WorldWideScience

Sample records for regulatory animal testing

  1. 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

  2. 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.

  3. 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.

  4. 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.

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

    Science.gov (United States)

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

    2012-07-01

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

  6. Reduction of use of animals in regulatory genotoxicity testing : Identification and implementation opportunities-Report from an ECVAM workshop

    NARCIS (Netherlands)

    Pfuhler, S.; Kirkland, D.; Kasper, P.; Hayashi, M.; Vanparys, P.; Carmichael, P.; Dertinger, S.; Eastmond, D.; Elhajouji, A.; Krul, C.A.M.; Rothfuss, A.; Schoening, G.; Smith, A.; Speit, G.; Thomas, C.; Benthem, J. van; Corvi, R.

    2009-01-01

    In vivo genetic toxicology tests measure direct DNA damage or the formation of gene or chromosomal mutations, and are used to predict the mutagenic and carcinogenic potential of compounds for regulatory purposes and/or to follow-up positive results from in vitro testing. These tests are widely used

  7. 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

  8. [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.

  9. Patients' attitudes towards animal testing

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 support is comparable to those held by the general public found in national surveys. A clear majority of researchers were positive towards animal testing, and large statistical differences between patients and researchers were found regarding their attitudes towards testing animals commonly held as pets...... (Pattitude towards animal testing is not shared to an equal degree with patients, who are the intended end-users and beneficiaries of medical...

  10. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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.

  12. Movement of regulatory RNA between animal cells.

    Science.gov (United States)

    Jose, Antony M

    2015-07-01

    Recent studies suggest that RNA can move from one cell to another and regulate genes through specific base-pairing. Mechanisms that modify or select RNA for secretion from a cell are unclear. Secreted RNA can be stable enough to be detected in the extracellular environment and can enter the cytosol of distant cells to regulate genes. Mechanisms that import RNA into the cytosol of an animal cell can enable uptake of RNA from many sources including other organisms. This role of RNA is akin to that of steroid hormones, which cross cell membranes to regulate genes. The potential diagnostic use of RNA in human extracellular fluids has ignited interest in understanding mechanisms that enable the movement of RNA between animal cells. Genetic model systems will be essential to gain more confidence in proposed mechanisms of RNA transport and to connect an extracellular RNA with a specific biological function. Studies in the worm C. elegans and in other animals have begun to reveal parts of this novel mechanism of cell-to-cell communication. Here, I summarize the current state of this nascent field, highlight the many unknowns, and suggest future directions. © 2015 Wiley Periodicals, Inc.

  13. 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.

  14. 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...

  15. 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.

  16. [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.

  17. 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......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...

  18. IAG ring test animal proteins 2015

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Rhee, van de N.E.; Scholtens-Toma, I.M.J.; Prins, T.W.; Vliege, J.J.M.; Pinckaers, V.G.Z.

    2015-01-01

    A ring test was organized for the detection of animal proteins in animal feed by microscopy in the framework of the annual ring tests of the IAG - International Association for Feeding stuff Analysis, Section Feeding stuff Microscopy. The organizer of the ring test was RIKILT - Wageningen UR, The

  19. IAG ring test animal proteins 2014

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Pinckaers, V.G.Z.; Scholtens-Toma, I.M.J.; Prins, T.W.; Voet, van der H.; Vliege, J.J.M.

    2014-01-01

    A ring test was organized for the detection of animal proteins in animal feed by microscopy in the framework of the annual ring tests of the IAG – International Association for Feeding stuff Analysis, Section Feeding stuff Microscopy. The aim of the ring study was to provide the participants

  20. IAG ring test animal proteins 2013

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Pinckaers, V.G.Z.; Scholtens-Toma, I.M.J.; Prins, T.W.; Vliege, J.J.M.

    2013-01-01

    A ring test was organized for the detection of animal proteins in animal feed by microscopy in the framework of the annual ring tests of the IAG - International Association for Feeding stuff Analysis, Section Feeding stuff Microscopy. The organizer of the the ring study was to provide the

  1. 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.

  2. 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.

  3. 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.

  4. IAG ring test animal proteins 2016

    NARCIS (Netherlands)

    Raamsdonk, van L.W.D.; Rhee, van de N.E.; Scholtens-Toma, I.M.J.; Prins, T.W.; Vliege, J.J.M.; Pinckaers, V.G.Z.

    2016-01-01

    The annual ring test for the detection of animal proteins in animal feed of the IAG - International Association for Feeding stuff Analysis, Section Feeding stuff Microscopy was organized by RIKILT - Wageningen UR, The Netherlands. The aim of the ring study was to provide the participants information

  5. 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…

  6. Animal Health Ireland: providing national leadership and coordination of non-regulatory animal health issues in Ireland.

    Science.gov (United States)

    More, S J; Doherty, M L; Downey, L; McKenzie, K; Devitt, C; O'Flaherty, J

    2011-12-01

    Livestock production plays an important role in the Irish economy. Regulatory animal health issues are the responsibility of government, but until recently there has been no national coordination of non-regulatory animal health issues. This gap has recently been filled with the establishment of Animal Health Ireland (AHI), a not-for-profit, partnership-based organisation providing national leadership and coordination of non-regulatory animal health issues in Ireland. Animal Health Ireland provides benefits to livestock producers and processors by providing the knowledge, education and coordination required to establish effective control strategies, both on-farm and nationally. This paper presents a brief overview of the context for AHI, and of its establishment and initial activities. Non-regulatory animal health issues have been prioritised. A series of work programmes (each focusing on a high-priority issue) have been established. Partnership is critical to success, both for AHI as an organisation and for effective farm-level transfer of knowledge. This model for national leadership and coordination of non-regulatory animal health issues may be of relevance elsewhere.

  7. 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.

  8. Animal Effects from Soviet Atmospheric Nuclear Tests

    Science.gov (United States)

    2008-03-01

    describes the effect on animal models of atmospheric nuclear weapons tests performed by the Soviet Union at the Semipalatinsk Test Site . Part I describes...understand the pathogenic mechanisms of injury and the likelihood of efficacy of proposed treatment measures. 15. SUBJECT TERMS Semipalatinsk Test Site ...the Semipalatinsk Test Site . Part 1 describes the air blast and thermal radiation effects. Part 2 covers the effects of primary (prompt) radiation and

  9. 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.

  10. 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.

  11. 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.

  12. The US FDA and animal cloning: risk and regulatory approach.

    Science.gov (United States)

    Rudenko, Larisa; Matheson, John C

    2007-01-01

    The Food and Drug Administration's (FDA's) Center for Veterinary Medicine issued a voluntary request to producers of livestock clones not to introduce food from clones or their progeny into commerce until the agency had assessed whether production of cattle, swine, sheep, or goats by somatic cell nuclear transfer (SCNT) posed any unique risks to the animal(s) involved in the process, humans, or other animals by consuming food from those animals, compared with any other assisted reproductive technology (ART) currently in use. Following a comprehensive review, no anomalies were observed in animals produced by cloning that have not also been observed in animals produced by other ARTs and natural mating. Further systematic review on the health of, and composition of meat and milk from, cattle, swine, and goat clones and the progeny of cattle and sheep did not result in the identification of any food-consumption hazards. The agency therefore concluded that food from cattle, swine, and goat clones was as safe to eat as food from animals of those species derived by conventional means. The agency also concluded that food from the progeny of the clone of any species normally consumed for food is as safe to eat as those animals. The article also describes the methodology used by the agency to analyze data and draw these conclusions, the plans the agency has proposed to manage any identified risks, and the risk communication approaches the agency has used.

  13. 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.

