these life-saving measures to more than a dozen industrial and emerging economies. 2013 FRAME.

  1. The EC/HO international validation study on alternatives to the draize eye irritation test.

    Science.gov (United States)

    Balls, M; Botham, P A; Bruner, L H; Spielmann, H

    1995-12-01

    This is the final report of the Management Team for a European Commission/British Home Office (EC/HO) validation study on alternatives to the Draize eye irritation test. The principal goal of the study was to establish whether one or more of nine non-animal tests could be used to replace the Draize test for all severely irritating materials (or those belonging to specific classes) or the animal test completely for chemicals with or without regard to chemical class. Sixty chemicals were independently selected, coded and supplied, then the data obtained in 37 laboratories were analysed independently. The results of comparisons between 27 alternative test index scores and the Modified Maximum Average Scores (MMASs) obtained in the Draize eye test were compared. Tables of results showing Pearson's product moment correlation coefficients and Spearman's rank coefficients for each laboratory are provided, and correlation matrices of alternative test index scores among the different groups of laboratories are shown for each endpoint. Scatterplots are provided, in which the alternative test scores obtained by the lead laboratories for the nine tests are plotted against the MMAS for the full set of chemicals and 12 surfactants. It is concluded that, with the possible exception of predicting the irritancy of surfactants, none of the nine tests met any of the four performance targets. Possible reasons for this outcome are discussed.

  2. [Non-animal toxicology in the safety testing of chemicals].

    Science.gov (United States)

    Heinonen, Tuula; Tähti, Hanna

    2013-01-01

    There is an urgent need to develop predictive test methods better than animal experiments for assessing the safety of chemical substances to man. According to today's vision this is achieved by using human cell based tissue and organ models. In the new testing strategy the toxic effects are assessed by the changes in the critical parameters of the cellular biochemical routes (AOP, adverse toxic outcome pathway-principle) in the target tissues. In vitro-tests are rapid and effective, and with them automation can be applied. The change in the testing paradigm is supported by all stakeholders: scientists, regulators and people concerned on animal welfare.

  3. Alternative testing strategies for predicting developmental toxicity of antifungal compound

    NARCIS (Netherlands)

    Li, H.

    2016-01-01

    Determination of safe human exposure levels of chemicals in toxicological risk assessments largely relies on animal toxicity data. In these toxicity studies, the highest number of animals are used for reproductive and developmental toxicity testing. Because of economic and ethical reasons, there

  4. Balancing animal welfare and assisted reproduction: ethics of preclinical animal research for testing new reproductive technologies.

    Science.gov (United States)

    Jans, Verna; Dondorp, Wybo; Goossens, Ellen; Mertes, Heidi; Pennings, Guido; de Wert, Guido

    2018-02-07

    In the field of medically assisted reproduction (MAR), there is a growing emphasis on the importance of introducing new assisted reproductive technologies (ARTs) only after thorough preclinical safety research, including the use of animal models. At the same time, there is international support for the three R's (replace, reduce, refine), and the European Union even aims at the full replacement of animals for research. The apparent tension between these two trends underlines the urgency of an explicit justification of the use of animals for the development and preclinical testing of new ARTs. Considering that the use of animals remains necessary for specific forms of ART research and taking account of different views on the moral importance of helping people to have a genetically related child, we argue that, in principle, the importance of safety research as part of responsible innovation outweighs the limited infringement of animal wellbeing involved in ART research.

  5. Food for Thought... on the Economics of Animal Testing

    OpenAIRE

    BOTTINI Annamaria; HARTUNG Thomas

    2009-01-01

    "Money makes the world go around". We all have heard this, but in the field of alternative methods, we use to talk about ethics, scientific progress, politics, animal welfare or consumer and environment safety. In this series of articles, however, we have occasionally come to issues which were difficult to separate from economical reasoning. Most obviously, the article on globalisation [Bottini et al. 2007] showed the resonance of a major economical trend and recent developments in the field ...

  6. A first vascularized skin equivalent as an alternative to animal experimentation.

    Science.gov (United States)

    Groeber, Florian; Engelhardt, Lisa; Lange, Julia; Kurdyn, Szymon; Schmid, Freia F; Rücker, Christoph; Mielke, Stephan; Walles, Heike; Hansmann, Jan

    2016-01-01

    Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin & eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.

  7. Animal models for testing anti-prion drugs.

    Science.gov (United States)

    Fernández-Borges, Natalia; Elezgarai, Saioa R; Eraña, Hasier; Castilla, Joaquín

    2013-01-01

    Prion diseases belong to a group of fatal infectious diseases with no effective therapies available. Throughout the last 35 years, less than 50 different drugs have been tested in different experimental animal models without hopeful results. An important limitation when searching for new drugs is the existence of appropriate models of the disease. The three different possible origins of prion diseases require the existence of different animal models for testing anti-prion compounds. Wild type, over-expressing transgenic mice and other more sophisticated animal models have been used to evaluate a diversity of compounds which some of them were previously tested in different in vitro experimental models. The complexity of prion diseases will require more pre-screening studies, reliable sporadic (or spontaneous) animal models and accurate chemical modifications of the selected compounds before having an effective therapy against human prion diseases. This review is intended to put on display the more relevant animal models that have been used in the search of new antiprion therapies and describe some possible procedures when handling chemical compounds presumed to have anti-prion activity prior to testing them in animal models.

  8. Political incentives towards replacing animal testing in nanotechnology?

    Science.gov (United States)

    Sauer, Ursula G

    2009-01-01

    The Treaty of Lisbon requests the European Union and the Member States to pay full regard to animal welfare issues when implementing new policies. The present article discusses how these provisions are met in the emerging area of nanotechnology. Political action plans in Europe take into account animal welfare issues to some extent. Funding programmes promote the development of non-animal test methods, however only in the area of nanotoxicology and also here not sufficiently to "pay full regard" to preventing animal testing, let alone to bring about a paradigm change in toxicology or in biomedical research as such. Ethical deliberations on nanotechnology, which influence future policies, so far do not address animal welfare at all. Considering that risk assessment of nanoproducts is conceived as a key element to protect human dignity, ethical deliberations should address the choice of the underlying testing methods and call for basing nanomaterial safety testing upon the latest scientific--and ethically acceptable--technologies. Finally, public involvement in the debate on nanotechnology should take into account information on resulting animal experiments.

  9. Rural and urban Ugandan primary school children's alternative ideas about animals

    Science.gov (United States)

    Otaala, Justine

    This study examined rural and urban Ugandan primary children's alternative ideas about animals through the use of qualitative research methods. Thirty-six children were selected from lower, middle, and upper primary grades in two primary schools (rural and urban). Data were collected using interview-about-instance technique. Children were shown 18 color photographs of instances and non-instances of familiar animals and asked to say if the photographed objects were animals or not. They were then asked to give reasons to justify their answers. The interviews were audiotaped and transcribed. The results indicate that children tended to apply the label "animal" to large mammals, usually found at home, on the farm, in the zoo, and in the wild. Humans were not categorized as animals, particularly by children in the lower grades. Although the children in upper grades correctly identified humans as animals, they used reasons that were irrelevant to animal attributes and improperly derived from the biological concept of evolution. Many attributes children used to categorize instances of animals were scientifically unacceptable and included superficial features, such as body outline, anatomical features (body parts), external features (visual cues), presence or absence and number of appendages. Movement and eating (nutrition) were the most popular attributes children used to identify instances of animals. The main differences in children's ideas emanated from the reasons used to identify animals. Older rural children drew upon their cultural and traditional practices more often than urban children. Anthropomorphic thinking was predominant among younger children in both settings, but diminished with progression in children's grade levels. Some of the implications of this study are: (1) teachers, teacher educators and curriculum developers should consider learners' ideas in planning and developing teaching materials and interventions. (2) Teachers should relate humans to other

  10. Non-animal Replacements for Acute Toxicity Testing.

    Science.gov (United States)

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

    2015-07-01

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

  11. Inconsistencies in data requirements of EU legislation involving tests on animals.

    Science.gov (United States)

    Wagner, Kristina; Fach, Bettina; Kolar, Roman

    2012-01-01

    European Union (EU) legislation on the protection of animals used for scientific purposes requires that alternative methods must be used instead of animal tests wherever they are available. Unfortunately, this provision is not implemented to its full extent when it comes to risk assessment of chemicals and new products prior to their authorization and placing on the market in the EU. In this study, we screened data requirements of relevant EU law regarding chemicals (REACH), biocides, pesticides, and food safety (Novel Food) and found that data requirements as part of the risk assessment do not always reflect state-of-the-art science and technology. Most of the data requirements we investigated still include testing on animals for many toxicological endpoints, even though more than 40 alternative testing methods accepted at the level of the EU or the OECD are available. This may be due to a multitude of reasons, including a shortage of both manpower to implement existing knowledge and expertise in the field of alternative methods, as well as unclear and misleading statements on the applicability and state of validation of alternative methods. In conclusion, we strongly suggest a homogeneous EU-wide approach for all areas involving risk assessment of substances with the goal of better implementing the 3Rs and complying with Directive 2010/63/EU. This also would streamline data requirements, save costs on various levels, and enhance product safety for consumers.

  12. Integrating non-animal test information into an adaptive testing strategy - skin sensitization proof of concept case.

    Science.gov (United States)

    Jaworska, Joanna; Harol, Artsiom; Kern, Petra S; Gerberick, G Frank

    2011-01-01

    There is an urgent need to develop data integration and testing strategy frameworks allowing interpretation of results from animal alternative test batteries. To this end, we developed a Bayesian Network Integrated Testing Strategy (BN ITS) with the goal to estimate skin sensitization hazard as a test case of previously developed concepts (Jaworska et al., 2010). The BN ITS combines in silico, in chemico, and in vitro data related to skin penetration, peptide reactivity, and dendritic cell activation, and guides testing strategy by Value of Information (VoI). The approach offers novel insights into testing strategies: there is no one best testing strategy, but the optimal sequence of tests depends on information at hand, and is chemical-specific. Thus, a single generic set of tests as a replacement strategy is unlikely to be most effective. BN ITS offers the possibility of evaluating the impact of generating additional data on the target information uncertainty reduction before testing is commenced.

  13. Animal models for dengue vaccine development and testing.

    Science.gov (United States)

    Na, Woonsung; Yeom, Minjoo; Choi, Il-Kyu; Yook, Heejun; Song, Daesub

    2017-07-01

    Dengue fever is a tropical endemic disease; however, because of climate change, it may become a problem in South Korea in the near future. Research on vaccines for dengue fever and outbreak preparedness are currently insufficient. In addition, because there are no appropriate animal models, controversial results from vaccine efficacy assessments and clinical trials have been reported. Therefore, to study the mechanism of dengue fever and test the immunogenicity of vaccines, an appropriate animal model is urgently needed. In addition to mouse models, more suitable models using animals that can be humanized will need to be constructed. In this report, we look at the current status of model animal construction and discuss which models require further development.

  14. 9 CFR 113.6 - Animal and Plant Health Inspection Service testing.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Animal and Plant Health Inspection Service testing. 113.6 Section 113.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION... STANDARD REQUIREMENTS Applicability § 113.6 Animal and Plant Health Inspection Service testing. A...

  15. 26 CFR 53.4942(b)-2 - Alternative tests.

    Science.gov (United States)

    2010-04-01

    ... facilities), and intangible assets (such as patents, copyrights, and trademarks) will be considered....4942(b)-2 Alternative tests. (a) Assets test—(1) In general. A private foundation will satisfy the assets test under the provisions of this paragraph if substantially more than half of the foundation's...

  16. Participation of Brazil in the World Congresses on Alternatives and Animal Use in the Life Sciences: an increase in commitment to the Three Rs.

    Science.gov (United States)

    Presgrave, Octavio; Caldeira, Cristiane; Moura, Wlamir; Cruz, Mayara; Méier, Gisele; Dos Santos, Elisabete; Boas, Maria H V

    2015-03-01

    Many Brazilian researchers have long been interested in the development and use of alternative methods. Most of their research groups work in isolation, due to the lack of funding for collaborative studies. Despite these problems, since the Third World Congress on Alternatives and Animal Use in the Life Sciences, Brazilian researchers have strongly participated, not only by presenting posters and oral presentations, but also by being involved in the World Congress Committees. The Brazilian Center for the Validation of Alternative Methods (BraCVAM) must play an important role in the development and validation of alternative methods, through the active participation of the National Network of Alternative Methods (ReNaMA). In Brazil, Law 11,794/2008 regulates the use of animals in experimentation and education, and Law 9,605/1998 clearly states that use of the original animal test is not permitted, if an alternative method is available. Therefore, given the current legal framework, it is very important that all the Ministries involved with animal use, and the organisations responsible for funding researchers, strive to increase the financial support of those groups that are involved in the development and use of alternative methods in Brazil. 2015 FRAME.

  17. Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing.

    Science.gov (United States)

    Walker, A; Srinivas, G B

    2013-09-01

    Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.

  18. Non-animal methodologies within biomedical research and toxicity testing.

    Science.gov (United States)

    Knight, Andrew

    2008-01-01

    Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked - and in some cases, prohibitive - logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower phylogenetic orders or early developmental vertebral stages may be used, as well as microorganisms and higher plants. A variety of tissue cultures, including immortalised cell lines, embryonic and adult stem cells, and organotypic cultures, are also available. In vitro assays utilising bacterial, yeast, protozoal, mammalian or human cell cultures exist for a wide range of toxic and other endpoints. These may be static or perfused, and may be used individually, or combined within test batteries. Human hepatocyte cultures and metabolic activation systems offer potential assessment of metabolite activity and organ-organ interaction. Microarray technology may allow genetic expression profiling, increasing the speed of toxin detection, well prior to more invasive endpoints. Enhanced human clinical trials utilising micro- dosing, staggered dosing, and more representative study populations and durations, as well as surrogate human tissues, advanced imaging modalities and human epidemiological, sociological and psycho- logical studies, may increase our understanding of illness aetiology and pathogenesis, and facilitate the development of safe and effective pharmacologic interventions. Particularly when human tissues

  19. Procoagulant snake venoms have differential effects in animal plasmas: Implications for antivenom testing in animal models.

    Science.gov (United States)

    Maduwage, Kalana P; Scorgie, Fiona E; Lincz, Lisa F; O'Leary, Margaret A; Isbister, Geoffrey K

    2016-01-01

    Animal models are used to test toxic effects of snake venoms/toxins and the antivenom required to neutralise them. However, venoms that cause clinically relevant coagulopathy in humans may have differential effects in animals. We aimed to investigate the effect of different procoagulant snake venoms on various animal plasmas. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer levels were measured in seven animal plasmas (human, rabbit, cat, guinea pig, pig, cow and rat). In vitro clotting times were then used to calculate the effective concentration (EC50) in each plasma for four snake venoms with different procoagulant toxins: Pseudonaja textilis, Daboia russelli, Echis carinatus and Calloselasma rhodostoma. Compared to human, PT and aPTT were similar for rat, rabbit and pig, but double for cat and cow, while guinea pig had similar aPTT but double PT. Fibrinogen and D-dimer levels were similar for all species. Human and rabbit plasmas had the lowest EC50 for P. textilis (0.1 and 0.4 μg/ml), D. russelli (0.4 and 0.1 μg/ml), E. carinatus (0.6 and 0.1 μg/ml) venoms respectively, while cat plasma had the lowest EC50 for C. rhodostoma (11 μg/ml) venom. Cow, rat, pig and guinea pig plasmas were highly resistant to all four venoms with EC50 10-fold that of human. Different animal plasmas have varying susceptibility to procoagulant venoms, and excepting rabbits, animal models are not appropriate to test procoagulant activity. In vitro assays on human plasma should instead be adopted for this purpose. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Validation of alternative tests for developmental and reproductive toxicology testing: an ILSI Health and Environmental Sciences Institute perspective.

    Science.gov (United States)

    Kim, James H

    2013-01-01

    The current political and societal climate is driving the science of toxicology towards developing non-animal testing methodologies. Though alternative and in vitro tests have always been a mainstay for toxicological testing, technological advances in the last decade have allowed toxicologists to move rapidly towards a better understanding of the relevance of in vitro endpoints for traditional apical endpoints. Non-animal research using new technologies have illuminated toxicologists on the mechanisms of protection and adverse health outcomes. In this context, the "validation" of alternative and in vitro tests has taken on significant importance, particularly in regard to satisfying safety concerns of drugs and chemicals in a regulatory setting. The purpose of this chapter is to briefly review the impetus for the development of alternative and in vitro tests, discuss the projects underway at the ILSI Health and Environmental Sciences Institute (HESI) that are oriented towards this topic, and summarize the processes for formal validation. It should be noted that though there are validated assays and tests, these are under constant evaluation by scientific researchers as our understanding of the underlying biological processes continues to evolve.

  1. Design, construction and testing of a DC bioeffects test enclosure for small animals. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Frazier, M J; Preache, M M

    1980-11-01

    This final report describes both the engineering development of a DC bioeffects test enclosure for small laboratory animals, and the biological protocol for the use of such enclosures in the testing of animals to determine possible biological effects of the environment associated with HVDC transmission lines. The test enclosure which has been designed is a modular unit, which will house up to eight rat-sized animals in individual compartments. Multiple test enclosures can be used to test larger numbers of animals. A prototype test enclosure has been fabricated and tested to characterize its electrical performance characteristics. The test enclosure provides a simulation of the dominant environment associated with HVDC transmission lines; namely, a static electric field and an ion current density. A biological experimental design has been developed for assessing the effects of the dominant components of the HVDC transmission line environment.

  2. The luminescent bacteria toxicity test: its potential as an in vitro alternative.

    Science.gov (United States)

    Bulich, A A; Tung, K K; Scheibner, G

    1990-01-01

    During the past several years, the use of animals for toxicity testing has come under critical surveillance. For ethical and economic reasons, various techniques have been developed and proposed as potential alternatives for some of the whole animal toxicity assays. One assay proposed as an alternative to animal testing is the luminescent bacteria toxicity test (LBT), provided under the trade name of Microtox. The sensitivity and specificity of the LBT was compared with two commonly used toxicity tests--the L-929 Minimal Eàgle's Medium (MEM) elution cytotoxicity test and the Draize test. Cytotoxicity and LBT test data from 709 medical device and biomaterial extracts were compared using a positive/negative ranking system which provided a measurement of false positive and false negative results. These data were compiled from nine separate laboratories producing or using a wide variety of biomaterials and medical device products. The LBT was more sensitive than the tissue culture assay and displayed few false negatives. LBT EC50 values were compared with eye irritancy categories for a group of 34 chemicals and 27 personal care products. As with tissue culture, the LBT was more sensitive and produced minimal false negatives. The data from this study indicate the LBT has potential as a rapid, simple method to screen biomaterials and personal care products for toxicity and irritancy.

  3. Alternative Testing Strategies for Nanomaterials: State of the Science and Considerations for Risk Analysis.

    Science.gov (United States)

    Shatkin, J A; Ong, K J

    2016-08-01

    The rapid growth of the nanotechnology industry has warranted equal progress in the nanotoxicology and risk assessment fields. In vivo models have traditionally been used to determine human and environmental risk for chemicals; however, the use of these tests has limitations, and there are global appeals to develop reliable alternatives to animal testing. Many have investigated the use of alternative (nonanimal) testing methods and strategies have quickly developed and resulted in the generation of large toxicological data sets for numerous nanomaterials (NMs). Due to the novel physicochemical properties of NMs that are related to surface characteristics, the approach toward toxicity test development has distinct considerations from traditional chemicals, bringing new requirements for adapting these approaches for NMs. The methodical development of strategies that combine multiple alternative tests can be useful for predictive NM risk assessment and help screening-level decision making. This article provides an overview of the main developments in alternative methods and strategies for reducing uncertainty in NM risk assessment, including advantages and disadvantages of in vitro, ex vivo, and in silico methods, and examples of existing comprehensive strategies. In addition, knowledge gaps are identified toward improvements for experimental and strategy design, specifically highlighting the need to represent realistic exposure scenarios and to consider NM-specific concerns such as characterization, assay interferences, and standardization. Overall, this article aims to improve the reliability and utility of alternative testing methods and strategies for risk assessment of manufactured NMs. © 2016 Society for Risk Analysis.

  4. Critical appraisal of alternative irritation models: three decades of testing ophthalmic pharmaceuticals.

    Science.gov (United States)

    Abdelkader, Hamdy; Pierscionek, Barbara; Carew, Mark; Wu, Zimei; Alany, Raid G

    2015-03-01

    Testing ocular tolerability of ocular pharmaceuticals is an essential regulatory requirement. The current approved reference model (gold standard) for ocular irritation testing is the Draize test. However this method is subjective and involves using live animals, hence the need to develop alternative in vitro and ex vivo testing strategies. Pubmed, Science Direct, Scopus, Google Scholar, Medline, Current Content, Web of Science and validation reports from international regulatory bodies; The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and European Centre for the Validation of Alternative Methods (ECVAM) were searched for in vitro alternatives. Whilst no single in vitro test can effectively replace the Draize eye irritation test, regulatory bodies and cosmetic/pharmaceutical industries agree that there is a need for in vitro alternatives with validated endpoints to evaluate pharmaceutical ingredients and finished eye products. There is no single in vitro test / assay that can predict the ocular irritation potential of mild to moderate test substances. This review provides a critical appraisal of the selected in vitro and ex vivo ocular toxicity models recommended by international regulatory bodies. These include cytotoxicity methods, biochemical systems and ex vivo assays. The latter are approved by ECVAM as in vitro alternatives for the well-known Draize test. Hen's egg test-chorioallantoic membrane and the isolated rabbit eye test are also accepted by regulatory agencies in France, Germany, the Netherlands and the UK. A combination of ex vivo assays along with histological examination of excised bovine cornea can predict the conjunctival and corneal tolerability and cover a wider range of ocular pharmaceutical substances. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Histopathological Analogies in Chronic Pulmonary Lesions between Cattle and Humans: Basis for an Alternative Animal Model

    Directory of Open Access Journals (Sweden)

    Rafael Ramírez-Romero

    2012-01-01

    Full Text Available Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP and chronic obstructive pulmonary disease (COPD in human beings, calves are proposed as an alternative animal model.

  6. Antimicrobial Resistance: Its Surveillance, Impact, and Alternative Management Strategies in Dairy Animals

    Science.gov (United States)

    Sharma, Chetan; Rokana, Namita; Chandra, Mudit; Singh, Brij Pal; Gulhane, Rohini Devidas; Gill, Jatinder Paul Singh; Ray, Pallab; Puniya, Anil Kumar; Panwar, Harsh

    2018-01-01

    Antimicrobial resistance (AMR), one among the most common priority areas identified by both national and international agencies, is mushrooming as a silent pandemic. The advancement in public health care through introduction of antibiotics against infectious agents is now being threatened by global development of multidrug-resistant strains. These strains are product of both continuous evolution and un-checked antimicrobial usage (AMU). Though antibiotic application in livestock has largely contributed toward health and productivity, it has also played significant role in evolution of resistant strains. Although, a significant emphasis has been given to AMR in humans, trends in animals, on other hand, are not much emphasized. Dairy farming involves surplus use of antibiotics as prophylactic and growth promoting agents. This non-therapeutic application of antibiotics, their dosage, and withdrawal period needs to be re-evaluated and rationally defined. A dairy animal also poses a serious risk of transmission of resistant strains to humans and environment. Outlining the scope of the problem is necessary for formulating and monitoring an active response to AMR. Effective and commendably connected surveillance programs at multidisciplinary level can contribute to better understand and minimize the emergence of resistance. Besides, it requires a renewed emphasis on investments into research for finding alternate, safe, cost effective, and innovative strategies, parallel to discovery of new antibiotics. Nevertheless, numerous direct or indirect novel approaches based on host–microbial interaction and molecular mechanisms of pathogens are also being developed and corroborated by researchers to combat the threat of resistance. This review places a concerted effort to club the current outline of AMU and AMR in dairy animals; ongoing global surveillance and monitoring programs; its impact at animal human interface; and strategies for combating resistance with an extensive

  7. Antimicrobial Resistance: Its Surveillance, Impact, and Alternative Management Strategies in Dairy Animals

    Directory of Open Access Journals (Sweden)

    Chetan Sharma

    2018-01-01

    Full Text Available Antimicrobial resistance (AMR, one among the most common priority areas identified by both national and international agencies, is mushrooming as a silent pandemic. The advancement in public health care through introduction of antibiotics against infectious agents is now being threatened by global development of multidrug-resistant strains. These strains are product of both continuous evolution and un-checked antimicrobial usage (AMU. Though antibiotic application in livestock has largely contributed toward health and productivity, it has also played significant role in evolution of resistant strains. Although, a significant emphasis has been given to AMR in humans, trends in animals, on other hand, are not much emphasized. Dairy farming involves surplus use of antibiotics as prophylactic and growth promoting agents. This non-therapeutic application of antibiotics, their dosage, and withdrawal period needs to be re-evaluated and rationally defined. A dairy animal also poses a serious risk of transmission of resistant strains to humans and environment. Outlining the scope of the problem is necessary for formulating and monitoring an active response to AMR. Effective and commendably connected surveillance programs at multidisciplinary level can contribute to better understand and minimize the emergence of resistance. Besides, it requires a renewed emphasis on investments into research for finding alternate, safe, cost effective, and innovative strategies, parallel to discovery of new antibiotics. Nevertheless, numerous direct or indirect novel approaches based on host–microbial interaction and molecular mechanisms of pathogens are also being developed and corroborated by researchers to combat the threat of resistance. This review places a concerted effort to club the current outline of AMU and AMR in dairy animals; ongoing global surveillance and monitoring programs; its impact at animal human interface; and strategies for combating resistance

  8. Alternative methods for ocular toxicology testing: validation, applications and troubleshooting.

    Science.gov (United States)

    Dholakiya, Sanjay L; Barile, Frank A

    2013-06-01

    Humanitarian concern, scientific progress and legislative action have lead to the development, validation and regulatory acceptance of alternative in vitro ocular models. However, to date not a single in vitro alternative ocular toxicity test has been validated as a full replacement for the in vivo Draize rabbit eye test for all classes of chemicals across whole irritancy ranges. Since the 1990s, ocular alternative methods have been validated but few have been accepted for regulatory purposes. These assays include: organotypic models, such as the bovine corneal opacity and permeability (BCOP) assay, the isolated chicken eye (ICE) test method and cell function-based in vitro assays, such as the cytosensor microphysiometer (CM) and the fluorescein leakage (FL) test methods. Some refinements to in vivo testing methods have been accepted by regulatory agencies, including humane endpoints to avoid or minimize pain and distress. The authors provide a review of the background, protocol overview, applications and their validation status of the tier-testing approach. Furthermore, the authors provide expert analysis and provide their perspective on this approach and potential future developments. In the search for a battery of methods that replaces the in vivo Draize test, it is necessary to prioritize techniques, define related mechanisms and justify statistical approaches. Overall, only when the reliability and relevance of a method is unequivocally supported will any technique be ready for regulatory acceptance.

  9. Workshop on acceleration of the validation and regulatory acceptance of alternative methods and implementation of testing strategies.

    Science.gov (United States)

    Piersma, A H; Burgdorf, T; Louekari, K; Desprez, B; Taalman, R; Landsiedel, R; Barroso, J; Rogiers, V; Eskes, C; Oelgeschläger, M; Whelan, M; Braeuning, A; Vinggaard, A M; Kienhuis, A; van Benthem, J; Ezendam, J

    2018-03-02

    This report describes the proceedings of the BfR-RIVM workshop on validation of alternative methods which was held 23 and 24 March 2017 in Berlin, Germany. Stakeholders from governmental agencies, regulatory authorities, universities, industry and the OECD were invited to discuss current problems concerning the regulatory acceptance and implementation of alternative test methods and testing strategies, with the aim to develop feasible solutions. Classical validation of alternative methods usually involves one to one comparison with the gold standard animal study. This approach suffers from the reductionist nature of an alternative test as compared to the animal study as well as from the animal study being considered as the gold standard. Modern approaches combine individual alternatives into testing strategies, for which integrated and defined approaches are emerging at OECD. Furthermore, progress in mechanistic toxicology, e.g. through the adverse outcome pathway approach, and in computational systems toxicology allows integration of alternative test battery results into toxicity predictions that are more fine-tuned to the human situation. The road towards transition to a mechanistically-based human-focused hazard and risk assessment of chemicals requires an open mind towards stepping away from the animal study as the gold standard and defining human biologically based regulatory requirements for human hazard and risk assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. 40 CFR 85.1414 - Alternative test procedures.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Urban Bus Rebuild Requirements § 85.1414 Alternative... shall be representative of in-use urban bus operation. The requestor shall supply relevant technical... test is representative of in-use urban bus operation, the Agency shall determine whether to set such...

  11. Development and Characterisation of a Human Chronic Skin Wound Cell Line-Towards an Alternative for Animal Experimentation.

    Science.gov (United States)

    Caley, Matthew; Wall, Ivan B; Peake, Matthew; Kipling, David; Giles, Peter; Thomas, David W; Stephens, Phil

    2018-03-27

    Background : Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. Objectives : To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). Methods and Results : Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). Conclusions : These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening.

  12. Using Alternative Approaches to Prioritize Testing for the Universe of Chemicals with Potential for Human Exposure (WC9)

    Science.gov (United States)

    One use of alternative methods is to target animal use at only those chemicals and tests that are absolutely necessary. We discuss prioritization of testing based on high-throughput screening assays (HTS), QSAR modeling, high-throughput toxicokinetics (HTTK), and exposure modelin...

  13. The Power of Unit Root Tests Against Nonlinear Local Alternatives

    DEFF Research Database (Denmark)

    Demetrescu, Matei; Kruse, Robinson

    This article extends the analysis of local power of unit root tests in a nonlinear direction by considering local nonlinear alternatives and tests built specically against stationary nonlinear models. In particular, we focus on the popular test proposed by Kapetanios et al. (2003, Journal...... by simulation. Furthermore, our own simulation results suggest that the user-specied adjustment scheme for deterministic components (e.g. OLS, GLS, or recursive adjustment) has a much higher impact on the power of unit root tests than accounting for nonlinearity, at least under local (linear or nonlinear...... of Econometrics 112, 359-379) in comparison to the linear Dickey-Fuller test. To this end, we consider different adjustment schemes for deterministic terms. We provide asymptotic results which imply that the error variance has a severe impact on the behavior of the tests in the nonlinear case; the reason...

  14. Refinement, Reduction, and Replacement of Animal Toxicity Tests by Computational Methods.

    Science.gov (United States)

    Ford, Kevin A

    2016-12-01

    Widespread public and scientific interest in promoting the care and well-being of animals used for toxicity testing has given rise to improvements in animal welfare practices and views over time, as well as laws and regulations that support means to reduce, refine, and replace animal use (known as the 3Rs) in certain toxicity studies. One way these regulations continue to achieve their aim is by promoting the research, development, and application of alternative testing approaches to characterize potential toxicities either without animals or with minimal use. An important example of an alternative approach is the use of computational toxicology models. Along with the potential capacity to reduce or replace the use of animals for the assessment of particular toxicological endpoints, computational models offer several advantages compared to in vitro and in vivo approaches, including cost-effectiveness, rapid availability of results, and the ability to fully standardize procedures. Pharmaceutical research incorporating the use of computational models has increased steadily over the past 15 years, likely driven by the motivation of companies to screen out toxic compounds in the early stages of development. Models are currently available to aid in the prediction of several important toxicological endpoints, including mutagenicity, carcinogenicity, eye irritation, hepatotoxicity, and skin sensitization, albeit with varying degrees of success. This review serves to introduce the concepts of computational toxicology and evaluate their role in the safety assessment of compounds, while also highlighting the application of in silico methods in the support of the goal and vision of the 3Rs. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research.All rights reserved. For permissions, please email: journals.permissions@oup.com.

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

    Science.gov (United States)

    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.

  16. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  17. Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches: a workshop report.

    Science.gov (United States)

    van der Laan, Jan Willem; Chapin, Robert E; Haenen, Bert; Jacobs, Abigail C; Piersma, Aldert

    2012-06-01

    Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include. One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free. A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Impact of Relationships between Test and Reference Animals and between Reference Animals on Reliability of Genomic Prediction

    DEFF Research Database (Denmark)

    Wu, Xiaoping; Lund, Mogens Sandø; Sun, Dongxiao

    This study investigated reliability of genomic prediction in various scenarios with regard to relationship between test and reference animals and between animals within the reference population. Different reference populations were generated from EuroGenomics data and 1288 Nordic Holstein bulls...... as a common test population. A GBLUP model and a Bayesian mixture model were applied to predict Genomic breeding values for bulls in the test data. Result showed that a closer relationship between test and reference animals led to a higher reliability, while a closer relationship between reference animal...

  19. Genetic parameters and alternatives for evaluation and ranking of Nellore young bulls in pasture performance tests

    Directory of Open Access Journals (Sweden)

    Breno de Oliveira Fragomeni

    2013-08-01

    Full Text Available The objective of this study was to estimate (covariance components for weight at 550 days, average daily gain and an index with both traits, and to compare alternatives for evaluation and ranking of Nellore young bulls in pasture performance tests. The heritability estimates were 0.73, 0.31 and 0.44 for weight at 550 days, average daily gain and index, respectively. Animals were ranked according to their predicted breeding values or the phenotypic deviations in relation to the mean of the test. Although the correlations between breeding values and phenotypic deviations were high, there were differences in the number of animals selected in common when the selection criteria were the predicted breeding values or the phenotypic deviations. Mixed models are more appropriate than the least squares method and should be utilized in the evaluation of young bulls in performance tests.

  20. Alternate immersion stress corrosion testing of 5083 aluminum

    International Nuclear Information System (INIS)

    Briggs, J.L.; Dringman, M.R.; Hausburg, D.E.; Jackson, R.J.

    1978-01-01

    The stress corrosion susceptibility of Type 5083 aluminum--magnesium alloy in plate form and press-formed shapes was determined in the short transverse direction. C-ring type specimens were exposed to alternate immersion in a sodium chloride solution. The test equipment and procedure, with several innovative features, are described in detail. Statistical test results are listed for seven thermomechanical conditions. A certain processing scheme was shown to yield a work-strengthened part that is not sensitized with respect to stress corrosion cracking

  1. Science Teachers to Ban Testing Harmful to Animals.

    Science.gov (United States)

    Sun, Marjorie

    1980-01-01

    This article reports the adoption of new policies to restrict experiments on animals in the elementary or secondary school classroom. The controversy involving animal welfare groups is discussed as it relates to animal abuse by students. (SA)

  2. Animal Testing for Acute Inhalation Toxicity: A Thing of the Past?

    DEFF Research Database (Denmark)

    Da Silva, Emilie; Sørli, Jorid Birkelund

    2018-01-01

    According to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year. Three OECD test guidelines for acute inhalation toxicity in vivo are adopted (TG 403,......, TG 436, and TG 433). Since animal testing is ethically, scientifically and economically questionable, adoption of alternative methods by the European Union and the OECD is needed. An in vitro system based on the study of lung surfactant function is introduced.......According to REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year. Three OECD test guidelines for acute inhalation toxicity in vivo are adopted (TG 403...

  3. Neutron activation analysis of alternative phosphate rocks used in animal nutrition

    International Nuclear Information System (INIS)

    Canella, Artur A.; Ferreira, Walter M.

    2005-01-01

    Since 1980's, Bovine Sponghiform Encephalophaty has insidiously created a fierce battleground between farmers, scientists, environmentalists and consumers. The use of meat and bone meals is currently prohibited in ruminant feeds throughout the world. Some inorganic sources offer the combination of high phosphorus content and acceptable animal digestibility make them options as supplemental phosphorus, for instance phosphate rocks, general term applied to minerals valued chiefly for their phosphorus content. However, phosphate rocks are long been known containing hazardous elements, make them sometimes unsuitable for animal nutrition. Neutron Activation Analysis has been supportive to the mineral evaluation of alternative phosphate rocks. This evaluation is subject of on-going doctoral thesis which has been carried-out by the main author. The NAA method has been very efficient due to its highly sensitive and multi-elemental nature. In this paper results of Vanadium content from three different phosphate rocks are presented. Their values have been pointed out that Brazilian phosphate rocks present hazardous elements at the same levels of phosphate rocks from some countries of Africa, North America and Middle East, data from our study (Brazilian data) and FAO - Food and Agriculture Organization (others countries). (author)

  4. Radioimmunoassay determination of the effect on animal reproduction of alternative of feeding suplementation in dairy cows

    International Nuclear Information System (INIS)

    Villalba, Patricio; Ambuludi, Eduardo

    1993-01-01

    The principal object of this trial was to evaluate the influence of three alternatives of feeding suplementation in dairy cows in the post-partum period in ecuadorian highlands. Thirty sic animals in fist lactation were used in this experiment and were divided in three groups according to the feed intake: Group A diet was 5 Kg. of a commercial concentrate mixture with 12 per cent of crude protein plus pasture ad libitum; Group B diet was green banans (Musa paradisiaca) and pasture and Group C diet was the control only pasture. Using Radioimmunoassay technique (RIA), progesterone values were determinated in milk from each cow. the sampling was sequential, two samples a week, starting 6 days after parturition, until the animal was pregnant or until the study was finished, 150 days after post-partum for each cow. This research allowed us to evaluate the ovaric post-partum activity of each group: Frequency and length of the oestrus cycles; efficiency of oestrus detection, calving-first, oestrus period, calving-conception length, conception rate, and services per conception. Additional datas were used in this study such as: milk production, palpations and treatments

  5. Presence of roosters in an alternative egg production system aiming at animal welfare

    Directory of Open Access Journals (Sweden)

    Dayana Cristina de Oliveira Pereira

    Full Text Available ABSTRACT The objective of this study was to evaluate the effect of the presence of roosters on welfare and egg production of laying hens reared in an alternative system. Two breeding systems were established: barn 1 - laying hens reared without roosters (4500 birds; and barn 2 - laying hens reared with roosters (4500 layers and 250 roosters. In the poultry facilities, microclimate, egg production, mortality rate, and bird behavior were evaluated. Microclimate analysis showed that the birds were subjected to periods of constant heat stress, except for the morning hours. However, even under these conditions, egg production results and mortality rate were consistent with the indices recommended in the Isa Brown management guide in the barn with roosters; the indices obtained were even better and were characterized by higher egg production and lower mortality rates. In addition to productivity benefits, the presence of roosters broadened the behavioral repertoire of the birds due to the introduction of reproductive behaviors. Moreover, there was a significant decrease in the tolerance-reflex behavior, which is associated with the impossibility of displaying reproductive behaviors. This alternative egg production system proved to promote animal welfare since it provides and stimulates the display of behaviors considered important for birds.