  14. 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

  15. 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

  16. GMOs in animal agriculture: time to consider both costs and benefits in regulatory evaluations.

    Science.gov (United States)

    Van Eenennaam, Alison L

    2013-09-25

    In 2012, genetically engineered (GE) crops were grown by 17.3 million farmers on over 170 million hectares. Over 70% of harvested GE biomass is fed to food producing animals, making them the major consumers of GE crops for the past 15 plus years. Prior to commercialization, GE crops go through an extensive regulatory evaluation. Over one hundred regulatory submissions have shown compositional equivalence, and comparable levels of safety, between GE crops and their conventional counterparts. One component of regulatory compliance is whole GE food/feed animal feeding studies. Both regulatory studies and independent peer-reviewed studies have shown that GE crops can be safely used in animal feed, and rDNA fragments have never been detected in products (e.g. milk, meat, eggs) derived from animals that consumed GE feed. Despite the fact that the scientific weight of evidence from these hundreds of studies have not revealed unique risks associated with GE feed, some groups are calling for more animal feeding studies, including long-term rodent studies and studies in target livestock species for the approval of GE crops. It is an opportune time to review the results of such studies as have been done to date to evaluate the value of the additional information obtained. Requiring long-term and target animal feeding studies would sharply increase regulatory compliance costs and prolong the regulatory process associated with the commercialization of GE crops. Such costs may impede the development of feed crops with enhanced nutritional characteristics and durability, particularly in the local varieties in small and poor developing countries. More generally it is time for regulatory evaluations to more explicitly consider both the reasonable and unique risks and benefits associated with the use of both GE plants and animals in agricultural systems, and weigh them against those associated with existing systems, and those of regulatory inaction. This would represent a shift away

  17. 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.

  18. [Animal testing ethics and human testing. Thoughts on our conduct with and our relationship to animals].

    Science.gov (United States)

    Locker, Alfred

    2004-01-01

    After many years of experimental work with animals of diverse species, the author felt confronted with the question whether the great expenditure of sacrificed animal life would pay off when compared with the results gained. By self-critically considering his work, he gradually experienced a conversion from an unconcerned experimenter to a man feeling a deep sympathy with his fellow creatures. This motivated him to ponder the true nature of animals. Instead of applying ethics--though justified in its own realm--the author preferred to look at the problem using the General Systems Theory (GST), which can describe "the other side" of any system, the side into which any system may occasionally or necessarily transform. It occurred to him to assume that--provided we see a living organism as a system (as Ludwig von Bertalanffy, the founder of GST, did)--the "other side" of the animal would correspond to an innocent "genius" who suffers for man (thereby assuming a Christ-like position), whereas in its transitory life the true essence of the animal is hidden. Thus, by fancifully viewing the role of animals destined to suffer, a connection between GST and theology or religion arises. The consequence for us would be to pay honour to the test animal, irrespective of whether or not painful experiments could be avoided. The differentiation between a sacrifice (spiritually surrendering for a greater good) and a victim (involuntarily subjected to suffering) reveals that the experimental animal primarily belongs to the latter. But it can be elevated to the former when the full meaning of its suffering becomes obvious. The same holds true for "human testing", if, in contrast to the formidable atrocities, e.g. of concentration camps, the momentum of voluntariness is guaranteed, as pioneers of medical research frequently demonstrated by carrying out experiments on themselves.

  19. 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 ...

  20. Steps towards the international regulatory acceptance of non-animal methodology in safety assessment.

    Science.gov (United States)

    Sewell, Fiona; Doe, John; Gellatly, Nichola; Ragan, Ian; Burden, Natalie

    2017-10-01

    The current animal-based paradigm for safety assessment must change. In September 2016, the UK National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs) brought together scientists from regulatory authorities, academia and industry to review progress in bringing new methodology into regulatory use, and to identify ways to expedite progress. Progress has been slow. Science is advancing to make this possible but changes are necessary. The new paradigm should allow new methodology to be adopted once it is developed rather than being based on a fixed set of studies. Regulatory authorities can help by developing Performance-Based Standards. The most pressing need is in repeat dose toxicology, although setting standards will be more complex than in areas such as sensitization. Performance standards should be aimed directly at human safety, not at reproducing the results of animal studies. Regulatory authorities can also aid progress towards the acceptance of non-animal based methodology by promoting "safe-haven" trials where traditional and new methodology data can be submitted in parallel to build up experience in the new methods. Industry can play its part in the acceptance of new methodology, by contributing to the setting of performance standards and by actively contributing to "safe-haven" trials. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. 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

    2011-01-01

    Simple Summary Many vaccines are tested for quality in experiments that require the use of large numbers of animals in procedures that often cause significant pain and distress. Newer technologies have fostered the development of vaccine quality control tests that reduce or eliminate the use of animals, but the availability of these newer methods has not guaranteed their acceptance by regulators or use by manufacturers. We discuss a strategic approach that has been used to assess and ultimately increase the use of non-animal vaccine quality tests in the U.S. and U.K. Abstract 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. PMID:26486625

  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. 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.

  4. 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.

  5. 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...

  6. Regulatory adequacy of aquatic ecotoxicity testing of nanomaterials

    DEFF Research Database (Denmark)

    Hjorth, Rune; Skjolding, Lars Michael; Sørensen, Sara Nørgaard

    2017-01-01

    between studies, which question the regulatory reliability of the data currently available. Accordingly, lack of data suited for regulatory decision-making is still a pressing issue in nanoecotoxicology even though the data availability has increased. Nevertheless, we emphasize that by deliberately...... to question whether ecotoxicity testing is now able to facilitate regulatory decision-making on manufactured nanomaterials (MNs). In this paper, we review the state of aquatic ecotoxicity testing of MNs as well as the overarching issues that challenge the reliability and relevance of such testing. We conclude...... that within the field there is an increased focus on characterization of the exposure rather than controlling exposure as it is traditionally done in guideline testing of chemicals. However, the lack of characterization options under actual testing conditions makes it difficult to make meaningful comparisons...

  7. [Regulatory effect of Erbao granules on brain-gut peptide in juvenile animal model of anorexia].

    Science.gov (United States)

    Zhang, Y; Du, Y; Wang, S

    2000-10-01

    To study the regulatory effect of Erbao granules (EBG) on central and peripheral brain-gut peptide in juvenile animal model of anorexia. Juvenile rat model of anorexia was established by imitating the major cause of infantile anorexia and treated with EBG. The cholocystokinin-octapeptide (CCK-8) and beta-endorphin (beta-EP) concentration in hypothalamus, antrum pyloricum and peripheral blood were examined by radioimmunoassay. CCK-8 concentration in hypothalamus and plasma in the model rats increased (P anorexia model.

  8. 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.

  9. Animal experimentation in Japan: regulatory processes and application for microbiological studies.

    Science.gov (United States)

    Takahashi-Omoe, H; Omoe, K

    2007-07-01

    We have conducted animal experimentation as a highly effective technique in biological studies. Also in microbiological studies, we have used experimentation to prevent and treat many infectious diseases in humans and animals. In Japan, the 'Law for the Humane Treatment and Management of Animals', which covers the consideration of the three R principles, refinement, replacement and reduction for an international humane approach to animal experimentation came into effect in June 2006. Looking towards the straightforward operation of the law in animal experimentation, three government ministries established new basic guidelines for experimentation performed in their jurisdictional research and testing facilities. For future microbiological studies involving animals in Japan, we need to perform animal experiments according to the basic guidelines in association with overseas management systems. In this report, we discussed essential actions for the management of animal experimentation in microbiological studies in Japan.

  10. 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

  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. 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

  13. Testing for Cognitive Function in Animals in a Regulatory Context

    Science.gov (United States)

    Superior cognitive functions have allowed the human species to dominate a world of incredible biological diversity. Threats to these essential capacities cannot be ignored, and a strategy is needed to evaluate the hazard posed by exposure to chemical and other agents. Because peo...

  14. 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

    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......-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....

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  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. 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.

  1. [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.

  2. 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.

  3. Regulatory and extra-regulatory testing to demonstrate radioactive material packaging safety

    International Nuclear Information System (INIS)

    Ammerman, D.J.

    1997-01-01

    Packages for the transportation of radioactive material must meet performance criteria to assure safety and environmental protection. The stringency of the performance criteria is based on the degree of hazard of the material being transported. Type B packages are used for transporting large quantities of radioisotopes (in terms of A 2 quantities). These packages have the most stringent performance criteria. Material with less than an A 2 quantity are transported in Type A packages. These packages have less stringent performance criteria. Transportation of LSA and SCO materials must be in open-quotes strong-tightclose quotes packages. The performance requirements for the latter packages are even less stringent. All of these package types provide a high level of safety for the material being transported. In this paper, regulatory tests that are used to demonstrate this safety will be described. The responses of various packages to these tests will be shown. In addition, the response of packages to extra-regulatory tests will be discussed. The results of these tests will be used to demonstrate the high level of safety provided to workers, the public, and the environment by packages used for the transportation of radioactive material

  4. RNA regulatory networks in animals and plants: a long noncoding RNA perspective.

    Science.gov (United States)

    Bai, Youhuang; Dai, Xiaozhuan; Harrison, Andrew P; Chen, Ming

    2015-03-01

    A recent highlight of genomics research has been the discovery of many families of transcripts which have function but do not code for proteins. An important group is long noncoding RNAs (lncRNAs), which are typically longer than 200 nt, and whose members originate from thousands of loci across genomes. We review progress in understanding the biogenesis and regulatory mechanisms of lncRNAs. We describe diverse computational and high throughput technologies for identifying and studying lncRNAs. We discuss the current knowledge of functional elements embedded in lncRNAs as well as insights into the lncRNA-based regulatory network in animals. We also describe genome-wide studies of large amount of lncRNAs in plants, as well as knowledge of selected plant lncRNAs with a focus on biotic/abiotic stress-responsive lncRNAs. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. 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.

  6. 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.

  7. Stability Testing of Herbal Drugs: Challenges, Regulatory Compliance and Perspectives.

    Science.gov (United States)

    Bansal, Gulshan; Suthar, Nancy; Kaur, Jasmeen; Jain, Astha

    2016-07-01

    Stability testing is an important component of herbal drugs and products (HDPs) development process. Drugs regulatory agencies across the globe have recommended guidelines for the conduct of stability studies on HDPs, which require that stability data should be included in the product registration dossier. From the scientific viewpoint, numerous chemical constituents in an herbal drug are liable to varied chemical reactions under the influence of different conditions during its shelf life. These reactions can lead to altered chemical composition of HDP and consequently altered therapeutic profile. Many reports on stability testing of HDPs have appeared in literature since the last 10 years. A review of these reports reveals that there is wide variability in temperature (-80 to 100 °C), humidity (0-100%) and duration (a few hours-36 months) for stability assessment of HDPs. Of these, only 1% studies are conducted in compliance with the regulatory guidelines for stability testing. The present review is aimed at compiling all stability testing reports, understanding key challenges in stability testing of HDPs and suggesting possible solutions for these. The key challenges are classified as chemical complexity and biochemical composition variability in raw material, selection of marker(s) and influences of enzymes. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  8. 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.

  9. Role of human neurobehavioural tests in regulatory activity on chemicals

    Science.gov (United States)

    Stephens, R.; Barker, P.

    1998-01-01

    Psychological performance tests have been used since the mid-1960s in occupational and environmental health toxicology. The interpretation of significantly different test scores in neurobehavioural studies is not straightforward in the regulation of chemicals. This paper sets out some issues which emerged from discussions at an international workshop, organised by the United Kingdom Health and Safety Executive (HSE), to discuss differences in interpretation of human neurobehavioural test data in regulatory risk assessments. The difficulties encountered by regulators confronted with neurobehavioural studies seem to be twofold; some studies lack scientific rigor; other studies, although scientifically sound, are problematic because it is not clear what interpretation to place on the results. Issues relating to each of these points are discussed. Next, scenarios within which to consider the outcomes of neurobehavioural studies are presented. Finally, conclusions and recommendations for further work are put forward.   PMID:9624273

  10. Discriminating tests of information and topological indices. Animals and trees.

    Science.gov (United States)

    Konstantinova, Elena V; Vidyuk, Maxim V

    2003-01-01

    In this paper we consider 13 information and topological indices based on the distance in a molecular graph with respect to their discrimination power. The numerical results of discriminating tests on 3490528 trees up to 21 vertices are given. The indices of the highest sensitivity are listed on the set of 1528775 alkane trees. The discrimination powers of indices are also examined on the classes of 849285 hexagonal, 298382 square, and 295365 triangular simply connected animals. The first class of animals corresponds to the structural formulas of planar benzenoid hydrocarbons. The values of all indices were calculated for all classes of animals as well as for the united set of 1443032 animals. The inspection of the data indicates the great sensitivity of four information indices and one topological index.

  11. 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.

  12. 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...

  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. Animal Models for Testing the DOHaD Hypothesis

    Science.gov (United States)

    Since the seminal work in human populations by David Barker and colleagues, several species of animals have been used in the laboratory to test the Developmental Origins of Health and Disease (DOHaD) hypothesis. Rats, mice, guinea pigs, sheep, pigs and non-human primates have bee...

  15. 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.

  16. 77 FR 12089 - Proposed Generic Communication; Regulatory Issue Summary 2012-XX: Developing Inservice Testing...

    Science.gov (United States)

    2012-02-28

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0048] Proposed Generic Communication; Regulatory Issue... CFR) Part 52, ``Licenses, Certifications, and Approvals for Nuclear Power Plants,'' to satisfy the... inservice testing programs during the initial 120-month program interval following nuclear power plant...

  17. 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.

  18. Leak testing United States Nuclear Regulatory Commission type b packaging

    International Nuclear Information System (INIS)

    Lacy, K.A.

    1995-01-01

    The Waste Isolation Pilot Plant (WTPP) is a one of its kind research and development facility operated by the Department of Energy, Carlsbad Area Office. Located in southeastern New Mexico, the WTPP is designed to demonstrate the safe, permanent disposal of transuranic (TRU) radioactive nuclear waste, accumulated from 40 years of nuclear weapons production. Before the waste can be disposed of, it must first be safely transported from generator storage sites to the WIPP. To accomplish this, the TRUPACT-II was designed and fabricated. This double containment, non-vented waste packaging successfully completed a rigorous testing program, and in 1989 received a Certificate of Compliance (C of C) from the Nuclear Regulatory Commission (NRC). Currently, the TRUPACT-II is in use at Idaho National Engineering Laboratory to transport waste on site for characterization. The DOE/CAO is responsible for maintaining the TRUPACT-II C of C. The C of C requires performance of nondestructive examination (NDE), e.g., visual testing (VT), dimensional inspections, Liquid Dye Penetrant testing (PT), and Helium Leak Detection (HLD). The Waste Isolation Division (WID) uses HLD for verification of the containment integrity. The following HLD tests are performed on annual basis or when required, i.e. repairs or component replacement: (1) fabrication verification leak tests on both the outer containment vessel (OCV) and the inner containment vessel (ICV); (2) assembly verification leak tests on the OCV and ICV upper main o-rings; and (3) assembly verification leak tests on the OCV and the ICV vent port plugs. These tests are addressed in detail as part of this presentation

  19. Animal models used for testing hydrogels in cartilage regeneration.

    Science.gov (United States)

    Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

    2018-05-14

    Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Regulatory changes raise troubling questions for genomic testing.