  6. Alternate thermoregulation and functional binding of Escherichia coli type 1 fimbriae in environmental and animal isolates.

    Science.gov (United States)

    Marshall, Jacqueline; Rossez, Yannick; Mainda, Geoffrey; Gally, David L; Daniell, Tim J; Holden, Nicola J

    2016-11-01

    Type 1 fimbriae (T1F) are well characterised cell surface organelles expressed by Escherichia coli and required for adherence to mannosylated host tissue. They satisfy molecular Koch's postulates as a virulence determinant and a host-adapted role has been reinforced by reports that T1F expression is repressed at submammalian temperatures. Analysis of a group of 136 environmental and animal E. coli isolates that express T1F at 37°C showed that 28% are also capable of expression at 20°C, in a phase variable manner. The heterogeneous proportions varied widely, and although growth temperature impacted the total proportion expressing T1F, there was no direct correlation between growth at 37°C and 20°C, indicative of differences in thermoregulation of the genetic switch (fimS) that controls phase variation. Specificities of the adhesin (FimH) also varied between the isolates: most bound to α-(1-3) mannan and yeast extracts as expected, but some recognised β-(1-4)-mannans and N-linked glycoproteins from plants, and T1F from two of the isolates mediated binding to plant roots. The results expand our view of a well-described adherence factor to show alternative expression profiles and adhesin specificities, which in turn may confer an advantage for certain isolates in alternative hosts and habitats. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. A new alternative for bony chest wall reconstruction using biomaterial artificial rib and pleura: animal experiment and clinical application.

    Science.gov (United States)

    Zhang, Lan-jun; Wang, Wu-ping; Li, Wei-yang; Hao, Chong-li; Li, Zhe; Wu, Qiu-liang; Wu, Rao-pan; Rong, Tie-hua

    2011-10-01

    To evaluate a new method for chest wall reconstruction using porcine-derived artificial rib and pleura in an animal experiment. Further, the clinical application was performed in five patients with large defects in the chest wall as a preliminary observation. In animal experiments, a full-thickness chest wall defect of 7 cm × 8 cm was created in 12 adult mongrel dogs. Six dogs underwent reconstruction with porcine-derived artificial ribs and pleura (test group), and six with methylmethacrylate and double polyester mesh in the form of traditional Marlex sandwich technique (control group). At follow-up of each for 3, 6, and 12 months postoperatively, a general performance assessment and thoracic radiography were performed. Gross and histopathological examinations were carried out following humane euthanasia at the time of last follow-up. In clinical application, five patients with wide tumor resection in the chest wall underwent reconstruction with porcine-derived artificial ribs and pleura as well. In animal experiment, no perioperative death or hyperpyrexia occurred and no difference in either infection or dyspnea was noted between the two groups. Postoperative radiography revealed good thoracic integrity with no evidence of collapse, deformation, or abnormal movement in the test group. In the control group, similar results were observed, except that two dogs had abnormal movement in the chest wall associated with respiration. Severe adhesions between the 'sandwich' complex and the host tissues were identified in the control group, but by contrast, only mild adhesions were noted in the test group. The non-degradable polyester mesh induced fibrous proliferation and rejection, whereas the artificial pleura was absorbed with mild fibrous hyperplasia after 12 months. In clinical application, no thoracic deformity, chronic pain, or respiratory discomfort were observed at 1 or 12 postoperative months. Porcine-derived ribs and pleura can be employed safely to create an

  8. How to assess the mutagenic potential of cosmetic products without animal tests?

    Science.gov (United States)

    Speit, Günter

    2009-08-01

    new in vitro genotoxicity testing will become much more complex and will require greater mechanistic understanding to build a weight of evidence decision, which will be demanding and time-consuming. At present, no validated alternative methods for the follow-up of positive results from the standard genotoxicity battery are available and an appropriate evaluation of the mutagenic potential of cosmetic ingredients without animal experiments is therefore not possible in many cases.

  9. Freshwater toxicity testing using rehydrated Philodina sp. (Rotifera) as test animals.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Matthews, Amelia B

    2017-10-01

    Rotifers have become widely used in aquatic toxicology as a rapid screening test for toxicity. The commercial availability of diapausing embryos (cysts) have facilitated their popularity because test animals can be obtained without having to master the details of culturing. Other rotifer species have life stages capable of surviving desiccation and also could be used in non-culture systems for toxicity assessment. In this article, we describe a system for toxicity testing in freshwater based on rehydrating desiccated bdelloid rotifers in the genus Philodina. These animals can remain in this anhydrobiotic state for more than one year and then rehydrate within hours to provide animals for toxicity tests. We describe three endpoints: a 1.5 h ingestion test, a 24 h mortality test, and a five day reproductive test. The latter test requires feeding and a method using a dried commercial product is explained. Using desiccated rotifers and dried food in toxicity tests make this system especially attractive because of its flexibility and low threshold of biological expertise required to execute the tests. The use of the Philodina toxicity test is illustrated with four metals: copper, lead, mercury and cadmium. Reproduction generally was the most sensitive endpoint, with EC50s of 0.33, 0.44, 0.60, and 0.12 mg/L, respectively. Ingestion was a close second with EC50s of 0.13, 1.64, 0.64, and 6.26 mg/L, respectively. © 2017 Wiley Periodicals, Inc.

  10. Testing flow diversion in animal models: a systematic review.

    Science.gov (United States)

    Fahed, Robert; Raymond, Jean; Ducroux, Célina; Gentric, Jean-Christophe; Salazkin, Igor; Ziegler, Daniela; Gevry, Guylaine; Darsaut, Tim E

    2016-04-01

    Flow diversion (FD) is increasingly used to treat intracranial aneurysms. We sought to systematically review published studies to assess the quality of reporting and summarize the results of FD in various animal models. Databases were searched to retrieve all animal studies on FD from 2000 to 2015. Extracted data included species and aneurysm models, aneurysm and neck dimensions, type of flow diverter, occlusion rates, and complications. Articles were evaluated using a checklist derived from the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Forty-two articles reporting the results of FD in nine different aneurysm models were included. The rabbit elastase-induced aneurysm model was the most commonly used, with 3-month occlusion rates of 73.5%, (95%CI [61.9-82.6%]). FD of surgical sidewall aneurysms, constructed in rabbits or canines, resulted in high occlusion rates (100% [65.5-100%]). FD resulted in modest occlusion rates (15.4% [8.9-25.1%]) when tested in six complex canine aneurysm models designed to reproduce more difficult clinical contexts (large necks, bifurcation, or fusiform aneurysms). Adverse events, including branch occlusion, were rarely reported. There were no hemorrhagic complications. Articles complied with 20.8 ± 3.9 of 41 ARRIVE items; only a small number used randomization (3/42 articles [7.1%]) or a control group (13/42 articles [30.9%]). Preclinical studies on FD have shown various results. Occlusion of elastase-induced aneurysms was common after FD. The model is not challenging but standardized in many laboratories. Failures of FD can be reproduced in less standardized but more challenging surgical canine constructions. The quality of reporting could be improved.

  11. Alternate performance standard project: Interpreting the post-construction test

    International Nuclear Information System (INIS)

    Williamson, A.D.; McDonough, S.E.

    1993-01-01

    The paper describes the results of a project commissioned by the State of Florida, in cooperation with the US Environmental Protection Agency, as one portion of the Florida Radon Research Program (FRRP). The purpose of the FRRP is to provide technical support for a statewide Building Standard for Radon-Resistant Construction currently in the rulemaking process. In this case the information provides technical background for a post-construction radon test specified as a performance element of the code which accompanies the prescriptive alternative that does not incorporate active radon reduction systems

  12. Impact of relationships between test and training animals and among training animals on reliability of genomic prediction.

    Science.gov (United States)

    Wu, X; Lund, M S; Sun, D; Zhang, Q; Su, G

    2015-10-01

    One of the factors affecting the reliability of genomic prediction is the relationship among the animals of interest. This study investigated the reliability of genomic prediction in various scenarios with regard to the relationship between test and training animals, and among animals within the training data set. Different training data sets were generated from EuroGenomics data and a group of Nordic Holstein bulls (born in 2005 and afterwards) as a common test data set. Genomic breeding values were predicted using a genomic best linear unbiased prediction model and a Bayesian mixture model. The results showed that a closer relationship between test and training animals led to a higher reliability of genomic predictions for the test animals, while a closer relationship among training animals resulted in a lower reliability. In addition, the Bayesian mixture model in general led to a slightly higher reliability of genomic prediction, especially for the scenario of distant relationships between training and test animals. Therefore, to prevent a decrease in reliability, constant updates of the training population with animals from more recent generations are required. Moreover, a training population consisting of less-related animals is favourable for reliability of genomic prediction. © 2015 Blackwell Verlag GmbH.

  13. Alternate Reductant Cold Cap Evaluation Furnace Phase II Testing

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, F. C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Stone, M. E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Miller, D. H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2014-09-03

    Savannah River Remediation (SRR) conducted a Systems Engineering Evaluation (SEE) to determine the optimum alternate reductant flowsheet for the Defense Waste Processing Facility (DWPF). Specifically, two proposed flowsheets (nitric–formic–glycolic and nitric–formic–sugar) were evaluated based upon results from preliminary testing. Comparison of the two flowsheets among evaluation criteria indicated a preference towards the nitric–formic–glycolic flowsheet. Further research and development of this flowsheet eliminated the formic acid, and as a result, the nitric–glycolic flowsheet was recommended for further testing. Based on the development of a roadmap for the nitric–glycolic acid flowsheet, Waste Solidification Engineering (WS-E) issued a Technical Task Request (TTR) to address flammability issues that may impact the implementation of this flowsheet. Melter testing was requested in order to define the DWPF flammability envelope for the nitric-glycolic acid flowsheet. The Savannah River National Laboratory (SRNL) Cold Cap Evaluation Furnace (CEF), a 1/12th scale DWPF melter, was selected by the SRR Alternate Reductant project team as the melter platform for this testing. The overall scope was divided into the following sub-tasks as discussed in the Task Technical and Quality Assurance Plan (TTQAP): Phase I - A nitric–formic acid flowsheet melter test (unbubbled) to baseline the CEF cold cap and vapor space data to the benchmark melter flammability models; Phase II - A nitric–glycolic acid flowsheet melter test (unbubbled and bubbled) to: Define new cold cap reactions and global kinetic parameters in support of the melter flammability model development; Quantify off-gas surging potential of the feed; Characterize off-gas condensate for complete organic and inorganic carbon species. After charging the CEF with cullet from Phase I CEF testing, the melter was slurry-fed with glycolic flowsheet based SB6-Frit 418 melter feed at 36% waste

  14. An alternative test for verifying electronic balance linearity

    International Nuclear Information System (INIS)

    Thomas, I.R.

    1998-02-01

    This paper presents an alternative method for verifying electronic balance linearity and accuracy. This method is being developed for safeguards weighings (weighings for the control and accountability of nuclear material) at the Idaho National Engineering and Environmental Laboratory (INEEL). With regard to balance linearity and accuracy, DOE Order 5633.3B, Control and Accountability of Nuclear Materials, Paragraph 2, 4, e, (1), (a) Scales and Balances Program, states: ''All scales and balances used for accountability purposes shall be maintained in good working condition, recalibrated according to an established schedule, and checked for accuracy and linearity on each day that the scale or balance is used for accountability purposes.'' Various tests have been proposed for testing accuracy and linearity. In the 1991 Measurement Science Conference, Dr. Walter E. Kupper presented a paper entitled: ''Validation of High Accuracy Weighing Equipment.'' Dr. Kupper emphasized that tolerance checks for calibrated, state-of-the-art electronic equipment need not be complicated, and he presented four easy steps for verifying that a calibrated balance is operating correctly. These tests evaluate the standard deviation of successive weighings (of the same load), the off-center error, the calibration error, and the error due to nonlinearity. This method of balance validation is undoubtedly an authoritative means of ensuring balance operability, yet it could have two drawbacks: one, the test for linearity is not intuitively obvious, especially from a statistical viewpoint; and two, there is an absence of definitively defined testing limits. Hence, this paper describes an alternative means of verifying electronic balance linearity and accuracy that is being developed for safeguards measurements at the INEEL

  15. Joint Test Report For Validation of Alternatives to Aliphatic Isocyanate Polyurethanes

    Science.gov (United States)

    Lewis, Pattie

    2007-01-01

    National Aeronautics and Space Administration (NASA) and Air Force Space Command (AFSPC) have similar missions and therefore similar facilities and structures in similar environments. The standard practice for protecting metallic substrates in atmospheric environments is the application of an applied coating system. The most common topcoats used in coating systems are polyurethanes that contain isocyanates. Isocyanates are classified as potential human carcinogens and are known to cause cancer in animals. The primary objective of this effort was to demonstrate and validate alternatives to aliphatic isocyanate polyurethanes resulting in one or more isocyanate-free coatings qualified for use at AFSPC and NASA installations participating in this project. This joint Test Report (JTR) documents the results of the laboratory and field testing as well as any test modifications made during the execution of the testing. The technical stakeholders agreed upon test procedure modifications documented in this document. This JTR is made available as a reference for future pollution prevention endeavors by other NASA centers, the Department of Defense and commercial users to minimize duplication of effort. All coating system candidates were tested using approved NASA and AFSPC standard coating systems as experimental controls. This study looked at eight alternative coating systems and two control coating systems and was divided into Phase I Screening Tests, Phase II Tests, and Field Testing. The Phase I Screening Tests were preliminary tests performed on all the selected candidate coating systems. Candidate coating systems that did not meet the acceptance criteria of the screening tests were eliminated from further testing. Phase I Screening Tests included: Ease of Application, Surface Appearance, Dry-To-Touch (Sanding), Accelerated Storage Stability, Pot Life (Viscosity), Cure Time (Solvent Rubs), Cleanability, Knife Test, Tensile (pull-off) Adhesion, and X-Cut Adhesion by Wet

  16. ALTERNATE REDUCTANT COLD CAP EVALUATION FURNACE PHASE I TESTING

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, F.; Miller, D.; Zamecnik, J.; Lambert, D.

    2014-04-22

    Savannah River Remediation (SRR) conducted a Systems Engineering Evaluation (SEE) to determine the optimum alternate reductant flowsheet for the Defense Waste Processing Facility (DWPF). Specifically, two proposed flowsheets (nitric–formic–glycolic and nitric–formic–sugar) were evaluated based upon results from preliminary testing. Comparison of the two flowsheets among evaluation criteria indicated a preference towards the nitric–formic–glycolic flowsheet. Further evaluation of this flowsheet eliminated the formic acid1, and as a result, the nitric–glycolic flowsheet was recommended for further testing. Based on the development of a roadmap for the nitric–glycolic acid flowsheet, Waste Solidification Engineering (WS-E) issued a Technical Task Request (TTR) to address flammability issues that may impact the implementation of this flowsheet. Melter testing was requested in order to define the DWPF flammability envelope for the nitric glycolic acid flowsheet. The Savannah River National Laboratory (SRNL) Cold Cap Evaluation Furnace (CEF), a 1/12th scale DWPF melter, was selected by the SRR Alternate Reductant project team as the melter platform for this testing. The overall scope was divided into the following sub-tasks as discussed in the Task Technical and Quality Assurance Plan (TTQAP): Phase I - A nitric–formic acid flowsheet melter test (unbubbled) to baseline the Cold Cap Evaluation Furnace (CEF) cold cap and vapor space data to the benchmark melter flammability models Phase II - A nitric–glycolic acid flowsheet melter test (unbubbled and bubbled) to: o Define new cold cap reactions and global kinetic parameters for the melter flammability models o Quantify off-gas surging potential of the feed o Characterize off-gas condensate for complete organic and inorganic carbon species Prior to startup, a number of improvements and modifications were made to the CEF, including addition of cameras, vessel support temperature measurement, and a heating

  17. Peran People for the Ethical Treatment of Animals (Peta) Dalam Kasus Animal Testing Terhadap Hewan Luwak Di Indonesia Tahun 2012-2014

    OpenAIRE

    Harto, Syafri; Ambarrini, Tantin

    2015-01-01

    More than 100 million animals every year suffer and die by fierce chemical test, medical, food, and cosmetic by giving poisonous, blinding and killing million animals every year for irresponsible companies. In medical world, all procedures that are done against the animals called animal testing.Animal testing happens in Indonesia against civet cat animal. The animal eats coffee fruit and digests it to be coffee fruit seed that is put out with its feces. This seed that has unique taste and hig...

  18. Full Scale Alternative Catalyst Testing for Bosch Reactor Optimization

    Science.gov (United States)

    Barton, Katherine; Abney, Morgan B.

    2011-01-01

    Current air revitalization technology onboard the International Space Station (ISS) cannot provide complete closure of the oxygen and hydrogen loops. This makes re-supply necessary, which is possible for missions in low Earth orbit (LEO) like the ISS, but unviable for long term space missions outside LEO. In comparison, Bosch technology reduces carbon dioxide with hydrogen, traditionally over a steel wool catalyst, to create water and solid carbon. The Bosch product water can then be fed to the oxygen generation assembly to produce oxygen for crew members and hydrogen necessary to reduce more carbon dioxide. Bosch technology can achieve complete oxygen loop closure, but has many undesirable factors that result in a high energy, mass, and volume system. Finding a different catalyst with an equal reaction rate at lower temperatures with less catalyst mass and longer lifespan would make a Bosch flight system more feasible. Developmental testing of alternative catalysts for the Bosch has been performed using the Horizontal Bosch Test Stand. Nickel foam, nickel shavings, and cobalt shavings were tested at 500 C and compared to the original catalyst, steel wool. This paper presents data and analysis on the performance of each catalyst tested at comparable temperatures and recycle flow rates.

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

    Science.gov (United States)

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

    2018-03-13

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

  20. Perceived game realism: a test of three alternative models.

    Science.gov (United States)

    Ribbens, Wannes

    2013-01-01

    Perceived realism is considered a key concept in explaining the mental processing of media messages and the societal impact of media. Despite its importance, little is known about its conceptualization and dimensional structure, especially with regard to digital games. The aim of this study was to test a six-factor model of perceived game realism comprised of simulational realism, freedom of choice, perceptual pervasiveness, social realism, authenticity, and character involvement and to assess it against an alternative single- and five-factor model. Data were collected from 380 male digital game users who judged the realism of the first-person shooter Half-Life 2 based upon their previous experience with the game. Confirmatory factor analysis was applied to investigate which model fits the data best. The results support the six-factor model over the single- and five-factor solutions. The study contributes to our knowledge of perceived game realism by further developing its conceptualization and measurement.

  1. Animals

    International Nuclear Information System (INIS)

    Skuterud, L.; Strand, P.; Howard, B.J.

    1997-01-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG)

  2. A dataset on 145 chemicals tested in alternative assays for skin sensitization undergoing prevalidation.

    Science.gov (United States)

    Natsch, Andreas; Ryan, Cindy A; Foertsch, Leslie; Emter, Roger; Jaworska, Joanna; Gerberick, Frank; Kern, Petra

    2013-11-01

    Skin sensitization is a key endpoint for cosmetic ingredients, with a forthcoming ban for animal testing in Europe. Four alternative tests have so far been submitted to ECVAM prevalidation: (i) MUSST and (ii) h-Clat assess surface markers on dendritic cell lines, (iii) the direct peptide reactivity assay (DPRA) measures reactivity with model peptides and (iv) the KeratinoSens(TM) assay which is based on detection of Nrf2-induced luciferase. It is anticipated that only an integrated testing strategy (ITS) based on a battery of tests might give a full replacement providing also a sensitization potency assessment, but this concept should be tested with a data-driven analysis. Here we report a database on 145 chemicals reporting the quantitative endpoints measured in a U937- test, the DPRA and KeratinoSens(TM) . It can serve to develop data-driven ITS approaches as we show in a parallel paper and provides a view as to the current ability to predict with in vitro tests as we are entering 2013. It may also serve as reference database when benchmarking new molecules with in vitro based read-across and find use as a reference database when evaluating new tests. The tests and combinations thereof were evaluated for predictivity, and overall a similar predictivity was found as before on three-fold smaller datasets. Analysis of the dose-response parameters of the individual tests indicates a correlation to sensitization potency. Detailed analysis of chemicals false-negative and false-positive in two tests helped to define limitations in the tests but also in the database derived from animal studies. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Improving animal welfare and reducing animal use for veterinary vaccine potency testing: state of the science and future directions

    OpenAIRE

    STOKES William; BROWN Karen; KULPA-EDDY Jodie; SRINIVAS Geetha; HALDER Maria; DRAAYER Hans; GALVIN Jeffrey; CLAASEN Ivo; GIFFORD Glen; WOODLAND Ralph; DOELLING Vivian; JONES Brett

    2011-01-01

    Veterinary vaccines contribute to improved human and animal health and welfare by preventing diseases and deaths caused by a wide range of infectious agents. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance ...

  4. In vitro vaccine potency testing: a proposal for reducing animal use for requalification testing.

    Science.gov (United States)

    Brown, K; Stokes, W

    2012-01-01

    This paper proposes a program under which the use of animals for requalification of in vitro potency tests could be eliminated. Standard References (USDA/CVB nomenclature) would be developed, characterized, stored and monitored by selected reference laboratories worldwide. These laboratories would employ scientists skilled in protein and glycoprotein chemistry and equipped with state-of-the-art instruments for required analyses. After Standard References are established, the reference laboratories would provide them to the animal health industry as "gold standards". Companies would then establish and validate a correlation between the Standard Reference and the company Master Reference (USDA/CVB nomenclature) using an internal in vitro assay. After this correlation is established, the company could use the Standard References for qualifying, monitoring and requalifying company Master References without the use of animals. Such a program would eliminate the need for animals for requalification of Master References and the need for each company to develop and validate a battery of Master Reference Monitoring assays. It would also provide advantages in terms of reduced costs and reduced time for requalification testing. As such it would provide a strong incentive for companies to develop and use in vitro assays for potency testing.

  5. “Play it Again”: a new method for testing metacognition in animals

    Science.gov (United States)

    Foote, Allison L.

    2011-01-01

    Putative metacognition data in animals may be explained by non-metacognition models (e.g., stimulus generalization). The primary objective of the present study was to develop a new method for testing metacognition in animals that may yield data that can be explained by meta-cognition but not by non-metacognition models. Next, we used the new method with rats. Rats were first presented with a brief noise duration which they would subsequently classify as short or long. Rats were sometimes forced to take an immediate duration test, forced to repeat the same duration, or had the choice to take the test or repeat the duration. Metacognition, but not an alternative non-meta-cognition model, predicts that accuracy on difficult durations is higher when subjects are forced to repeat the stimulus compared to trials in which the subject chose to repeat the stimulus, a pattern observed in our data. Simulation of a non-metacognition model suggests that this part of the data from rats is consistent with metacognition, but other aspects of the data are not consistent with metacognition. The current results call into question previous findings suggesting that rats have metacognitive abilities. Although a mixed pattern of data does not support metacognition in rats, we believe the introduction of the method may be valuable for testing with other species to help evaluate the comparative case for metacognition. PMID:21909935

  6. [Study on the use of haemoglobin denaturation test as an alternative to Draize eye irritation test].

    Science.gov (United States)

    Liao, Yan; Wang, Xue; Zhang, Li-shi; Li, Guan-min; Zhang, Bao-xu

    2004-09-01

    To use haemoglobin denaturation test (HD test) as an alternative to Draize eye irritation test (Draize test). Fourteen cosmetic ingredients were tested by HD test. The results were compared with two kinds of scores in Draize test, i.e. Maximum average Draize total score (MAS) and Score of 24 h after application (S24). The correlation coefficient between RDC50 and MAS and that between RDC50 and S24 were 0.926 and 0.921 respectively, while that between 1%lambdamax and MAS, and between 1%lambdamax and S24 were 0.881 and 0.791 respectively. The results showed that RDC50 had a higher correlation with Draize test than 1%lambdamax did, but in the use of RDC50 some information of data would be lost. On the other hand, 1%lambdamax, which had a greater correlation with corneal score in the three component scores of the Draize test, could be used for assessing water-insoluble chemicals. The results showed that HD test could be used as an effective alternative to Draize eye irritation test.

  7. State of the art in non-animal approaches for skin sensitization testing: from individual test methods towards testing strategies.

    Science.gov (United States)

    Ezendam, Janine; Braakhuis, Hedwig M; Vandebriel, Rob J

    2016-12-01

    The hazard assessment of skin sensitizers relies mainly on animal testing, but much progress is made in the development, validation and regulatory acceptance and implementation of non-animal predictive approaches. In this review, we provide an update on the available computational tools and animal-free test methods for the prediction of skin sensitization hazard. These individual test methods address mostly one mechanistic step of the process of skin sensitization induction. The adverse outcome pathway (AOP) for skin sensitization describes the key events (KEs) that lead to skin sensitization. In our review, we have clustered the available test methods according to the KE they inform: the molecular initiating event (MIE/KE1)-protein binding, KE2-keratinocyte activation, KE3-dendritic cell activation and KE4-T cell activation and proliferation. In recent years, most progress has been made in the development and validation of in vitro assays that address KE2 and KE3. No standardized in vitro assays for T cell activation are available; thus, KE4 cannot be measured in vitro. Three non-animal test methods, addressing either the MIE, KE2 or KE3, are accepted as OECD test guidelines, and this has accelerated the development of integrated or defined approaches for testing and assessment (e.g. testing strategies). The majority of these approaches are mechanism-based, since they combine results from multiple test methods and/or computational tools that address different KEs of the AOP to estimate skin sensitization potential and sometimes potency. Other approaches are based on statistical tools. Until now, eleven different testing strategies have been published, the majority using the same individual information sources. Our review shows that some of the defined approaches to testing and assessment are able to accurately predict skin sensitization hazard, sometimes even more accurate than the currently used animal test. A few defined approaches are developed to provide an

  8. In search of acceptable alternatives to the murine histamine sensitisation test (HIST): what is possible and practical?

    Science.gov (United States)

    Wagner, L; Isbrucker, R; Locht, C; Arciniega, J; Costanzo, A; McFarland, R; Oh, H; Hoonakker, M; Descamps, J; Andersen, S R; Gupta, R K; Markey, K; Chapsal, J M; Lidster, K; Casey, W; Allen, D

    2016-01-01

    The 'International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: In Search of Acceptable Alternatives to the Murine Histamine Sensitization Test (HIST): What is Possible and Practical?' was held on 4 and 5 March 2015 in London, United Kingdom. Participants discussed the results of the data generated from an international collaborative study (BSP114 Phase 2) sponsored by the European Directorate for the Quality of Medicines & Health Care (EDQM) to determine if a modified Chinese hamster ovary (CHO) cell-based clustering assay is a suitable alternative to replace HIST. Workshop participants agreed that protocol transferability demonstrated in the collaborative study indicates that a standardised CHO cell assay is adequate for measuring pure PTx in reference preparations. However, vaccine manufacturers would still need to demonstrate that the method is valid to detect or measure residual PTx in their specific adjuvanted products. The 2 modified CHO cell protocols included in the study (the Direct and the Indirect Methods) deserve further consideration as alternatives to HIST. Using the CHO cell assay, an in vitro alternative, for acellular pertussis (aP) vaccine batch release testing would reduce the number of animals used for aP vaccine safety testing. A strategic, stepwise adoption plan was proposed, in which the alternative test would be used for release purposes first, and then, once sufficient confidence in its suitable performance has been gained, its use would be extended to stability testing.

  9. Animals

    Energy Technology Data Exchange (ETDEWEB)

    Skuterud, L.; Strand, P. [Norwegian Radiation Protection Authority (Norway); Howard, B.J. [Inst. of Terrestrial Ecology (United Kingdom)

    1997-10-01

    The radionuclides of most concern with respect to contamination of animals after a nuclear accident are radioiodine, radiocaesium and radiostrontium (ICRP 30, 1979). Of the other significant anthropogenic radionuclides likely to be released in most accidents, only small proportions of that ingested will be absorbed in an animals gut, and the main animal products, milk and meat, will not normally be contaminated to a significant extent. Animal products will mostly be contaminated as a result of ingestion of contaminated feed and possibly, but to a much lesser extent, from inhalation (for radioiodine only). Direct external contamination of animals is of little or no consequence in human food production. Radioiodine and radiostrontium are important with respect to contamination of milk; radiocaesium contaminates both milk and meat. The physical and chemical form of a radionuclide can influence its absorption in the animal gut. For example, following the Chernobyl accident radiocaesium incorporated into vegetation by root uptake was more readily absorbed than that associated with the original deposit. The transfer of radiocaesium and radiostrontium to animals will be presented both as transfer coefficients and aggregated transfer coefficients. For most animal meat products, only radiocaesium is important as other radionuclides do not significantly contaminate muscle. Farm animal products are the most important foodstuff determining radiocaesium intake by the average consumer in the Nordic countries. The major potential source of radioiodine and radiostrontium to humans is milk and milk products. Of the different species, the smaller animals have the highest transfer of radiocaesium from fodder to meat and milk. (EG). 68 refs.

  10. Animal models for microbicide safety and efficacy testing.

    Science.gov (United States)

    Veazey, Ronald S

    2013-07-01

    Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

  11. Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals: Mode of action in modulating cross-talks amonh immunity, disease resistance and gut microbiota

    Science.gov (United States)

    New antibiotic regulatory policies affecting agricultural animal production now challenge animal scientists to think outside of the box to develop alternative strategies for sustainable animal agriculture. For those animal infectious diseases for which effective vaccines are lacking, there is a cri...

  12. The development of an in vitro model for studying mechanisms of nephrotoxicity as an alternative for animal experiments

    NARCIS (Netherlands)

    Mertens, J.J.W.M.

    1991-01-01

    SUMMARY

    Presently in our society animal tests still form the main starting point for the assessment of the possible risks of chemicals with regard to human and animal health. For scientific. economic, and ethical reasons. attempts are undertaken continuously to develop cell models as

  13. Workshop on Alternatives to Animals in Research Held in Suffield, Ralston, Alberta on 16-17 September 1987

    Science.gov (United States)

    1989-10-01

    precise LD.0 tests , no generally accepted alternative seems to have emerged", the report states. In discussing the Draize ( eye irritancy) test using...Salmonella, a bacterium. The public has soundly criticized use of the LD,0 where half the test ani- mals die, and the Draize ( eye irritancy) test in rabbits...Regarding the Draize test , as a veterinary pathologist, I would like to know why the test could not be stopped at the point when the eye shows

  14. [A NEW APPROACH FOR FOOD PREFERENCE TESTING IN ANIMAL EXPERIMENTATION].

    Science.gov (United States)

    Albertin, S V

    2015-10-01

    An article describes the original method allowing to study a mechanism of food preference related to the sensory properties of foods in animals. The method gives a good possibility to select the role of visual and orosensory signaling in food preference as well as to model the processes of physiological and pathological food and drug dependence in animal experiments. The role of discrete food presentation in the formation of the current motivations and food preferences was discussed.

  15. Testing alternative theories of dark matter with the CMB

    International Nuclear Information System (INIS)

    Li Baojiu; Barrow, John D.; Mota, David F.; Zhao, HongSheng

    2008-01-01

    We propose a method to study and constrain modified gravity theories for dark matter using CMB temperature anisotropies and polarization. We assume that the theories considered here have already passed the matter power-spectrum test of large-scale structure. With this requirement met, we show that a modified gravity theory can be specified by parametrizing the time evolution of its dark-matter density contrast, which is completely controlled by the dark-matter stress history. We calculate how the stress history with a given parametrization affects the CMB observables, and a qualitative discussion of the physical effects involved is supplemented with numerical examples. It is found that, in general, alternative gravity theories can be efficiently constrained by the CMB temperature and polarization spectra. There exist, however, special cases where modified gravity cannot be distinguished from the CDM model even by using both CMB and matter power spectrum observations, nor can they be efficiently restricted by other observables in perturbed cosmologies. Our results show how the stress properties of dark matter, which determine the evolutions of both density perturbations and the gravitational potential, can be effectively investigated using just the general conservation equations and without assuming any specific theoretical gravitational theory within a wide class.

  16. 9 CFR 80.3 - Movement of domestic animals that are positive to an official Johne's disease test.

    Science.gov (United States)

    2010-01-01

    ... positive to an official Johne's disease test. 80.3 Section 80.3 Animals and Animal Products ANIMAL AND... animals that are positive to an official Johne's disease test. (a) Movement of domestic animals for slaughter. Domestic animals that are positive to an official Johne's disease test may be moved interstate...

  17. 9 CFR 80.4 - Segregation of animals positive to an official Johne's disease test during interstate movement.

    Science.gov (United States)

    2010-01-01

    ... official Johne's disease test during interstate movement. 80.4 Section 80.4 Animals and Animal Products... animals positive to an official Johne's disease test during interstate movement. Animals that are positive... from the animals positive to an official Johne's disease test to the healthy animals in the vehicle. ...

  18. Cost-effectiveness analysis of chemical testing for decision-support: How to include animal welfare?

    NARCIS (Netherlands)

    Gabbert, S.G.M.; Ierland, van E.C.

    2010-01-01

    Toxicity testing for regulatory purposes raises the question of test selection for a particular endpoint. Given the public's concern for animal welfare, test selection is a multi-objective decision problem that requires balancing information outcome, animal welfare loss, and monetary testing costs.

  19. Enabling Passive Immunization as an Alternative to Antibiotics for Controlling Enteric Infections in Production Animals

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Hald, Birthe; Madsen, M.

    massive use of antibiotics in food animals. Thus there is a pressing need for economically feasible, efficient, non-antibiotics based means for controlling the problem. Passive immunization has been known for decades as an efficient way of endowing humans or animals with short-term (weeks) immunity...

  20. Experiment data report for Semiscale Mod-1 Test S-05-1 (alternate ECC injection test)

    Energy Technology Data Exchange (ETDEWEB)

    Feldman, E. M.; Patton, Jr., M. L.; Sackett, K. E.

    1977-02-01

    Recorded test data are presented for Test S-05-1 of the Semiscale Mod-1 alternate ECC injection test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-05-1 was conducted from initial conditions of 2263 psia and 544/sup 0/F to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the cold leg broken loop piping. During the test, cooling water was injected into the vessel lower plenum to simulate emergency core coolant injection in a PWR, with the flow rate based on system volume scaling.

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

    OpenAIRE

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Cen...

  2. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    Science.gov (United States)

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Review of urban and suburban experiences of animal breeding as an alternative of food security

    Directory of Open Access Journals (Sweden)

    Camilo Ernesto Seija Flórez

    2011-10-01

    Full Text Available The urban and suburban animal production in tropical countries is a valid strategy to improve human nutrition, family consumption, income generation, savings and living conditions. Through case studies experiences of breeding animal (pigs, aquaculture, dairy, poultry, rabbits and bees were reviewed in some cities around the world to help in solving problems of food supply in urban and suburban areas. It should highlight the constraints (political, legal, health and environmental and intervention strategies to find solutions to problems. It was concluded that the positive experiences from around the world can introduce considerations of sustainability in urban and suburban animal breeding.

  4. Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods.

    Science.gov (United States)

    Casati, S; Aschberger, K; Barroso, J; Casey, W; Delgado, I; Kim, T S; Kleinstreuer, N; Kojima, H; Lee, J K; Lowit, A; Park, H K; Régimbald-Krnel, M J; Strickland, J; Whelan, M; Yang, Y; Zuang, Valérie

    2018-02-01

    Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate

  5. Hen egg chorioallantoic membrane bioassay: an in vitro alternative to draize eye irritation test for pesticide screening.

    Science.gov (United States)

    Kishore, A S; Surekha, P A; Sekhar, P V R; Srinivas, A; Murthy, P Balakrishna

    2008-11-01

    As an alternative to the standard Draize eye irritation test, the potential irritancy of compounds was evaluated by observing adverse changes that occur in chorioallantoic membrane CAM) of the hen egg (HECAM) after exposure to a test chemical placed directly on the CAM. The occurrence of hemorrhage, coagulation, and lysis in response to a test compound is the basis for employing this technique to evaluate its potential for in vivo damage to mucous membrane, in particular the eye. Irritancy is scored according to the severity and speed at which damage occurs. In the present study, five different classes of pesticides were screened for irritation potential. There was good correlation between the HECAM assay and the in vivo Draize eye irritation test. The proposed HECAM assay, which reduces the requirement for laboratory animals, could be a painless alternative to the Draize test.

  6. Animal testing, 3R models and regulatory acceptance : Technology transition in a risk-averse context

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.