    Science.gov (United States)

    Evans, Barbara J; Dorschner, Michael O; Burke, Wylie; Jarvik, Gail P

    2014-11-01

    By 6 October 2014, many laboratories in the United States must begin honoring new individual data access rights created by recent changes to federal privacy and laboratory regulations. These access rights are more expansive than has been widely understood and pose complex challenges for genomic testing laboratories. This article analyzes regulatory texts and guidances to explore which laboratories are affected. It offers the first published analysis of which parts of the vast trove of data generated during next-generation sequencing will be accessible to patients and research subjects. Persons tested at affected laboratories seemingly will have access, upon request, to uninterpreted gene variant information contained in their stored variant call format, binary alignment/map, and FASTQ files. A defect in the regulations will subject some non-CLIA-regulated research laboratories to these new access requirements unless the Department of Health and Human Services takes swift action to avert this apparently unintended consequence. More broadly, all affected laboratories face a long list of daunting operational, business, compliance, and bioethical issues as they adapt to this change and to the Food and Drug Administration's recently announced plan to publish draft guidance outlining a new oversight framework for lab-developed tests.

  1. 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.

  2. Regulatory RNA at the root of animals: dynamic expression of developmental lincRNAs in the calcisponge Sycon ciliatum.

    Science.gov (United States)

    Bråte, Jon; Adamski, Marcin; Neumann, Ralf S; Shalchian-Tabrizi, Kamran; Adamska, Maja

    2015-12-22

    Long non-coding RNAs (lncRNAs) play important regulatory roles during animal development, and it has been hypothesized that an RNA-based gene regulation was important for the evolution of developmental complexity in animals. However, most studies of lncRNA gene regulation have been performed using model animal species, and very little is known about this type of gene regulation in non-bilaterians. We have therefore analysed RNA-Seq data derived from a comprehensive set of embryogenesis stages in the calcareous sponge Sycon ciliatum and identified hundreds of developmentally expressed intergenic lncRNAs (lincRNAs) in this species. In situ hybridization of selected lincRNAs revealed dynamic spatial and temporal expression during embryonic development. More than 600 lincRNAs constitute integral parts of differentially expressed gene modules, which also contain known developmental regulatory genes, e.g. transcription factors and signalling molecules. This study provides insights into the non-coding gene repertoire of one of the earliest evolved animal lineages, and suggests that RNA-based gene regulation was probably present in the last common ancestor of animals. © 2015 The Authors.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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... PROGRAMS GOOD LABORATORY PRACTICE STANDARDS Testing Facilities Operation § 160.90 Animal and other test... care of animals and other test systems. (b) All newly received test systems from outside sources shall...

  8. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  10. Extra-regulatory impact tests and analyses of the structural evaluation test unit

    International Nuclear Information System (INIS)

    Ludwigsen, J.S.; Ammerman, D.J.

    1995-01-01

    The structural evaluation test unit is roughly equivalent to a 1/3 scale model of a high level waste rail cask. The test unit was designed to just meet the requirements of NRC Regulatory Guide 7.6 when subjected to a 9 m (30 ft) free drop resulting in an impact velocity of 13.4 m/s (30 mph) onto an unyielding target in the end-on orientation. The test unit was then subjected to impacts with higher velocities to determine the amount of built-in conservatism in this design approach. Test impacts of 13.4, 20.1 and 26.8 m/s (30, 45, and 60 mph) were performed. This paper will describe the design, testing, and comparison of measured strains and deformations to the equivalent analytical predictions

  11. 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.

  12. Fluorine and fluorine tolerance in fodder of domestic animals. Part 2. Pathophysiology of fluorine and fodder tests on domestic animals

    Energy Technology Data Exchange (ETDEWEB)

    Bronsch, K; Grieser, N

    1964-01-01

    Important tests with fluorine on domestic animals were critically evaluated with the aim of coming to some conclusion about fluorine tolerance in fodder for domestic animals, keeping various different factors in mind. Slightly lower concentrations were reached than those of the NRC in the USA, reckoning on a non-optimal mineral content, especially in calcium and phosphorus, since the USA obviously used a basis for feeding which was otherwise sufficient. According to these tests, fluoride is tolerated within certain limits by domestic animals without recognisable disadvantages. There are, however, important differences between different types of animals in regard to dosage.

  13. Regulatory and biosafety issues in relation to transgenic animals in food and agriculture, feeds containing genetically modified organisms (GMO) and veterinary biologics

    International Nuclear Information System (INIS)

    Kochhar, H.P.S.; Gifford, G.A.; Kahn, S.

    2005-01-01

    Development of an effective regulatory system for genetically engineered animals and their products has been the subject of increasing discussion among researchers, industry and policy developers, as well as the public. Since transgenesis and cloning are relatively new scientific techniques, transgenic animals are new organisms for which there is limited information. The issues associated with the regulation and biosafety of transgenic animals pertain to environmental impact, human food safety, animal health and welfare, trade and ethics. To regulate this new and powerful technology predicated on limited background information is a challenge not only for the regulators, but also for the developers of such animals, who strive to prove that the animals are safe and merit bio-equivalency to their conventional counterparts. In principle, an effective regulatory sieve should permit safe products while forming a formidable barrier for those assessed of posing an unacceptable risk. Adoption of transgenic technology for use in agriculture will depend upon various factors that range from perceived benefits for humans and animals, to safe propagation, animal welfare considerations and integrity of species, as well as effects on bio-diversity. A regulatory framework designed to address the concerns connected with the environmental release of transgenic animals needs to also take into account the ability of genetically modified animals to survive and compete with conventional populations. Regulatory initiatives for biotechnology-derived animals and their products should ensure high standards for human and animal health; a sound scientific basis for evaluation; transparency and public involvement; and maintenance of genetic diversity. Feeds obtained by use of biotechnology have to be evaluated for animal and human safety by using parameters that define their molecular characterization, nutritional qualities and toxicological aspects, while veterinary biologics derived from

  14. 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.

  15. 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... Animal and other test system care. (a) There shall be standard operating procedures for the housing, feeding, handling, and care of animals and other test systems. (b) All newly received test systems from...

  16. 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...

  17. Implementation of the 3Rs (refinement, reduction, and replacement): validation and regulatory acceptance considerations for alternative toxicological test methods.