    2016-01-01

    Risk avoidance has resulted in a broad range of regulations to guarantee the safety of products such as pharmaceuticals and chemicals. Many of these regulations rely on animal tests. About 3 million laboratory animals are used annually in Europe to meet such regulatory requirements.Regulatory animal

  7. Putting it to the test : alternative exploration techniques seek recognition

    Energy Technology Data Exchange (ETDEWEB)

    Cope, G.

    2005-06-01

    In the past, remote sensing techniques such as magnetic surveying, geochemical sampling and radiometric surveys, were efficient in hard rock mining exploration but were limited in hydrocarbon detection due to problems such as diurnal and weather variations. This article discussed some of the recent advances in technology that have been developed to overcome many of the drawbacks of older systems. Two Calgary-based companies are currently offering innovative and viable exploration alternatives. The Gore-Sorber module is the most accurate and comprehensive surface geochemical sampling technology currently available to the oil and gas industry. The testing module consists of 2 portions of expanded polytetrafluoroethylene polymer material sealed into a GORE-TEX sheath to prevent water and particle contamination. The module is then inserted into a shallow hole to a depth of 50 centimetres and left there for up to 2 weeks. The sample position is marked and surveyed. Over the course of the 2 weeks, volatile and semi-volatile soil gases in the C2-C15 range are absorbed into the material. The modules are analysed in mass spectrometers and gas chromatographs to determine zone and phase information. Advantages of the system include a reduction in soil contamination; the elimination of day-to-day fluctuations; and the fact that lab analysis allows for higher sensitivity. Costs are approximately $60,000 to $70,000 for an area of 16 square kilometres. Disadvantages include the inability to define the amount of hydrocarbons in place or their depth and the fact that proper field operation and collection of data by trained personnel is critical to the analysis process. The technique has been gaining in popularity in Canada as more exploration is directed towards environmentally sensitive frontier areas. Radiometric surveys record the gamma ray emissions of potassium, uranium and thorium as they decay radioactively. As hydrocarbons leak to the surface, they cause geochemical changes

  8. A campaign to end animal testing: introducing the PETA International Science Consortium Ltd.

    Science.gov (United States)

    Stoddart, Gilly; Brown, Jeffrey

    2014-12-01

    The successful development and validation of non-animal techniques, or the analysis of existing data to satisfy regulatory requirements, provide no guarantee that this information will be used in place of animal experiments. In order to advocate for the replacement of animal-based testing requirements, the PETA International Science Consortium Ltd (PISC) liaises with industry, regulatory and research agencies to establish and promote clear paths to validation and regulatory use of non-animal techniques. PISC and its members use an approach that identifies, promotes and verifies the implementation of good scientific practices in place of testing on animals. Examples of how PISC and its members have applied this approach to minimise the use of animals for the Registration, Evaluation, Authorisation and Restriction of Chemicals regulation in the EU and testing of cosmetics on animals in India, are described. 2014 FRAME.

  9. A Comparison of Alternative Narrative Approaches to Video Description for Animated Comedy

    Science.gov (United States)

    Fels, Deborah I.; Udo, John Patrick; Diamond, Jonas E.; Diamond, Jeremy I.

    2006-01-01

    This study explored the feasibility of using a first-person narrative style for video description of an animated comedy, "Odd Job Jack." It found that viewers who are blind find the first-person style more engaging, entertaining, and preferable but less trustworthy than the more conventional third-person description style.

  10. Tests of sex allocation theory in simultaneously hermaphroditic animals.

    Science.gov (United States)

    Schärer, Lukas

    2009-06-01

    Sex allocation is a crucial life-history parameter in all sexual organisms. Over the last decades a body of evolutionary theory, sex allocation theory, was developed, which has yielded capital insight into the evolution of optimal sex allocation patterns and adaptive evolution in general. Most empirical work, however, has focused on species with separate sexes. Here I review sex allocation theory for simultaneous hermaphrodites and summarize over 50 empirical studies, which have aimed at evaluating this theory in a diversity of simultaneous hermaphrodites spanning nine animal phyla. These studies have yielded considerable qualitative support for several predictions of sex allocation theory, such as a female-biased sex allocation when the number of mates is limited, and a shift toward a more male-biased sex allocation with increasing numbers of mates. In contrast, many fundamental assumptions, such as the trade-off between male and female allocation, and numerous predictions, such as brooding limiting the returns from female allocation, are still poorly supported. Measuring sex allocation in simultaneously hermaphroditic animals remains experimentally demanding, which renders evaluation of more quantitative predictions a challenging task. I identify the main questions that need to be addressed and point to promising avenues for future research.

  11. Medical records for animals used in research, teaching, and testing: public statement from the American College of Laboratory Animal Medicine.

    Science.gov (United States)

    Field, Karl; Bailey, Michele; Foresman, Larry L; Harris, Robert L; Motzel, Sherri L; Rockar, Richard A; Ruble, Gaye; Suckow, Mark A

    2007-01-01

    Medical records are considered to be a key element of a program of adequate veterinary care for animals used in research, teaching, and testing. However, prior to the release of the public statement on medical records by the American College of Laboratory Animal Medicine (ACLAM), the guidance that was available on the form and content of medical records used for the research setting was not consistent and, in some cases, was considered to be too rigid. To address this concern, ACLAM convened an ad hoc Medical Records Committee and charged the Committee with the task of developing a medical record guideline that was based on both professional judgment and performance standards. The Committee provided ACLAM with a guidance document titled Public Statements: Medical Records for Animals Used in Research, Teaching, and Testing, which was approved by ACLAM in late 2004. The ACLAM public statement on medical records provides guidance on the definition and content of medical records, and clearly identifies the Attending Veterinarian as the individual who is charged with authority and responsibility for oversight of the institution's medical records program. The document offers latitude to institutions in the precise form and process used for medical records but identifies typical information to be included in such records. As a result, the ACLAM public statement on medical records provides practical yet flexible guidelines to assure that documentation of animal health is performed in research, teaching, and testing situations.

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

    NARCIS (Netherlands)

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

    2017-01-01

    There is a paucity of information concerning the developmental neurotoxicity (DNT) hazard posed by industrial and environmental chemicals. New testing approaches will most likely be based on batteries of alternative and complementary (non-animal) tests. As DNT is assumed to result from the

  13. Animal models of toxicology testing: the role of pigs.

    Science.gov (United States)

    Helke, Kristi L; Swindle, Marvin Michael

    2013-02-01

    In regulatory toxicological testing, both a rodent and non-rodent species are required. Historically, dogs and non-human primates (NHP) have been the species of choice of the non-rodent portion of testing. The pig is an appropriate option for these tests based on metabolic pathways utilized in xenobiotic biotransformation. This review focuses on the Phase I and Phase II biotransformation pathways in humans and pigs and highlights the similarities and differences of these models. This is a growing field and references are sparse. Numerous breeds of pigs are discussed along with specific breed differences in these enzymes that are known. While much available data are presented, it is grossly incomplete and sometimes contradictory based on methods used. There is no ideal species to use in toxicology. The use of dogs and NHP in xenobiotic testing continues to be the norm. Pigs present a viable and perhaps more reliable model of non-rodent testing.

  14. Cardiomyocyte H9c2 cells present a valuable alternative to fish lethal testing for azoxystrobin

    International Nuclear Information System (INIS)

    Rodrigues, Elsa T.; Pardal, Miguel Â.; Laizé, Vincent; Cancela, M. Leonor; Oliveira, Paulo J.; Serafim, Teresa L.

    2015-01-01

    The present study aims at identifying, among six mammalian and fish cell lines, a sensitive cell line whose in vitro median inhibitory concentration (IC 50 ) better matches the in vivo short-term Sparus aurata median lethal concentration (LC 50 ). IC 50s and LC 50 were assessed after exposure to the widely used fungicide azoxystrobin (AZX). Statistical results were relevant for most cell lines after 48 h of AZX exposure, being H9c2 the most sensitive cells, as well as the ones which provided the best prediction of fish toxicity, with a LC 50,96h /IC 50,48h  = 0.581. H9c2 cell proliferation upon 72 h of AZX exposure revealed a LC 50,96h /IC 50,72h  = 0.998. Therefore, identical absolute sensitivities were attained for both in vitro and in vivo assays. To conclude, the H9c2 cell-based assay is reliable and represents a suitable ethical alternative to conventional fish assays for AZX, and could be used to get valuable insights into the toxic effects of other pesticides. - Highlights: • Fish toxicity data are still considered standard information in ecotoxicology. • Alternatives to animal testing have become an important topic of research. • Cell-based assays are currently a promising in vitro alternative. • Comparative studies to accelerate the validation of cell-based methods are required. • H9c2 cell line proved to produce in vitro reliable toxicity results for azoxystrobin. - The application of cell-based assays for environmental toxicity studies would greatly reduce the number of fish needed for toxicity testing without any loss of reliability.

  15. An alternative approach to absolute-value test for the parameters of ...

    African Journals Online (AJOL)

    An alternative approach to absolute-value test statistic Mn is developed for conducting tests simultaneously on all the parameters of multiple linear regression models. Under certain null and alternative hypotheses, the new test statistic is shown to have limiting central and noncentral chisquare distributions, respectively.

  16. 'Human-on-a-chip' developments: a translational cutting-edge alternative to systemic safety assessment and efficiency evaluation of substances in laboratory animals and man?

    Science.gov (United States)

    Marx, Uwe; Walles, Heike; Hoffmann, Silke; Lindner, Gerd; Horland, Reyk; Sonntag, Frank; Klotzbach, Udo; Sakharov, Dmitry; Tonevitsky, Alexander; Lauster, Roland

    2012-10-01

    Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in 'organ-on-a-chip' devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in 'human-on-a-chip' systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and micro-systems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in 'human-on-a-chip' systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals. 2012 FRAME.

  17. In search of memory tests equivalent for experiments on animals and humans.

    Science.gov (United States)

    Brodziak, Andrzej; Kołat, Estera; Różyk-Myrta, Alicja

    2014-12-19

    Older people often exhibit memory impairments. Contemporary demographic trends cause aging of the society. In this situation, it is important to conduct clinical trials of drugs and use training methods to improve memory capacity. Development of new memory tests requires experiments on animals and then clinical trials in humans. Therefore, we decided to review the assessment methods and search for tests that evaluate analogous cognitive processes in animals and humans. This review has enabled us to propose 2 pairs of tests of the efficiency of working memory capacity in animals and humans. We propose a basic set of methods for complex clinical trials of drugs and training methods to improve memory, consisting of 2 pairs of tests: 1) the Novel Object Recognition Test - Sternberg Item Recognition Test and 2) the Object-Location Test - Visuospatial Memory Test. We postulate that further investigations of methods that are equivalent in animals experiments and observations performed on humans are necessary.

  18. Experiment data report for Semiscale Mod-1 Test S-05-2 (alternate ECC injection test)

    Energy Technology Data Exchange (ETDEWEB)

    Feldman, E. M.; Collins, B. L.; Sackett, K. E.

    1977-02-01

    Recorded test data are presented for Test S-05-2 of the Semiscale Mod-1 alternate emergency core coolant (ECC) injection test series. This test is one of several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-05-2 was conducted from an initial cold leg fluid temperature of 545/sup 0/F and an initial pressure of 2263 psia. A simulated double-ended offset shear cold leg break was used to investigate core and system response to a depressurization and reflood transient with ECC injection at the intact loop pump suction and broken loop cold leg. A reduced lower plenum volume was used for this test to more accurately represent the lower plenum of a PWR, based on system volume scaling. System flow was set to achieve a core fluid temperature differential of 65/sup 0/F at a core power level of 1.44 MW. The flow resistance of the intact loop was based on core area scaling. An electrically heated core with a slightly peaked radial power profile was used in the pressure vessel to simulate the predicted surface heat flux of nuclear fuel rods during a loss-of-coolant accident.

  19. 77 FR 73286 - Codification of Animal Testing Policy

    Science.gov (United States)

    2012-12-10

    ... approved by other regulatory bodies, such as the Organisation for Economic Cooperation and Development..., structure-activity analysis). If a manufacturer or other entity performs a hazard test for FHSA labeling...

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

    NARCIS (Netherlands)

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

    2018-01-01

    Developmental neurotoxicity entails one of the most complex areas in toxicology. Animal studies provide only limited information as to human relevance. A multitude of alternative models have been developed over the years, providing insights into mechanisms of action. We give an overview of

  1. Development of a 10-day chorioallantoic membrane vascular assay as an alternative to the Draize rabbit eye irritation test.

    Science.gov (United States)

    Bagley, D M; Waters, D; Kong, B M

    1994-12-01

    The chorioallantoic membrane (CAM) of a fertilized hen's egg has been studied extensively as a promising alternative model for predicting eye irritation potential. The specific methodology used with this model has varied among investigators but the basic premise of applying test material to the membrane surface and evaluating changes in the vasculature is relatively consistent. The CAM vascular assay (CAMVA) has shown high correlation with in vivo rabbit eye irritation data. This method uses the CAM of a 14-day-old egg and the response at 30 min after treatment as the endpoint. The primary CAM methods being evaluated in Europe use 9-10-day-old eggs because older eggs are considered 'live animals'; the possibility of using 10-day-old eggs to make the method more globally acceptable as a non-animal test was therefore investigated. By keeping the original CAMVA dosing and evaluation procedures the same, and only altering the age of the eggs from 14-day to 10-day, the results were found to be nearly identical for the two methods and both produce equivalent correlations to the in vivo eye irritation test results. Maintaining the original CAMVA methodology but using a younger egg, therefore, provides a good alternative method for predicting eye irritation potential that is more globally acceptable as a non-animal test.

  2. Nipple Aspirate Test Is Not An Alternative To Mammography

    Science.gov (United States)

    ... special pump and testing it for abnormal cells. Companies have marketed this test as a way to screen for abnormal cells (instead of a mammogram), but the U.S. Food and Drug Administration is reminding you that this kind of test ...

  3. Placental perfusion - a human alternative

    DEFF Research Database (Denmark)

    Mose, Tina; Knudsen, Lisbeth E

    2006-01-01

    and represents a supplement and alternative to animal testing, bypassing the animal to human extrapolation. Placentas are readily obtainable from most births upon informed consent from the mothers and are considered a promising tissue alternative/supplement to animal experiments. The system is validated...... as a part of work package 2 of the integrated project ReProTect....

  4. Workshop on acceleration of the validation and regulatory acceptance of alternative methods and implementation of testing strategies

    DEFF Research Database (Denmark)

    Piersma, A. H.; Burgdorf, T.; Louekari, K.

    2018-01-01

    This report describes the proceedings of the BfR-RIVM workshop on validation of alternative methods which was held 23 and 24 March 2017 in Berlin, Germany. Stakeholders from governmental agencies, regulatory authorities, universities, industry and the OECD were invited to discuss current problems......-focused hazard and risk assessment of chemicals requires an open mind towards stepping away from the animal study as the gold standard and defining human biologically based regulatory requirements for human hazard and risk assessment.......This report describes the proceedings of the BfR-RIVM workshop on validation of alternative methods which was held 23 and 24 March 2017 in Berlin, Germany. Stakeholders from governmental agencies, regulatory authorities, universities, industry and the OECD were invited to discuss current problems...... concerning the regulatory acceptance and implementation of alternative test methods and testing strategies, with the aim to develop feasible solutions. Classical validation of alternative methods usually involves one to one comparison with the gold standard animal study. This approach suffers from...

  5. Neutron activation analysis of alternative phosphate rocks used in animal nutrition; Analise por ativacao neutronica por fontes alternativas de fosforo para a nutricao animal

    Energy Technology Data Exchange (ETDEWEB)

    Canella, Artur A.; Ferreira, Walter M. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Escola de Veterinaria]. E-mail: avelara@ufmg.br; Menezes, Maria Angela de B.C. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, MG (Brazil)]. E-mail: menezes@cdtn.br

    2005-07-01

    Since 1980's, Bovine Sponghiform Encephalophaty has insidiously created a fierce battleground between farmers, scientists, environmentalists and consumers. The use of meat and bone meals is currently prohibited in ruminant feeds throughout the world. Some inorganic sources offer the combination of high phosphorus content and acceptable animal digestibility make them options as supplemental phosphorus, for instance phosphate rocks, general term applied to minerals valued chiefly for their phosphorus content. However, phosphate rocks are long been known containing hazardous elements, make them sometimes unsuitable for animal nutrition. Neutron Activation Analysis has been supportive to the mineral evaluation of alternative phosphate rocks. This evaluation is subject of on-going doctoral thesis which has been carried-out by the main author. The NAA method has been very efficient due to its highly sensitive and multi-elemental nature. In this paper results of Vanadium content from three different phosphate rocks are presented. Their values have been pointed out that Brazilian phosphate rocks present hazardous elements at the same levels of phosphate rocks from some countries of Africa, North America and Middle East, data from our study (Brazilian data) and FAO - Food and Agriculture Organization (others countries). (author)

  6. Radioiodine (131I) in animal thyroids during nuclear tests in both hemispheres

    International Nuclear Information System (INIS)

    Van Middlesworth, L.

    1975-01-01

    In mid-1974 a small increase of 131 I was observed in animal thyroids following a nuclear test in China. In late 1974 there was no public announcement of an atmospheric nuclear test in the Northern Hemisphere, but 131 I was readily measured in animal thyroids. This latter increase occurred while animals in the Southern Hemisphere accumulated 131 I from nuclear tests in the Southern Hemisphere. It is suggested that in late 1974 the Northern Hemisphere was contaminated by either late fallout from tests in June or by interhemispheric mixing or by a combination of these sources. (author)

  7. [About the question of ethical admissibility versus unadmissibility of animal tests in basic research

    Science.gov (United States)

    Teutsch, Gotthard M.

    1994-01-01

    When discussing responsibility for laboratory animals, always and again people refer to the Swiss self-commitment "Ethical principles and guidelines about scientific animal tests". This is justified, as item no. 4.6 of that text contains - among other many comparable codices - the remarkable claim to dispense with animal tests and the hoped-for findings if the test leads to unavoidable serious suffering of laboratory animals. Very characteristic examples for such tests are those conducted without anesthesia, because the findings sought after can only be derived from the reaction of the non-anaesthetized animal. Therefore the obvious question arises whether the sacrifice ought to be commenced in basic research. Good will towards good care of our fellow creatures would, by this, assume more concrete forms and gain power of persuasion.

  8. Toxicogenomics-based in vitro alternatives for estrogenicity testing

    NARCIS (Netherlands)

    Wang, S.

    2013-01-01

    Testing chemicals for their endocrine-disrupting potential, including interference with estrogen receptor signaling, is an important aspect to assess the safety of currently used and newly developed chemicals. The standard test for disruption of normal estrogen function is the in vivo uterotrophic

  9. Nonparametric tests for data in randomised blocks with Ordered alternatives

    OpenAIRE

    Rayner, J. C. W.; Best, D. J.

    1999-01-01

    For randomized block designs, nonparametric treatment comparisons are usually made using the Friedman test for complete designs, and the Durbin test for incomplete designs; see, for example, Conover (1998). This permits assessment of only the mean rankings. Such comparisons are here extended to permit assessments of bivariate effects such as the linear by linear effect and the quadratic by linear, or umbrella effect.

  10. Inappropriate Practices in Fitness Testing and Reporting: Alternative Strategies

    Science.gov (United States)

    Zhu, Xihe; Davis, Summer; Kirk, T. Nicole; Haegele, Justin A.; Knott, Stephen E.

    2018-01-01

    Fitness education is becoming an integrated component for many physical education programs. As such, many physical educators conduct health-related fitness tests on a regular basis. Some states even mandate certain types of physical fitness tests to be administered and reported annually or by semester. Yet, inappropriate practices have been…

  11. 76 FR 9777 - Recent Postings of Broadly Applicable Alternative Test Methods

    Science.gov (United States)

    2011-02-22

    ... Performance for Method 16A Stationary Kraft Pulp wherein the Sources Mills. titration (Impinger analysis is... Applicable Alternative Test Methods AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of availability. SUMMARY: This notice announces the broadly applicable alternative test method approval decisions...

  12. Alternate retrieval technology demonstrations program - test report (ARD Environmental, Inc.)

    International Nuclear Information System (INIS)

    Berglin, E.J.

    1997-01-01

    A prototype vehicle, control system, and waste and water scavenging system were designed and fabricated with essentially the full capabilities of the vehicle system proposed by ARD Environmental. A test tank mockup, including riser and decontamination chamber were designed and fabricated, and approximately 830 cubic feet of six varieties of waste simulants poured. The tests were performed by ARD Environmental personnel at its site in Laurel, Maryland, from 4/22/97 through 5/2/97. The capabilities tested were deployment and retrieval, extended mobility and productivity, the ability to operate the system using video viewing only, retrieval after simulated failure, and retrieval and decontamination. Testing commenced with deployment of the vehicle into the tank. Deployment was accomplished using a crane and auxiliary winch to position the vehicle and lower it through the decontamination chamber, into the 36'' diameter x 6' high riser, and touch down on the waste field in the tank. The initial mobility tests were conducted immediately after deployment, prior to sluicing, as the waste field exhibited the greatest amount of variation at this time. This test demonstrated the ability of the vehicle to maneuver over the simulated waste field, and the ability of the operator to work with only video viewing available. In addition, the ability of the vehicle to right itself after being turned on its side was demonstrated. The production rate was evaluated daily through the testing period by measuring the surface and estimating the amount of material removed. The test demonstrated the ability of the vehicle to reduce the waste surface using 400 psi (nominal) water jets, scavenge water and material from the work area, and move to any location, even in the relatively confined space of the 20' diameter test tank. In addition, the ability to sluice to a remote scavenging module was demonstrated. The failure mode test demonstrated the ability to retrieve a stuck vehicle by pulling

  13. Demagnetization Tests Performed on a Linear Alternator for a Stirling Power Convertor

    Science.gov (United States)

    Geng, Steven M.; Niedra, Janis M.; Schwarze, Gene E.

    2012-01-01

    The NASA Glenn Research Center (GRC) is conducting in-house research on rare-earth permanent magnets and linear alternators to assist in developing free-piston Stirling convertors for radioisotope space power systems and for developing advanced linear alternator technology. This research continues at GRC, but, with the exception of Advanced Stirling Radioisotope Generator references, the work presented in this paper was conducted in 2005. A special arc-magnet characterization fixture was designed and built to measure the M-H characteristics of the magnets used in Technology Demonstration Convertors developed under the 110-W Stirling Radioisotope Generator (SRG110) project. This fixture was used to measure these characteristics of the arc magnets and to predict alternator demagnetization temperatures in the SRG110 application. Demagnetization tests using the TDC alternator on the Alternator Test Rig were conducted for two different magnet grades: Sumitomo Neomax 44AH and 42AH. The purpose of these tests was to determine the demagnetization temperatures of the magnets for the alternator under nominal loads. Measurements made during the tests included the linear alternator terminal voltage, current, average power, magnet temperatures, and stator temperatures. The results of these tests were found to be in good agreement with predictions. Alternator demagnetization temperatures in the Advanced Stirling Convertor (ASC-developed under the Advanced Stirling Radioisotope Generator project) were predicted as well because the prediction method had been validated through the SRG110 alternator tests. These predictions led to a specification for maximum temperatures of the ASC pressure vessel.

  14. Ending the use of animals in toxicity testing and risk evaluation.

    Science.gov (United States)

    Rowan, Andrew N

    2015-10-01

    This article discusses the use of animals for the safety testing of chemicals, including pharmaceuticals, household products, pesticides, and industrial chemicals. It reviews changes in safety testing technology and what those changes mean from the perspective of industrial innovation, public policy and public health, economics, and ethics. It concludes that the continuing use of animals for chemical safety testing should end within the decade as cheaper, quicker, and more predictive technologies are developed and applied.

  15. Impact Testing of a Stirling Converter's Linear Alternator

    Science.gov (United States)

    Suarez, Vicente J.; Goodnight, Thomas W.; Hughes, William O.; Samorezov, Sergey

    2002-01-01

    The U.S. Department of Energy (DOE), in conjunction with the NASA John H. Glenn Research Center and Stirling Technology Company, are currently developing a Stirling convertor for a Stirling Radioisotope Generator (SRG). NASA Headquarters and DOE have identified the SRG for potential use as an advanced spacecraft power system for future NASA deep-space and Mars surface missions. Low-level dynamic impact tests were conducted at NASA Glenn Research Center's Structural Dynamics Laboratory as part of the development of this technology. The purpose of this test was to identify dynamic structural characteristics of the Stirling Technology Demonstration Convertor (TDC). This paper addresses the test setup, procedure, and results of the impact testing conducted on the Stirling TDC in May 2001.

  16. The effluent toxicity assessment toolbox international perspective on tools and concepts and opportunities for animal alternatives

    Science.gov (United States)

    Effluent testing has been utilized in many countries to assess potential ecological impacts and assist in determining necessary treatment options for environmental protection. However, it was only relatively recently that toxicity-based effluent assessments and subsequent dischar...

  17. Animal Testing in the Risk Society and Violation of the Principle of Equal Consideration of Interests

    OpenAIRE

    Souza, Rafael Speck de

    2015-01-01

    This paper seeks to analyze the practice of animal testing under the paradigm of the Risk Society, Animal Rights, and in which point such research hurts the principle of equal consideration of like interests advocated by Peter Singer and other moral philosophers. On the one hand, this paper calls into question the attempt to transfer the results of an experiment with animals to reactions in humans, and the security criteria (or insecurity) adopted by science. On the other hand, an evaluation ...

  18. Testing alternative models of climate-mediated extirpations

    Science.gov (United States)

    Beever, E.A.; Chris, R.A.Y.; Mote, P.W.; Wilkening, J.L.

    2010-01-01

    Biotic responses to climate change will vary among taxa and across latitudes, elevational gradients, and degrees of insularity. However, due to factors such as phenotypic plasticity, ecotypic variation, and evolved tolerance to thermal stress, it remains poorly understood whether losses should be greatest in populations experiencing the greatest climatic change or living in places where the prevailing climate is closest to the edge of the species' bioclimatic envelope (e.g., at the hottest, driest sites). Research on American pikas (Ochotona princeps) in montane areas of the Great Basin during 1994-1999 suggested that 20th-century population extirpations were predicted by a combination of biogeographic, anthropogenic, and especially climatic factors. Surveys during 2005-2007 documented additional extirpations and within-site shifts of pika distributions at remaining sites. To evaluate the evidence in support of alternative hypotheses involving effects of thermal stress on pikas, we placed temperature sensors at 156 locations within pika habitats in the vicinity of 25 sites with historical records of pikas in the Basin. We related these time series of sensor data to data on ambient temperature from weather stations within the Historical Climate Network. We then used these highly correlated relationships, combined with long-term data from the same weather stations, to hindcast temperatures within pika habitats from 1945 through 2006. To explain patterns of loss, we posited three alternative classes of direct thermal stress: (1) acute cold stress (number of days below a threshold temperature); (2) acute heat stress (number of days above a threshold, temperature); and. (3) chronic heat stress (average summer temperature). Climate change was defined as change in our thermal metrics between two 31-y.r periods: 1945-1975 and 1976-2006. We found that patterns of persistence were well predicted by metrics of climate. Our best models suggest some effects of climate change

  19. Testing alternative models of climate-mediated extirpations.

    Science.gov (United States)

    Beever, Erik A; Ray, Chris; Mote, Philip W; Wilkening, Jennifer L

    2010-01-01

    Biotic responses to climate change will vary among taxa and across latitudes, elevational gradients, and degrees of insularity. However, due to factors such as phenotypic plasticity, ecotypic variation, and evolved tolerance to thermal stress, it remains poorly understood whether losses should be greatest in populations experiencing the greatest climatic change or living in places where the prevailing climate is closest to the edge of the species' bioclimatic envelope (e.g., at the hottest, driest sites). Research on American pikas (Ochotona princeps) in montane areas of the Great Basin during 1994-1999 suggested that 20th-century population extirpations were predicted by a combination of biogeographic, anthropogenic, and especially climatic factors. Surveys during 2005-2007 documented additional extirpations and within-site shifts of pika distributions at remaining sites. To evaluate the evidence in support of alternative hypotheses involving effects of thermal stress on pikas, we placed temperature sensors at 156 locations within pika habitats in the vicinity of 25 sites with historical records of pikas in the Basin. We related these time series of sensor data to data on ambient temperature from weather stations within the Historical Climate Network. We then used these highly correlated relationships, combined with long-term data from the same weather stations, to hindcast temperatures within pika habitats from 1945 through 2006. To explain patterns of loss, we posited three alternative classes of direct thermal stress: (1) acute cold stress (number of days below a threshold temperature); (2) acute heat stress (number of days above a threshold temperature); and (3) chronic heat stress (average summer temperature). Climate change was defined as change in our thermal metrics between two 31-yr periods: 1945-1975 and 1976-2006. We found that patterns of persistence were well predicted by metrics of climate. Our best models suggest some effects of climate change

  20. Fluorescence And Alternative Methods In Urine Drug Testing

    Science.gov (United States)

    Jain, Naresh C.

    1988-04-01

    Drug abuse has become-one of the most compelling realities _ ot contemporary society. It has penetrated every segment ot our population: trom schools to sports and trom organized crime to board rooms . Drugs in tie w9rkplace allegedly cost government agencies and business millions ot dollars each year in increased absenteeism,. poor work performance, thefts,accidents andwastedtime. The President's Commission on Organized Crime and the federal government are in tavor ot urine drug testing. In fact many employers are now resorting to urine drug testing on current and prospective employees. This presep.tation discusses different laboratory methods used in urine drug.testing, including immunoassays, fluorescence polarization, thin layer chromatography, high pressure liquid chromatography, gas chromatography and gas-chromatography-mass spectrometry.

  1. Evolving the Principles and Practice of Validation for New Alternative Approaches to Toxicity Testing.

    Science.gov (United States)

    Whelan, Maurice; Eskes, Chantra

    Validation is essential for the translation of newly developed alternative approaches to animal testing into tools and solutions suitable for regulatory applications. Formal approaches to validation have emerged over the past 20 years or so and although they have helped greatly to progress the field, it is essential that the principles and practice underpinning validation continue to evolve to keep pace with scientific progress. The modular approach to validation should be exploited to encourage more innovation and flexibility in study design and to increase efficiency in filling data gaps. With the focus now on integrated approaches to testing and assessment that are based on toxicological knowledge captured as adverse outcome pathways, and which incorporate the latest in vitro and computational methods, validation needs to adapt to ensure it adds value rather than hinders progress. Validation needs to be pursued both at the method level, to characterise the performance of in vitro methods in relation their ability to detect any association of a chemical with a particular pathway or key toxicological event, and at the methodological level, to assess how integrated approaches can predict toxicological endpoints relevant for regulatory decision making. To facilitate this, more emphasis needs to be given to the development of performance standards that can be applied to classes of methods and integrated approaches that provide similar information. Moreover, the challenge of selecting the right reference chemicals to support validation needs to be addressed more systematically, consistently and in a manner that better reflects the state of the science. Above all however, validation requires true partnership between the development and user communities of alternative methods and the appropriate investment of resources.

  2. Skin sensitisation: the Colipa strategy for developing and evaluating non-animal test methods for risk assessment.

    Science.gov (United States)

    Maxwell, Gavin; Aeby, Pierre; Ashikaga, Takao; Bessou-Touya, Sandrine; Diembeck, Walter; Gerberick, Frank; Kern, Petra; Marrec-Fairley, Monique; Ovigne, Jean-Marc; Sakaguchi, Hitoshi; Schroeder, Klaus; Tailhardat, Magali; Teissier, Silvia; Winkler, Petra

    2011-01-01

    Allergic contact dermatitis is a delayed-type hypersensitivity reaction induced by small reactive chemicals (haptens). Currently, the sensitising potential and potency of new chemicals is usually characterised using data generated via animal studies, such as the local lymph node assay (LLNA). There are, however, increasing public and political concerns regarding the use of animals for the testing of new chemicals. Consequently, the development of in vitro, in chemico or in silico models for predicting the sensitising potential and/or potency of new chemicals is receiving widespread interest. The Colipa Skin Tolerance task force currently collaborates with and/or funds several academic research groups to expand our understanding of the molecular and cellular events occurring during the acquisition of skin sensitisation. Knowledge gained from this research is being used to support the development and evaluation of novel alternative approaches for the identification and characterisation of skin sensitizing chemicals. At present three non-animal test methods (Direct Peptide Reactivity Assay (DPRA), Myeloid U937 Skin Sensitisation Test (MUSST) and human Cell Line Activation Test (hCLAT)) have been evaluated in Colipa interlaboratory ring trials for their potential to predict skin sensitisation potential and were recently submitted to ECVAM for formal pre-validation. Data from all three test methods will now be used to support the study and development of testing strategy approaches for skin sensitiser potency prediction. This publication represents the current viewpoint of the cosmetics industry on the feasibility of replacing the need for animal test data for informing skin sensitisation risk assessment decisions.

  3. Recruiting Source Effects: A Test of Two Alternative Explanations.

    Science.gov (United States)

    Breaugh, James A.; Mann, Rebecca B.

    The source of employee recruitment has been related to numerous important work outcomes (e.g., turnover, performance), but reasons for this relationship are not known. To test the viability of two possible explanations for recruiting source effects, i.e., employee level of realistic expectation, or individual differences, information was gathered…

  4. Gas Test Loop Facilities Alternatives Assessment Report Rev 1

    Energy Technology Data Exchange (ETDEWEB)

    William J. Skerjanc; William F. Skerjanc

    2005-07-01

    An important task in the Gas Test Loop (GTL) conceptual design was to determine the best facility to serve as host for this apparatus, which will allow fast-flux neutron testing in an existing nuclear facility. A survey was undertaken of domestic and foreign nuclear reactors and accelerator facilities to arrive at that determination. Two major research reactors in the U.S. were considered in detail, the Advanced Test Reactor (ATR) and the High Flux Isotope Reactor (HFIR), each with sufficient power to attain the required neutron fluxes. HFIR routinely operates near its design power limit of 100 MW. ATR has traditionally operated at less than half its design power limit of 250 MW. Both of these reactors should be available for at least the next 30 years. The other major U.S. research reactor, the Missouri University Research Reactor, does not have sufficient power to reach the required neutron flux nor do the smaller research reactors. Of the foreign reactors investigated, BOR-60 is perhaps the most attractive. Monju and BN 600 are power reactors for their respective electrical grids. Although the Joyo reactor is vigorously campaigning for customers, local laws regarding transport of radioactive material mean it would be very difficult to retrieve test articles from either Japanese reactor for post irradiation examination. PHENIX is scheduled to close in 2008 and is fully booked until then. FBTR is limited to domestic (Indian) users only. Data quality is often suspect in Russia. The only accelerator seriously considered was the Fuel and Material Test Station (FMTS) currently proposed for operation at Los Alamos National Laboratory. The neutron spectrum in FMTS is similar to that found in a fast reactor, but it has a pronounced high-energy tail that is atypical of fast fission reactor spectra. First irradiation in the FMTS is being contemplated for 2008. Detailed review of these facilities resulted in the recommendation that the ATR would be the best host for the GTL.

  5. [Food intolerance: reliability and characteristics of different diagnostic alternative tests].

    Science.gov (United States)

    Palmieri, B; Esposito, A; Capone, S; Fistetto, G; Iannitti, T

    2011-03-01

    The expression "food intolerance" dates back to the ancient Greece and can be generally defined as a sum of unpleasant symptoms of varying etiology that can onset in some patients after the ingestion of various food products. Adverse reactions to food can be divided into toxic and non-toxic. The last ones are classified as immunologically mediated, called "allergies", and non-immunologically mediated, commonly defined as "intolerances". The gut wall is directly involved in these adverse reactions to some foods, since it plays a key role in food absorption and in the regulation of the immunitary system. In this paper we discuss food intolerances and allergies, evaluating the available diagnostic methods and their scientific reliability and focusing on IgG analysis based immunoenzymatic test which is the most relevant test for intolerance diagnosis.

  6. Testing of Alternative Materials for Advanced Suit Bladders

    Science.gov (United States)

    Bue, Grant; Orndoff, Evelyne; Makinen, Janice; Tang, Henry

    2011-01-01

    Several candidate advanced pressure bladder membrane materials have been developed for NASA Johnson Space Center by DSM Biomedical for selective permeability of carbon dioxide and water vapor. These materials were elasthane and two other formulations of thermoplastic polyether polyurethane. Each material was tested in two thicknesses for permeability to carbon dioxide, oxygen and water vapor. Although oxygen leaks through the suit bladder would amount to only about 60 cc/hr in a full size suit, significant amounts of carbon dioxide would not be rejected by the system to justify its use. While the ratio of carbon dioxide to oxygen permeability is about 48 to 1, this is offset by the small partial pressure of carbon dioxide in acceptable breathing atmospheres of the suit. Humidity management remains a possible use of the membranes depending on the degree to which the water permeability is inhibited by cations in the sweat. Tests are underway to explore cation fouling from sweat.

  7. The Impact of Animal Rights on the Use of Animals for Biomedical Research, Product Testing and Evaluation.

    Science.gov (United States)

    Baier, Stephen W.

    1993-01-01

    Clarifies the issues of animal rights as they effect animal use in research and education through an examination of the current use of animals, a historical look at animal use, and a consideration of the philosophical underpinnings of the animal rights and pro-use viewpoints. (PR)

  8. Allergic Contact Dermatitis to Ophthalmic Medications: Relevant Allergens and Alternative Testing Methods.

    Science.gov (United States)

    Grey, Katherine R; Warshaw, Erin M

    Allergic contact dermatitis is an important cause of periorbital dermatitis. Topical ophthalmic agents are relevant sensitizers. Contact dermatitis to ophthalmic medications can be challenging to diagnose and manage given the numerous possible offending agents, including both active and inactive ingredients. Furthermore, a substantial body of literature reports false-negative patch test results to ophthalmic agents. Subsequently, numerous alternative testing methods have been described. This review outlines the periorbital manifestations, causative agents, and alternative testing methods of allergic contact dermatitis to ophthalmic medications.

  9. An Alternative to the Conventional Tri-Axial Compression Test

    DEFF Research Database (Denmark)

    Nielsen, Morten Storgaard; Bay, Niels; Eriksen, Morten

    2006-01-01

    A new test for measurement of the mechanical properties of granular powders is proposed, consisting of upsetting the powder inside a metal tube. The radial pressure is found by correlating measurements of radial bulging of the tube with numerical analysis of tube bulging. Estimates of the error o...... on the determination of the radial pressure are given along with an evaluation of the coefficient of friction for a specific case. New data for the yield surfaces for BSCCO are given and found to be in good agreement with previously published data....

  10. GSDO Program Hexavalent Chrome Alternatives: Final Pretreatments Test Report

    Science.gov (United States)

    Kessel, Kurt

    2013-01-01

    Hexavalent chrome free pretreatments should be considered for use on Ground Support Equipment (OSE) and Electrical Ground Support Equipment (EOSE). Both of the hexavalent chrome free pretreatments (Metalast TCP HF and SurTec 650C) evaluated by this project met, and in some instances exceeded, the requirements ofMIL-DTL-5541 "Chemical Conversion Coatings on Aluminum and Aluminum Alloys". For DC resistance measurements, both Metalast TCP HF and SurTec (!50C met initial requirements following assembly and in many cases continued to maintain passing readings for the duration of testing.

  11. [Lymphocyte stimulation test, a possible alternative for verifying chloroacetophenone sensitization].

    Science.gov (United States)

    Brand, C U; Schmidli, J; Ballmer-Weber, B; Hunziker, T

    1995-10-01

    We report on a case of pronounced sensitization to chloroacetophenone tear gas that developed after repeated occupational skin exposure in a 57-year-old police officer. Mainly in the presence of moisture and occlusion, cutaneous application of chloroacetophenone leads to severe irritant, and often also allergic, skin reactions. In patch testing the demonstration of allergic contact dermatitis in response to chloroacetophenone is hampered by the irritative potential of this substance even at low concentrations. This diagnostic bias can be overcome by the lymphocyte proliferation assay.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  13. Systematic evaluation of non-animal test methods for skin sensitisation safety assessment

    OpenAIRE

    Reisinger, Kerstin; Hoffmann, Sebastian; Alépée, Nathalie; Ashikaga, Takao; Barroso, Joao; Elcombe, Cliff; Gellatly, Nicola; Galbiati, Valentina; Gibbs, Susan; Groux, Hervé; Hibatallah, Jalila; Keller, Donald; Kern, Petra; Klaric, Martina; Kolle, Susanne

    2015-01-01

    The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitisation potency prediction. The results of the first phase - systematic evaluation of 16 test methods -...

  14. FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

    Science.gov (United States)

    Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

    2018-02-01

    This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

  15. Conditional dependence between tests affects the diagnosis and surveillance of animal diseases

    DEFF Research Database (Denmark)

    Gardner, I.A.; Stryhn, Henrik; Lind, Peter

    2000-01-01

    Dependence between the sensitivities or specificities of pairs of tests affects the sensitivity and specificity of tests when used in combination. Compared with values expected if tests are conditionally independent, a positive dependence in test sensitivity reduces the sensitivity of parallel te...... for toxoplasmosis and brucellosis in swine, and Johne's disease in cattle to illustrate calculation methods and to indicate the likely magnitude of the dependence between serologic tests used for diagnosis and surveillance of animal diseases....

  16. A critique of the EC's expert (draft) reports on the status of alternatives for cosmetics testing to meet the 2013 deadline.

    Science.gov (United States)

    Taylor, Katy; Casalegno, Carlotta; Stengel, Wolfgang

    2011-01-01

    The 7th Amendment to the EU's Cosmetic Directive (now recast as Regulation 1223/2009) bans the testing of cosmetic ingredients and products on animals, effective 2009. An extension until 2013 was granted, for marketing purposes only, for three endpoints: repeated dose, toxicokinetics, and reproductive toxicity. If the European Commission determines that alternatives for these endpoints are not likely to be available, it can propose a further extension. To this end, the Commission has instructed experts to produce reports on the status of alternatives for the 2013 deadline. We criticized the draft reports on a number of issues. First, the experts fell into the "high fidelity fallacy trap," i.e. asserting that full replication of the in vivo response, as opposed to high predictivity, is required before an animal test can be considered useful for regulatory purposes. Second, the experts' reports were incomplete, omitting various methods and failing to provide data on the validity, reliability, and applicability of all the methods discussed, regardless of whether the methods were in vivo, in vitro, or in silico. In this paper we provide a summary of our criticisms and provide some of the missing data in an alternative proposal for replacement of animal tests by 2013. It is our belief that use of the Threshold of Toxicological Concern (TTC) will be a useful method to mitigate much animal testing. Alternative approaches for carcinogenicity and skin sensitization could be considered sufficient in the very near future, even though these tests are not listed under the 2013 extension. For repeated dose, toxicokinetics, and reproductive toxicity a combination of in vitro methods may be able to provide appropriate protection for consumers, especially when viewed in the context of the poor predictivity of the animal models they replace. We hope the revised report will incorporate these comments, since a more thorough and positive review is required if the elimination of animal

  17. Performance Testing of a High Temperature Linear Alternator for Stirling Convertors

    Science.gov (United States)

    Metscher, Jonathan F.; Geng, Steven M.

    2016-01-01

    The NASA Glenn Research Center has conducted performance testing of a high temperature linear alternator (HTLA) in support of Stirling power convertor development for potential future Radioisotope Power Systems (RPS). The high temperature linear alternator is a modified version of that used in Sunpower's Advanced Stirling Convertor (ASC), and is capable of operation at temperatures up to 200 deg. Increasing the temperature capability of the linear alternator could expand the mission set of future Stirling RPS designs. High temperature Neodymium-Iron-Boron (Nd-Fe-B) magnets were selected for the HTLA application, and were fully characterized and tested prior to use. Higher temperature epoxy for alternator assembly was also selected and tested for thermal stability and strength. A characterization test was performed on the HTLA to measure its performance at various amplitudes, loads, and temperatures. HTLA endurance testing at 200 deg is currently underway.

  18. Report on the international workshop on alternative methods for Leptospira vaccine potency testing: state of the science and the way forward.

    Science.gov (United States)

    Stokes, William; Srinivas, Geetha; McFarland, Richard; Kulpa-Eddy, Jodie; Casey, Warren; Walker, Angela; Draayer, Hans; Sebring, Randy; Brown, Karen; Balks, Elisabeth; Stirling, Catrina; Klaasen, Eric; Hill, Richard; Rippke, Byron; Ruby, Kevin; Alt, David; Mukhopadhyay, Suman; Kojima, Hajime; Johnson, Nelson; Rinckel, Lori; Doelling, Vivian; Jones, Brett

    2013-09-01

    Routine potency testing of Leptospira vaccines is mostly conducted using a vaccination-challenge test that involves large numbers of hamsters and unrelieved pain and distress. NICEATM, ICCVAM, and their international partners organized a workshop to review the state of the science of alternative methods that might replace, reduce, and refine the use of animals for veterinary Leptospira vaccine potency testing and to identify ways to advance improved alternative methods. Vaccine manufacturers were encouraged to initiate or continue product-specific validation using in vitro enzyme-linked immunosorbent assays as replacements for potency testing of four common Leptospira serogroups. Participants discussed the potential for eliminating the back-titration procedure in the hamster challenge assay, which could reduce animal use by 50% for each individual potency test. Further animal reduction may also be possible by using cryopreserved Leptospira stock to replace continual passaging through hamsters. Serology assays were identified as a way to further reduce and refine animal use but should be considered only after attempting in vitro assays. Workshop participants encouraged consideration of analgesics and use of earlier humane endpoints when the hamster vaccination-challenge potency assay is used. International harmonization of alternative potency methods was recommended to avoid duplicative potency testing to meet regionally different requirements. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  19. Teaching Animal Physiology: a 12-year experience transitioning from a classical to interactive approach with continual assessment and computer alternatives.

    Science.gov (United States)

    Kaisarevic, Sonja N; Andric, Silvana A; Kostic, Tatjana S

    2017-09-01

    In response to the Bologna Declaration and contemporary trends in Animal Physiology education, the Animal Physiology course at the Faculty of Sciences, University of Novi Sad, Serbia, has evolved over a 12-yr period (2001-2012): from a classical two-semester course toward a one-semester course utilizing computer simulations of animal experiments, continual assessment, lectures, and an optional oral exam. This paper presents an overview of student achievement, the impact of reforms on learning outcomes, and lessons that we as educators learned during this process. The reforms had a positive impact on the percentage of students who completed the course within the same academic year. In addition, the percentage of students who completed the practical exam increased from 54% to >95% following the transition to a Bologna-based approach. However, average final grades declined from 8.0 to 6.8 over the same period. Students also appear reluctant to take the optional oral exam, and 82-91% of students were satisfied with the lower final grade obtained from only assessments and tests administered during the semester. In our endeavor to achieve learning outcomes set during the pre-Bologna period, while adopting contemporary teaching approaches, we sought to increase students' motivation to strive toward better performance, while ensuring that the increased quantity of students who complete the course is coupled with increased quality of education and a more in-depth understanding of animal physiology. Copyright © 2017 the American Physiological Society.

  20. Skin sensitisation--moving forward with non-animal testing strategies for regulatory purposes in the EU.

    Science.gov (United States)

    Basketter, David; Alépée, Nathalie; Casati, Silvia; Crozier, Jonathan; Eigler, Dorothea; Griem, Peter; Hubesch, Bruno; de Knecht, Joop; Landsiedel, Robert; Louekari, Kimmo; Manou, Irene; Maxwell, Gavin; Mehling, Annette; Netzeva, Tatiana; Petry, Thomas; Rossi, Laura H

    2013-12-01

    In a previous EPAA-Cefic LRI workshop in 2011, issues surrounding the use and interpretation of results from the local lymph node assay were addressed. At the beginning of 2013 a second joint workshop focused greater attention on the opportunities to make use of non-animal test data, not least since a number of in vitro assays have progressed to an advanced position in terms of their formal validation. It is already recognised that information produced from non-animal assays can be used in regulatory decision-making, notably in terms of classifying a substance as a skin sensitiser. The evolution into a full replacement for hazard identification, where the decision is not to classify, requires the generation of confidence in the in vitro alternative, e.g. via formal validation, the existence of peer reviewed publications and the knowledge that the assay(s) are founded on key elements of the Adverse Outcome Pathway for skin sensitisation. It is foreseen that the validated in vitro assays and relevant QSAR models can be organised into formal testing strategies to be applied for regulatory purposes by the industry. To facilitate progress, the European Partnership for Alternative Approaches to animal testing (EPAA) provided the platform for cross-industry and regulatory dialogue, enabling an essential and open debate on the acceptability of an in vitro based integrated strategy. Based on these considerations, a follow up activity was agreed upon to explore an example of an Integrated Testing Strategy for skin sensitisation hazard identification purposes in the context of REACH submissions. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. The Effect of Extremely Low Frequency Alternating Magnetic Field on the Behavior of Animals in the Presence of the Geomagnetic Field

    Directory of Open Access Journals (Sweden)

    Natalia A. Belova

    2015-01-01

    Full Text Available It is known that the geomagnetic field can influence animal migration and homing. The magnetic field detection by animals is known as magnetoreception and it is possible due to two different transduction mechanisms: the first one through magnetic nanoparticles able to respond to the geomagnetic field and the second one through chemical reactions influenced by magnetic fields. Another behavior is the magnetic alignment where animals align their bodies to the geomagnetic field. It has been observed that magnetic alignment of cattle can be disrupted near electric power lines around the world. Experimentally, it is known that alternating magnetic fields can influence living beings, but the exact mechanism is unknown. The parametric resonance model proposes a mechanism to explain that effect on living beings and establishes that, in the presence of a constant magnetic field, molecules associated with biochemical reactions inside cells can absorb resonantly alternating magnetic fields with specific frequencies. In the present paper, a review is made about animal magnetoreception and the effects of alternating magnetic fields in living beings. It is suggested how alternating magnetic fields can interfere in the magnetic alignment of animals and a general conclusion is obtained: alternating magnetic field pollution can affect the magnetic sensibility of animals.

  2. Transition towards replacing animal tests in safety assessment of cosmetics and chemicals: a combined TIS-MLP framework

    OpenAIRE

    Kooijman, M.; Meer, P. van de; Moors, E.H.M.; Schellekens, H.; Hekkert, M.P.

    2012-01-01

    The urgency of the transition to replace animal tests in safety assessment of chemicals and cosmetics was triggered by societal resistance to animal testing (Rowan, 2007) and the scientific dispute concerning the value of animal testing (Olson et al., 2000). Since the 1980s the European Union (EU) has been developing policies to reduce an-imal studies. However, these policies have not been very successful, since only a few regulatory safety assessments in animals (among which the Draize eye t...

  3. Generation of Alternative Assessment Scores using TEST and online data sources

    Science.gov (United States)

    Alternatives assessment frameworks such as DfE (Design for the Environment) evaluate chemical alternatives in terms of human health effects, ecotoxicity, and fate. T.E.S.T. (Toxicity Estimation Software Tool) can be utilized to evaluate human health in terms of acute oral rat tox...

  4. Review of Evidence of Environmental Impacts of Animal Research and Testing

    Directory of Open Access Journals (Sweden)

    Katherine Groff

    2014-06-01

    Full Text Available Millions of animals are used in research and toxicity testing, including in drug, medical device, chemical, cosmetic, personal care, household, and other product sectors, but the environmental consequences are yet to be adequately addressed. Evidence suggests that their use and disposal, and the associated use of chemicals and supplies, contribute to pollution as well as adverse impacts on biodiversity and public health. The objective of this review is to examine such evidence. The review includes examinations of (1 resources used in animal research; (2 waste production in laboratories; (3 sources of pollution; (4 impacts on laboratory workers’ health; and (5 biodiversity impacts. The clear conclusion from the review is that the environmental implications of animal testing must be acknowledged, reported, and taken into account as another factor in addition to ethical and scientific reasons weighing heavily in favor of moving away from allowing and requiring animal use in research and testing.

  5. Safety testing of GM-rice expressing PHA-E lectin using a new animal test design

    DEFF Research Database (Denmark)

    Poulsen, Morten; Schrøder, Malene; Wilcks, Andrea

    2007-01-01

    The 90-day animal study is the core study for the safety assessment of genetically modified foods in the SAFOTEST project. The model compound tested in the 90-day study was a rice variety expressing the kidney bean Phaseolus vulgaris lectin agglutinin E-form (PHA-E lectin). Female Wistar rats were...... safety testing of genetically modified foods....

  6. Reducing animal experimentation in foot-and-mouth disease vaccine potency tests.

    Science.gov (United States)

    Reeve, Richard; Cox, Sarah; Smitsaart, Eliana; Beascoechea, Claudia Perez; Haas, Bernd; Maradei, Eduardo; Haydon, Daniel T; Barnett, Paul

    2011-07-26

    The World Organisation for Animal Health (OIE) Terrestrial Manual and the European Pharmacopoeia (EP) still prescribe live challenge experiments for foot-and-mouth disease virus (FMDV) immunogenicity and vaccine potency tests. However, the EP allows for other validated tests for the latter, and specifically in vitro tests if a "satisfactory pass level" has been determined; serological replacements are also currently in use in South America. Much research has therefore focused on validating both ex vivo and in vitro tests to replace live challenge. However, insufficient attention has been given to the sensitivity and specificity of the "gold standard"in vivo test being replaced, despite this information being critical to determining what should be required of its replacement. This paper aims to redress this imbalance by examining the current live challenge tests and their associated statistics and determining the confidence that we can have in them, thereby setting a standard for candidate replacements. It determines that the statistics associated with the current EP PD(50) test are inappropriate given our domain knowledge, but that the OIE test statistics are satisfactory. However, it has also identified a new set of live animal challenge test regimes that provide similar sensitivity and specificity to all of the currently used OIE tests using fewer animals (16 including controls), and can also provide further savings in live animal experiments in exchange for small reductions in sensitivity and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Alternative Test Methods for Developmental Neurotoxicity: A History and Path Forward (OECD EFSA workshop)

    Science.gov (United States)

    Exposure to environmental contaminants is well documented to adversely impact the development of the nervous system. However, the time, animal and resource intensive EPA and OECD testing guideline methods for developmental neurotoxicity (DNT) are not a viable solution to characte...

  8. The ICLAS/CCAC International Symposium on Regulatory Testing and Animal Welfare.

    Science.gov (United States)

    Griffin, Gilly; Stokes, William S; Pakes, Steven P; Gauthier, Célement

    2004-06-01

    The first International Symposium on Regulatory Testing and Animal Welfare (ISRTAW), held 21-23 June 2001, in Quebec City, Canada, brought together 160 experts from 22 countries from North and South America, Europe and Asia. The experts included representatives from national research and regulatory agencies, universities, and industry involved in chemicals, pesticides and drug safety testing. Representatives from European, Canadian and US animal welfare groups also participated in the discussions. The Symposium was organised by the International Council for Laboratory Animal Science (ICLAS) and the Canadian Council on Animal Care (CCAC), with the support and assistance of many sponsors and advisors. ICLAS is a worldwide organisation whose purpose is to foster the international harmonisation of animal care and use practices. CCAC is the national agency responsible for overseeing the ethical use of animals in Canadian science. Both organisations are committed to fostering an environment in which global efforts to harmonise testing procedures using animals in a more-humane manner can be realised.

  9. Alternate Material Pallet, 40" x 48", MIL-STD-1660, Engineering Evaluation Tests

    National Research Council Canada - National Science Library

    Dugan, Jeffery

    2003-01-01

    The U.S. Army Defense Ammunition Center (DAC), Validation Engineering Division (SJMAC-DEV) conducted Engineering Evaluation Tests to determine if the Alternate Material Pallet manufactured by Hunter Paine Enterprise, Inc...

  10. A step forward in the quality control testing of inactivated rabies vaccines - extensive evaluation of European vaccines by using alternative methods to the in vivo potency tests.

    Science.gov (United States)

    Servat, Alexandre; Kempff, Sébastien; Brogat, Valère; Litaize, Estelle; Schereffer, Jean-Luc; Cliquet, Florence

    2015-03-01

    The mouse challenge test still remains the reference method for the potency determination of human and animal inactivated rabies vaccines, and it is still widely used throughout the world. This test suffers from many disadvantages - it is expensive and time consuming, uses a large number of mice, causes significant animal distress, and suffers from high variability. Recently, the European Pharmacopoeia has recognised the use of a serological potency assay (SPA) as an alternative method to the challenge test. This new test is based on the determination of rabies neutralising antibody titres in vaccinated mice, by using the modified Rapid Fluorescent Focus Inhibition Test (mRFFIT). With the objective of adopting this new method for the batch release of inactivated rabies vaccines, we evaluated its performance on a large collection of rabies vaccines currently assessed in our laboratory. The Fluorescent Antibody Virus Neutralisation test (FAVNt) was used in parallel with the mRFFIT, and the results were compared to the mouse challenge test. Our results demonstrate that the SPA is capable of estimating the potency of vaccines formulated with a potency margin well above the minimum of 1IU/dose. For low potency vaccines, this new method demonstrated some limitations, due to the recurrent invalidation of the assay. We have also demonstrated the superior sensitivity of the FAVNt when compared to the mRFFIT, and the importance of minimising the risk of detecting non-responders in vaccinated mice. 2015 FRAME.

  11. A generalized Jonckheere test against ordered alternatives for repeated measures in randomized blocks.

    Science.gov (United States)

    Zhang, Ying; Cabilio, Paul

    2013-05-10

    Focusing on statistical methods in patient-reported outcomes, we propose and develop a generalized Jonckheere test against ordered alternatives for repeated measures in a randomized block design. We derive its asymptotic null distribution properties and describe methods for estimating the null distribution for testing the hypothesis. We present a numerical example to illustrate the test procedure. Copyright © 2012 John Wiley & Sons, Ltd.

  12. Assuring consumer safety without animal testing: a feasibility case study for skin sensitisation.

    Science.gov (United States)

    Maxwell, Gavin; Aleksic, Maja; Aptula, Aynur; Carmichael, Paul; Fentem, Julia; Gilmour, Nicola; Mackay, Cameron; Pease, Camilla; Pendlington, Ruth; Reynolds, Fiona; Scott, Daniel; Warner, Guy; Westmoreland, Carl

    2008-11-01

    Allergic Contact Dermatitis (ACD; chemical-induced skin sensitisation) represents a key consumer safety endpoint for the cosmetics industry. At present, animal tests (predominantly the mouse Local Lymph Node Assay) are used to generate skin sensitisation hazard data for use in consumer safety risk assessments. An animal testing ban on chemicals to be used in cosmetics will come into effect in the European Union (EU) from March 2009. This animal testing ban is also linked to an EU marketing ban on products containing any ingredients that have been subsequently tested in animals, from March 2009 or March 2013, depending on the toxicological endpoint of concern. Consequently, the testing of cosmetic ingredients in animals for their potential to induce skin sensitisation will be subject to an EU marketing ban, from March 2013 onwards. Our conceptual framework and strategy to deliver a non-animal approach to consumer safety risk assessment can be summarised as an evaluation of new technologies (e.g. 'omics', informatics), leading to the development of new non-animal (in silico and in vitro) predictive models for the generation and interpretation of new forms of hazard characterisation data, followed by the development of new risk assessment approaches to integrate these new forms of data and information in the context of human exposure. Following the principles of the conceptual framework, we have been investigating existing and developing new technologies, models and approaches, in order to explore the feasibility of delivering consumer safety risk assessment decisions in the absence of new animal data. We present here our progress in implementing this conceptual framework, with the skin sensitisation endpoint used as a case study. 2008 FRAME.

  13. Permutation Test Approach for Ordered Alternatives in Randomized Complete Block Design: A Comparative Study

    OpenAIRE

    GOKPINAR, Esra; GUL, Hasan; GOKPINAR, Fikri; BAYRAK, Hülya; OZONUR, Deniz

    2013-01-01

    Randomized complete block design is one of the most used experimental designs in statistical analysis. For testing ordered alternatives in randomized complete block design, parametric tests are used if random sample are drawn from Normal distribution. If normality assumption is not provide, nonparametric methods are used. In this study, we are interested nonparametric tests and we introduce briefly the nonparametric tests, such as Page, Modified Page and Hollander tests. We also give Permutat...

  14. Structured approach to design of diagnostic test evaluation studies for chronic progressive infections in animals

    DEFF Research Database (Denmark)

    Nielsen, Søren Saxmose; Toft, Nils; Gardner, Ian Andrew

    2011-01-01

    ) than originally intended. The objective of this paper is to outline a structured approach to the design and conduct of a DTE for diagnostic tests used for chronic infections in animals, and intended for different purposes. We describe the process from reflections about test purpose and the underlying......Diagnostic test evaluations (DTEs) for chronic infections are challenging because a protracted incubation period has to be considered in the design of the DTE, and the adverse effects of infection may be widespread and progressive over an animal's entire life. Frequently, the specific purpose...

  15. Mixed grazing systems of goats with cattle in tropical conditions: an alternative to improving animal production in the pasture.

    Science.gov (United States)

    d'Alexis, S; Periacarpin, F; Jackson, F; Boval, M

    2014-08-01

    Mixed grazing systems combining sheep and cattle have shown better growth performance for one or both species. This observation has been attributed to their complementary feeding behaviour and the reduced host infection by gastrointestinal nematodes. Less attention has been paid to mixed grazing systems combining goats and cattle. Here, continuously grazing goats mixed with cattle (M) were compared with control goats reared alone (C) under tropical conditions. The comparison was conducted with gastrointestinal nematode-infected (I) and non-infected (nI) goats. Thus, the four treatments were cattle with gastrointestinal nematode-infected goats (MI), gastrointestinal nematode-infected goats alone (CI), cattle with non-infected goats (MnI) and non-infected goats (CnI). Average daily gain (ADG, g/day) and grass production were measured for the four groups of animals (six goats and two heifers treated with MI or MnI) grazing for 3 months on 4 subplots. Monthly measurements were performed over 5-day periods. This pattern was replicated in space for a second set of four subplots and in time for six successive cohorts of animals (bands 1 to 6). The ADG of goats in mixed grazing conditions was higher than controls irrespective of the infection status (32.6 v. 18.4 g/day for MI v. CI; 44.2 v. 33.5 g/day for MnI v. CnI). Concomitantly, the average biomass was lower for mixed grazing animals compared with controls (174 v. 170 for MI and MnI; 235 v. 208 for CI and CnI, respectively), suggesting better use of the sward. For daily BW gain (g/kg DM), mixed grazing also yielded better results than the control (1.88 v. 0.52 g BW/kg DM per day for MI v. CI; 2.08 v. 1.47 g BW/kg DM per day for MnI and CnI). Mixed grazing of goats and heifers offers a promising alternative for increasing goat and overall animal production as well as improving the management of pastures.

  16. Transition towards replacing animal tests in safety assessment of cosmetics and chemicals: a combined TIS-MLP framework

    NARCIS (Netherlands)

    Kooijman, M.; Meer, P. van de; Moors, E.H.M.; Schellekens, H.; Hekkert, M.P.

    2012-01-01

    The urgency of the transition to replace animal tests in safety assessment of chemicals and cosmetics was triggered by societal resistance to animal testing (Rowan, 2007) and the scientific dispute concerning the value of animal testing (Olson et al., 2000). Since the 1980s the European Union (EU)

  17. No Humans Have Been Injured in the Testing of this Drug: The New Animal Efficacy Rule

    OpenAIRE

    Campbell, Carrie

    2004-01-01

    This paper examines the “Animal Efficacy Rule,†a regulation that provides for the approval of products by the FDA when efficacy testing on humans is ethically impossible. It gives a summary of the history of the enactment of this regulation and outlines its structure and major features. Next, the regulation is analyzed in light of statutory authority, ethics, and practicality. Finally the approval of pyridostigmine bromide under the Animal Efficacy Rule is eval...

  18. Alternatives to animals

    NARCIS (Netherlands)

    M.A.T. Teunis

    2013-01-01

    International Innovation is the leading global dissemination resource for the wider scientific, technology and research communities, dedicated to disseminating the latest science, research and technological innovations on a global level. More information and a complimentary subscription offer to the

  19. 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.

    Science.gov (United States)

    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.

  20. Induced pluripotent stem cell-derived limbal epithelial cells (LiPSC) as a cellular alternative for in vitro ocular toxicity testing

    OpenAIRE

    Aberdam, Edith; Petit, Isabelle; Sangari, Linda; Aberdam, Daniel

    2017-01-01

    Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to evaluate the risks of drugs and cosmetic products before their application to human patients by preventing eye irritation or insult. Since the global ban to use animals, many human-derived alternatives have been proposed, from ex-vivo enucleated p...

  1. Herd-level interpretation of test results for epidemiologic studies of animal diseases

    DEFF Research Database (Denmark)

    Christensen, Jette; Gardner, Ian A.

    2000-01-01

    Correct classification of the true status of herds is an important component of epidemiologic studies and animal disease-control programs. We review theoretical aspects of herd-level testing through consideration of test performance (herd-level sensitivity, specificity and predictive values......), the factors affecting these estimates, and available software for calculations. We present new aspects and considerations concerning the effect of precision and bias in estimation of individual-test performance on herd-test performance and suggest methods (pooled testing, targeted sampling of subpopulations...... with higher prevalence, and use of combinations of tests) to improve herd-level sensitivity when the expected within-herd prevalence is low....

  2. Expert opinions on the acceptance of alternative methods in food safety evaluations: Formulating recommendations to increase acceptance of non-animal methods for kinetics.

    Science.gov (United States)

    Punt, Ans; Bouwmeester, Hans; Schiffelers, Marie-Jeanne W A; Peijnenburg, Ad A C M

    2018-02-01

    Inclusion of alternative methods that replace, reduce, or refine (3R) animal testing within regulatory safety evaluations of chemicals generally faces many hurdles. The goal of the current work is to i) collect responses from key stakeholders involved in food safety evaluations on what they consider the most relevant factors that influence the acceptance and use of 3R methods and to ii) use these responses to formulate activities needed to increase the acceptance and use of 3R methods, particularly for kinetics. The stakeholders were contacted by e-mail for their opinions, asking the respondents to write down three barriers and/or drivers and scoring these by distributing 5 points over the three factors. The main barriers that obtained the highest aggregated scores were i) uncertain predictability 3R methods/lack of validation, ii) insufficient guidance regulators/industry and iii) insufficient harmonization of legislation. The major driver identified was the possibility of 3R methods to provide more mechanistic information. Based on the results, recommendations are given to enhance the acceptance and application of 3R toxicokinetic methods in food safety evaluations. These include steering of regulatory data requirements as well as creating (funding) opportunities for development and validation of alternative methods for kinetics and development of guidances. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Animal investigation program 1974 annual report: Nevada Test Site and vicinity

    International Nuclear Information System (INIS)

    Smith, D.D.; Giles, K.R.; Bernhardt, D.E.; Brown, K.R.

    1977-06-01

    Data are presented from the radioanalysis of tissues collected from cattle, deer, desert bighorn sheep, and other wildlife that resided on or near the Nevada Test Site during 1974. Routine activities and special investigations of the Animal Investigation Program are also discussed. Other than the naturally occurring potassium-40, gamma-emitting radionuclides were detected infrequently. For example, cesium-137 was found only in the muscle tissues from 3 of the 12 Nevada Test Site cattle sampled during 1974. Tritium concentrations in the tissues from most of the animals sampled are at background levels. Animals from the experimental farm tended to have slightly higher concentrations than those sampled at other locations on the Nevada Test Site. Strontium-90 levels in bones from deer, desert bighorn sheep, and cattle were slightly lower than those reported for the preceding year. A graph depicts the average levels found in the bones of the three species from 1956 through 1974

  4. Large animal and primate models of spinal cord injury for the testing of novel therapies.

    Science.gov (United States)

    Kwon, Brian K; Streijger, Femke; Hill, Caitlin E; Anderson, Aileen J; Bacon, Mark; Beattie, Michael S; Blesch, Armin; Bradbury, Elizabeth J; Brown, Arthur; Bresnahan, Jacqueline C; Case, Casey C; Colburn, Raymond W; David, Samuel; Fawcett, James W; Ferguson, Adam R; Fischer, Itzhak; Floyd, Candace L; Gensel, John C; Houle, John D; Jakeman, Lyn B; Jeffery, Nick D; Jones, Linda Ann Truett; Kleitman, Naomi; Kocsis, Jeffery; Lu, Paul; Magnuson, David S K; Marsala, Martin; Moore, Simon W; Mothe, Andrea J; Oudega, Martin; Plant, Giles W; Rabchevsky, Alexander Sasha; Schwab, Jan M; Silver, Jerry; Steward, Oswald; Xu, Xiao-Ming; Guest, James D; Tetzlaff, Wolfram

    2015-07-01

    Large animal and primate models of spinal cord injury (SCI) are being increasingly utilized for the testing of novel therapies. While these represent intermediary animal species between rodents and humans and offer the opportunity to pose unique research questions prior to clinical trials, the role that such large animal and primate models should play in the translational pipeline is unclear. In this initiative we engaged members of the SCI research community in a questionnaire and round-table focus group discussion around the use of such models. Forty-one SCI researchers from academia, industry, and granting agencies were asked to complete a questionnaire about their opinion regarding the use of large animal and primate models in the context of testing novel therapeutics. The questions centered around how large animal and primate models of SCI would be best utilized in the spectrum of preclinical testing, and how much testing in rodent models was warranted before employing these models. Further questions were posed at a focus group meeting attended by the respondents. The group generally felt that large animal and primate models of SCI serve a potentially useful role in the translational pipeline for novel therapies, and that the rational use of these models would depend on the type of therapy and specific research question being addressed. While testing within these models should not be mandatory, the detection of beneficial effects using these models lends additional support for translating a therapy to humans. These models provides an opportunity to evaluate and refine surgical procedures prior to use in humans, and safety and bio-distribution in a spinal cord more similar in size and anatomy to that of humans. Our results reveal that while many feel that these models are valuable in the testing of novel therapies, important questions remain unanswered about how they should be used and how data derived from them should be interpreted. Copyright © 2015 Elsevier

  5. Multivariate classification of animal communication signals: a simulation-based comparison of alternative signal processing procedures using electric fishes.

    Science.gov (United States)

    Crampton, William G R; Davis, Justin K; Lovejoy, Nathan R; Pensky, Marianna

    2008-01-01

    Evolutionary studies of communication can benefit from classification procedures that allow individual animals to be assigned to groups (e.g. species) on the basis of high-dimension data representing their signals. Prior to classification, signals are usually transformed by a signal processing procedure into structural features. Applications of these signal processing procedures to animal communication have been largely restricted to the manual or semi-automated identification of landmark features from graphical representations of signals. Nonetheless, theory predicts that automated time-frequency-based digital signal processing (DSP) procedures can represent signals more efficiently (using fewer features) than can landmark procedures or frequency-based DSP - allowing more accurate classification. Moreover, DSP procedures are objective in that they require little previous knowledge of signal diversity, and are relatively free from potentially ungrounded assumptions of cross-taxon homology. Using a model data set of electric organ discharge waveforms from five sympatric species of the electric fish Gymnotus, we adopted an exhaustive simulation approach to investigate the classificatory performance of different signal processing procedures. We considered a landmark procedure, a frequency-based DSP procedure (the fast Fourier transform), and two kinds of time-frequency-based DSP procedures (a short-time Fourier transform, and several implementations of the discrete wavelet transform -DWT). The features derived from each of these signal processing procedures were then subjected to dimension reduction procedures to separate those features which permit the most effective discrimination among groups of signalers. We considered four alternative dimension reduction methods. Finally, each combination of reduced data was submitted to classification by linear discriminant analysis. Our results support theoretical predictions that time-frequency DSP procedures (especially DWT

  6. Animal Investigation Program: Nevada Test Site and Vicinity. Annual report, 1979

    International Nuclear Information System (INIS)

    Smith, D.D.; Giles, Jr.; Bernhardt, D.E.

    1981-05-01

    Data are presented from the radioanalyses of tissues collected from cattle, mule deer, desert bighorn sheep, rabbits, chukar, golden eagles, and other wildlife that resided on or near the Nevada Test Site during 1979. Routine and special activities of the Animal Investigation Program are also discussed. Other than the naturally occurring potassium-40, gamma-emitting radionuclides were detected infrequently. Strontium-90 concentrations in bones from deer, cattle, and desert bighorn sheep were lower than those of recent years. Tritium concentrations were generally within expected environmental limits with the exception of animals exposed to known sources of contamination; e.g., drainage ponds from Area 12 tunnels or the Sedan Crater. Plutonium levels in all tissues from all species showed little variation to those levels in samples collected in recent years. Radionuclide tissue concentrations were generally higher in the tissues of animals residing in Area 15 than in similar animals collected from other Nevada Test Site areas. Hypothetical annual dose estimates to man were calculated on the basis of the daily consumption of 0.5 kilogra of liver or muscle from animals that contained peak radionuclide levels. The movements of 25 mule deer outfitted with collars containing a radio transmitter unit were monitored on a weekly basis. No gross or microscopic lesions were found in necropsied animals that could be directly attributed to the effects of ionizing radiation

  7. Situational Judgment Tests in High-Stakes Settings: Issues and Strategies with Generating Alternate Forms

    Science.gov (United States)

    Lievens, Filip; Sackett, Paul R.

    2007-01-01

    This study used principles underlying item generation theory to posit competing perspectives about which features of situational judgment tests might enhance or impede consistent measurement across repeat test administrations. This led to 3 alternate-form development approaches (random assignment, incident isomorphism, and item isomorphism). The…

  8. 76 FR 5319 - Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline

    Science.gov (United States)

    2011-01-31

    ... producing gasoline are required to test Reformulated Gasoline (RFG), and conventional gasoline (CG) for... Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline AGENCY: Environmental... gasoline. This proposed rule will provide flexibility to the regulated community by allowing an additional...

  9. 76 FR 65382 - Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline

    Science.gov (United States)

    2011-10-21

    ... blenders producing gasoline are required to test Reformulated Gasoline (RFG), and conventional gasoline (CG... Regulation of Fuel and Fuel Additives: Alternative Test Method for Olefins in Gasoline AGENCY: Environmental... gasoline. This final rule will provide flexibility to the regulated community by allowing an additional...

  10. 76 FR 50221 - International Workshop on Alternative Methods for Human and Veterinary Rabies Vaccine Testing...

    Science.gov (United States)

    2011-08-12

    ... and Veterinary Rabies Vaccine Testing: State of the Science and Planning the Way Forward AGENCY... (NICEATM) announces an ``International Workshop on Alternative Methods for Human and Veterinary Rabies... rabies vaccine potency testing, and to develop an implementation strategy to achieve global acceptance...