    Science.gov (United States)

    Schechtman, Leonard M

    2002-01-01

    Toxicological testing in the current regulatory environment is steeped in a history of using animals to answer questions about the safety of products to which humans are exposed. That history forms the basis for the testing strategies that have evolved to satisfy the needs of the regulatory bodies that render decisions that affect, for the most part, virtually all phases of premarket product development and evaluation and, to a lesser extent, postmarketing surveillance. Only relatively recently have the levels of awareness of, and responsiveness to, animal welfare issues reached current proportions. That paradigm shift, although sluggish, has nevertheless been progressive. New and alternative toxicological methods for hazard evaluation and risk assessment have now been adopted and are being viewed as a means to address those issues in a manner that considers humane treatment of animals yet maintains scientific credibility and preserves the goal of ensuring human safety. To facilitate this transition, regulatory agencies and regulated industry must work together toward improved approaches. They will need assurance that the methods will be reliable and the results comparable with, or better than, those derived from the current classical methods. That confidence will be a function of the scientific validation and resultant acceptance of any given method. In the United States, to fulfill this need, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and its operational center, the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), have been constituted as prescribed in federal law. Under this mandate, ICCVAM has developed a process and established criteria for the scientific validation and regulatory acceptance of new and alternative methods. The role of ICCVAM in the validation and acceptance process and the criteria instituted toward that end are described. Also

  18. 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)

  19. 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

  20. Restrictions on antimicrobial use in food animal production: an international regulatory and economic survey

    Science.gov (United States)

    2013-01-01

    Background The administration of antimicrobial drugs to food animals at low doses for extended durations for growth promotion and disease prevention has been linked to the global health crisis of antimicrobial resistance. Internationally, multiple jurisdictions have responded by restricting antimicrobial use for these purposes, and by requiring a veterinary prescription to use these drugs in food animals. Opponents of these policies have argued that restrictions have been detrimental to food animal production where they have been adopted. Methods We surveyed the antimicrobial use policies of 17 political jurisdictions outside of the United States with respect to growth promotion, disease prevention, and veterinary oversight, and reviewed the available evidence regarding their production impacts, including measures of animal health. Jurisdictions were included if they were a top-five importer of a major U.S. food animal product in 2011, as differences between the policies of the U.S. and other jurisdictions may lead to trade barriers to U.S. food animal product exports. Jurisdictions were also included if information on their policies was publicly available in English. We searched the peer-reviewed and grey literatures and corresponded with jurisdictions’ U.S. embassies, regulators, and local experts. Results Jurisdictions were categorized by whether they prohibit use of antimicrobials for growth promotion and/or use of antimicrobials without a veterinary prescription. Of the 17 jurisdictions surveyed, six jurisdictions have prohibited both types of use, five jurisdictions have prohibited one use but not the other use, and five jurisdictions have not prohibited either use, while information was not available for one jurisdiction. Data on the production impacts of these prohibitions were limited, although available data, especially from Denmark and Sweden, suggest that restrictions on growth promotion use can be implemented with minimal production consequences

  1. Restrictions on antimicrobial use in food animal production: an international regulatory and economic survey.

    Science.gov (United States)

    Maron, Dina Fine; Smith, Tyler J S; Nachman, Keeve E

    2013-10-16

    The administration of antimicrobial drugs to food animals at low doses for extended durations for growth promotion and disease prevention has been linked to the global health crisis of antimicrobial resistance. Internationally, multiple jurisdictions have responded by restricting antimicrobial use for these purposes, and by requiring a veterinary prescription to use these drugs in food animals. Opponents of these policies have argued that restrictions have been detrimental to food animal production where they have been adopted. We surveyed the antimicrobial use policies of 17 political jurisdictions outside of the United States with respect to growth promotion, disease prevention, and veterinary oversight, and reviewed the available evidence regarding their production impacts, including measures of animal health. Jurisdictions were included if they were a top-five importer of a major U.S. food animal product in 2011, as differences between the policies of the U.S. and other jurisdictions may lead to trade barriers to U.S. food animal product exports. Jurisdictions were also included if information on their policies was publicly available in English. We searched the peer-reviewed and grey literatures and corresponded with jurisdictions' U.S. embassies, regulators, and local experts. Jurisdictions were categorized by whether they prohibit use of antimicrobials for growth promotion and/or use of antimicrobials without a veterinary prescription. Of the 17 jurisdictions surveyed, six jurisdictions have prohibited both types of use, five jurisdictions have prohibited one use but not the other use, and five jurisdictions have not prohibited either use, while information was not available for one jurisdiction. Data on the production impacts of these prohibitions were limited, although available data, especially from Denmark and Sweden, suggest that restrictions on growth promotion use can be implemented with minimal production consequences. A majority of leading U.S. trade

  2. Future time perspective, regulatory focus, and selection, optimization, and compensation: Testing a longitudinal model

    NARCIS (Netherlands)

    Baltes, B.B.; Wynne, K.; Sirabian, M.; Krenn, D.; Lange, A.H. de

    2014-01-01

    This study examines the behavioral processes through which future time perspective (FTP) and regulatory focus may influence coping behaviors in older workers. A three-wave longitudinal study was conducted to test a novel model, positing that FTP affects regulatory focus, which then influences the

  3. 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...... resulted in a lower reliability. Therefore, the design of reference population is important for improving the reliability of genomic prediction. With regard to model, the Bayesian mixture model in general led to slightly a higher reliability of genomic prediction than the GBLUP model...

  4. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

    OpenAIRE

    Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

  5. Animator

    Science.gov (United States)

    Tech Directions, 2008

    2008-01-01

    Art and animation work is the most significant part of electronic game development, but is also found in television commercials, computer programs, the Internet, comic books, and in just about every visual media imaginable. It is the part of the project that makes an abstract design idea concrete and visible. Animators create the motion of life in…

  6. NRC review of passive reactor design certification testing programs: Overview, progress, and regulatory perspective

    Energy Technology Data Exchange (ETDEWEB)

    Levin, A.E.

    1995-09-01

    New reactor designs, employing passive safety systems, are currently under development by reactor vendors for certification under the U.S. Nuclear Regulatory Commission`s (NRC`s) design certification rule. The vendors have established testing programs to support the certification of the passive designs, to meet regulatory requirements for demonstration of passive safety system performance. The NRC has, therefore, developed a process for the review of the vendors` testing programs and for incorporation of the results of those reviews into the safety evaluations for the passive plants. This paper discusses progress in the test program reviews, and also addresses unique regulatory aspects of those reviews.

  7. 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.

  8. 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.

  9. 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.

  10. Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation.

    Science.gov (United States)

    Thomson, Angus W; Zahorchak, Alan F; Ezzelarab, Mohamed B; Butterfield, Lisa H; Lakkis, Fadi G; Metes, Diana M

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

  11. 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.

  12. [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.

  13. 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. ...

  14. 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...

  15. 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.

  16. 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.

  17. 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...

  18. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M; Leist, Marcel; Allen, Sandra; Arand, Michael; Buetler, Timo; Delrue, Nathalie; FitzGerald, Rex E; Hartung, Thomas; Heinonen, Tuula; Hogberg, Helena; Bennekou, Susanne Hougaard; Lichtensteiger, Walter; Oggier, Daniela; Paparella, Martin; Axelstad, Marta; Piersma, Aldert; Rached, Eva; Schilter, Benoît; Schmuck, Gabriele; Stoppini, Luc; Tongiorgi, Enrico; Tiramani, Manuela; Monnet-Tschudi, Florianne; Wilks, Martin F; Ylikomi, Timo; Fritsche, Ellen

    2015-02-01

    A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

  19. Testing the new animal phylogeny: a phylum level molecular analysis of the animal kingdom.

    Science.gov (United States)

    Bourlat, Sarah J; Nielsen, Claus; Economou, Andrew D; Telford, Maximilian J

    2008-10-01

    The new animal phylogeny inferred from ribosomal genes some years ago has prompted a number of radical rearrangements of the traditional, morphology based metazoan tree. The two main bilaterian clades, Deuterostomia and Protostomia, find strong support, but the protostomes consist of two sister groups, Ecdysozoa and Lophotrochozoa, not seen in morphology based trees. Although widely accepted, not all recent molecular phylogenetic analyses have supported the tripartite structure of the new animal phylogeny. Furthermore, even if the small ribosomal subunit (SSU) based phylogeny is correct, there is a frustrating lack of resolution of relationships between the phyla that make up the three clades of this tree. To address this issue, we have assembled a dataset including a large number of aligned sequence positions as well as a broad sampling of metazoan phyla. Our dataset consists of sequence data from ribosomal and mitochondrial genes combined with new data from protein coding genes (5139 amino acid and 3524 nucleotide positions in total) from 37 representative taxa sampled across the Metazoa. Our data show strong support for the basic structure of the new animal phylogeny as well as for the Mandibulata including Myriapoda. We also provide some resolution within the Lophotrochozoa, where we confirm support for a monophyletic clade of Echiura, Sipuncula and Annelida and surprising evidence of a close relationship between Brachiopoda and Nemertea.