  11. Effects of weak transcranial Alternating Current Stimulation on brain activity – a review of known mechanisms from animal studies

    Directory of Open Access Journals (Sweden)

    Davide eReato

    2013-10-01

    Full Text Available Rhythmic neuronal activity is ubiquitous in the human brain. These rhythms originate from a variety of different network mechanisms, which give rise to a wide-ranging spectrum of oscillation frequencies. In the last few years an increasing number of clinical research studies have explored transcranial alternating current stimulation (tACS with weak current as a tool for affecting brain function. The premise of these interventions is that tACS will interact with ongoing brain oscillations. However, the exact mechanisms by which weak currents could affect neuronal oscillations at different frequency bands are not well known and this, in turn, limits the rational optimization of human experiments. Here we review the available in vitro and in vivo animal studies that attempt to provide mechanistic explanations. The findings can be summarized into a few generic principles, such as periodic modulation of excitability, shifts in spike timing, modulation of firing rate, and shifts in the balance of excitation and inhibition. These effects result from weak but simultaneous polarization of a large number of neurons. Whether this can lead to an entrainment or a modulation of brain oscillations, or whether AC currents have no effect at all, depends entirely on the specific dynamic that gives rise to the different brain rhythms, as discussed here for slow wave oscillations (~1 Hz and gamma oscillations (~30 Hz. We conclude with suggestions for further experiments to investigate the role of AC stimulation for other physiologically relevant brain rhythms.

  12. Animal investigation program 1980 annual report: Nevada Test Site and vicinity

    International Nuclear Information System (INIS)

    Smith, D.D.; Bernhardt, D.E.; Giles, K.R.

    1982-07-01

    This report summarizes the data collected through the Animal Investigation Program during 1980. A major goal of the Program is to assess the radionuclide burden in the tissues of wild and domesticated animals around the Nevada Test Site and to detect pathological effects resulting from the burdens. Other than naturally occurring potassium-40, gamma emitting radionuclides were detected infrequently. Strontium-90 and plutonium concentrations in tissues from deer, cattle, and desert bighorn sheep were similar to those found in samples collected during recent years. Lesions found in necropsied animals were similar to those found in animals from other areas of the U.S. and would not be attributable to ionizing radiation exposure. The report also describes other activities of the program, including the deer migration study and census

  13. Report on the international workshop on alternative methods for human and veterinary rabies vaccine testing: state of the science and planning the way forward.

    Science.gov (United States)

    Stokes, William; McFarland, Richard; Kulpa-Eddy, Jodie; Gatewood, Donna; Levis, Robin; Halder, Marlies; Pulle, Gayle; Kojima, Hajime; Casey, Warren; Gaydamaka, Alexander; Miller, Timothy; Brown, Karen; Lewis, Charles; Chapsal, Jean-Michel; Bruckner, Lukas; Gairola, Sunil; Kamphuis, Elisabeth; Rupprecht, Charles E; Wunderli, Peter; McElhinney, Lorraine; De Mattia, Fabrizio; Gamoh, Koichiro; Hill, Richard; Reed, David; Doelling, Vivian; Johnson, Nelson; Allen, David; Rinckel, Lori; Jones, Brett

    2012-09-01

    Potency testing of most human and veterinary rabies vaccines requires vaccination of mice followed by a challenge test using an intracerebral injection of live rabies virus. NICEATM, ICCVAM, and their international partners organized a workshop to review the availability and validation status of alternative methods that might reduce, refine, or replace the use of animals for rabies vaccine potency testing, and to identify research and development efforts to further advance alternative methods. Workshop participants agreed that general anesthesia should be used for intracerebral virus injections and that humane endpoints should be used routinely as the basis for euthanizing animals when conducting the mouse rabies challenge test. Workshop participants recommended as a near-term priority replacement of the mouse challenge with a test validated to ensure potency, such as the mouse antibody serum neutralization test for adjuvanted veterinary rabies vaccines for which an international collaborative study was recently completed. The workshop recommended that an in vitro antigen quantification test should be a high priority for product-specific validation of human and non-adjuvanted veterinary rabies vaccines. Finally, workshop participants recommended greater international cooperation to expedite development, validation, regulatory acceptance, and implementation of alternative test methods for rabies vaccine potency testing. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

  14. Systematic evaluation of non-animal test methods for skin sensitisation safety assessment.

    Science.gov (United States)

    Reisinger, Kerstin; Hoffmann, Sebastian; Alépée, Nathalie; Ashikaga, Takao; Barroso, Joao; Elcombe, Cliff; Gellatly, Nicola; Galbiati, Valentina; Gibbs, Susan; Groux, Hervé; Hibatallah, Jalila; Keller, Donald; Kern, Petra; Klaric, Martina; Kolle, Susanne; Kuehnl, Jochen; Lambrechts, Nathalie; Lindstedt, Malin; Millet, Marion; Martinozzi-Teissier, Silvia; Natsch, Andreas; Petersohn, Dirk; Pike, Ian; Sakaguchi, Hitoshi; Schepky, Andreas; Tailhardat, Magalie; Templier, Marie; van Vliet, Erwin; Maxwell, Gavin

    2015-02-01

    The need for non-animal data to assess skin sensitisation properties of substances, especially cosmetics ingredients, has spawned the development of many in vitro methods. As it is widely believed that no single method can provide a solution, the Cosmetics Europe Skin Tolerance Task Force has defined a three-phase framework for the development of a non-animal testing strategy for skin sensitization potency prediction. The results of the first phase – systematic evaluation of 16 test methods – are presented here. This evaluation involved generation of data on a common set of ten substances in all methods and systematic collation of information including the level of standardisation, existing test data,potential for throughput, transferability and accessibility in cooperation with the test method developers.A workshop was held with the test method developers to review the outcome of this evaluation and to discuss the results. The evaluation informed the prioritisation of test methods for the next phase of the non-animal testing strategy development framework. Ultimately, the testing strategy – combined with bioavailability and skin metabolism data and exposure consideration – is envisaged to allow establishment of a data integration approach for skin sensitisation safety assessment of cosmetic ingredients.

  15. Animal investigation program 1978 annual report: Nevada Test Site and vicinity

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D D; Bernhardt, D E; Giles, K R

    1980-12-01

    Data are presented from the radioanalyses of tissues collected from cattle, mule deer, desert bighorn sheep, rabbits, golden eagles, and other wildlife that resided on or near the Nevada Test Site during 1978. Routine and special activities of the Animal Investigation Program are also discussed. Other than the naturally occurring Potassium-40, gamma-emitting radionuclides were detected infrequently with the exception of short-lived radionuclides found in samples from animals collected soon after March 14 (the date of a nuclear test by the People's Republic of China). Strontium-90 concentrations in bones from deer, cattle, and desert bighorn sheep were consistent with those of recent years. Tritium concentrations were generally within expected environmental limits with the exception of animals exposed to sources of contamination; e.g., drainage ponds from Area 12 tunnels. Plutonium levels in all tissues from all species showed little variation from recent years. However, cattle tissue sampled in the fall were higher than those collected in the spring. Radionuclide tissue concentrations were generally higher in the tissues of animals residing in Area 15 than in similar animals collected from other Nevada Test Site areas. Hypothetical dose estimates to man were calculated on the basis of the daily consumption of 0.5 kilogram of liver or muscle from animals that contained peak radionuclide levels. The movements of 13 mule deer outfitted with collars containing a radio transmitter unit were monitored on a weekly basis. No gross or microscopic lesions were found in necropsied animals that could be directly attributed to the effects of ionizing radiation.

  16. [Alternate form of the test de aprendizaje verbal España-Complutense (TAVEC)].

    Science.gov (United States)

    Nieto, Antonieta; Hernández-Rodríguez, Edith; Hernández-Torres, Atteneri; Velasco Rodríguez-Solís, Pedro; Hess-Medler, Stephany; Machado-Fernández, Alejandra; Molina-Rodríguez, Yaiza; Barroso, José

    2014-05-01

    Parallel forms of neuropsychological tests are scarce. Practice effects associated to repeated testing with the same test confound the interpretation of observed changes in serial assessments. Practice effects are especially likely with memory testing. To develop an alternate form to the test de aprendizaje verbal España-Complutense (TAVEC), one of the most common memory tests used for Spanish speaking population. Participants in the normative study were 110 undergraduates. Participants in the study of the alternate vs original forms were 70 neurologically normal volunteers ranged in age from 18 to 89 years. Forms were administered in counterbalanced order, with a test-retest interval of 15-20 days. Multivariate analyses showed that none of the effects for form, order of administration or session achieved significance. Interactions also failed to reach significance. Aforementioned results were observed in the total sample and the different age groups: young adults (18-29 years), middle-age (30-59 years) and older (60-89 years). Correlational analyses supported the validity and internal consistence of the alternate form. Results indicate the equivalence between the original TAVEC and the form elaborated in this study. This alternate form may be used in serial assessment of learning and memory deterioration.

  17. Earthworm avoidance test for soil assessments. An alternative for acute and reproduction tests

    Energy Technology Data Exchange (ETDEWEB)

    Hund-Rinke, K.; Wiechering, H. [Fraunhofer-Inst. fuer Umweltchemie und Oekotoxikologie, Schmallenberg (Germany)

    2001-07-01

    For ecotoxicological assessments of contaminated or remediated soils pointing to the habitat function of soils for biocenoses, standardized tests with earthworms (acute test, reproduction test) are available among others. Tests used for routine applications should be sensitive and indicate impacts on test organisms after short test periods. The usually applied earthworm tests do not satisfactorily fulfil these criteria. Therefore, in the present work, a behavioural test with earthworms (test criterion: avoidance) was investigated in detail using uncontaminated, artificially contaminated and originally contaminated soils. It was demonstrated that the avoidance behaviour is primarily determined by pollutants, and not by chemical-physical soil properties. The sensitivity of the presented test reaches the sensitivity of established tests. For waste sites, a considerably higher sensitivity was determined. An avoidance behaviour of at least 80% of the worms leaving the soil to be assessed is proposed as a criterion for toxicity. (orig.)

  18. A proposal for an alternative quality control test procedure for inactivated vaccines against food-and-mouth disease virus.

    Science.gov (United States)

    Molin-Capeti, K C; Sepulveda, L; Terra, F; Torres-Pioli, M F; Costa-Casagrande, T; França, S C; Thomaz-Soccol, V

    2013-02-18

    Foot-and-mouth disease (FMD) control in Brazil includes a strict mandatory vaccination program with vaccines produced in certified laboratories subject to inspection by the Brazilian Ministry of Agriculture, Livestock, and Food Supply (MAPA). The FMD vaccine's potency is tested through antibodies titration against structural viral proteins in sera from cattle that have not had any exposure to food-and-mouth disease virus (FMDV), at 28 days post-vaccination. Biological product testing using large animals is expensive and unwieldy. Thus, alternative testing procedures using laboratory animals have been proposed for quality control of these products. Such biological methods for vaccine evaluation using animals from vivarium facilities can have a significant impact through reduced costs, easier handling, and shorter testing times. The present study was designed to access Balb/C mice's humoral immune responses to a FMDV experimental vaccine, the composition of which contains three virus serotypes of FMDV (O1 Campos, A24 Cruzeiro, and C3 Indaial). Balb/C mice were immunized at doses that were 5% and 10% of the vaccine volume administered in cattle. Immunized mice had their antibody titers probed at 14, 21, and 28 DPV (days post vaccination). The results obtained were compared to those previously known from cattle's immune responses to the FMDV vaccine. An adequate immune response to the vaccine was seen with 10% formulation at 21 DPV. The study results are encouraging and indicate that the mouse model can be used for quality control in experimental vaccine testing. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  20. 40 CFR 160.90 - Animal and other test system care.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Animal and other test system care. 160.90 Section 160.90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE... clean. (i) If any pest control materials are used, the use shall be documented. Cleaning and pest...

  1. 40 CFR 792.90 - Animal and other test system care.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Animal and other test system care. 792.90 Section 792.90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC... clean. (i) If any pest control materials are used, the use shall be documented. Cleaning and pest...

  2. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods

    Directory of Open Access Journals (Sweden)

    Alistair Currie

    2011-11-01

    Full Text Available In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

  3. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

    Directory of Open Access Journals (Sweden)

    Boos Alois

    2006-08-01

    Full Text Available Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

  4. A novel implantable electromechanical ventricular assist device - First acute animal testing

    NARCIS (Netherlands)

    Kaufmann, R; Rakhorst, G; Mihaylov, D; Elstrodt, J; Nix, C; Reul, H; Rau, G

    1997-01-01

    A novel ventricular assist device (HIA-EMLVAD-AT1, Helmholtz Institute Aachen-electromechanical Left Ventricular Assist Device-Animal Test Version 1), driven by a uniformly and unidirectionally rotating actuator and a patented hypocycloidic pusherplate displacement gear unit, was developed and

  5. Bridging the Gap Between Validation and Implementation of Non-Animal Veterinary Vaccine Potency Testing Methods.

    Science.gov (United States)

    Dozier, Samantha; Brown, Jeffrey; Currie, Alistair

    2011-11-29

    In recent years, technologically advanced high-throughput techniques have been developed that replace, reduce or refine animal use in vaccine quality control tests. Following validation, these tests are slowly being accepted for use by international regulatory authorities. Because regulatory acceptance itself has not guaranteed that approved humane methods are adopted by manufacturers, various organizations have sought to foster the preferential use of validated non-animal methods by interfacing with industry and regulatory authorities. After noticing this gap between regulation and uptake by industry, we began developing a paradigm that seeks to narrow the gap and quicken implementation of new replacement, refinement or reduction guidance. A systematic analysis of our experience in promoting the transparent implementation of validated non-animal vaccine potency assays has led to the refinement of our paradigmatic process, presented here, by which interested parties can assess the local regulatory acceptance of methods that reduce animal use and integrate them into quality control testing protocols, or ensure the elimination of peripheral barriers to their use, particularly for potency and other tests carried out on production batches.

  6. GCSE Students' Attitudes to Dissection and Using Animals in Research and Product Testing.

    Science.gov (United States)

    Lock, Roger

    1995-01-01

    Questionnaires from students passing the General Certificate of Secondary Education (GCSE) that explored attitudes to dissection and using animals in product testing administered to (n=469) students ages 14-15 showed a high level of support for peers who object to dissection, although objectors are likely to be met with derogatory comments,…

  7. The current status of alternatives to animal testing and predictive toxicology methods using liver microfluidic biochips.

    Science.gov (United States)

    Prot, Jean Matthieu; Leclerc, Eric

    2012-06-01

    In this paper, we will consider new in vitro cell culture platforms and the progress made, based on the microfluidic liver biochips dedicated to pharmacological and toxicological studies. Particular emphasis will be given to recent developments in the microfluidic tools dedicated to cell culture (more particularly liver cell culture), in silico opportunities for Physiologically Based PharmacoKinetic (PBPK) modelling, the challenge of the mechanistic interpretations offered by the approaches resulting from "multi-omics" data (transcriptomics, proteomics, metabolomics, cytomics) and imaging microfluidic platforms. Finally, we will discuss the critical features regarding microfabrication, design and materials, and cell functionality as the key points for the future development of new microfluidic liver biochips.

  8. TCR-Vß8 as alternative to animal testing for quantifying active SEE

    Science.gov (United States)

    Staphylococcal food poisoning is a result of ingestion of Staphylococcal enterotoxins (SEs) produced by the bacterium Staphylococcus aureus. SEs cause gastroenteritis and also cause activation of T cells and massive cytokine release. A current method for the detection of active SEs relies on its eme...

  9. Investigation of thyroid parameters in farm animal by means of 125I in vitro tests

    International Nuclear Information System (INIS)

    Reinecke, P.; Leuthold, G.

    1988-01-01

    125 I in vitro tests especially thyroid hormone radioimmunoassays rendered it possible to study thyroidal activity of domestic animals even in large random tests. Parameters of thyroidal activity, such as effective T 4 quotient, T 3 value and total T 3 content, were investigated as to their connection to growth and environmental influence. The estimation of the hereditability yielded only low h 2 coefficients except in the T 3 value. All parameters studied depended to a great extent on farm conditions

  10. Economic potential of alternative land and natural resource uses at the Nevada Test Site, Nye County, Nevada

    International Nuclear Information System (INIS)

    Richard-Haggard, K.

    1983-03-01

    The economic potentials of several alternative land uses at the Nevada Test Site (NTS) are estimated. Alternatives considered include mining, agriculture, grazing, and hunting. There are two known tungsten ore bodies located in the Oak Spring mining district. The economic potential of the reserves is estimated to be $42,840. It is also possible that there are other economic mineral resources on the NTS whose values are yet unknown. There are an estimated 5000 ha of agricultural land on the Test Site; the cash value of alfalfa grown on this acreage is approximately $564,030. The economic potential of grazing at the Test Site lies somewhere in the range of $10,340 to $41,220. The assumed annual worth of mule deer to hunters is $90,440. The gross potential of hunting at the NTS is probably somewhat higher if trophy species, game birds and fur-bearing animals are also considered. It should be noted that the above values indicate gross worth; no costs are included in the estimates

  11. Alternative testing methods for skin sensitization: NMR spectroscopy for probing the reactivity and classification of potential skin sensitizers.

    Science.gov (United States)

    Chittiboyina, Amar G; Avonto, Cristina; Rua, Diego; Khan, Ikhlas A

    2015-09-21

    Evaluating consumer products for potentially harmful side effects of chemical ingredients is important for the protection of both the consumer and those involved in the manufacturing process. In order to assess the risk potential of chemicals, regulatory agencies have encouraged the development of several in silico, in vitro, and in chemico methods as alternatives to eliminate or minimize the use of animals. To add structural information to the existing in chemico methods, an NMR-based method is proposed for probing the reactivity and classification of the potential electrophiles (E) using a model thiol, DCYA, as a nucleophile. The major advantage of the NMR method is the quantitation of the actual adduct, DCYA-E. The degree of reaction is here provided as a direct measurement of adduct formation and/or electrophile depletion, in contrast to other in chemico assays, e.g., ADRA and DPRA, where the reactivity is inferred from the quantification of the test nucleophile depletion. Moreover, the developed NMR method should serve as a qualitative and quantitative tool in understanding the site of reaction and other structural information associated with test sensitizer. This is particularly valuable and advantageous over methods encouraged by regulatory agencies, which merely provide quantification of the reaction but lack any structural information. Several compounds with multiple reaction sites were successfully tested with the proposed NMR method. Otherwise, these compounds have proven to be a challenge to identify and classify using existing alternative methods.

  12. 75 FR 25867 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

    Science.gov (United States)

    2010-05-10

    ... Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing... alternative methods for vaccine potency and safety testing while ensuring the protection of human and animal... Challenge Testing Refinement Alternatives: Using Earlier Humane Endpoints to Avoid or Minimize Animal Pain...

  13. A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

    Science.gov (United States)

    Hooper, Patrick; Lasher, Jason; Alexander, Kenneth S; Baki, Gabriella

    2016-02-20

    Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Cost benefit and risk assessment for selected tank waste process testing alternatives

    International Nuclear Information System (INIS)

    Gasper, K.A.

    1995-01-01

    The US Department of Energy has established the Tank Waste Remediation System (TWRS) program to safely manage wastes currently stored in underground tank at the Hanford Site. A TWRS testing and development strategy was recently developed to define long-range TWRS testing plans. The testing and development strategy considered four alternatives. The primary variable in the alternatives is the level of pilot-scale testing involving actual waste. This study evaluates the cost benefit and risks associated with the four alternatives. Four types of risk were evaluated: programmatic schedule risk, process mishap risk, worker risk, and public health risk. The structure of this report is as follows: Section 1 introduces the report subject; Section 2 describes the test strategy alternative evaluation; Section 3 describes the approach used in this study to assess risk and cost benefit; Section 4 describes the assessment methodologies for costs and risks; Section 5 describes the bases and assumptions used to estimate the costs and risks; Section 6 presents the detailed costs and risks; and Section 7 describes the results of the cost benefit analysis and presents conclusions

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

    Science.gov (United States)

    Leist, Marcel; Hasiwa, Nina; Rovida, Costanza; Daneshian, Mardas; Basketter, David; Kimber, Ian; Clewell, Harvey; Gocht, Tilman; Goldberg, Alan; Busquet, Francois; Rossi, Anna-Maria; Schwarz, Michael; Stephens, Martin; Taalman, Rob; Knudsen, Thomas B; McKim, James; Harris, Georgina; Pamies, David; Hartung, Thomas

    2014-01-01

    Since March 2013, animal use for cosmetics testing for the European market has been banned. This requires a renewed view on risk assessment in this field. However, in other fields as well, traditional animal experimentation does not always satisfy requirements in safety testing, as the need for human-relevant information is ever increasing. A general strategy for animal-free test approaches was outlined by the US National Research Council`s vision document for Toxicity Testing in the 21st Century in 2007. It is now possible to provide a more defined roadmap on how to implement this vision for the four principal areas of systemic toxicity evaluation: repeat dose organ toxicity, carcinogenicity, reproductive toxicity and allergy induction (skin sensitization), as well as for the evaluation of toxicant metabolism (toxicokinetics) (Fig. 1). CAAT-Europe assembled experts from Europe, America and Asia to design a scientific roadmap for future risk assessment approaches and the outcome was then further discussed and refined in two consensus meetings with over 200 stakeholders. The key recommendations include: focusing on improving existing methods rather than favoring de novo design; combining hazard testing with toxicokinetics predictions; developing integrated test strategies; incorporating new high content endpoints to classical assays; evolving test validation procedures; promoting collaboration and data-sharing of different industrial sectors; integrating new disciplines, such as systems biology and high throughput screening; and involving regulators early on in the test development process. A focus on data quality, combined with increased attention to the scientific background of a test method, will be important drivers. Information from each test system should be mapped along adverse outcome pathways. Finally, quantitative information on all factors and key events will be fed into systems biology models that allow a probabilistic risk assessment with flexible

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

    Science.gov (United States)

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

    2011-06-01

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

  17. Possibilities of using alternative biotest tests on invertebrates in radiobiology - review

    International Nuclear Information System (INIS)

    Spalkova, M.; Benova, K.

    2017-01-01

    The effects of high doses of ionizing radiation have been described by many authors as on vertebrates, as well as on invertebrates. On the other hand, low doses of radiation can have positive effects (so-called radiation hormone). This process involves the activation of many processes, such as seed germination and growth of many plant species, enhancement of enzyme activity, stimulation of bacterial and isolated cell division, prolongation of life of plankton, drosophila, mice and rats exposed to long-term extremely low dose radiation, high doses (so-called adaptive response) and reduced mortality in human oncology patients. The rapid development of leading disciplines such as pharmacology, toxicology, immunology, virology, genetics and others brings a steep rise in animal consumption and legislation and legislation to protect them, with focus on reducing consumption and gradually replacing them with other methods. Within the framework of the European Convention on the protection of vertebrate animals for experimental and other scientific purposes, one of the main requirements is to limit the number of animal experiments to a minimum, whereas all live vertebrates, other than humans, are considered to be animals within the meaning of the 1986 Council of Europe Directive wild and breeding capable larvae, but not fruits or embryos. For this reason, alternative bioassays on invertebrates, plants, but also cell, tissue and organ cultures are increasingly being used. (authors)

  18. [Study on using the hen's egg test-chorioallantoic membrane as an alternative method of draize eye irritation test].

    Science.gov (United States)

    Liao, Yan; Wang, Xue; Zhang, Lishi; Li, Guanmin

    2004-05-01

    To establish and study the hen's egg test-chorioallantoic membrane (HET-CAM) as an alternative method of Draize eye irritation test (Draize test). 14 cosmetic ingredients were tested by the Hen's egg test-chorioallantoic membrane score (HET-CAM score) and the chorioallantoic membrane-trypan blue staining (CAM-TB) methods. Showed that compared with two kinds of scores in Draize test, i.e. Maximum average Draize total score (MAS) and score of 24 h after application (S24), the correlation coefficient between HET-CAM score and MAS or S24 was 0.847 or 0.779, while that between CAB-TB and MAS or S24 was 0.862 or 0.831 respectively. The results also showed that CAM-TB had a higher correlation with Draize test than HET-CAM score, partly because it is objective and quantitative. Also, the results showed that HET-CAM score had the greatest correlation with conjunctivae score of the three components, and so did the CAM-TB with corneal score. It is suggested that the two types of HET-CAM can be used in a combined manner as an effective alternative method to Draize test.

  19. Evaluation of the zebrafish embryo as an alternative model for hepatotoxicity testing

    NARCIS (Netherlands)

    Driessen, Marja

    2014-01-01

    In this thesis we showed the applicability of the zebrafish embryo as an alternative model for hepatotoxicity testing using analysis of mechanisms through toxicogenomics. By applying a variety of toxicogenomics techniques, we were able to characterize specific responses. NGS revealed that

  20. Alternate Form and Test-Retest Reliability of easyCBM Reading Measures. Technical Report # 0906

    Science.gov (United States)

    Alonzo, Julie; Tindal, Gerald

    2009-01-01

    We report the results of a test-retest and alternate form reliability study of grade 1, 3, 5, and 8 reading measures from the easyCBM assessment system. Approximately 50 students in each grade participated in the study. In Grade 1, we studied the following measures: Phoneme Segmenting, Letter Sounds, Letter Names, Word Reading Fluency, and Passage…

  1. Animal Testing in the Risk Society and Violation of the Principle of Equal Consideration of Interests

    Directory of Open Access Journals (Sweden)

    Rafael Speck de Souza

    2015-12-01

    Full Text Available This paper seeks to analyze the practice of animal testing under the paradigm of the Risk Society, Animal Rights, and in which point such research hurts the principle of equal consideration of like interests advocated by Peter Singer and other moral philosophers. On the one hand, this paper calls into question the attempt to transfer the results of an experiment with animals to reactions in humans, and the security criteria (or insecurity adopted by science. On the other hand, an evaluation is made of how much these animal models are considered speciesist practice, which does not take into account the interests of non-human sentient species (which are capable of suffering. The historical, comparative and deductive methods have been used in order to reach the intended goals. The sources of research used are mostly bibliographical: books, papers and journals. Theoretical references adopted were the risk society theory proposed by German sociologist Ulrich Beck and the animal ethics theory advocated by the Australian philosopher Peter Singer.

  2. What are the best animal models for testing early intervention in cerebral palsy?

    Directory of Open Access Journals (Sweden)

    Gavin John Clowry

    2014-12-01

    Full Text Available Interventions to treat cerebral palsy should be initiated as soon as possible in order to restore the nervous system to the correct developmental trajectory. One drawback to this approach is that interventions have to undergo exceptionally rigorous assessment for both safety and efficacy prior to use in infants. Part of this process should involve research using animals but how good are our animal models? Part of the problem is that cerebral palsy is an umbrella term that covers a number of conditions. There are also many causal pathways to cerebral palsy, such as periventricular white matter injury in premature babies, perinatal infarcts of the middle cerebral artery or generalised anoxia at the time of birth, indeed multiple causes, including intra-uterine infection or a genetic predisposition to infarction, may need to interact to produce a clinically significant injury. In this review we consider which animal models best reproduce certain aspects of the condition, and the extent to which the multifactorial nature of cerebral palsy has been modelled. The degree to which the corticospinal system of various animals models human corticospinal system function and development is also explored. Where attempts have already been made to test early intervention in animal models, the outcomes are evaluated in light of the suitability of the model.

  3. Conditional dependence between tests affects the diagnosis and surveillance of animal diseases

    DEFF Research Database (Denmark)

    Gardner, I.A.; Stryhn, Henrik; Lind, Peter

    2000-01-01

    Dependence between the sensitivities or specificities of pairs of tests affects the sensitivity and specificity of tests when used in combination. Compared with values expected if tests are conditionally independent, a positive dependence in test sensitivity reduces the sensitivity of parallel te...... for toxoplasmosis and brucellosis in swine, and Johne's disease in cattle to illustrate calculation methods and to indicate the likely magnitude of the dependence between serologic tests used for diagnosis and surveillance of animal diseases.......Dependence between the sensitivities or specificities of pairs of tests affects the sensitivity and specificity of tests when used in combination. Compared with values expected if tests are conditionally independent, a positive dependence in test sensitivity reduces the sensitivity of parallel test...... interpretation and a positive dependence in test specificity reduces the specificity of serial interpretation. We calculate conditional covariances as a measure of dependence between binary tests and show their relationship to kappa (a chance-corrected measure of test agreement). We use published data...

  4. Advantages of the experimental animal hollow organ mechanical testing system for the rat colon rupture pressure test.

    Science.gov (United States)

    Ji, Chengdong; Guo, Xuan; Li, Zhen; Qian, Shuwen; Zheng, Feng; Qin, Haiqing

    2013-01-01

    Many studies have been conducted on colorectal anastomotic leakage to reduce the incidence of anastomotic leakage. However, how to precisely determine if the bowel can withstand the pressure of a colorectal anastomosis experiment, which is called anastomotic bursting pressure, has not been determined. A task force developed the experimental animal hollow organ mechanical testing system to provide precise measurement of the maximum pressure that an anastomotic colon can withstand, and to compare it with the commonly used method such as the mercury and air bag pressure manometer in a rat colon rupture pressure test. Forty-five male Sprague-Dawley rats were randomly divided into the manual ball manometry (H) group, the tracing machine manometry pressure gauge head (MP) group, and the experimental animal hollow organ mechanical testing system (ME) group. The rats in each group were subjected to a cut colon rupture pressure test after injecting anesthesia in the tail vein. Colonic end-to-end anastomosis was performed, and the rats were rested for 1 week before anastomotic bursting pressure was determined by one of the three methods. No differences were observed between the normal colon rupture pressure and colonic anastomotic bursting pressure, which were determined using the three manometry methods. However, several advantages, such as reduction in errors, were identified in the ME group. Different types of manometry methods can be applied to the normal rat colon, but the colonic anastomotic bursting pressure test using the experimental animal hollow organ mechanical testing system is superior to traditional methods. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  5. Evaluation of serological tests for detecting tick-borne encephalitis virus (TBEV) antibodies in animals.

    Science.gov (United States)

    Klaus, Christine; Beer, Martin; Saier, Regine; Schubert, Harald; Bischoff, Sabine; Süss, Jochen

    2011-01-01

    Tick-borne encephalitis (TBE) in animals is not well understood yet. TBE virus (TBEV) serology in several host species could be valuable for epidemiological analyses in the field as well as for the detection of clinical cases. However, performance and suitability of the available test systems are not well assessed. Therefore, we evaluated two commercial TBEV-ELISA kits in a pilot study and compared them for their suitability in veterinary applications. For this purpose, we tested 163 field collected goat sera and evaluated the results by serum neutralization test (SNT) as "gold standard". Twenty-eight SNT positive sera (17.2%) were detected. The best suited ELISA kit was used for determination of a species-specific cutoff for horses, cattle, sheep, goats, pigs, mice, dogs, rabbits and monkeys with defined sera from animals without known or with improbable contact to TBEV. The level of non-specific ELISA results does not only differ between animal species but may also be influenced by the age of the tested animals. The number of sera which tested false positive by ELISA was higher in older than in young sheep. In order to obtain defined polyclonal sera as references, two dogs, cattle, goats, sheep, rabbits and pigs each, as well as one horse and 90 mice were immunized four times with a commercially available TBEV vaccine. In conclusion, our results demonstrated that commercial TBEV-ELISA kits are suitable for application in veterinary medicine for both, verification of clinical TBE cases and epidemiological screening. However, positive ELISA results should be verified by SNT. Only a very low number of false negative ELISA-results were found.

  6. Cartilage regeneration and repair testing in a surrogate large animal model.

    Science.gov (United States)

    Simon, Timothy M; Aberman, Harold M

    2010-02-01

    The aging human population is experiencing increasing numbers of symptoms related to its degenerative articular cartilage (AC), which has stimulated the investigation of methods to regenerate or repair AC. However, the seemingly inherent limited capacity for AC to regenerate persists to confound the various repair treatment strategies proposed or studied. Animal models for testing AC implant devices and reparative materials are an important and required part of the Food and Drug Administration approval process. Although final testing is ultimately performed in humans, animal testing allows for a wider range of parameters and combinations of test materials subjected to all the biological interactions of a living system. We review here considerations, evaluations, and experiences with selection and use of animal models and describe two untreated lesion models useful for testing AC repair strategies. These created lesion models, one deep (6 mm and through the subchondral plate) the other shallow (to the level of the subchondral bone plate) were placed in the middle one-third of the medial femoral condyle of the knee joints of goats. At 1-year neither the deep nor the shallow full-thickness chondral defects generated a repair that duplicated natural AC. Moreover, progressive deleterious changes occurred in the AC surrounding the defects. There are challenges in translation from animals to humans as anatomy and structures are different and immobilization to protect delicate repairs can be difficult. The tissues potentially generated by proposed cartilage repair strategies must be compared with the spontaneous changes that occur in similarly created untreated lesions. The prevention of the secondary changes in the surrounding cartilage and subchondral bone described in this article should be addressed with the introduction of treatments for repairs of the articulating surface.

  7. Pedicle Screw Fixation Study in Immature Porcine Spines to Improve Pullout Resistance during Animal Testing.

    Directory of Open Access Journals (Sweden)

    Sophie Le Cann

    Full Text Available The porcine model is frequently used during development and validation of new spinal devices, because of its likeness to the human spine. These spinal devices are frequently composed of pedicle screws with a reputation for stable fixation but which can suffer pullouts during preclinical implantation on young animals, leading to high morbidity. With a view to identifying the best choices to optimize pedicle screw fixation in the porcine model, this study evaluates ex vivo the impact of weight (age of the animal, the level of the vertebrae (lumbar or thoracic and the type of screw anchorage (mono- or bi-cortical on pedicle screw pullouts. Among the 80 pig vertebrae (90- and 140-day-old tested in this study, the average screw pullout forces ranged between 419.9N and 1341.2N. In addition, statistical differences were found between test groups, pointing out the influence of the three parameters stated above. We found that the the more caudally the screws are positioned (lumbar level, the greater their pullout resistance is, moreover, screw stability increases with the age, and finally, the screws implanted with a mono-cortical anchorage sustained lower pullout forces than those implanted with a bi-cortical anchorage. We conclude that the best anchorage can be obtained with older animals, using a lumbar fixation and long screws traversing the vertebra and inducing bi-cortical anchorage. In very young animals, pedicle screw fixations need to be bi-cortical and more numerous to prevent pullout.

  8. Pedicle Screw Fixation Study in Immature Porcine Spines to Improve Pullout Resistance during Animal Testing.

    Science.gov (United States)

    Le Cann, Sophie; Cachon, Thibaut; Viguier, Eric; Miladi, Lotfi; Odent, Thierry; Rossi, Jean-Marie; Chabrand, Patrick

    2015-01-01

    The porcine model is frequently used during development and validation of new spinal devices, because of its likeness to the human spine. These spinal devices are frequently composed of pedicle screws with a reputation for stable fixation but which can suffer pullouts during preclinical implantation on young animals, leading to high morbidity. With a view to identifying the best choices to optimize pedicle screw fixation in the porcine model, this study evaluates ex vivo the impact of weight (age) of the animal, the level of the vertebrae (lumbar or thoracic) and the type of screw anchorage (mono- or bi-cortical) on pedicle screw pullouts. Among the 80 pig vertebrae (90- and 140-day-old) tested in this study, the average screw pullout forces ranged between 419.9N and 1341.2N. In addition, statistical differences were found between test groups, pointing out the influence of the three parameters stated above. We found that the the more caudally the screws are positioned (lumbar level), the greater their pullout resistance is, moreover, screw stability increases with the age, and finally, the screws implanted with a mono-cortical anchorage sustained lower pullout forces than those implanted with a bi-cortical anchorage. We conclude that the best anchorage can be obtained with older animals, using a lumbar fixation and long screws traversing the vertebra and inducing bi-cortical anchorage. In very young animals, pedicle screw fixations need to be bi-cortical and more numerous to prevent pullout.

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

    Science.gov (United States)

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

    2016-10-01

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

  10. The Sequential Probability Ratio Test: An efficient alternative to exact binomial testing for Clean Water Act 303(d) evaluation.

    Science.gov (United States)

    Chen, Connie; Gribble, Matthew O; Bartroff, Jay; Bay, Steven M; Goldstein, Larry

    2017-05-01

    The United States's Clean Water Act stipulates in section 303(d) that states must identify impaired water bodies for which total maximum daily loads (TMDLs) of pollution inputs into water bodies are developed. Decision-making procedures about how to list, or delist, water bodies as impaired, or not, per Clean Water Act 303(d) differ across states. In states such as California, whether or not a particular monitoring sample suggests that water quality is impaired can be regarded as a binary outcome variable, and California's current regulatory framework invokes a version of the exact binomial test to consolidate evidence across samples and assess whether the overall water body complies with the Clean Water Act. Here, we contrast the performance of California's exact binomial test with one potential alternative, the Sequential Probability Ratio Test (SPRT). The SPRT uses a sequential testing framework, testing samples as they become available and evaluating evidence as it emerges, rather than measuring all the samples and calculating a test statistic at the end of the data collection process. Through simulations and theoretical derivations, we demonstrate that the SPRT on average requires fewer samples to be measured to have comparable Type I and Type II error rates as the current fixed-sample binomial test. Policymakers might consider efficient alternatives such as SPRT to current procedure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. LESSONS FROM A RETROSPECTIVE ANALYSIS OF A 5-YR PERIOD OF PRESHIPMENT TESTING AT SAN DIEGO ZOO: A RISK-BASED APPROACH TO PRESHIPMENT TESTING MAY BENEFIT ANIMAL WELFARE.

    Science.gov (United States)

    Marinkovich, Matt; Wallace, Chelsea; Morris, Pat J; Rideout, Bruce; Pye, Geoffrey W

    2016-03-01

    The preshipment examination, with associated transmissible disease testing, has become standard practice in the movement of animals between zoos. An alternative disease risk-based approach, based on a comprehensive surveillance program including necropsy and preventive medicine examination testing and data, has been in practice since 2006 between the San Diego Zoo and San Diego Zoo Safari Park. A retrospective analysis, evaluating comprehensive necropsy data and preshipment testing over a 5-yr study period, was performed to determine the viability of this model for use with sending animals to other institutions. Animals (607 birds, 704 reptiles and amphibians, and 341 mammals) were shipped to 116 Association of Zoos and Aquariums (AZA)-accredited and 29 non-AZA-accredited institutions. The evaluation showed no evidence of the specific transmissible diseases tested for during the preshipment exam being present within the San Diego Zoo collection. We suggest that a risk-based animal and institution-specific approach to transmissible disease preshipment testing is more cost effective and is in the better interest of animal welfare than the current industry standard of dogmatic preshipment testing.

  12. Detailed design, fabrication and testing of an engineering prototype compensated pulsed alternator. Final report

    International Nuclear Information System (INIS)

    Bird, W.L. Jr.; Woodson, H.H.

    1980-03-01

    The design, fabrication, and test results of a prototype compensated pulsed alternator are discussed. The prototype compulsator is a vertical shaft single phase alternator with a rotating armature and salient pole stator. The machine is designed for low rep rate pulsed duty and is sized to drive a modified 10 cm Beta amplifier. The load consists of sixteen 15 mm x 20 mm x 112 cm long xenon flashlamps connected in parallel. The prototype compulsator generates an open circuit voltage of 6 kV, 180 Hz, at a maximum design speed of 5400 rpm. At maximum speed, the inertial energy stored in the compulsator rotor is 3.4 megajoules

  13. Review of Evidence of Environmental Impacts of Animal Research and Testing

    OpenAIRE

    Katherine Groff; Eric Bachli; Molly Lansdowne; Theodora Capaldo

    2014-01-01

    Millions of animals are used in research and toxicity testing, including in drug, medical device, chemical, cosmetic, personal care, household, and other product sectors, but the environmental consequences are yet to be adequately addressed. Evidence suggests that their use and disposal, and the associated use of chemicals and supplies, contribute to pollution as well as adverse impacts on biodiversity and public health. The objective of this review is to examine such evidence. The review in...

  14. Alternative Forms of the Rey Auditory Verbal Learning Test: A Review

    Directory of Open Access Journals (Sweden)

    Keith A. Hawkins

    2004-01-01

    Full Text Available Practice effects in memory testing complicate the interpretation of score changes over repeated testings, particularly in clinical applications. Consequently, several alternative forms of the Auditory Verbal Learning Test (AVLT have been developed. Studies of these typically indicate that the forms examined are equivalent. However, the implication that the forms in the literature are interchangeable must be tempered by several caveats. Few studies of equivalence have been undertaken; most are restricted to the comparison of single pairs of forms, and the pairings vary across studies. These limitations are exacerbated by the minimal overlapping across studies in variables reported, or in the analyses of equivalence undertaken. The data generated by these studies are nonetheless valuable, as significant practice effects result from serial use of the same form. The available data on alternative AVLT forms are summarized, and recommendations regarding form development and the determination of form equivalence are offered.

  15. The Drosera Extract as an Alternative In Vitro Supplement to Animal Semen: Effects on Bovine Spermatozoa Activity and Oxidative Balance

    Directory of Open Access Journals (Sweden)

    Eva Tvrdá

    2015-05-01

    Full Text Available In vitro storage and processing of animal semen is considered to be a risk factor to spermatozoa activity, possibly leading to reduced fertility and litter sizes following artificial insemination (AI. A variety of substances isolated from natural resources have the potential to exhibit protective or antioxidant properties on the spermatozoon, thus they may extend the lifespan of stored semen. Drosera (Drosera rotundifolia L. has been shown to possess antimicrobial, anti-inflammatory and antioxidant properties, making the plant extract a potential candidate for preserving liquid animal semen during in vitro storage. This study compared the ability of different concentrations of Drosera extract on the motility, viability and superoxide production of bovine spermatozoa during different time periods (0, 2, 6, 12 and 24h of in vitro culture. Spermatozoa motility was assessed using the SpermVisionTM CASA (Computer aided sperm analysis system. Cell viability was examined using the metabolic activity MTT assay and the nitroblue-tetrazolium (NBT test was applied to quantify the intracellular superoxide formation. The CASA analysis revealed that Drosera extract supplementation was able to prevent a rapid decline of spermatozoa motility, especially in the case of concentrations ranging between 1 and 5 mg/mL (P<0.001 with respect to Times 6h, 12h and 24h. At the same time, concentrations ranging between 1 and 10 mg/mL of the extract led to a significant preservation of the cell viability throughout short-term (P<0.05 in case of Time 6h as well as long-term periods of the experiment (P<0.01 with respect to Time 12h, and P<0.001 in case of Time 24h. 10 and 5 mg/mL of the extract exhibited antioxidant characteristics, translated into a significant reduction of the intracellular superoxide production, particularly notable at Times 12h (P<0.01 and 24h (P<0.001. The results indicate that the Drosera extract is capable of delaying the damage inflicted to the

  16. Teaching Animal Physiology: A 12-Year Experience Transitioning from a Classical to Interactive Approach with Continual Assessment and Computer Alternatives

    Science.gov (United States)

    Kaisarevic, Sonja N.; Andric, Silvana A.; Kostic, Tatjana S.

    2017-01-01

    In response to the Bologna Declaration and contemporary trends in Animal Physiology education, the Animal Physiology course at the Faculty of Sciences, University of Novi Sad, Serbia, has evolved over a 12-year period (2001-2012): from a classical two-semester course toward a one-semester course utilizing computer simulations of animal…

  17. EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on the „Biomation‟ application for an alternative method for the treatment of animal-by-products

    DEFF Research Database (Denmark)

    Hald, Tine

    A method alternative to the ones already approved in the current legislation, called ‘Biomation’ process, for the treatment of Category (Cat.) 2 and 3 Animal By-Products (ABP) was assessed. The process consists of an alkaline treatment. The target parameters are: particle size ≤ 5mm, temperature 70...... the material under real scale conditions. Major deficiencies were noticed in the HACCP plan provided. It was concluded that there is no evidence that the proposed alternative method is equivalent to the sterilization process defined in the current legislation....

  18. A Possible Alternative Exercise Test for Youths with Cystic Fibrosis : The Steep Ramp Test

    NARCIS (Netherlands)

    Bongers, Bart C.; Werkman, Maarten S.; Arets, H. G. M.; Takken, Tim; Hulzebos, H. J.

    Purpose: The steep ramp test (SRT) can be used to provide an indication of exercise capacity when gas exchange measurements are not possible. This study evaluated the clinical usefulness of the SRT in adolescents with cystic fibrosis (CF) and compared the physiological responses of the SRT with the

  19. Validation of an automatic system (DoubleCage) for detecting the location of animals during preference tests.

    Science.gov (United States)

    Tsai, P P; Nagelschmidt, N; Kirchner, J; Stelzer, H D; Hackbarth, H

    2012-01-01

    Preference tests have often been performed for collecting information about animals' acceptance of environmental refinement objects. In numerous published studies animals were individually tested during preference experiments, as it is difficult to observe group-housed animals with an automatic system. Thus, videotaping is still the most favoured method for observing preferences of socially-housed animals. To reduce the observation workload and to be able to carry out preference testing of socially-housed animals, an automatic recording system (DoubleCage) was developed for determining the location of group-housed animals in a preference test set-up. This system is able to distinguish the transition of individual animals between two cages and to record up to 16 animals at the same time (four animals per cage). The present study evaluated the reliability of the DoubleCage system. The data recorded by the DoubleCage program and the data obtained by human observation were compared. The measurements of the DoubleCage system and manual observation of the videotapes are comparable and significantly correlated (P animals and a considerable reduction of animal observation time.

  20. Generalist predator, cyclic voles and cavity nests: testing the alternative prey hypothesis.

    Science.gov (United States)

    Pöysä, Hannu; Jalava, Kaisa; Paasivaara, Antti

    2016-12-01

    The alternative prey hypothesis (APH) states that when the density of the main prey declines, generalist predators switch to alternative prey and vice versa, meaning that predation pressure on the alternative prey should be negatively correlated with the density of the main prey. We tested the APH in a system comprising one generalist predator (pine marten, Martes martes), cyclic main prey (microtine voles, Microtus agrestis and Myodes glareolus) and alternative prey (cavity nests of common goldeneye, Bucephala clangula); pine marten is an important predator of both voles and common goldeneye nests. Specifically, we studied whether annual predation rate of real common goldeneye nests and experimental nests is negatively associated with fluctuation in the density of voles in four study areas in southern Finland in 2000-2011. Both vole density and nest predation rate varied considerably between years in all study areas. However, we did not find support for the hypothesis that vole dynamics indirectly affects predation rate of cavity nests in the way predicted by the APH. On the contrary, the probability of predation increased with vole spring abundance for both real and experimental nests. Furthermore, a crash in vole abundance from previous autumn to spring did not increase the probability of predation of real nests, although it increased that of experimental nests. We suggest that learned predation by pine marten individuals, coupled with efficient search image for cavities, overrides possible indirect positive effects of high vole density on the alternative prey in our study system.

  1. Test person operated 2-Alternative Forced Choice Audiometry compared to traditional audiometry

    DEFF Research Database (Denmark)

    Schmidt, Jesper Hvass; Brandt, Christian; Christensen-Dalsgaard, Jakob

      Background: With a newly developed technique, hearing thresholds can be estimated with a system operated by the test persons themselves. This technique is based on the 2 Alternative Forced Choice paradigm known from the psychoacoustic research theory. Test persons can operate the system very......-likelihood and up-down methods has proven effective and reliable even under suboptimal test settings. In non-optimal testing conditions i.e. as a part of a hearing conservation programme the headphone Sennheiser HDA-200 has been used as it contains hearing protection. This test-method has been validated...... as a comparison with traditional audiometry. A series of 30 persons (60 ears) have conducted traditional audiometry as well as self-operated 2AFC-audiometry. Test subjects are normal as well as moderately hearing impaired people. The different thresholds are compared.   Results: 2 AFC Audiometry is reliable...

  2. Animal investigation program 1975 annual report: Nevada Test Site and vicinity

    International Nuclear Information System (INIS)

    Smith, D.D.; Giles, K.R.; Bernhardt, D.E.; Brown, K.W.

    1978-02-01

    Data are presented from the radioanalysis of tissues collected from cattle, deer, desert bighorn sheep, and other wildlife that resided on or near the Nevada Test Site during 1975. Routine activities and special investigations of the Animal Investigation Program are also discussed. Other than the naturally occurring potassium-40, gamma-emitting radionuclides are detected infrequently. Tritium concentrations in the tissues from most of the animals sampled were at background levels. Strontium-90 levels in bones from deer and cattle were slightly lower than those reported for the preceding year while levels in desert bighorn sheep bones were elevated. A graph depicts the average levels found in the bones of the three species from 1956 through 1975. The gross and microscopic lesions found in necropsied animals are discussed. In general, these lesions are consistent with the physical condition of the animal and type of population sampled. No gross or microscopic lesions were detected that could be directly attributed to the effects of ionizing radiation

  3. Animal Investigation Program 1976 annual report: Nevada test site and vicinity

    International Nuclear Information System (INIS)

    Smith, D.D.; Giles, K.R.; Bernhardt, D.E.; Brown, K.W.

    1978-11-01

    Data are presented from the radioanalysis of tissues collected from cattle and mule deer, desert bighorn sheep, feral horses, and other wildlife that resided on or near the Nevada Test Site during 1976. Other than the naturally occurring potassium-40, gamma-emitting radionuclides were detected infrequently with the exception of 131 I in animal thyroid samples collected after September 25 (the date of a Chinese nuclear test). Strontium-90 concentrations in bones from deer, cattle, and desert bighorn sheep continued the downward trend of recent years. Tritium concentrations were generally within ambient limits with the exception of animals exposed to sources of contamination; e.g., Sedan Crater, drainage ponds from Area 12 tunnels, etc. Analysis of actinide in tissues was emphasized during 1976. Graphs illustrate the 239 P levels in lungs, livers, and femurs from Nevada Test Site beef cattle for the years 1971 through 1976. Femur and lung residue data are nearly identical for each year with liver concentrations being a factor of 2 or 3 lower. Hypothetical dose estimates to man were calculated on the basis of the daily consumption of 0.5 kilogram of liver or muscle from animals that contained peak actinide levels. The highest postulated dose was 11 millirem from tritium from tissues for a mule deer. This dose is about 2% of the 500 millirems/year guide for radiation doses to an individual in the general public. All other postulated doses for consumption of the tissue containing other radionuclides are less than 0.1% of this guide. The food habits of desert bighorn sheep were discussed according to the geographic locations of the animals at time of collection. Grasses made up approximately 60% of the diet at all locations, with shrubs content approaching 30%, and the remainder consisting of various forbs. The movement of 13 mule deer fitted with collars containing a radiotransmitter unit was monitored on a weekly basis

  4. Animal investigation program 1980 annual report: Nevada Test Site and vicinity

    International Nuclear Information System (INIS)

    Smith, D.D.; Giles, K.R.; Bernhardt, D.E.

    1982-08-01

    Data are presented from the radioanalyses of tissues collected from cattle, mule deer, desert bighorn sheep, rabbits, and a horse that resided on or near the Nevada Test Site during 1980. Routine and special activities of the Animal Investigation Program are also discussed. Other than the naturally occurring 40 K, gamma-emitting radionuclides were detected infrequently. 131 I was found in the thyroid of a deer 3 weeks after a nuclear test by the People's Republic of China. Concentrations of 90 Sr in bones from deer, cattle, and desert bighorn sheep were similar to those of recent years. Plutonium levels in all tissues from all species showed little variation from those levels in samples collected in recent years. Radionuclide concentrations were generally higher in the tissues of animals residing in Area 15 than in similar animals collected from other Nevada Test Site areas. Surface soil samples from the Area 15 farm contained 238 Pu and 239 Pu in nanocurie per kilogram concentrations. Hypothetical annual dose estimates to man were calculated on the basis of the daily consumption of 0.5 kilogram of liver or muscle from animals that contained peak radionuclide levels. The highest postulated dose was 0.4 millirems to whole body for 137 Cs in muscle obtained from cattle. This dose is about 0.1 percent of the 500 millirems per year radiation protection guide for individuals in the general population. All other postulated doses for consumption of tissues containing other radionuclides were less than 0.1 percent of the standard

  5. Risk-based testing of imported animals: A case study for bovine tuberculosis in The Netherlands.

    Science.gov (United States)

    de Vos, Clazien J; van der Goot, Jeanet A; van Zijderveld, Fred G; Swanenburg, Manon; Elbers, Armin R W

    2015-09-01

    In intra-EU trade, the health status of animals is warranted by issuing a health certificate after clinical inspection in the exporting country. This certificate cannot provide guarantee of absence of infection, especially not for diseases with a long incubation period and no overt clinical signs such as bovine tuberculosis (bTB). The Netherlands are officially free from bTB since 1999. However, frequent reintroductions occurred in the past 15 years through importation of infected cattle. Additional testing (AT) of imported cattle could enhance the probability of detecting an imported bTB infection in an early stage. The goal of this study was to evaluate the effectiveness of risk-based AT for bTB in cattle imported into The Netherlands. A generic stochastic import risk model was developed that simulates introduction of infection into an importing country through importation of live animals. Main output parameters are the number of infected animals that is imported (Ninf), the number of infected animals that is detected by testing (Ndet), and the economic losses incurred by importing infected animals (loss). The model was parameterized for bTB. Model calculations were optimized to either maximize Ndet or to minimize loss. Model results indicate that the risk of bTB introduction into The Netherlands is very high. For the current situation in which Dutch health checks on imported cattle are limited to a clinical inspection of a random sample of 5-10% of imported animals, the calculated annual Ninf=99 (median value). Random AT of 8% of all imported cattle results in Ndet=7 (median value), while the median Ndet=75 if the sampling strategy for AT is optimized to maximize Ndet. However, in the latter scenario, loss is more than twice as large as in the current situation, because only calves are tested for which cost of detection is higher than the expected gain of preventing a possible outbreak. When optimizing the sampling strategy for AT to minimize loss, only breeding

  6. USING COMPUTER-BASED TESTING AS ALTERNATIVE ASSESSMENT METHOD OF STUDENT LEARNING IN DISTANCE EDUCATION

    Directory of Open Access Journals (Sweden)

    Amalia SAPRIATI

    2010-04-01

    Full Text Available This paper addresses the use of computer-based testing in distance education, based on the experience of Universitas Terbuka (UT, Indonesia. Computer-based testing has been developed at UT for reasons of meeting the specific needs of distance students as the following: Ø students’ inability to sit for the scheduled test, Ø conflicting test schedules, and Ø students’ flexibility to take examination to improve their grades. In 2004, UT initiated a pilot project in the development of system and program for computer-based testing method. Then in 2005 and 2006 tryouts in the use of computer-based testing methods were conducted in 7 Regional Offices that were considered as having sufficient supporting recourses. The results of the tryouts revealed that students were enthusiastic in taking computer-based tests and they expected that the test method would be provided by UT as alternative to the traditional paper and pencil test method. UT then implemented computer-based testing method in 6 and 12 Regional Offices in 2007 and 2008 respectively. The computer-based testing was administered in the city of the designated Regional Office and was supervised by the Regional Office staff. The development of the computer-based testing was initiated with conducting tests using computers in networked configuration. The system has been continually improved, and it currently uses devices linked to the internet or the World Wide Web. The construction of the test involves the generation and selection of the test items from the item bank collection of the UT Examination Center. Thus the combination of the selected items compromises the test specification. Currently UT has offered 250 courses involving the use of computer-based testing. Students expect that more courses are offered with computer-based testing in Regional Offices within easy access by students.

  7. [The battery of tests for behavioral phenotyping of aging animals in the experiment].

    Science.gov (United States)

    Gorina, Ya V; Komleva, Yu K; Lopatina, O L; Volkova, V V; Chernykh, A I; Shabalova, A A; Semenchukov, A A; Olovyannikova, R Ya; Salmina, A B

    2017-01-01

    The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals. We found that aging male mice in a contrast to young ones have demonstrated lower social interest to female mice in the social recognition task. EPM and light-dark box tests showed increased level of anxiety in the group of aged mice comparing to the control group. Fear conditioning protocol revealed impairment of associative learning and memory in the group of aged mice, particularly, fear memory consolidation was dramatically suppressed. Analysis of behavioral factors, social interactions and anxiety level in the experimental mice has confirmed age-related neurodegeneration in the 1st group. We found that the most informative approach to identifying neurological impairments in aging mice (social interaction deficit, limitation of interests, increased level of anxiety) should be based on the open field test light-dark box test, and Fear conditioning protocol. Such combination allows obtaining new data on behavioral alterations in the age-associated of neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.

  8. Architecture optimization at IPEN animal facility in order to improve the welfare and the quality of the animals employed at radiopharmaceutical tests

    International Nuclear Information System (INIS)

    Lainetti, Elizabeth Brigagao de Faria; Nascimento, Nanci do; Passos, Luiz Augusto Correa

    2009-01-01

    The production and the issue of high quality laboratory animals are essentials for the accomplishment of vanguard scientific research, with reproducibility and universality. The quality of those animals depends, largely, of the available facilities for their production and lodging, to assure the demanded sanitary control and animals' well being, in agreement with the ethical principles that control the activity. The facilities also have to fill out other requirements, such as: the functionality of the environments to make possible the suitable and efficient handling of the animals, facilitating the execution of the routine activities; the respect to ergonomic principles to provide a safe environment and the operators' well being. The facilities design is of vital importance so that the mentioned requirements can be reached. The project of the Nuclear and Energy Research Institute (IPEN) Animal House Facilities was accomplished in the year of 1964. However, by that time there were not the current recommendations with respect to the sanitary, genetic and environmental controls. The facility was planned with the objective of being a production unit and a local for keeping of defined animals from sanitary, genetic and environmental point of view. Nevertheless, the original unit drawing presents an unsuitable distribution of the area where animals are stockpiled and different activities are performed. The Animal House Facilities occupies an area of 840 m 2 , with one pavement, where the production areas and the stock of original animal models of the own institution are distributed, as well as the maintenance of animals from other national or foreigner institutions. It supplies rats and mice for biological tests of radiopharmaceutical lots, produced in IPEN, before they be sent to hospitals and clinics spread out in Brazil, for use in Nuclear Medicine. It also supplies rats and mice for tests of odontologic materials, for tests with growth hormones and for researches of

  9. Building on a solid foundation: SAR and QSAR as a fundamental strategy to reduce animal testing.

    Science.gov (United States)

    Sullivan, K M; Manuppello, J R; Willett, C E

    2014-01-01

    The development of more efficient, ethical, and effective means of assessing the effects of chemicals on human health and the environment was a lifetime goal of Gilman Veith. His work has provided the foundation for the use of chemical structure for informing toxicological assessment by regulatory agencies the world over. Veith's scientific work influenced the early development of the SAR models in use today at the US Environmental Protection Agency. He was the driving force behind the Organisation for Economic Co-operation and Development QSAR Toolbox. Veith was one of a few early pioneers whose vision led to the linkage of chemical structure and biological activity as a means of predicting adverse apical outcomes (known as a mode of action, or an adverse outcome pathway approach), and he understood at an early stage the power that could be harnessed when combining computational and mechanistic biological approaches as a means of avoiding animal testing. Through the International QSAR Foundation he organized like-minded experts to develop non-animal methods and frameworks for the assessment of chemical hazard and risk for the benefit of public and environmental health. Avoiding animal testing was Gil's passion, and his work helped to initiate the paradigm shift in toxicology that is now rendering this feasible.

  10. TestSmart-high production volume chemicals: an approach to implementing alternatives into regulatory toxicology.

    Science.gov (United States)

    Green, S; Goldberg, A; Zurlo, J

    2001-09-01

    This article examines the status and application of alternatives defined as replacements, refinements, and reduction for screening high production volume (HPV) chemicals. It specifically focuses on the Screening Information Data Set (SIDS), a series of toxicological tests recommended by the Organization for Economic Cooperation and Development to screen such chemicals. Alternative tests associated with acute, repeat-dose, genetic, and reproductive and developmental toxicity were examined at 2 meetings of academic, industry, and regulatory scientists and their status determined. Tests were placed in 1 of 3 categories: ready for immediate use, in need of or currently undergoing validation, or needing research/developmental work. With respect to traditional acute toxicity testing, the basal cytotoxicity approach was placed in the category of research with the up-and-down, fixed-dose, limit test, and the acute toxic class categorized as available for immediate use and the neutral red assay under validation. Cell culture methods that could provide information on acute target organ toxicity were all categorized in the research stage. Studies of the Ah receptor were placed under validation. All alternative tests for repeat-dose toxicity were placed in the category of research. With regard to genetic toxicity, the Ames, mouse lymphoma, and Chinese hamster ovary methods were considered ready for immediate use, while the in vitro micronucleus and Syrian hamster ovary assays were placed in the validation category. All alternatives for developmental toxicity, with the exception of gene chip technology, were placed in the category of validation. Gene chip technology is considered to be in the research stage. For reproductive toxicity, sperm motility and morphology were considered as ready for immediate use, with the other assays categorized as needing validation or in the research stage. Follow-up to these results is obvious. Work needs to be conducted to move those tests from

  11. 21 CFR 312.160 - Drugs for investigational use in laboratory research animals or in vitro tests.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drugs for investigational use in laboratory research animals or in vitro tests. 312.160 Section 312.160 Food and Drugs FOOD AND DRUG ADMINISTRATION... Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests § 312.160 Drugs for...

  12. Evaluation of research activities and research needs to increase the impact and applicability of alternative testing strategies in risk assessment practice.

    Science.gov (United States)

    Punt, Ans; Schiffelers, Marie-Jeanne W A; Jean Horbach, G; van de Sandt, Johannes J M; Groothuis, Geny M M; Rietjens, Ivonne M C M; Blaauboer, Bas J

    2011-10-01

    The present paper aims at identifying strategies to increase the impact and applicability of alternative testing strategies in risk assessment. To this end, a quantitative and qualitative literature evaluation was performed on (a) current research efforts in the development of in vitro methods aiming for alternatives to animal testing, (b) the possibilities and limitations of in vitro methods for regulatory purposes and (c) the potential of physiologically-based kinetic (PBK) modeling to improve the impact and applicability of in vitro methods in risk assessment practice. Overall, the evaluation showed that the focus of state-of-the-art research activities does not seem to be optimally directed at developing in vitro alternatives for those endpoints that are most animal-demanding, such as reproductive and developmental toxicity, and carcinogenicity. A key limitation in the application of in vitro alternatives to such systemic endpoints is that in vitro methods do not provide so-called points of departure, necessary for regulators to set safe exposure limits. PBK-modeling could contribute to overcoming this limitation by providing a method that allows extrapolation of in vitro concentration-response curves to in vivo dose-response curves. However, more proofs of principle are required. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Food preference, keeper ratings, and reinforcer effectiveness in exotic animals: the value of systematic testing.

    Science.gov (United States)

    Gaalema, Diann E; Perdue, Bonnie M; Kelling, Angela S

    2011-01-01

    Food preference describes the behavior of selecting between items for consumption; reinforcer effectiveness is the functional effect of that item in controlling behavior. Food preference and reinforcer effectiveness were examined in giant pandas (Ailuropoda melanoleuca) and African elephants (Loxodonta africana). A pairwise comparison between food items was used to assess food preference. High-, moderate-, and low-preference items were selected and tested for reinforcer effectiveness. High-preference items controlled behavior more effectively than less-preferred items. Caregiver ratings of food preferences were also collected for each subject, but these reports did not necessarily coincide with actual subject preferences. Caregiver ratings correlated with the food preferences of only 1 individual of each species; thus, preferences of 1 nonhuman animal may be falsely generalized to all animals of that species. Results suggest that food choice and reinforcer effectiveness should be investigated empirically and not rely on anecdotal reports.

  14. Campylobacter species in animal, food, and environmental sources, and relevant testing programs in Canada.

    Science.gov (United States)

    Huang, Hongsheng; Brooks, Brian W; Lowman, Ruff; Carrillo, Catherine D

    2015-10-01

    Campylobacter species, particularly thermophilic campylobacters, have emerged as a leading cause of human foodborne gastroenteritis worldwide, with Campylobacter jejuni, Campylobacter coli, and Campylobacter lari responsible for the majority of human infections. Although most cases of campylobacteriosis are self-limiting, campylobacteriosis represents a significant public health burden. Human illness caused by infection with campylobacters has been reported across Canada since the early 1970s. Many studies have shown that dietary sources, including food, particularly raw poultry and other meat products, raw milk, and contaminated water, have contributed to outbreaks of campylobacteriosis in Canada. Campylobacter spp. have also been detected in a wide range of animal and environmental sources, including water, in Canada. The purpose of this article is to review (i) the prevalence of Campylobacter spp. in animals, food, and the environment, and (ii) the relevant testing programs in Canada with a focus on the potential links between campylobacters and human health in Canada.

  15. Testing of Early Ripening Strawberry Cultivars Tolerant to Soil-Borne Pathogens as Alternative to 'Elsanta'

    OpenAIRE

    Spornberger, Andreas; Steffek, Robert; Altenburger, Josef

    2007-01-01

    Soil-borne pathogens, above all Verticillium sp., cause plant loss and yield decrease in many Austrian strawberry regions. As part of a research project 13 cultivars were planted in 2005 at 11 sites on nine farms in five different Austrian regions. The aim was to test early ripening Verticillium tolerant cultivars which are winter hardy, with high yield and good fruit characteristics as alternative to the highly susceptible cultivar ‘Elsanta’. Although in 2005 climatic conditions where not fa...

  16. Development And Testing Of Biogas-Petrol Blend As An Alternative Fuel For Spark Ignition Engine

    Directory of Open Access Journals (Sweden)

    Awogbemi

    2015-08-01

    Full Text Available Abstract This research is on the development and testing of a biogas-petrol blend to run a spark ignition engine. A2080 ratio biogaspetrol blend was developed as an alternative fuel for spark ignition engine test bed. Petrol and biogas-petrol blend were comparatively tested on the test bed to determine the effectiveness of the fuels. The results of the tests showed that biogas petrol blend generated higher torque brake power indicated power brake thermal efficiency and brake mean effective pressure but lower fuel consumption and exhaust temperature than petrol. The research concluded that a spark ignition engine powered by biogas-petrol blend was found to be economical consumed less fuel and contributes to sanitation and production of fertilizer.

  17. A Modified Carbon Monoxide Breath Test for Measuring Erythrocyte Lifespan in Small Animals

    Directory of Open Access Journals (Sweden)

    Yong-Jian Ma

    2016-01-01

    Full Text Available This study was to develop a CO breath test for RBC lifespan estimation of small animals. The ribavirin induced hemolysis rabbit models were placed individually in a closed rebreath cage and air samples were collected for measurement of CO concentration. RBC lifespan was calculated from accumulated CO, blood volume, and hemoglobin concentration data. RBC lifespan was determined in the same animals with the standard biotin-labeling method. RBC lifespan data obtained by the CO breath test method for control (CON, 49.0±5.9 d rabbits, rabbits given 10 mg/kg·d−1 of ribavirin (RIB10, 31.0±4.0 d, and rabbits given 20 mg/kg·d−1 of ribavirin (RIB20, 25.0±2.9 d were statistically similar (all p>0.05 to and linearly correlated (r=0.96, p<0.01 with the RBC lifespan data obtained for the same rabbits by the standard biotin-labeling method (CON, 51.0±2.7 d; RIB10, 33.0±1.3 d; and RIB20, 27.0±0.8 d. The CO breath test method takes less than 3 h to complete, whereas the standard method requires at least several weeks. In conclusion, the CO breath test method provides a simple and rapid means of estimating RBC lifespan and is feasible for use with small animal models.

  18. Comparison of Nonculture Blood-Based Tests for Diagnosing Invasive Aspergillosis in an Animal Model.

    Science.gov (United States)

    White, P Lewis; Wiederhold, Nathan P; Loeffler, Juergen; Najvar, Laura K; Melchers, Willem; Herrera, Monica; Bretagne, Stephane; Wickes, Brian; Kirkpatrick, William R; Barnes, Rosemary A; Donnelly, J Peter; Patterson, Thomas F

    2016-04-01

    The EuropeanAspergillusPCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and β-d-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and β-d-glucan were 73%, 65%, 68%, and 46%, respectively. The corresponding specificities were 92%, 79%, 80%, and 100%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and β-d-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and β-d-glucan proved optimal (area under the curve [AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests. Copyright © 2016 White et al.

  19. The Role of Alternative Testing Strategies in Environmental Risk Assessment of Engineered Nanomaterials

    DEFF Research Database (Denmark)

    Hjorth, Rune; Holden, Patricia; Hansen, Steffen Foss

    2017-01-01

    ) workshop in Washington, D.C. and serves as the point of depature for this paper. Here we present the main outcomes by describing and defining the use of ATS for ENMs as well as discussing its future role in environmental risk science. We conclude that diversity in testing should be encouraged to avoid...... chemicals are challenged. Nonetheless, standardized whole organism animal testing is still considered the gold standard for environmental risk assessment. Advancing risk analysis of engineered nanomaterials (ENMs) through ATS was discussed in September 2014 at an international Society for Risk Analysis (SRA...... be utilized to skip uncertain environmental extrapolations and give rise to more accurate risk analysis....

  20. Construction of Three-Dimensional Dermo-Epidermal Skin Equivalents Using Cell Coating Technology and Their Utilization as Alternative Skin for Permeation Studies and Skin Irritation Tests.

    Science.gov (United States)

    Akagi, Takami; Nagura, Mayuka; Hiura, Ayami; Kojima, Hajime; Akashi, Mitsuru

    2017-06-01

    In vitro generated human skin equivalents are generating interest as promising tools in basic study, as alternatives to animal testing, and for clinical applications in regenerative medicine. For prediction of skin irritation and corrosion, three-dimensional human skin equivalents consisting of differentiated human keratinocytes (KCs) have been developed and some models have been internationally accepted. However, more delicate assessments using full-thickness skin models, such as skin sensitization tests, cannot be performed due to the lack of a dermis containing fibroblasts or appendages. In a previous study, we developed dermo-epidermal human skin equivalents (DESEs) using a cell coating technique, which employs cell surface coating by layer-by-layer assembled extracellular matrix (ECM) films. The DESEs with dermis consisting of normal human dermal fibroblasts (NHDFs) and epidermis consisting of human KCs were easily fabricated by using this technology. In this study, the constructed DESEs were evaluated as an alternative skin for skin permeation and irritation tests. A good relationship of permeability coefficient of chemicals was observed between the DESEs and human skin data. We investigated whether the DESEs, a new in vitro skin model, are capable of identifying skin irritant and nonirritant substances among 20 reference chemicals. It was confirmed that the DESEs are applicable to skin irritation testing as defined in the European Centre for the Validation of Alternative Methods (ECVAM) Performance Standard (OECD Test Guideline 439). We further studied the construction of DESEs with density-controlled blood capillary networks using human umbilical vein endothelial cells (HUVECs). The results suggest that DESEs allowing incorporation of skin appendages are more promising alternatives to animal testing and can be applied to the design of physiologically relevant in vitro skin models.

  1. Animal Investigation Program 1973 annual report: Nevada Test Site and vicinity

    International Nuclear Information System (INIS)

    Smith, D.D.; Giles, K.R.; Bernhardt, D.E.

    1977-05-01

    Data are presented from the radioanalysis of tissues collected from cattle, deer, desert bighorn sheep, and other wildlife that resided on or near the Nevada Test Site during 1973. Routine activities and special investigations are discussed. Iodine-131 was detected in the thyroid of a Nevada Test Site mule deer. The postulated source was worldwide fallout from a nuclear detonation conducted by the People's Republic of China. Other than the naturally occurring potassium-40, cesium-137 was the only gamma-emitting radionuclide detected with any consistency in soft tissues. Nine muscle samples from the Nevada Test Site beef herd contained levels of cesium-137 ranging from 14 to 50 pCi/kilogram. Muscle from two deer contained 20 and 30 pCi/kilogram. Rabbit muscle contained 200 pCi/kilogram and muscle from a feral horse contained 40 pCi/kilogram. Tritium levels in all animal tissues sampled were at background except for animals residing at the Area 15 farm and for a feral horse. Postulated sources of these exposures are discussed. The strontium content in bones continued the downward trend observed during recent years

  2. Reduction of animal suffering in rabies vaccine potency testing by introduction of humane endpoints.

    Science.gov (United States)

    Takayama-Ito, Mutsuyo; Lim, Chang-Kweng; Nakamichi, Kazuo; Kakiuchi, Satsuki; Horiya, Madoka; Posadas-Herrera, Guillermo; Kurane, Ichiro; Saijo, Masayuki

    2017-03-01

    Potency controls of inactivated rabies vaccines for human use are confirmed by the National Institutes of Health challenge test in which lethal infection with severe neurological symptoms should be observed in approximately half of the mice inoculated with the rabies virus. Weight loss, decreased body temperature, and the presence of rabies-associated neurological signs have been proposed as humane endpoints. The potential for reduction of animal suffering by introducing humane endpoints in the potency test for inactivated rabies vaccine for human use was investigated. The clinical signs were scored and body weight was monitored. The average times to death following inoculation were 10.49 and 10.99 days post-inoculation (dpi) by the potency and challenge control tests, respectively, whereas the average times to showing Score-2 signs (paralysis, trembling, and coma) were 6.26 and 6.55 dpi, respectively. Body weight loss of more than 15% appeared at 5.82 and 6.42 dpi. The data provided here support the introduction of obvious neuronal signs combined with a body weight loss of ≥15% as a humane endpoint to reduce the time of animal suffering by approximately 4 days. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  3. Anticoccidial efficacy testing: In vitro Eimeria tenella assays as replacement for animal experiments.

    Science.gov (United States)

    Thabet, Ahmed; Zhang, Runhui; Alnassan, Alaa-Aldin; Daugschies, Arwid; Bangoura, Berit

    2017-01-15

    Availability of an accurate in vitro assay is a crucial demand to determine sensitivity of Eimeria spp. field strains toward anticoccidials routinely. In this study we tested in vitro models of Eimeria tenella using various polyether ionophores (monensin, salinomycin, maduramicin, and lasalocid) and toltrazuril. Minimum inhibitory concentrations (MIC 95 , MIC 50/95 ) for the tested anticoccidials were defined based on a susceptible reference (Houghton strain), Ref-1. In vitro sporozoite invasion inhibition assay (SIA) and reproduction inhibition assay (RIA) were applied on sensitive laboratory (Ref-1 and Ref-2) and field (FS-1, FS-2, and FS-3) strains to calculate percent of inhibition under exposure of these strains to the various anticoccidials (%I SIA and%I RIA, respectively). The in vitro data were related to oocyst excretion, lesion scores, performance, and global resistance indices (GI) assessed in experimentally infected chickens. Polyether ionophores applied in the RIA were highly effective at MIC 95 against Ref-1 and Ref-2 (%I RIA ≥95%). In contrast, all tested field strains displayed reduced to low efficacy (%I RIA animal model (p89%) against all strains used in this study. However, adjusted GI (GI adj ) for toltrazuril-treated groups exhibited differences between reference and field strains which might indicate varying sensitivity. RIA is a suitable in vitro tool to detect sensitivity of E. tenella towards polyether ionophores, and may thus help to reduce, replace, or refine use of animal experimentation for in vivo sensitivity assays. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. A Modified Jonckheere Test Statistic for Ordered Alternatives in Repeated Measures Design

    Directory of Open Access Journals (Sweden)

    Hatice Tül Kübra AKDUR

    2016-09-01

    Full Text Available In this article, a new test based on Jonckheere test [1] for  randomized blocks which have dependent observations within block is presented. A weighted sum for each block statistic rather than the unweighted sum proposed by Jonckheereis included. For Jonckheere type statistics, the main assumption is independency of observations within block. In the case of repeated measures design, the assumption of independence is violated. The weighted Jonckheere type statistic for the situation of dependence for different variance-covariance structure and the situation based on ordered alternative hypothesis structure of each block on the design is used. Also, the proposed statistic is compared to the existing test based on Jonckheere in terms of type I error rates by performing Monte Carlo simulation. For the strong correlations, circular bootstrap version of the proposed Jonckheere test provides lower rates of type I error.