  20. Testing Experimental Compounds against Leishmaniansis in Laboratory Animal Model Systems

    Science.gov (United States)

    1984-09-01

    consulted in five human and two canine cases of suspected leishmaniasis. Two of the 5 human cases were isoenzyme typed as L. b. braziliensis ( Peru ...animal. The latter may be of use in controlling some of the complications of diabetes . %’Wr WF ’ 56 PU BLICAT I ONS_ Griffith, O.W., "Mechanism of

  1. 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

  2. HIV testing updates and challenges: when regulatory caution and public health imperatives collide.

    Science.gov (United States)

    Branson, Bernard M

    2015-03-01

    Numerous improvements in HIV testing technology led recently to the first revision of recommendations for diagnostic laboratory testing in the USA in 25 years. Developments in HIV testing continue to produce tests that identify HIV infection earlier with faster turnaround times for test results. These play an important role in identifying HIV infection during the highly infectious acute phase, which has implication for both patient management and public health interventions to control the spread of HIV. Access to these developments, however, is often delayed by the regulatory apparatus for approval and oversight of HIV testing in the USA. This article summarizes recent developments in HIV diagnostic testing technology, outlines their implications for clinical management and public health, describes current systems of regulatory oversight for HIV testing in the USA, and proposes alternatives that could expedite access to improved tests as they become available.

  3. 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.

  4. Regulatory Guide 1.79 safety injection recirculation test requirements, fact or fiction

    International Nuclear Information System (INIS)

    Roberts, J.K.

    1976-01-01

    The overwhelming concern of the general public in this day of state nuclear initiatives is the basic question, ''is nuclear power safe.'' Much of this concern has focused on the emergency core cooling systems. This public attention spotlights the testing organization's responsibility during startup of proving the operation and reliability of the emergency core cooling systems. The standard established by the Nuclear Regulatory Commission for testing emergency core cooling systems is Regulatory Guide 1.79 ''Preoperational Testing of Emergency Core Cooling Systems for Pressurized Water Reactors''. The nuclear industry must satisfy the testing requirements of Regulatory Guide 1.79 to meet their responsibility to the public; and to prevent future embarrassment when questioned on the adequacy of emergency core cooling systems

  5. Implementation of in vitro replacement technologies in regulatory drug testing - An innovation systems perspective

    NARCIS (Netherlands)

    Kooijman, M.; Van Meer, P.J.K.; Moors, E.H.M.; Hekkert, M.P.; Schellekens, H.

    2011-01-01

    The replacement of in vivo methods by in vitro methods in regulatory drug testing is rare. The aim of this research is to identify barriers and drivers of the replacement of in vivo methods by in vitro methods in Europe. We studied two cases. The first case is the Draize eye test. Since 2009, the in

  6. 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.

  7. 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.

  8. Advancing the 3Rs in regulatory toxicology - Carcinogenicity testing: Scope for harmonisation and advancing the 3Rs in regulated sectors of the European Union.

    Science.gov (United States)

    Annys, Erwin; Billington, Richard; Clayton, Rick; Bremm, Klaus-Dieter; Graziano, Michael; McKelvie, Jo; Ragan, Ian; Schwarz, Michael; van der Laan, Jan Willem; Wood, Charles; Öberg, Mattias; Wester, Piet; Woodward, Kevin N

    2014-07-01

    Different government agencies operating in the European Union regulate different types of chemical products but all require testing for carcinogenicity to support applications for product marketing and commercialisation. A conference was held in Brussels in 2013 where representatives of the pharmaceutical, animal health, chemical and plant protection industries, together with representatives of regulatory agencies, universities and other stakeholders, met under the auspices of The European Partnership for Alternative Approaches to Animal Testing (EPAA) to discuss the varying requirements for carcinogenicity testing, and how these studies might be refined to improve hazard evaluation and risk assessment while implementing principles of the 3Rs (replacement, refinement and reduction in animal studies). While there are some similarities, the regulatory approaches in pharmaceutical, animal health, chemical and plant protection sectors have varying degrees of flexibility in requirements for carcinogenicity testing, to an extent reflecting concerns over the magnitude and duration of human exposure, either directly as in therapeutic exposure to pharmaceuticals, or indirectly through the ingestion of residues of veterinary drugs or plant protection chemicals. The article discusses these differences and other considerations for modified carcinogenicity testing paradigms on the basis of scientific and 3Rs approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Real-Time Target Motion Animation for Missile Warning System Testing

    Science.gov (United States)

    2006-04-01

    T. Perkins, R. Sundberg, J. Cordell, Z. Tun , and M. Owen, Real-time Target Motion Animation for Missile Warning System Testing, Proc. SPIE Vol 6208...Z39-18 Real-time target motion animation for missile warning system testing Timothy Perkins*a, Robert Sundberga, John Cordellb, Zaw Tunb, Mark

  10. 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.

  11. 77 FR 38751 - Codification of Animal Testing Policy

    Science.gov (United States)

    2012-06-29

    ... opinion. The 1984 Policy stated: It is important to keep in mind that neither the FHSA nor the Commission... testing, ``[The CPSC Directorate for] Health Sciences will incorporate the techniques into the Commission... developed.'' Id. Since the 1984 Policy, there have been new methods accepted by the scientific community as...

  12. 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)

  13. 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.

  14. Regulatory risk control through mandatory occupational safety and health (OSH) certification and testing regimes (CTRs)

    NARCIS (Netherlands)

    Zwetsloot, G.I.J.M.; Hale, A.; Zwanikken, S.

    2011-01-01

    Governments make increasing use of private certification and testing infrastructures as an alternative for traditional regulatory arrangements in several areas including occupational safety and health (OSH).This research, commissioned by the Dutch Inspectorate for Work and Income (IWI), concerns an

  15. TEST OF AN ANIMAL DRAWN FIELD IMPLEMENT CART

    Directory of Open Access Journals (Sweden)

    Paolo Spugnoli

    2008-06-01

    Full Text Available The field performance of a horse-drawn hitch cart equipped with a PTO system powered by the two cart ground wheels have been investigated. For this purpose field tests on clay and turf soil, with varying ballast and PTO torque, have been carried out pulling the cart by a tractor. Preliminary tests were aimed at assessing the traction capability of horse breed. These tests showed that the mean draught force given by two of these horses was 173daN, average working speed was about 1m*s-1, resulting a mean draught power developed by each horse of about 0.86kW. The PTO cart system performance has shown that the torque has not exceeded 2.4daN*m, maximum draught or PTO power was 1.15kW, rotation speed just higher than 400min-1, with mean efficiency of about 50%. These values are consistent with horse performance and small haymaking, fertilizing, seeding and chemical application machine requirements.

  16. 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.

  17. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  18. International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes

    DEFF Research Database (Denmark)

    Bal-Price, Anna; Crofton, Kevin M.; Leist, Marcel

    2015-01-01

    . The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified...... as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment...