  5. The effect of alternative permutation testing strategies on the performance of multifactor dimensionality reduction

    Directory of Open Access Journals (Sweden)

    Motsinger-Reif Alison A

    2008-12-01

    Full Text Available Abstract Background Multifactor Dimensionality Reduction (MDR is a novel method developed to detect gene-gene interactions in case-control association analysis by exhaustively searching multi-locus combinations. While the end-goal of analysis is hypothesis generation, significance testing is employed to indicate statistical interest in a resulting model. Because the underlying distribution for the null hypothesis of no association is unknown, non-parametric permutation testing is used. Lately, there has been more emphasis on selecting all statistically significant models at the end of MDR analysis in order to avoid missing a true signal. This approach opens up questions about the permutation testing procedure. Traditionally omnibus permutation testing is used, where one permutation distribution is generated for all models. An alternative is n-locus permutation testing, where a separate distribution is created for each n-level of interaction tested. Findings In this study, we show that the false positive rate for the MDR method is at or below a selected alpha level, and demonstrate the conservative nature of omnibus testing. We compare the power and false positive rates of both permutation approaches and find omnibus permutation testing optimal for preserving power while protecting against false positives. Conclusion Omnibus permutation testing should be used with the MDR method.

  6. The effect of alternative permutation testing strategies on the performance of multifactor dimensionality reduction

    Science.gov (United States)

    Motsinger-Reif, Alison A

    2008-01-01

    Background Multifactor Dimensionality Reduction (MDR) is a novel method developed to detect gene-gene interactions in case-control association analysis by exhaustively searching multi-locus combinations. While the end-goal of analysis is hypothesis generation, significance testing is employed to indicate statistical interest in a resulting model. Because the underlying distribution for the null hypothesis of no association is unknown, non-parametric permutation testing is used. Lately, there has been more emphasis on selecting all statistically significant models at the end of MDR analysis in order to avoid missing a true signal. This approach opens up questions about the permutation testing procedure. Traditionally omnibus permutation testing is used, where one permutation distribution is generated for all models. An alternative is n-locus permutation testing, where a separate distribution is created for each n-level of interaction tested. Findings In this study, we show that the false positive rate for the MDR method is at or below a selected alpha level, and demonstrate the conservative nature of omnibus testing. We compare the power and false positive rates of both permutation approaches and find omnibus permutation testing optimal for preserving power while protecting against false positives. Conclusion Omnibus permutation testing should be used with the MDR method. PMID:19116021

  7. The effect of alternative permutation testing strategies on the performance of multifactor dimensionality reduction.

    Science.gov (United States)

    Motsinger-Reif, Alison A

    2008-12-30

    Multifactor Dimensionality Reduction (MDR) is a novel method developed to detect gene-gene interactions in case-control association analysis by exhaustively searching multi-locus combinations. While the end-goal of analysis is hypothesis generation, significance testing is employed to indicate statistical interest in a resulting model. Because the underlying distribution for the null hypothesis of no association is unknown, non-parametric permutation testing is used. Lately, there has been more emphasis on selecting all statistically significant models at the end of MDR analysis in order to avoid missing a true signal. This approach opens up questions about the permutation testing procedure. Traditionally omnibus permutation testing is used, where one permutation distribution is generated for all models. An alternative is n-locus permutation testing, where a separate distribution is created for each n-level of interaction tested. In this study, we show that the false positive rate for the MDR method is at or below a selected alpha level, and demonstrate the conservative nature of omnibus testing. We compare the power and false positive rates of both permutation approaches and find omnibus permutation testing optimal for preserving power while protecting against false positives. Omnibus permutation testing should be used with the MDR method.

  8. Alternative approaches to vertebrate ecotoxicity tests in the 21st century: A review of developments over the last 2 decades and current status

    Science.gov (United States)

    Lillicrap, Adam; Belanger, Scott; Burden, Natalie; Du Pasquier, David; Embry, Michelle; Halder, Marlies; Lampi, Mark; Lee, Lucy; Norberg-King, Teresa J.; Rattner, Barnett A.; Schirmer, Kristin; Thomas, Paul

    2016-01-01

    The need for alternative approaches to the use of vertebrate animals for hazard assessment of chemicals and pollutants has become of increasing importance. It is now the first consideration when initiating a vertebrate ecotoxicity test, to ensure that unnecessary use of vertebrate organisms is minimized wherever possible. For some regulatory purposes, the use of vertebrate organisms for environmental risk assessments has been banned; in other situations, the number of organisms tested has been dramatically reduced or the severity of the procedure refined. However, there is still a long way to go to achieve a complete replacement of vertebrate organisms to generate environmental hazard data. The development of animal alternatives is based not just on ethical considerations but also on reducing the cost of performing vertebrate ecotoxicity tests and in some cases on providing better information aimed at improving environmental risk assessments. The present Focus article provides an overview of the considerable advances that have been made toward alternative approaches for ecotoxicity assessments over the last few decades.

  9. 16 CFR 1610.40 - Use of alternate apparatus, procedures, or criteria for tests for guaranty purposes.

    Science.gov (United States)

    2010-01-01

    ... with apparatus or procedures other than those in Subpart A of this part to serve as the basis for... its requirements may base those guaranties on any alternate test utilizing apparatus or procedures... of this part. Any person using such an alternate test must have data or information to demonstrate...

  10. 78 FR 37463 - Expedited Approval of Alternative Test Procedures for the Analysis of Contaminants Under the Safe...

    Science.gov (United States)

    2013-06-21

    ... Titration. Amperometric 4500-ClO2 E 4500-ClO2 E Titration. Ozone Indigo Method....... 4500-O3 B 4500-O3 B... Titration. 141.132(b)(2)(i)(A). Alternative Testing Methods for Disinfectant Residuals Listed at 40 CFR 141... page 32570, with the table entitled ``ALTERNATIVE TESTING METHODS FOR CONTAMINANTS LISTED AT 40 CFR 141...

  11. Development of a non-engine fuel injector deposit test for alternative fuels (ENIAK-project)

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Hajo; Pohland vom Schloss, Heide [OWI - Oel Waerme Institut GmbH, Herzogenrath (Germany)

    2013-06-01

    Deposit formation in and on the injectors of diesel engines may lead to injector malfunction, resulting in a loss in power, rough engine operation and poor emission levels. Poor Biodiesel quality, contamination with copper and zinc as well as undesired reactions between (several) additives and biodiesel components are known causes for nozzle fouling. Therefore, good housekeeping when using biodiesel is required, and all additives have to pass a no-harm test concerning injector fouling. The standard fouling tests are two engine tests: The XUD9-test (CEC F-23-01) and the DW-10-test (CEC DF 98-08). The XUD9 is a cost efficient, fast and proven testing method. It uses, however, an obsolete indirect injection diesel engine and cannot reproduce internal diesel injector deposits (IDID). The newer DW10 test is complex, costly and designed for high stress. This reduces the engine life and leads to a fuel consumption of approximately 1,000 1 per test, both contributing to the high costs of the test. The ENIAK-Project is funded by the FNR (''Fachagentur Nachwachsende Rohstoffe'', Agency for Renewable Resources) and conducted in cooperation with AGQM, ASG and ERC. Its main goal is the development, assembly, commissioning, and evaluation of a non-engine fuel injector test. It uses a complete common rail system. The injection takes place in a self-designed reactor instead of an engine, and the fuel is not combusted, but re-condensed and pumped in a circle, leading to a low amount of fuel required. If the test method proves to be as reliable as expected, it can be used as an alternative test method for injector fouling with low requirements regarding infrastructure on the testing site and sample volume. (orig.)

  12. Results of the Alternative Water Processor Test, A Novel Technology for Exploration Wastewater Remediation

    Science.gov (United States)

    Vega, Leticia; Meyer, Caitlin

    2016-01-01

    Biologically-based water recovery systems are a regenerative, low energy alternative to physiochemical processes to reclaim water from wastewater. This paper summarizes the results of the Alternative Water Processor (AWP) test conducted over one year. The AWP recovered 90% of water from four crewmembers using (4) membrane aerated bioreactors (MABRs) to remove carbon and nitrogen from an exploration mission wastewater, including urine, hygiene, laundry and humidity condensate. Downstream, a coupled forward and reverse osmosis system removed large organics and inorganic salts from the biological system effluent. The system exceeded the overall objectives of the test by recovering 90% of the influent wastewater processed and a 29% reduction of consumables from the current state of the art water recovery system on the International Space Station (ISS). However the biological system fell short of its test goals, failing to remove 75% and 90% of the influent ammonium and organic carbon, respectively. Despite not meeting its test goals, the BWP demonstrated the feasibility of an attached-growth biological system for simultaneous nitrification and denitrification, an innovative, volume and consumable-saving design that doesn't require toxic pretreatment. This paper will explain the reasons for this and will discuss steps to optimize each subsystem to increase effluent quality from the MABRs and the FOST to advance the system.

  13. Results of the Alternative Water Processor Test, A Novel Technology for Exploration Wastewater Remediation

    Science.gov (United States)

    Meyer, Caitlin E.; Pensinger, Stuart; Adam, Niklas; Pickering, Karen D.; Barta, Daniel; Shull, Sarah A.; Vega, Leticia M.; Lange, Kevin; Christenson, Dylan; Jackson, W. Andrew

    2016-01-01

    Biologically-based water recovery systems are a regenerative, low energy alternative to physiochemical processes to reclaim water from wastewater. This report summarizes the results of the Alternative Water Processor (AWP) Integrated Test, conducted from June 2013 until April 2014. The system was comprised of four (4) membrane aerated bioreactors (MABRs) to remove carbon and nitrogen from an exploration mission wastewater and a coupled forward and reverse osmosis system to remove large organic and inorganic salts from the biological system effluent. The system exceeded the overall objectives of the test by recovering 90% of the influent wastewater processed into a near potable state and a 64% reduction of consumables from the current state of the art water recovery system on the International Space Station (ISS). However, the biological system fell short of its test goals, failing to remove 75% and 90% of the influent ammonium and organic carbon, respectively. Despite not meeting its test goals, the BWP demonstrated the feasibility of an attached-growth biological system for simultaneous nitrification and denitrification, an innovative, volume- and consumable-saving design that does not require toxic pretreatment.

  14. Bridging the Gap of Standardized Animals Models for Blast Neurotrauma: Methodology for Appropriate Experimental Testing.

    Science.gov (United States)

    VandeVord, Pamela J; Leonardi, Alessandra Dal Cengio; Ritzel, David

    2016-01-01

    Recent military combat has heightened awareness to the complexity of blast-related traumatic brain injuries (bTBI). Experiments using animal, cadaver, or biofidelic physical models remain the primary measures to investigate injury biomechanics as well as validate computational simulations, medical diagnostics and therapies, or protection technologies. However, blast injury research has seen a range of irregular and inconsistent experimental methods for simulating blast insults generating results which may be misleading, cannot be cross-correlated between laboratories, or referenced to any standard for exposure. Both the US Army Medical Research and Materiel Command and the National Institutes of Health have noted that there is a lack of standardized preclinical models of TBI. It is recommended that the blast injury research community converge on a consistent set of experimental procedures and reporting of blast test conditions. This chapter describes the blast conditions which can be recreated within a laboratory setting and methodology for testing in vivo models within the appropriate environment.

  15. Animal model for the comparison of 13C-with 14C-breath test

    International Nuclear Information System (INIS)

    Sasaki, Y.; Oh-hara, H.; Maeda, T.; Someya, K.; Sano, M.

    1975-01-01

    As a preliminary study prior to the clinical application of a 13 C-breath test, an animal experiment using the rat was carried out for the comparison of 14 CO 2 and 13 CO 2 excretion after administration of 14 C- and 13 C-compounds. Under pentobarbital anesthesia, the trachea of male rats of Wister strain was cannulated and the cannula was connected to a Harvard rodent respirator. After the animal woke up, muscle relaxant was administered and the respiration was kept under control. Vials were attached to the outlet of the respirator and CO 2 in the exhaled breath was collected by the neutralization of the alkaline solution. 14 C and 13 C specific activity in exhaled CO 2 was measured in a liquid scintillation counter and a mass spectrometer, respectively. Excretion of 14 CO 2 and 13 CO 2 after simultaneous administration (i.v. and p.o.) of 14 C- and 13 C-1-glycine was identical. Serial administration of 13 C-glycine and then 14 C-glycine 120 minutes later suggests the possibility that the trace dose of 14 C-compounds and loading dose of 13 C-compounds may cause different results in the breath test

  16. Alternatives toIn VivoDraize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models.

    Science.gov (United States)

    Lee, Miri; Hwang, Jee-Hyun; Lim, Kyung-Min

    2017-07-01

    Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility.

  17. Alternatives to In Vivo Draize Rabbit Eye and Skin Irritation Tests with a Focus on 3D Reconstructed Human Cornea-Like Epithelium and Epidermis Models

    Science.gov (United States)

    Lee, Miri; Hwang, Jee-Hyun; Lim, Kyung-Min

    2017-01-01

    Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornea-like epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility. PMID:28744350

  18. Towards the development of improved tests for negative symptoms of schizophrenia in a validated animal model.

    Science.gov (United States)

    Sahin, Ceren; Doostdar, Nazanin; Neill, Joanna C

    2016-10-01

    Negative symptoms in schizophrenia remain an unmet clinical need. There is no licensed treatment specifically for this debilitating aspect of the disorder and effect sizes of new therapies are too small to make an impact on quality of life and function. Negative symptoms are multifactorial but often considered in terms of two domains, expressive deficit incorporating blunted affect and poverty of speech and avolition incorporating asociality and lack of drive. There is a clear need for improved understanding of the neurobiology of negative symptoms which can be enabled through the use of carefully validated animal models. While there are several tests for assessing sociability in animals, tests for blunted affect in schizophrenia are currently lacking. Two paradigms have recently been developed for assessing negative affect of relevance to depression in rats. Here we assess their utility for studying negative symptoms in schizophrenia using our well validated model for schizophrenia of sub-chronic (sc) treatment with Phencyclidine (PCP) in adult female rats. Results demonstrate that sc PCP treatment produces a significant negative affect bias in response to a high value reward in the optimistic and affective bias tests. Our results are not easily explained by the known cognitive deficits induced by sc PCP and support the hypothesis of a negative affective bias in this model. We suggest that further refinement of these two tests will provide a means to investigate the neurobiological basis of negative affect in schizophrenia, thus supporting the assessment of efficacy of new targets for this currently untreated symptom domain. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Alternative procedure for the cold test for soybean seeds Procedimento alternativo para o teste de frio em semente de soja

    Directory of Open Access Journals (Sweden)

    Bruno Guilherme Torres Licursi Vieira

    2010-10-01

    Full Text Available The growing demand for high quality soybean [Glycine max (L. Merrill] seeds requires a precise seed quality control system from the seed industry. One way to accomplish this is by improving vigor testing. Cold test has been traditionally employed for corn seeds. However, it has also been used for other seed crops such as cotton (Gossypium spp., soybean (Glycine Max, dry bean (Phaseolus vulgaris and pea (Pisum sativum. This study was carried out with the objective of adjusting an alternative procedure for the cold test to determine soybean seed vigor. Six commercial soybean seed lots of the cultivar BRS 133 were used. The physiological potential of the seed lots was evaluated by germination on paper towel and sand box, seedling field emergence, tetrazolium, accelerated aging and electrical conductivity tests. Seed moisture content was also determined. The temperature used for the cold test procedures was 10ºC during five days. Four cold test procedures were evaluated: i plastic boxes with soil; ii rolled paper towel with soil; iii rolled paper towel without soil, and iv an alternative procedure, using rolled paper towel without soil under cold water. A completely randomized experimental design with eight replications was used and the means were compared by the Tukey test (p = 0.05. To verify the dependence between the alternative test and others single linear correlation was used. All cold test procedures had similar coefficients of variation (CV, highlighting that rolled paper towel with soil and the alternative procedure had the best performance, with an average of 94% and 93% normal seedlings and CV of 3.2% and 3.6%, respectively. The alternative procedure has satisfactory results for estimating soybean seed vigor, yielding consistent results compared to the traditional procedure.A crescente demanda por semente de soja [Glycine max (L. Merrill] de alta qualidade tem requerido da indústria de sementes um controle de qualidade mais preciso

  20. Sonification of Animal Tracks as an Alternative Representation of Multi-Dimensional Data: A Northern Elephant Seal Example

    KAUST Repository

    Duarte, Carlos M.

    2018-04-20

    Understanding movement of marine megafauna across the ocean is largely based on approaches and models based on analysis of tracks of single animals. While this has led to major progress, the possibility of concerted group dynamics has not been sufficiently examined, possibly due to challenges in exploring massive amounts of data required to this end. Here we report a sonification experiment, where the collective movement of northern elephant seals (Mirounga angustirostris) was explored by coding their group dynamics into sound. Specifically, we converted into sound data derived from a tagging program involving a total of 321 tagged animals tracked over a decade, between 20 February 2004 and 30 May 2014, consisting of an observation period of 90,063 h, composed of 1,027,839 individual positions. The data parameters used to provide the sound are position (longitude) and spread (degree of displacement taken for the active group). These data parameters are mapped to the sonic parameters of frequency (pitch) and amplitude (volume), respectively. Examination of the resulting sound revealed features of motion that translate into specific patterns in space. The serial departure of elephant seals to initiate their trips into waves is clearly reflected in the addition of tonalities, with coherent swimming of the animals conforming a wave reflected in the modulated fluctuations in volume, suggesting coordinated fluctuations in dispersion of the wave. Smooth changes in volume, coordinated with pitch variability, indicate that the animals spread out as they move further away from the colony, with one or a few animals exploring an ocean area away from that explored by the core wave. The shift in volume and pitch also signals at group coordination in initiating the return home. Coordinated initiation of the return to the colony is also clearly revealed by the sonification, as reflected in an increase in volume and pitch of the notes denoting the movement of each animal in a

  1. Human hemoglobin denaturation as an alternative to the Draize test for predicting eye irritancy of surfactants.

    Science.gov (United States)

    Mitjans, Montserrat; Infante, M Rosa; Vinardell, M Pilar

    2008-11-01

    Quantification of eye irritancy has been a problem for both the consumer product industry and ophthalmic researchers because of the need to predict the toxic potential of preparations that may come into contact with the ocular surface. The Draize rabbit eye test has been used for 60 years in attempts to predict human ocular irritancy based on topical instillation of the potential irritant and subjective scoring of ocular inflammation by direct visualization of the rabbit eye. The inadequacies of the Draize test have led to efforts in several laboratories to develop alternatives. We propose an alternative to the Draize eye irritation test, using human hemoglobin rather than bovine hemoglobin and studying the protein denaturation induced by potential irritants. Among the factors that affect eye irritation, protein denaturation has been reported as one of the most important factors that can result in corneal opacity. Human protein denaturation was measured as indicative of eye irritation. We studied different known irritant and non-irritant compounds to establish the predictability of the method. The compounds considered as irritants in vivo had the greatest effect in terms of decreased human hemoglobin absorbance. The proposed method is able to easily differentiate between irritant and non-irritants products in an easy manner. The method is easy, rapid, economical, and provides enough information about the potential eye irritant action of different surfactants.

  2. A mobile, high-throughput semi-automated system for testing cognition in large non-primate animal models of Huntington disease.

    Science.gov (United States)

    McBride, Sebastian D; Perentos, Nicholas; Morton, A Jennifer

    2016-05-30

    For reasons of cost and ethical concerns, models of neurodegenerative disorders such as Huntington disease (HD) are currently being developed in farm animals, as an alternative to non-human primates. Developing reliable methods of testing cognitive function is essential to determining the usefulness of such models. Nevertheless, cognitive testing of farm animal species presents a unique set of challenges. The primary aims of this study were to develop and validate a mobile operant system suitable for high throughput cognitive testing of sheep. We designed a semi-automated testing system with the capability of presenting stimuli (visual, auditory) and reward at six spatial locations. Fourteen normal sheep were used to validate the system using a two-choice visual discrimination task. Four stages of training devised to acclimatise animals to the system are also presented. All sheep progressed rapidly through the training stages, over eight sessions. All sheep learned the 2CVDT and performed at least one reversal stage. The mean number of trials the sheep took to reach criterion in the first acquisition learning was 13.9±1.5 and for the reversal learning was 19.1±1.8. This is the first mobile semi-automated operant system developed for testing cognitive function in sheep. We have designed and validated an automated operant behavioural testing system suitable for high throughput cognitive testing in sheep and other medium-sized quadrupeds, such as pigs and dogs. Sheep performance in the two-choice visual discrimination task was very similar to that reported for non-human primates and strongly supports the use of farm animals as pre-clinical models for the study of neurodegenerative diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The Future of Animals, Cells, Models, and Systems in Research, Development, Education, and Testing: Proceedings of a Symposium.

    Science.gov (United States)

    National Academy of Sciences - National Research Council, Washington, DC. Inst. of Lab. Animal Resources.

    This volume contains the prepared papers and discussions of a National Academy of Sciences - National Research Council Symposium on the Future of Animals, Cells, Models, and Systems in Research, Development, Education, and Testing. The purpose of the symposium was to examine the past, present, and future contributions of animals to human health…

  4. A rapid field test for sylvatic plague exposure in wild animals

    Science.gov (United States)

    Abbott, Rachel C.; Hudak, Robert; Mondesire, Roy; Baeten, Laurie A.; Russell, Robin E.; Rocke, Tonie E.

    2014-01-01

    Plague surveillance is routinely conducted to predict future epizootics in wildlife and exposure risk for humans. The most common surveillance method for sylvatic plague is detection of antibodies to Yersinia pestis F1 capsular antigen in sentinel animals, such as coyotes (Canis latrans). Current serologic tests for Y. pestis, hemagglutination (HA) test and enzyme-linked immunosorbent assay (ELISA), are expensive and labor intensive. To address this need, we developed a complete lateral flow device for the detection of specific antibodies to Y. pestis F1 and V antigens. Our test detected anti-F1 and anti-V antibodies in serum and Nobuto filter paper samples from coyotes, and in serum samples from prairie dogs (Cynomys ludovicianus), lynx (Lynx canadensis), and black-footed ferrets (Mustela nigripes). Comparison of cassette results for anti-F1 and anti-V antibodies with results of ELISA or HA tests showed correlations ranging from 0.68 to 0.98. This device provides an affordable, user-friendly tool that may be useful in plague surveillance programs and as a research tool.

  5. A rapid field test for sylvatic plague exposure in wild animals.

    Science.gov (United States)

    Abbott, Rachel C; Hudak, Robert; Mondesire, Roy; Baeten, Laurie A; Russell, Robin E; Rocke, Tonie E

    2014-04-01

    Plague surveillance is routinely conducted to predict future epizootics in wildlife and exposure risk for humans. The most common surveillance method for sylvatic plague is detection of antibodies to Yersinia pestis F1 capsular antigen in sentinel animals, such as coyotes (Canis latrans). Current serologic tests for Y. pestis, hemagglutination (HA) test and enzyme-linked immunosorbent assay (ELISA), are expensive and labor intensive. To address this need, we developed a complete lateral flow device for the detection of specific antibodies to Y. pestis F1 and V antigens. Our test detected anti-F1 and anti-V antibodies in serum and Nobuto filter paper samples from coyotes, and in serum samples from prairie dogs (Cynomys ludovicianus), lynx (Lynx canadensis), and black-footed ferrets (Mustela nigripes). Comparison of cassette results for anti-F1 and anti-V antibodies with results of ELISA or HA tests showed correlations ranging from 0.68 to 0.98. This device provides an affordable, user-friendly tool that may be useful in plague surveillance programs and as a research tool.

  6. The lateral flow card test: an alternative method for the detection of Trichinella infection in swine

    Directory of Open Access Journals (Sweden)

    Patrascu I.

    2001-06-01

    Full Text Available A novel lateral flow card (TS-Card pork test was developed for the serological detection of Trichinella infected pigs. Based on extensive studies performed in Romania during 1 999-2000 this test proved to be highly specific, sensitive, rapid (3-12 minutes and easy to use (no need for laboratory facilities. It can be used both for the detection of Trichinella infection in carcasses and for epizootiological studies using a variety of samples including whole or dried blood, serum, or tissue fluids. The TS-Card pork test, used as a screening test, can be the foundation of an on-farm or field based inspection system to significantly improve food safety in countries with a high prevalence of Trichinella in pigs or other food animal species. The results presented are also promising for application of the test in an on-line laboratory based inspection system since the speed of the test allows sufficient time to rail out suspected hog carcasses during the slaughter process.

  7. The Ex Vivo Eye Irritation Test as an alternative test method for serious eye damage/eye irritation.

    Science.gov (United States)

    Spöler, Felix; Kray, Oya; Kray, Stefan; Panfil, Claudia; Schrage, Norbert F

    2015-07-01

    Ocular irritation testing is a common requirement for the classification, labelling and packaging of chemicals (substances and mixtures). The in vivo Draize rabbit eye test (OECD Test Guideline 405) is considered to be the regulatory reference method for the classification of chemicals according to their potential to induce eye injury. In the Draize test, chemicals are applied to rabbit eyes in vivo, and changes are monitored over time. If no damage is observed, the chemical is not categorised. Otherwise, the classification depends on the severity and reversibility of the damage. Alternative test methods have to be designed to match the classifications from the in vivo reference method. However, observation of damage reversibility is usually not possible in vitro. Within the present study, a new organotypic method based on rabbit corneas obtained from food production is demonstrated to close this gap. The Ex Vivo Eye Irritation Test (EVEIT) retains the full biochemical activity of the corneal epithelium, epithelial stem cells and endothelium. This permits the in-depth analysis of ocular chemical trauma beyond that achievable by using established in vitro methods. In particular, the EVEIT is the first test to permit the direct monitoring of recovery of all corneal layers after damage. To develop a prediction model for the EVEIT that is comparable to the GHS system, 37 reference chemicals were analysed. The experimental data were used to derive a three-level potency ranking of eye irritation and corrosion that best fits the GHS categorisation. In vivo data available in the literature were used for comparison. When compared with GHS classification predictions, the overall accuracy of the three-level potency ranking was 78%. The classification of chemicals as irritating versus non-irritating resulted in 96% sensitivity, 91% specificity and 95% accuracy. 2015 FRAME.

  8. An alternative strategy to western blot as a confirmatory diagnostic test for HIV infection.

    Science.gov (United States)

    Feng, Xia; Wang, Jibao; Gao, Zhiyun; Tian, Yu; Zhang, Ling; Chen, Huichao; Zhang, Tong; Xiao, Lin; Yao, Jun; Xing, Wenge; Qiu, Maofeng; Jiang, Yan

    2017-03-01

    In China, western blot (WB) is the recommended procedure for the diagnosis of HIV infection. However, this technique is time consuming and labor intensive, and its complexity restricts wide application in resource-limited regions. The aim of this study was to evaluate the efficacy of a dry blood spots (DBS)-urine paired enzyme-linked immunosorbent assay (ELISA) test, instead of WB, for HIV antibody detection. Plasma, DBS, and urine samples were collected from 1213 subjects from different populations. Two diagnostic testing strategies were conducted in parallel. The equivalence of the paired ELISA and WB strategies was assessed. A diagnosis of HIV was determined in 250 subjects according to the paired ELISA test, and in 249 according to the WB strategy. The discordant case was judged HIV-positive during follow-up. In total, 18 subjects were diagnosed with possible HIV using the paired ELISA test, among whom, 11 subjects tested negative with WB, and one was confirmed to be HIV-positive during follow-up. For the remaining 945 subjects, both strategies indicated a negative result. The kappa test indicated good conformity (kappa=0.954) between the two diagnostic strategies. The DBS-urine paired ELISA could be applied as an alternative to WB in HIV diagnosis, which would be valuable in resource-limited regions owing to the associated affordability and ease of use. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Meat juice: An alternative matrix for assessing animal health by measuring acute phase proteins. Correlations of pig-MAP and haptoglobin concentrations in pig meat juice and plasma.

    Science.gov (United States)

    Piñeiro, M; Gymnich, S; Knura, S; Piñeiro, C; Petersen, B

    2009-10-01

    Quantification of acute phase proteins (APPs) in blood can be used for monitoring animal health and welfare on farms, and could be also of interest for the detection of diseased animals during the meat inspection process. However serum or plasma is not always available for end-point analysis at slaughter. Meat juice might provide an adequate, alternative matrix that can be easily obtained for post-mortem analysis at abattoirs. The concentrations of pig Major Acute phase Protein (pig-MAP) and haptoglobin, two of the main APPs in pigs, were determined in approximately 300 paired samples of plasma and meat juice from the diaphragm (pars costalis), obtained after freezing and thawing the muscle. APPs concentrations in meat juice were closely correlated to those in plasma (r=0.695 for haptoglobin, r=0.858 for pig-MAP, panimal health in pig production, with implications for food safety and meat quality.

  10. NASA and ESA Collaboration on Hexavalent Chrome Alternatives Pretreatments Only Interim Test Report

    Science.gov (United States)

    Kessel, Kurt R.

    2015-01-01

    NASA and ESA continue to search for an alternative to hexavalent chromium in coatings applications that meet their performance requirements in corrosion protection, cost, operability, and health and safety, while typically specifying that performance must be equal to or greater than existing systems. The overall objective of the collaborative effort between NASA TEERM and ESA is to test and evaluate coating systems (pretreatments, pretreatments with primer, and pretreatments with primer and topcoat) as replacements for hexavalent chrome coatings in aerospace applications. This objective will be accomplished by testing promising coatings identified from previous NASA, ESA, Department of Defense (DOD), and other project experience. Additionally, several new materials will be analyzed according to ESA-identified specifications.

  11. Annual Report, Fall 2016: Alternative Chemical Cleaning of Radioactive High Level Waste Tanks - Corrosion Test Results

    Energy Technology Data Exchange (ETDEWEB)

    Wyrwas, R. B. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-09-01

    The testing presented in this report is in support of the investigation of the Alternative Chemical Cleaning program to aid in developing strategies and technologies to chemically clean radioactive High Level Waste tanks prior to tank closure. The data and conclusions presented here were the examination of the corrosion rates of A285 carbon steel and 304L stainless steel exposed to two proposed chemical cleaning solutions: acidic permanganate (0.18 M nitric acid and 0.05M sodium permanganate) and caustic permanganate. (10 M sodium hydroxide and 0.05M sodium permanganate). These solutions have been proposed as a chemical cleaning solution for the retrieval of actinides in the sludge in the waste tanks, and were tested with both HM and PUREX sludge simulants at a 20:1 ratio.

  12. Testing on novel neutron detectors as alternative to 3He for security applications

    Science.gov (United States)

    Peerani, Paolo; Tomanin, Alice; Pozzi, Sara; Dolan, Jennifer; Miller, Eric; Flaska, Marek; Battaglieri, Marco; De Vita, Raffaella; Ficini, Luisa; Ottonello, Giacomo; Ricco, Giovanni; Dermody, Geraint; Giles, Calvin

    2012-12-01

    Detection of illicit trafficking of nuclear material relies on the detection of the radiation emitted. In the case of plutonium, one of the characteristic signatures derives from neutron emission. For this reason, neutron detectors cover an important role in detection systems. Most current neutron detection systems used for nuclear security are based on the 3He technology. Unfortunately, in the last few years the market of 3He has encountered huge problems in matching the supply and the demand. The need has grown significantly due to the increasing demand of instrumentation for security. This has caused an exponential increase of the price from one side and on the other side a serious strategic problem of resources. In order to guarantee the availability of detection systems for nuclear security, it is necessary to develop alternative detection systems based on technologies different from 3He. Many research projects have been devoted for the development of novel neutron detectors both by research organisations and by industries. Scientists from the PERLA laboratory of the Joint Research Centre (JRC) in Ispra, Italy, and their collaborators have tested several of these novel concepts in the last couple of years. This paper describes the detector systems tested at JRC and preliminary results on detectors that can be considered as promising alternatives to 3He.

  13. A test of alternative supervision strategies for family planning services in Guatemala.

    Science.gov (United States)

    Vernon, R; Staunton, A; García, M; Arroyo, J J; Rosenberg, R

    1994-01-01

    This report presents results of an operations research project that tested the impact and cost-effectiveness of alternative supervision schemes of reproductive health services in Guatemala. The strategies tested were (1) indirect supervision, in which one of the two annual supervised visits to each health unit was replaced by a one-day meeting at the district level with the supervisor; and (2) self-assessment, in which one supervised visit was replaced by a two-day workshop where participants filled out self-assessment checklists identifying quality of care problems and made a plan to solve identified problems during the following months. Health units in the two experimental groups showed greater increases in productivity than units receiving traditional supervision. In both alternative strategies, supervisors were able to reach a larger proportion of health units and service providers than through the traditional supervision system. The supervised cost per unit was also lower in the two experimental groups than in the control group. Few differences were observed between the experimental and control groups in terms of the satisfaction of service providers with their jobs and of clients with services received.

  14. Alternative buffer material. Status of the ongoing laboratory investigation of reference materials and test package 1

    International Nuclear Information System (INIS)

    Svensson, Daniel; Dueck, Ann; Nilsson, Ulf; Olsson, Siv; Sanden, Torbjoern; Lydmark, Sara; Jaegerwall, Sara; Pedersen, Karsten; Hansen, Staffan

    2011-07-01

    Bentonite clay is part of the Swedish KBS-3 design of final repositories for high level radioactive waste. Wyoming bentonite with the commercial name MX-80 (American Colloid Co) has long been the reference for buffer material in the KBS-3 concept. Extending the knowledge base of alternative buffer materials will make it possible to optimize regarding safety, availability and cost. For this reason the field experiment Alternative Buffer Material (ABM) was started at Aespoe Hard Rock Laboratory during 2006. The experiment includes three medium-scale test packages, each consisting of a central steel tube with heaters, and a buffer of compacted clay. Eleven different clays were chosen for the buffers to examine effects of smectite content, interlayer cations and overall iron content. Also bentonite pellets with and without additional quartz are being tested. The buffer in package 1 had been subjected to wetting by formation water and heating for more than two years (at 130 deg C for ∼ 1 year) when it was retrieved and analyzed. The main purposes of the project were to characterise the clays with respect to hydro-mechanical properties, mineralogy and chemical composition and to identify any differences in behaviour or long term stability. The diversity of clays and the heater of steel also make the experiment suitable for studies of iron-bentonite interactions. This report concerns the work accomplished up to now and is not to be treated as any final report of the project

  15. Alternative buffer material. Status of the ongoing laboratory investigation of reference materials and test package 1

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Daniel [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Dueck, Ann; Nilsson, Ulf; Olsson, Siv; Sanden, Torbjoern [Clay Technology AB, Lund (Sweden); Lydmark, Sara; Jaegerwall, Sara; Pedersen, Karsten [Microbial Analytics Sweden AB, Moelnlycke (Sweden); Hansen, Staffan [LTH Lund Univ., Lund (Sweden)

    2011-07-15

    Bentonite clay is part of the Swedish KBS-3 design of final repositories for high level radioactive waste. Wyoming bentonite with the commercial name MX-80 (American Colloid Co) has long been the reference for buffer material in the KBS-3 concept. Extending the knowledge base of alternative buffer materials will make it possible to optimize regarding safety, availability and cost. For this reason the field experiment Alternative Buffer Material (ABM) was started at Aespoe Hard Rock Laboratory during 2006. The experiment includes three medium-scale test packages, each consisting of a central steel tube with heaters, and a buffer of compacted clay. Eleven different clays were chosen for the buffers to examine effects of smectite content, interlayer cations and overall iron content. Also bentonite pellets with and without additional quartz are being tested. The buffer in package 1 had been subjected to wetting by formation water and heating for more than two years (at 130 deg C for {approx} 1 year) when it was retrieved and analyzed. The main purposes of the project were to characterise the clays with respect to hydro-mechanical properties, mineralogy and chemical composition and to identify any differences in behaviour or long term stability. The diversity of clays and the heater of steel also make the experiment suitable for studies of iron-bentonite interactions. This report concerns the work accomplished up to now and is not to be treated as any final report of the project.

  16. Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research.

    Science.gov (United States)

    Bert, Bettina; Dörendahl, Antje; Leich, Nora; Vietze, Julia; Steinfath, Matthias; Chmielewska, Justyna; Hensel, Andreas; Grune, Barbara; Schönfelder, Gilbert

    2017-12-01

    In the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.

  17. Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research.

    Directory of Open Access Journals (Sweden)

    Bettina Bert

    2017-12-01

    Full Text Available In the European Union (EU, animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models.

  18. Rethinking 3R strategies: Digging deeper into AnimalTestInfo promotes transparency in in vivo biomedical research

    Science.gov (United States)

    Dörendahl, Antje; Leich, Nora; Vietze, Julia; Steinfath, Matthias; Chmielewska, Justyna; Hensel, Andreas; Grune, Barbara; Schönfelder, Gilbert

    2017-01-01

    In the European Union (EU), animal welfare is seen as a matter of great importance. However, with respect to animal experimentation, European citizens feel quite uninformed. The European Directive 2010/63/EU for the protection of laboratory animals aims for greater transparency and requires that a comprehensible, nontechnical summary (NTS) of each authorised research project involving animals is published by the respective Member State. However, the NTSs remain sleeping beauties if their contents are not easily and systematically accessible. The German web-based NTS database AnimalTestInfo is a unique channel for scientists to communicate their work, and provides the opportunity for large-scale analyses of planned animal studies to inform researchers and the public. For an in-depth meta-analysis, we classified the duly completed NTSs submitted to AnimalTestInfo in 2014 and 2015 according to the International Classification of Diseases and Related Health Problems (ICD) system. Indexing the NTSs with ICD codes provided a fine-grained overview of the prospective uses of experimental animals. Using this approach, transparency, especially for highly controversial animal research involving, for example, nonhuman primates, is fostered, as it enables pinpointing the envisaged beneficiary down to the level of the addressed disease. Moreover, research areas with many planned projects involving animals can be specified in detail. The development of 3R (replacement, reduction, and refinement) measures in these research areas may be most efficient, as a large number of experimental animals would benefit from it. Indexing NTSs with ICD codes can support governments and funding agencies in advancing target-oriented funding of 3R research. Data drawn from NTSs can provide a basis for the development, validation, and implementation of directed 3R strategies as well as guidance for rethinking the role of animal research models. PMID:29240762

  19. Development and preliminary testing of a computerized Animated Activity Questionnaire (AAQ) in patients with hip and knee osteoarthritis

    DEFF Research Database (Denmark)

    Peter, Wf; Loos, M; de Vet, Hcw

    2015-01-01

    Objective To develop an Animated Activity Questionnaire (AAQ), based on video animations, for assessing activity limitations in patients with hip/knee osteoarthritis (OA), which combines the advantages of self-reported questionnaires and performance-based tests, without many of their limitations...... correlations with performance-based tests (Stair Climbing Test , Timed Up and Go test, 30 second Chair Stand Test ) were calculated. Results 17 basic daily activities were chosen for the AAQ. Video animations were made showing a person performing each activity with 3 to 5 different levels of difficulty......, and to preliminary assess its reliability and validity. We hypothesize that the AAQ correlates highly with performance-based tests, and moderately with self-reports. Methods Item selection was based on 1) the pilot AAQ; 2) pre-specified conditions; 3) the International Classification of Functioning core set for OA...

  20. Using pilot test data to refine an alternative cover design in northern California.

    Science.gov (United States)

    Smesrud, Jason K; Benson, Craig H; Albright, William H; Richards, James H; Wright, Shannon; Israel, Tim; Goodrich, Keith

    2012-01-01

    Two instrumented test sections were constructed in summer 1999 at the Kiefer Landfill near Sacramento, California to test the hydraulic performance of two proposed alternative final covers. Both test sections simulated monolithic evapotranspiration (ET) designs that differed primarily in thickness. Both were seeded with a mix of two perennial and one annual grass species. Oleander seedlings were also planted in the thicker test section. Detailed hydrologic performance monitoring of the covers was conducted from 1999 through 2005, The thicker test section met the performance criterion (average percolation of percolation (average of 55 mm/y). Both test sections were decommissioned in summer 2005 to investigate changes in soil hydraulic properties, geomorphology, and vegetation and to collect data to support a revised design. Field data from hydrologic monitoring and the decommissioning study were subsequently included in a hydrologic modeling study to estimate the performance of an optimized cover system for full-scale application. The decommissioning study showed that properties of the soils changed over the monitoring period (saturated hydraulic conductivity and water holding capacity increased, density decreased) and that the perennial grasses and shrubs intended for the cover were out-competed by annual species with shallower roots and lesser capacity for water uptake. Of these changes, reduced ET from the shallow-rooted annual vegetation is believed to be the primary cause for the high percolation rate from the thinner test section. Hydrologic modeling suggests that the target hydraulic performance can be achieved using an ET cover with similar thickness to the thin test section if perennial vegetation species observed in surrounding grasslands can be established. This finding underscores the importance of establishing and maintaining the appropriate vegetation on ET covers in this climate.

  1. ELISA and some biochemical tests of heterophyidae infection in laboratory animals.

    Science.gov (United States)

    El-Seify, Mahmoud A; El-Bahy, Nasr M; Desouky, Abdelrazek Y; Bazh, Eman K

    2012-02-01

    Heterophyiasis is an important food-borne parasitic zoonosis in Egypt, among the inhabitants living around brackish-water lakes especially fishermen, and it is a common human parasite in the Nile Delta. The experiment was done on two laboratory animals (rats and dogs), and the time of sample collection was done periodically at 6, 9, 15, 21, and 28 days post-infection to evaluate different tests required. Whole blood was collected with heparin or ethylenediamine tetra-acetic acid as anticoagulant to help in the hematological studies such as red blood cells count (RBCs), white blood cells count, packed cell volume (PCV), and hemoglobin (Hb). Only marked increase in the total leuckocytic count was recorded while RBCs, PCV, and Hb were decreased in most of the results obtained. Total protein and globulin decreased while albumin and A/G ratio increased. Liver enzymes showing marked increase in aspartate aminotransferase and increase in alanine aminotransferase in dogs and rats denoting that liver has a role in the response to that infection. Kidney-function tests, urea, and creatinine showed slight increase at 6 days post-infection (d.p.i.). After preparation of different Ag (antigen) from different collected helminthes, the protein content of each was determined. The sera of infected animals were collected to find antibodies in their blood against the parasite using enzyme-linked immunosorbent assay and using crude heterophyid antigen collected from their intestines after scarification. The worms washed, homogenized, and then centrifuged to collect supernatant fluid as antigens. The results indicated that antibody starts to appear at 9 d.p.i. and increases till 21 and 28 d.p.i. and detection depends on antigen concentration.

  2. First meeting "Cystic echinococcosis in Chile, update in alternatives for control and diagnostics in animals and humans".

    Science.gov (United States)

    Alvarez Rojas, Cristian A; Fredes, Fernando; Torres, Marisa; Acosta-Jamett, Gerardo; Alvarez, Juan Francisco; Pavletic, Carlos; Paredes, Rodolfo; Cortés, Sandra

    2016-09-13

    This report summarizes the outcomes of a meeting on cystic echinococcosis (CE) in animals and humans in Chile held in Santiago, Chile, between the 21st and 22nd of January 2016. The meeting participants included representatives of the Departamento de Zoonosis, Ministerio de Salud (Zoonotic Diseases Department, Ministry of Health), representatives of the Secretarias Regionales del Ministerio de Salud (Regional Department of Health, Ministry of Health), Instituto Nacional de Desarrollo Agropecuario (National Institute for the Development of Agriculture and Livestock, INDAP), Instituto de Salud Pública (National Institute for Public Health, ISP) and the Servicio Agrícola y Ganadero (Animal Health Department, SAG), academics from various universities, veterinarians and physicians. Current and future CE control activities were discussed. It was noted that the EG95 vaccine was being implemented for the first time in pilot control programmes, with the vaccine scheduled during 2016 in two different regions in the South of Chile. In relation to use of the vaccine, the need was highlighted for acquiring good quality data, based on CE findings at slaughterhouse, previous to initiation of vaccination so as to enable correct assessment of the efficacy of the vaccine in the following years. The current world's-best-practice concerning the use of ultrasound as a diagnostic tool for the screening population in highly endemic remote and poor areas was also discussed.

  3. Data Exploration and Analysis of Alternative Learning System Accreditation and Equivalency Test Result Using Data Mining

    Science.gov (United States)

    Talingdan, J. A.; Trinidad, J. T., Jr.; Palaoag, T. D.

    2018-03-01

    Alternative Learning System (ALS) is a subsystem of Depatment of Education (DepEd) that serves as an option of learners who cannot afford to go in a formal education. The research focuses on the data exploration and analysis of ALS accreditation and equivalency test result using data mining. The ALS 2014 to 2016 A & E test results in the secondary level were used as data sets in the study. The A & E test results revealed that the passing rate is doubled per year. The results were clustered using k- means clustering algorithm and they were grouped into good, medium, and low standard learners to identify students need exceptional stuff for enhancement. From the clustered data, it was found out that the strand they are weak in is strand 4 which is the Development of Self and a Sense of Community with a general average of 84.23. It also revealed that the essay type of exam got the lowest score with a general average of 2.14 compared to the multiple type of exam that covers the five learning strands. Furthermore, decision tree and naive bayes were also employed in the study to predict the performance of the learners in the A & E test and determine which is better to use for prediction. It was concluded that naive bayes performs better because the accuracy rate is higher than the decision tree algorithm.

  4. A TaqMan real-time PCR method based on alternative oxidase genes for detection of plant species in animal feed samples.

    Directory of Open Access Journals (Sweden)

    Maria Doroteia Campos

    Full Text Available Traceability of processed food and feed products has been gaining importance due to the impact that those products can have on human/animal health and to the associated economic and legal concerns, often related to adulterations and frauds as it can be the case for meat and milk. Despite mandatory traceability requirements for the analysis of feed composition, few reliable and accurate methods are presently available to enforce the legislative frame and allow the authentication of animal feeds. In this study, nine sensitive and species-specific real-time PCR TaqMan MGB assays are described for plant species detection in animal feed samples. The method is based on selective real-time qPCR (RT-qPCR amplification of target genes belonging to the alternative oxidase (AOX gene family. The plant species selected for detection in feed samples were wheat, maize, barley, soybean, rice and sunflower as common components of feeds, and cotton, flax and peanut as possible undesirable contaminants. The obtained results were compared with end-point PCR methodology. The applicability of the AOX TaqMan assays was evaluated through the screening of commercial feed samples, and by the analysis of plant mixtures with known composition. The RT-qPCR methodology allowed the detection of the most abundant species in feeds but also the identification of contaminant species present in lower amounts, down to 1% w/w. AOX-based methodology provides a suitable molecular marker approach to ascertain plant species composition of animal feed samples, thus supporting feed control and enforcement of the feed sector and animal production.

  5. A TaqMan real-time PCR method based on alternative oxidase genes for detection of plant species in animal feed samples.

    Science.gov (United States)

    Campos, Maria Doroteia; Valadas, Vera; Campos, Catarina; Morello, Laura; Braglia, Luca; Breviario, Diego; Cardoso, Hélia G

    2018-01-01

    Traceability of processed food and feed products has been gaining importance due to the impact that those products can have on human/animal health and to the associated economic and legal concerns, often related to adulterations and frauds as it can be the case for meat and milk. Despite mandatory traceability requirements for the analysis of feed composition, few reliable and accurate methods are presently available to enforce the legislative frame and allow the authentication of animal feeds. In this study, nine sensitive and species-specific real-time PCR TaqMan MGB assays are described for plant species detection in animal feed samples. The method is based on selective real-time qPCR (RT-qPCR) amplification of target genes belonging to the alternative oxidase (AOX) gene family. The plant species selected for detection in feed samples were wheat, maize, barley, soybean, rice and sunflower as common components of feeds, and cotton, flax and peanut as possible undesirable contaminants. The obtained results were compared with end-point PCR methodology. The applicability of the AOX TaqMan assays was evaluated through the screening of commercial feed samples, and by the analysis of plant mixtures with known composition. The RT-qPCR methodology allowed the detection of the most abundant species in feeds but also the identification of contaminant species present in lower amounts, down to 1% w/w. AOX-based methodology provides a suitable molecular marker approach to ascertain plant species composition of animal feed samples, thus supporting feed control and enforcement of the feed sector and animal production.

  6. Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations.

    Science.gov (United States)

    Mitra, Biplob; Wolfe, Chad; Wu, Sy-Juen

    2018-05-01

    The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60 °C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25 °C/60% RH and 40 °C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.

  7. How the environment shapes animal signals: a test of the acoustic adaptation hypothesis in frogs.

    Science.gov (United States)

    Goutte, S; Dubois, A; Howard, S D; Márquez, R; Rowley, J J L; Dehling, J M; Grandcolas, P; Xiong, R C; Legendre, F

    2018-01-01

    Long-distance acoustic signals are widely used in animal communication systems and, in many cases, are essential for reproduction. The acoustic adaptation hypothesis (AAH) implies that acoustic signals should be selected for further transmission and better content integrity under the acoustic constraints of the habitat in which they are produced. In this study, we test predictions derived from the AAH in frogs. Specifically, we focus on the difference between torrent frogs and frogs calling in less noisy habitats. Torrents produce sounds that can mask frog vocalizations and constitute a major acoustic constraint on call evolution. We combine data collected in the field, material from scientific collections and the literature for a total of 79 primarily Asian species, of the families Ranidae, Rhacophoridae, Dicroglossidae and Microhylidae. Using phylogenetic comparative methods and including morphological and environmental potential confounding factors, we investigate putatively adaptive call features in torrent frogs. We use broad habitat categories as well as fine-scale habitat measurements and test their correlation with six call characteristics. We find mixed support for the AAH. Spectral features of torrent frog calls are different from those of frogs calling in other habitats and are related to ambient noise levels, as predicted by the AAH. However, temporal call features do not seem to be shaped by the frogs' calling habitats. Our results underline both the complexity of call evolution and the need to consider multiple factors when investigating this issue. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  8. Testing of breakdates in agricultural prices of selected representatives of animal production

    Directory of Open Access Journals (Sweden)

    Petra Bubáková

    2012-01-01

    Full Text Available This paper deals with an investigation of breakdates in agricultural prices. A structural break has occurred if at least one of the model parameters has changed at some date. This date is a breakdate. Ignoring structural breaks in time series can lead to serious problems with economic models of time series. The aim is to determine the number and date of the breakdates in individual time series and connect them with changes in the market and economic environment. The time series of agricultural price relating to animal production, namely the prices of pork, beef, chicken, milk and eggs, are analyzed for the period from January 1996 to December 2011. The autoregressive model (AR model of Box-Jenkins methodology and stability testing according to Quandt or Wald statistics are used for the purposes of this paper. Multiple breakdates are found in the case of eggs (September 1998, May 2004, milk (October 1999, December 2007 and chicken (October 2002, February 2005 prices. One breakdate was detected in the prices of beef (April 2002 and none in the case of pork prices. The results show the importance of multiple breakdate testing. The Quandt statistic provides one possible way of applying a multiple approach. All breakdates which were confirmed using these statistics can be associated with changes in the agri-food market and economic environment. Information about the date of changes in the time series can be used for other unbiased modelling in more complex models.

  9. Rat animal model for preclinical testing of microparticle urethral bulking agents.

    Science.gov (United States)

    Mann-Gow, Travis K; Blaivas, Jerry G; King, Benjamin J; El-Ghannam, Ahmed; Knabe, Christine; Lam, Michael K; Kida, Masatoshi; Sikavi, Cameron S; Plante, Mark K; Krhut, Jan; Zvara, Peter

    2015-04-01

    To develop an economic, practical and readily available animal model for preclinical testing of urethral bulking therapies, as well as to establish feasible experimental methods that allow for complete analysis of hard microparticle bulking agents. Alumina ceramic beads suspended in hyaluronic acid were injected into the proximal urethra of 15 female rats under an operating microscope. We assessed overall lower urinary tract function, bulking material intraurethral integrity and local host tissue response over time. Microphotographs were taken during injection and again 6 months postoperatively, before urethral harvest. Urinary flow rate and voiding frequency were assessed before and after injection. At 6 months, the urethra was removed and embedded in resin. Hard tissue sections were cut using a sawing microtome, and processed for histological analysis using scanning electron microscopy, light microscopy and immunohistochemistry. Microphotographs of the urethra showed complete volume retention of the bulking agent at 6 months. There was no significant difference between average urinary frequency and mean urinary flow rate at 1 and 3 months postinjection as compared with baseline. Scanning electron microscopy proved suitable for evaluation of microparticle size and integrity, as well as local tissue remodeling. Light microscopy and immunohistochemistry allowed for evaluation of an inflammatory host tissue reaction to the bulking agent. The microsurgical injection technique, in vivo physiology and novel hard tissue processing for histology, described in the present study, will allow for future comprehensive preclinical testing of urethral bulking therapy agents containing microparticles made of a hard material. © 2015 The Japanese Urological Association.

  10. Animal testing is still the best way to find new treatments for patients.

    Science.gov (United States)

    Garattini, Silvio; Grignaschi, Giuliano

    2017-04-01

    Experimental research proceeds by hypotheses formulated on the basis of previous or new knowledge and then tested. If they are accepted, they serve as the basis for further hypotheses, and if they are rejected new hypotheses can be developed. In other words, when we are at the frontiers of knowledge the path is forged by "trial and error". When a trial shows a hypothesis is wrong, this is a step toward making fewer errors. This process also applies to drug development. There is no magic formula at present to predict - at the pre-clinical level - the therapeutic value of a drug for people with a disease. However, pre-clinical studies are needed in order to formulate hypotheses that justify clinical trials. Without these preliminary studies in vitro and in vivo in selected animal species it would be unethical to test still unproven chemicals in humans. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  11. ENIAK. Development of a non-motor injector coking test facility for alternative fuels; ENIAK. Entwicklung eines nichtmotorischen Injektorverkokungspruefstands fuer alternative Kraftstoffe

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Hajo; Schloss, Heide vom; Yang, Zhi; Grote, Melanie [OWI Oel-Waerme-Institut GmbH, Aachen (Germany). Gruppe Anwendungstechnik

    2013-10-01

    Poor Biodiesel quality, contamination with copper and zinc as well as undesired reactions between (several) additives and biodiesel components are known causes for nozzle fouling. Therefore, among other things, all additives have to pass a no-harm test. The standard fouling tests are two engine tests: the XUD9-test (CEC F-23-01) and the DW-10-test (CEC DF 98-08). The XUD9 is a cost efficient, fast and proven testing method. It uses, however, an obsolete indirect injection diesel engine. The newer DW10 test is complex, costly and designed for high stress. This reduces the engine life and leads to a fuel consumption of approximately 1,000 l per test, both contributing to the high costs of the test. The main goal of the project ENIAK is the development, assembly, commissioning, and evaluation of a non-engine fuel injector test. It uses four complete common rail systems. The injection takes place in four self-designed reactors instead of an engine, and the fuel is not combusted, but re-condensed and pumped in a circle. If the test method proves to be as reliable as expected, it can be used as an alternative test method for injector fouling with low requirements regarding infrastructure on the testing site and sample volume. The project is funded by the the federal ministry of consumer protection, food and agriculture via FNR (''Fachagentur Nachwachsende Rohstoffe'', Agency for Renewable Resources). (orig.)

  12. Animal Investigation Program 1976 annual report: Nevada test site and vicinity. [Radioanalysis of tissues from animals residing on or near NTS in 1976

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.D.; Giles, K.R.; Bernhardt, D.E.; Brown, K.W.

    1978-11-01

    Data are presented from the radioanalysis of tissues collected from cattle and mule deer, desert bighorn sheep, feral horses, and other wildlife that resided on or near the Nevada Test Site during 1976. Other than the naturally occurring potassium-40, gamma-emitting radionuclides were detected infrequently with the exception of /sup 131/I in animal thyroid samples collected after September 25 (the date of a Chinese nuclear test). Strontium-90 concentrations in bones from deer, cattle, and desert bighorn sheep continued the downward trend of recent years. Tritium concentrations were generally within ambient limits with the exception of animals exposed to sources of contamination; e.g., Sedan Crater, drainage ponds from Area 12 tunnels, etc. Analysis of actinide in tissues was emphasized during 1976. Graphs illustrate the /sup 239/P levels in lungs, livers, and femurs from Nevada Test Site beef cattle for the years 1971 through 1976. Femur and lung residue data are nearly identical for each year with liver concentrations being a factor of 2 or 3 lower. Hypothetical dose estimates to man were calculated on the basis of the daily consumption of 0.5 kilogram of liver or muscle from animals that contained peak actinide levels. The highest postulated dose was 11 millirem from tritium from tissues for a mule deer. This dose is about 2% of the 500 millirems/year guide for radiation doses to an individual in the general public. All other postulated doses for consumption of the tissue containing other radionuclides are less than 0.1% of this guide. The food habits of desert bighorn sheep were discussed according to the geographic locations of the animals at time of collection. Grasses made up approximately 60% of the diet at all locations, with shrubs content approaching 30%, and the remainder consisting of various forbs. The movement of 13 mule deer fitted with collars containing a radiotransmitter unit was monitored on a weekly basis.

  13. Testing animal-assisted cleaning prior to transplantation in coral reef restoration

    Directory of Open Access Journals (Sweden)

    Sarah Frias-Torres

    2015-09-01

    Full Text Available Rearing coral fragments in nurseries and subsequent transplantation onto a degraded reef is a common approach for coral reef restoration. However, if barnacles and other biofouling organisms are not removed prior to transplantation, fish will dislodge newly cemented corals when feeding on biofouling organisms. This behavior can lead to an increase in diver time due to the need to reattach the corals. Thus, cleaning nurseries to remove biofouling organisms such as algae and invertebrates is necessary prior to transplantation, and this cleaning constitutes a significant time investment in a restoration project. We tested a novel biomimicry technique of animal-assisted cleaning on nursery corals prior to transplantation at a coral reef restoration site in Seychelles, Indian Ocean. To determine whether animal-assisted cleaning was possible, preliminary visual underwater surveys were performed to quantify the fish community at the study site. Then, cleaning stations consisting of nursery ropes carrying corals and biofouling organisms, set at 0.3 m, 2 m, 4 m, 6 m and 8 m from the seabed, were placed at both the transplantation (treatment site and the nursery (control site. Remote GoPro video cameras recorded fish feeding at the nursery ropes without human disturbance. A reef fish assemblage of 32 species from 4 trophic levels (18.8% herbivores, 18.8% omnivores, 59.3% secondary consumers and 3.1% carnivores consumed 95% of the barnacles on the coral nursery ropes placed 0.3 m above the seabed. Using this cleaning station, we reduced coral dislodgement from 16% to zero. This cleaning station technique could be included as a step prior to coral transplantation worldwide on the basis of location-specific fish assemblages and during the early nursery phase of sexually produced juvenile corals.

  14. Testing animal-assisted cleaning prior to transplantation in coral reef restoration

    Science.gov (United States)

    van de Geer, Casper

    2015-01-01

    Rearing coral fragments in nurseries and subsequent transplantation onto a degraded reef is a common approach for coral reef restoration. However, if barnacles and other biofouling organisms are not removed prior to transplantation, fish will dislodge newly cemented corals when feeding on biofouling organisms. This behavior can lead to an increase in diver time due to the need to reattach the corals. Thus, cleaning nurseries to remove biofouling organisms such as algae and invertebrates is necessary prior to transplantation, and this cleaning constitutes a significant time investment in a restoration project. We tested a novel biomimicry technique of animal-assisted cleaning on nursery corals prior to transplantation at a coral reef restoration site in Seychelles, Indian Ocean. To determine whether animal-assisted cleaning was possible, preliminary visual underwater surveys were performed to quantify the fish community at the study site. Then, cleaning stations consisting of nursery ropes carrying corals and biofouling organisms, set at 0.3 m, 2 m, 4 m, 6 m and 8 m from the seabed, were placed at both the transplantation (treatment) site and the nursery (control) site. Remote GoPro video cameras recorded fish feeding at the nursery ropes without human disturbance. A reef fish assemblage of 32 species from 4 trophic levels (18.8% herbivores, 18.8% omnivores, 59.3% secondary consumers and 3.1% carnivores) consumed 95% of the barnacles on the coral nursery ropes placed 0.3 m above the seabed. Using this cleaning station, we reduced coral dislodgement from 16% to zero. This cleaning station technique could be included as a step prior to coral transplantation worldwide on the basis of location-specific fish assemblages and during the early nursery phase of sexually produced juvenile corals. PMID:26468440

  15. Testing animal-assisted cleaning prior to transplantation in coral reef restoration.

    Science.gov (United States)

    Frias-Torres, Sarah; van de Geer, Casper

    2015-01-01

    Rearing coral fragments in nurseries and subsequent transplantation onto a degraded reef is a common approach for coral reef restoration. However, if barnacles and other biofouling organisms are not removed prior to transplantation, fish will dislodge newly cemented corals when feeding on biofouling organisms. This behavior can lead to an increase in diver time due to the need to reattach the corals. Thus, cleaning nurseries to remove biofouling organisms such as algae and invertebrates is necessary prior to transplantation, and this cleaning constitutes a significant time investment in a restoration project. We tested a novel biomimicry technique of animal-assisted cleaning on nursery corals prior to transplantation at a coral reef restoration site in Seychelles, Indian Ocean. To determine whether animal-assisted cleaning was possible, preliminary visual underwater surveys were performed to quantify the fish community at the study site. Then, cleaning stations consisting of nursery ropes carrying corals and biofouling organisms, set at 0.3 m, 2 m, 4 m, 6 m and 8 m from the seabed, were placed at both the transplantation (treatment) site and the nursery (control) site. Remote GoPro video cameras recorded fish feeding at the nursery ropes without human disturbance. A reef fish assemblage of 32 species from 4 trophic levels (18.8% herbivores, 18.8% omnivores, 59.3% secondary consumers and 3.1% carnivores) consumed 95% of the barnacles on the coral nursery ropes placed 0.3 m above the seabed. Using this cleaning station, we reduced coral dislodgement from 16% to zero. This cleaning station technique could be included as a step prior to coral transplantation worldwide on the basis of location-specific fish assemblages and during the early nursery phase of sexually produced juvenile corals.

  16. The Fragility of Individual-Based Explanations of Social Hierarchies: A Test Using Animal Pecking Orders.

    Directory of Open Access Journals (Sweden)

    Ivan D Chase

    Full Text Available The standard approach in accounting for hierarchical differentiation in biology and the social sciences considers a hierarchy as a static distribution of individuals possessing differing amounts of some valued commodity, assumes that the hierarchy is generated by micro-level processes involving individuals, and attempts to reverse engineer the processes that produced the hierarchy. However, sufficient experimental and analytical results are available to evaluate this standard approach in the case of animal dominance hierarchies (pecking orders. Our evaluation using evidence from hierarchy formation in small groups of both hens and cichlid fish reveals significant deficiencies in the three tenets of the standard approach in accounting for the organization of dominance hierarchies. In consequence, we suggest that a new approach is needed to explain the organization of pecking orders and, very possibly, by implication, for other kinds of social hierarchies. We develop an example of such an approach that considers dominance hierarchies to be dynamic networks, uses dynamic sequences of interaction (dynamic network motifs to explain the organization of dominance hierarchies, and derives these dynamic sequences directly from observation of hierarchy formation. We test this dynamical explanation using computer simulation and find a good fit with actual dynamics of hierarchy formation in small groups of hens. We hypothesize that the same dynamic sequences are used in small groups of many other animal species forming pecking orders, and we discuss the data required to evaluate our hypothesis. Finally, we briefly consider how our dynamic approach may be generalized to other kinds of social hierarchies using the example of the distribution of empty gastropod (snail shells occupied in populations of hermit crabs.

  17. Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yan SUN

    2015-06-01

    Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

  18. [Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer].

    Science.gov (United States)

    Sun, Yan; Song, Zhengbo

    2015-06-01

    Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

  19. 75 FR 71155 - Market Test of Experimental Product: “Alternative Postage Payment Method for Greeting Cards”

    Science.gov (United States)

    2010-11-22

    ... From the Federal Register Online via the Government Publishing Office POSTAL SERVICE Market Test... Service TM . ACTION: Notice. SUMMARY: The Postal Service gives notice of a market test of an experimental... gives notice pursuant to 39 U.S.C. 3641(c)(1) that it will begin a market test of its ``Alternative...

  20. Is it possible to replace stimulus animals by scent-filled cups in the social discrimination test?

    Science.gov (United States)

    van den Bos, Ruud; van der Horst, Klaske J; Baars, Annemarie M; Spruijt, Berry M

    2002-01-01

    A study in which the rat social discrimination test was refined is described. This test measures social memory by using, in general, juvenile rats as stimulus animals. Rats are offered a first juvenile to investigate (learning trial), and after a specified interval, the rats are offered the same rat and a second juvenile rat to investigate again (retrieval trial). When the rats sniff the second juvenile in the retrieval trial more than the first, social memory for the second juvenile is said to be present. This test is mainly based on scents from the juvenile. Attempts were made to refine the test to reduce the number of animals used, to enhance the scope of the test, and to improve its validity. Firstly, the stimulus animals were replaced by the scent of juveniles, in the form of cups filled with sawdust taken from cages of juvenile rats. Similar results to those in the original test were obtained when using these scents. Furthermore, male and female scents were tested, and showed the same results as for the juvenile scents. Secondly, rats were also given two cups (one scent-filled and one filled with plain sawdust) in the learning trial, to determine which allowed a more-precise delineation of motivational, discriminatory and memory components. Overall, it is possible to replace stimulus animals by scent-filled cups in the social discrimination test, to enhance the scope of the test, and to draw more-valid conclusions with respect to social memory.

  1. Next generation sequencing for gut microbiome characterization in rainbow trout (Oncorhynchus mykiss) fed animal by-product meals as an alternative to fishmeal protein sources.

    Science.gov (United States)

    Rimoldi, Simona; Terova, Genciana; Ascione, Chiara; Giannico, Riccardo; Brambilla, Fabio

    2018-01-01

    Animal by-product meals from the rendering industry could provide a sustainable and commercially viable alternative to fishmeal (FM) in aquaculture, as they are rich in most essential amino acids and contain important amounts of water-soluble proteins that improve feed digestibility and palatability. Among them, poultry by-product meal (PBM) have given encouraging results in rainbow trout (Oncorhynchus mykiss). However, the introduction of new ingredients in the diet needs to be carefully evaluated since diet is one of the main factors affecting the gut microbiota, which is a complex community that contributes to host metabolism, nutrition, growth, and disease resistance. Accordingly, we investigated the effects of partial replacement of dietary FM with a mix of animal by-product meals and plant proteins on intestinal microbiota composition of rainbow trout in relation to growth and feeding efficiency parameters. We used 1540 trout with an initial mean body weight of 94.6 ± 14.2 g. Fish were fed for 12 weeks with 7 different feed formulations. The growth data showed that trout fed on diets rich in animal by-product meals grew as well as fish fed on control diet, which was rich in FM (37.3%) and PBM-free. High-throughput 16S rRNA gene amplicon sequencing (MiSeq platform, Illumina) was utilised to study the gut microbial community profile. After discarding Cyanobacteria (class Chloroplast) and mitochondria reads a total of 2,701,274 of reads taxonomically classified, corresponding to a mean of 96,474 ± 68,056 reads per sample, were obtained. Five thousand three hundred ninety-nine operational taxonomic units (OTUs) were identified, which predominantly mapped to the phyla of Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The ratio between vegetable and animal proteins proved to play a central role in determining microbiome profiles and Firmicutes and Proteobacteria phyla were particularly discriminatory for diet type in trout. Plant ingredients

  2. Next generation sequencing for gut microbiome characterization in rainbow trout (Oncorhynchus mykiss) fed animal by-product meals as an alternative to fishmeal protein sources

    Science.gov (United States)

    Rimoldi, Simona; Ascione, Chiara; Giannico, Riccardo; Brambilla, Fabio

    2018-01-01

    Animal by-product meals from the rendering industry could provide a sustainable and commercially viable alternative to fishmeal (FM) in aquaculture, as they are rich in most essential amino acids and contain important amounts of water-soluble proteins that improve feed digestibility and palatability. Among them, poultry by-product meal (PBM) have given encouraging results in rainbow trout (Oncorhynchus mykiss). However, the introduction of new ingredients in the diet needs to be carefully evaluated since diet is one of the main factors affecting the gut microbiota, which is a complex community that contributes to host metabolism, nutrition, growth, and disease resistance. Accordingly, we investigated the effects of partial replacement of dietary FM with a mix of animal by-product meals and plant proteins on intestinal microbiota composition of rainbow trout in relation to growth and feeding efficiency parameters. We used 1540 trout with an initial mean body weight of 94.6 ± 14.2 g. Fish were fed for 12 weeks with 7 different feed formulations. The growth data showed that trout fed on diets rich in animal by-product meals grew as well as fish fed on control diet, which was rich in FM (37.3%) and PBM-free. High-throughput 16S rRNA gene amplicon sequencing (MiSeq platform, Illumina) was utilised to study the gut microbial community profile. After discarding Cyanobacteria (class Chloroplast) and mitochondria reads a total of 2,701,274 of reads taxonomically classified, corresponding to a mean of 96,474 ± 68,056 reads per sample, were obtained. Five thousand three hundred ninety-nine operational taxonomic units (OTUs) were identified, which predominantly mapped to the phyla of Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The ratio between vegetable and animal proteins proved to play a central role in determining microbiome profiles and Firmicutes and Proteobacteria phyla were particularly discriminatory for diet type in trout. Plant ingredients

  3. Overall migration test in food packaging: Evaluation of alternative internal standards

    Directory of Open Access Journals (Sweden)

    Edgar Andres Avendaño Florez

    2018-01-01

    Full Text Available In the global migration test for plastic packaging intended for fatty foods, glyceryl triheptadecanoate (GTM is used as the internal standard for the quantification of fatty acid methyl esters (FAMEs by gas chromatography. In this work, ethyl 3-phenyl propanoate (EFP and tetradecanoic acid (AM were evaluated as alternative internal standards. The use of (AM presented linear behavior (r > 0.99 and %Sb < 5%, good intermediate precision (HORRATr = 0.9, and accuracy (%R = 100.6%. In contrast, the evaluation of (EFP demonstrated that this is not an adequate internal standard for the quantification of FAMEs. In addition, it was statistically evaluated that there are no significant differences in the calculation of the global migration from FAMEs quantified using GTM or AM as internal standards, but the use of EFP presents significant differences.

  4. NASA and ESA Collaboration on Hexavalent Chrome Alternatives: Pretreatments Only Final Test Report

    Science.gov (United States)

    Kessel, Kurt R.

    2015-01-01

    Hexavalent chromium (hex chrome or CR(VI)) is a widely used element within applied coating systems because of its self-healing and corrosion-resistant properties. The replacement of hex chrome in the processing of aluminum for aviation and aerospace applications remains a goal of great significance. Aluminum is the major manufacturing material of structures and components in the space flight arena. The National Aeronautics and Space Administration (NASA) and the European Space Agency (ESA) are engaged in a collaborative effort to test and evaluate alternatives to hexavalent chromium containing corrosion coating systems. NASA and ESA share common risks related to material obsolescence associated with hexavalent chromium used in corrosion-resistant coatings.

  5. Testing of Snorre Field Foam Assisted Water Alternating Gas (FAWAG Performance in New Foam Screening Model

    Directory of Open Access Journals (Sweden)

    Spirov Pavel

    2015-11-01

    Full Text Available Eclipse Functional Foam Model was used in order to provide a guideline for the history matching process (Gas-Oil Ratio (GOR, oil and gas production rates to the Foam Assisted Water Alternating Gas method in the Snorre field, Norway, where the surfactant solution was injected in two slugs to control gas mobility and prevent gas breakthrough. The simulation showed that the first short slug was not efficient while significant GOR decrease and incremental oil production was obtained after the second longer slug in some periods. This study shows that the Eclipse foam model is applicable to the planning of water and gas injections, the testing of various surfactant properties, and the evaluation of the efficiency of the method at the field scale.

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

    Science.gov (United States)

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

    2017-01-01

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

  7. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis.

    Directory of Open Access Journals (Sweden)

    Karina E Egüez

    2017-04-01

    Full Text Available Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or indirect hemagglutination assays. Agreement in at least two tests must be obtained due to parasite wide antigenic variability. These techniques require equipped labs and trained personnel and are not available in distant regions. As a result, many infected people often remain undiagnosed until it is too late, as the two available chemotherapies show diminished efficacy in the advanced chronic stage. Easy-to-use rapid diagnostic tests have been developed to be implemented in remote areas as an alternative to conventional tests. They do not need electricity, nor cold chain, they can return results within an hour and some even work with whole blood as sample, like Chagas Stat-Pak (ChemBio Inc. and Chagas Detect Plus (InBIOS Inc.. Nonetheless, in order to qualify a rapidly diagnosed positive patient for treatment, conventional serological confirmation is obligatory, which might risk its start. In this study two rapid tests based on distinct antigen sets were used in parallel as a way to obtain a fast and conclusive Chagas disease diagnosis using whole blood samples. Chagas Stat-Pak and Chagas Detect Plus were validated by comparison with three conventional tests yielding 100% sensitivity and 99.3% specificity over 342 patients seeking Chagas disease diagnosis in a reference centre in Sucre (Bolivia. Combined used of RDTs in distant regions could substitute laborious conventional serology, allowing immediate treatment and favouring better adhesion to it.

  8. Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis

    Science.gov (United States)

    Egüez, Karina E.; Terán, Carolina; Chipana, Zenobia; García, Wilson; Torrico, Faustino; Gascon, Joaquim; Lozano-Beltran, Daniel-Franz; Pinazo, María-Jesús

    2017-01-01

    Chagas disease is caused by the parasite Trypanosoma cruzi. It affects several million people, mainly in Latin America, and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients. Disease acute stage is mostly asymptomatic and infection goes undiagnosed. In the chronic phase direct parasite detection is hampered due to its concealed presence and diagnosis is achieved by serological methods, like ELISA or