  19. Animal experimentation.

    Science.gov (United States)

    Kolar, Roman

    2006-01-01

    Millions of animals are used every year in often times extremely painful and distressing scientific procedures. Legislation of animal experimentation in modern societies is based on the supposition that this is ethically acceptable when certain more or less defined formal (e.g. logistical, technical) demands and ethical principles are met. The main parameters in this context correspond to the "3Rs" concept as defined by Russel and Burch in 1959, i.e. that all efforts to replace, reduce and refine experiments must be undertaken. The licensing of animal experiments normally requires an ethical evaluation process, often times undertaken by ethics committees. The serious problems in putting this idea into practice include inter alia unclear conditions and standards for ethical decisions, insufficient management of experiments undertaken for specific (e.g. regulatory) purposes, and conflicts of interest of ethics committees' members. There is an ongoing societal debate about ethical issues of animal use in science. Existing EU legislation on animal experimentation for cosmetics testing is an example of both the public will for setting clear limits to animal experiments and the need to further critically examine other fields and aspects of animal experimentation.

  20. Balancing technical and regulatory concerns related to testing and control of performance assessment software

    International Nuclear Information System (INIS)

    Seitz, R.R.; Matthews, S.D.; Kostelnik, K.M.

    1990-01-01

    What activities are required to assure that a performance assessment (PA) computer code operates as it is intended? Answers to this question will vary depending on the individual's area of expertise. Different perspectives on testing and control of PA software are discussed based on interpretations of the testing and control process associated with the different involved parties. This discussion leads into the presentation of a general approach to software testing and control that address regulatory requirements. Finally, the need for balance between regulatory and scientific concerns is illustrated through lessons learned in previous implementations of software testing and control programs. Configuration control and software testing are required to provide assurance that a computer code performs as intended. Configuration control provides traceability and reproducibility of results produced with PA software and provides a system to assure that users have access to the current version of the software. Software testing is conducted to assure that the computer code has been written properly, solution techniques have been properly implemented, and the software is capable of representing the behavior of the specific system to be modeled. Comprehensive software testing includes: software analysis, verification testing, benchmark testing, and site-specific calibration/validation testing

  1. 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)

  2. Can TTIP Improve Laboratory Animal Welfare in Safety Testing and 3Rs?

    Science.gov (United States)

    Busquet, Francois; Zurlo, Joanne; Hartung, Thomas

    2016-05-01

    In the context of the current negotiations between the European Union (EU) and the United States under the Transatlantic Trade Investment Partnership (TTIP), there is the opportunity to look at both legislative frameworks to better pinpoint convergences, synergies, and gaps when it comes to use of laboratory animals for scientific purposes and bring together the best of both worlds. The objectives in this article are to indicate what are the current EU pieces of legislation that are relevant under TTIP regarding the uses of laboratory animals for scientific purposes under the regulations about cosmetics and chemicals, among others. The same approach will be taken to look at the relevant American legal frameworks, that is, the Food and Cosmetics Act and the Toxic Safety Control Act as well as its most recent reauthorization. In conclusion, the authors will identify future frameworks that can contribute to the harmonization of regulatory standards and further steps where TTIP negotiators should strengthen regulatory cooperation. © 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.

  3. Innovative approaches to reduce animal testing : replace whenever possible, reduce through refinement and mechanistic understanding

    NARCIS (Netherlands)

    Ravenzwaay, van B.

    2013-01-01

    'Many of the in vitro toxicological studies have not been sufficiently validated to determine their applicability domain, even less have gained regulatory acceptance. Major advantage of in vitro testing today is the early identification of significant hazards in compound development and reduced and

  4. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones.

    Science.gov (United States)

    Nuss, Katja M R; Auer, Joerg A; Boos, Alois; von Rechenberg, Brigitte

    2006-08-15

    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. 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. 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. 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.

  5. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

    Science.gov (United States)

    Nuss, Katja MR; Auer, Joerg A; Boos, Alois; Rechenberg, Brigitte von

    2006-01-01

    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. PMID:16911787

  6. 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...

  7. An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

    OpenAIRE

    Nuss, Katja MR; Auer, Joerg A; Boos, Alois; Rechenberg, Brigitte von

    2006-01-01

    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. Result...

  8. 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.

  9. Operating the Advanced Test Reactor in today's economic and regulatory environment

    International Nuclear Information System (INIS)

    Furstenau, R.V.; Patrick, M.E.; Mecham, D.C.

    1999-01-01

    The Advanced Test Reactor (ATR), located at the Idaho National Engineering and Environmental Laboratory, is the US Department of Energy's largest and most versatile test reactor. Base programs at ATR are planned well into the 21st century. The ATR and support facilities along with an overview of current programs will be reviewed, but the main focus of the presentation will be on the impact that today's economic and regulatory concerns have had on the operation of this test reactor. Today's economic and regulatory concerns have demanded more work be completed at lower cost while increasing the margin of safety. By the beginning of the 1990 s, federal budgets for research generally and particularly for nuclear research had decreased dramatically. Many national needs continued to require testing in the ATR; but demanded lower cost, increased efficiency, improved performance, and an increased margin of safety. At the same time budgets were decreasing, there was an increase in regulatory compliance activity. The new standards imposed higher margins of safety. The new era of greater openness and higher safety standards complemented research demands to work safer, smarter and more efficiently. Several changes were made at the ATR to meet the demands of the sponsors and public. Such changes included some workforce reductions, securing additional program sponsors, upgrading some facilities, dismantling other facilities, and implementing new safety programs. (author)

  10. Debate on GMOs health risks after statistical findings in regulatory tests.

    Science.gov (United States)

    de Vendômois, Joël Spiroux; Cellier, Dominique; Vélot, Christian; Clair, Emilie; Mesnage, Robin; Séralini, Gilles-Eric

    2010-10-05

    We summarize the major points of international debate on health risk studies for the main commercialized edible GMOs. These GMOs are soy, maize and oilseed rape designed to contain new pesticide residues since they have been modified to be herbicide-tolerant (mostly to Roundup) or to produce mutated Bt toxins. The debated alimentary chronic risks may come from unpredictable insertional mutagenesis effects, metabolic effects, or from the new pesticide residues. The most detailed regulatory tests on the GMOs are three-month long feeding trials of laboratory rats, which are biochemically assessed. The tests are not compulsory, and are not independently conducted. The test data and the corresponding results are kept in secret by the companies. Our previous analyses of regulatory raw data at these levels, taking the representative examples of three GM maize NK 603, MON 810, and MON 863 led us to conclude that hepatorenal toxicities were possible, and that longer testing was necessary. Our study was criticized by the company developing the GMOs in question and the regulatory bodies, mainly on the divergent biological interpretations of statistically significant biochemical and physiological effects. We present the scientific reasons for the crucially different biological interpretations and also highlight the shortcomings in the experimental protocols designed by the company. The debate implies an enormous responsibility towards public health and is essential due to nonexistent traceability or epidemiological studies in the GMO-producing countries.

  11. 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....

  12. Leak rates and structural integrity tests for Laguna Verde Nuclear Power Plant primary containment. Regulatory experience

    International Nuclear Information System (INIS)

    Mamani Alegria, Yuri Raul; Salgado Gonzalez, Julio Ricardo

    1996-01-01

    In the Appendix A General Design Criteria for Nuclear Power Plants of the US Code of Federal Regulations title 10 part 50 (10CFR50) is established the Criterion 1 Quality standards and records which requires that structures, systems and components important to safety should be tested to quality standards according with the importance of the safety function to be performed. This regulation has been adopted by the Mexican Regulatory Body (CNSNS) for their nuclear power plants. (author)

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

    Science.gov (United States)

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

    2012-04-01

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

  14. 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.

  15. Antigen-specific tolerance inhibits autoimmune uveitis in pre-sensitized animals by deletion and CD4+CD25+ T-regulatory cells.

    Science.gov (United States)

    Matta, Bharati; Jha, Purushottam; Bora, Puran S; Bora, Nalini S

    2010-02-01

    The objective of this study was to inhibit experimental autoimmune anterior uveitis (EAAU) by establishing antigen-specific immune tolerance in animals pre-sensitized with melanin-associated antigen (MAA). Intravenous administration of MAA on days 6, 7, 8 and 9 post-immunization induced tolerance and inhibited EAAU in all Lewis rats. The number of cells (total T cells, CD4(+) T cells and CD8(+) T cells) undergoing apoptosis dramatically increased in the popliteal lymph nodes (LNs) of the tolerized animals compared with non-tolerized animals. In addition, Fas ligand (FasL), TNF receptor 1 (TNFR1) and caspase-8 were upregulated in tolerized rats. Proliferation of total lymphocytes, CD4(+)T cells and CD8(+) T cells (harvested from the popliteal LNs) in response to antigenic stimulation was drastically reduced in the state of tolerance compared with the cells from non-tolerized animals. The level of interferon (IFN)-gamma and IL-2 decreased, whereas TGF-beta2 was elevated in the state of tolerance. Furthermore, the number of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) increased in the popliteal LNs of tolerized animals compared with non-tolerized animals. In conclusion, our results suggest that deletion of antigen-specific T cells by apoptosis and active suppression mediated by Tregs has an important role in the induction of antigen specific immune tolerance in animals with an established immune response against MAA.

  16. 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.

  17. 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....

  18. A comprehensive review of regulatory test methods for endocrine adverse health effects.

    Science.gov (United States)

    Manibusan, M K; Touart, L W

    2017-07-01

    Development of new endocrine disruption-relevant test methods has been the subject of intensive research efforts for the past several decades, prompted in part by mandates in the 1996 Food Quality Protection Act (FQPA). While scientific understanding and test methods have advanced, questions remain on whether current scientific methods are capable of adequately addressing the complexities of the endocrine system for regulatory health and ecological risk assessments. The specific objective of this article is to perform a comprehensive, detailed evaluation of the adequacy of current test methods to inform regulatory risk assessments of whether a substance has the potential to perturb endocrine-related pathways resulting in human adverse effects. To that end,  approximately 42 existing test guidelines (TGs) were considered in the evaluation of coverage for endocrine-related adverse effects. In addition to evaluations of whether test methods are adequate to capture endocrine-related effects, considerations of further enhancements to current test methods, along with the need to develop novel test methods to address existing test method gaps are described. From this specific evaluation, up to 35 test methods are capable of informing whether a chemical substance perturbs known endocrine related biological pathways. Based on these findings, it can be concluded that current validated test methods are adequate to discern substances that may perturb the endocrine system, resulting in an adverse health effect. Together, these test methods predominantly form the core data requirements of a typical food-use pesticide registration submission. It is recognized, however, that the current state of science is rapidly advancing and there is a need to update current test methods to include added enhancements to ensure continued coverage and public health and environmental protection.

  19. 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.

  20. The Issue Animal in the Perspective of the Federal Supreme Court and the "Regulatory Aspects Of Legal Status

    Directory of Open Access Journals (Sweden)

    Mery Chalfun

    2016-12-01

    Full Text Available The present work aims to analyze the legal nature of nonhuman animals in the doctrine of Animal Law, legal order and position of the Federal Supreme Court based on judgments that deal with conflict between cultural manifestation and cruelty to animals. Brazilian legislation calls for a multiplicity of positions on the legal nature of animals, which may influence positively or negatively the treatment accorded to them. It can be seen that in the STF the predominance of two understandings: anthropocentric, equivalent to good, while of another biocentric, moral consideration as to the animals and possibility of change of the legal nature.

  1. A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

    Directory of Open Access Journals (Sweden)

    Giannakou C

    2016-06-01

    Full Text Available Christina Giannakou,1,2 Margriet VDZ Park,1 Wim H de Jong,1 Henk van Loveren,1,2 Rob J Vandebriel,1 Robert E Geertsma1 1Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 2Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands Abstract: Nanomaterials (NMs are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome

  2. Setting priorities for non-regulatory animal health in Ireland: results from an expert Policy Delphi study and a farmer priority identification survey.

    Science.gov (United States)

    More, Simon J; McKenzie, Ken; O'Flaherty, Joe; Doherty, Michael L; Cromie, Andrew R; Magan, Mike J

    2010-07-01

    Agriculture is a very important contributor to the Irish economy. In Ireland, national animal health services have been a government, rather than an industry, responsibility. In 2009, Animal Health Ireland (AHI) was established to provide a partnership approach to national leadership of non-regulatory animal health issues (those not subject to national and/or EU regulation). The objectives of this study were to elicit opinion from experts and farmers about non-regulatory animal health issues facing Irish livestock industries, including prioritisation of animal health issues and identification of opportunities to maximise the effective use of AHI resources. The study was conducted with experts using Policy Delphi methodology over three rounds, and with farmers using a priority identification survey. Non-regulatory bovine diseases/conditions were prioritised by both experts and farmers based on impact and international competitiveness. For each high-priority disease/condition, experts were asked to provide an assessment based on cost, impact, international perception, impediment to international market access and current resource usage effectiveness. Further information was also sought from experts about resource allocation preferences, methods to improve education and coordination, and innovative measures to improve prevention and management. There was close agreement between responses from experts and dairy farmers: each gave highest priority to 3 diseases with a biosecurity risk (subsequently termed 'biosecure diseases') (bovine viral diarrhoea [BVD], infectious bovine rhinotracheitis [IBR], paratuberculosis) and 4 diseases/conditions generally without a biosecurity risk ('non-biosecure diseases/conditions') (fertility, udder health/milk quality, lameness, calf health). Beef farmers also prioritised parasitic conditions and weanling pneumonia. The adverse impact of biosecure diseases is currently considered relatively minor by experts, but would increase

  3. Measuring Cognitive Load in Test Items: Static Graphics versus Animated Graphics

    Science.gov (United States)

    Dindar, M.; Kabakçi Yurdakul, I.; Inan Dönmez, F.

    2015-01-01

    The majority of multimedia learning studies focus on the use of graphics in learning process but very few of them examine the role of graphics in testing students' knowledge. This study investigates the use of static graphics versus animated graphics in a computer-based English achievement test from a cognitive load theory perspective. Three…

  4. 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...

  5. 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)

  6. 21 CFR 312.160 - Drugs for investigational use in laboratory research animals or in vitro tests.

    Science.gov (United States)

    2010-04-01

    ... 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 investigational use in laboratory research animals or in vitro tests. (a) Authorization to ship. (1)(i) A person...

  7. 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

    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......) 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...... of the test is not formally considered when a test is evaluated. Therefore, the result is often a DTE where test sensitivity and specificity estimates are biased, either because of problems with establishing the true infection status or because the test detects another aspect of the infection (and analyte...

  8. 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

  9. 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.

  10. 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....

  11. 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.

  12. 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

  13. Juvenile Animal Testing: Assessing Need and Use in the Drug Product Label.

    Science.gov (United States)

    Baldrick, Paul

    2018-01-01

    Juvenile animal testing has become an established part of drug development to support safe clinical use in the human pediatric population and for eventual drug product label use. A review of European Paediatric Investigation Plan decisions showed that from 2007 to mid-2017, 229 drugs had juvenile animal work requested, almost exclusively incorporating general toxicology study designs, in rat (57.5%), dog (8%), mouse (4.5%), monkey (4%), pig (2%), sheep (1%), rabbit (1%), hamster (0.5%), and species not specified (21.5%). A range of therapeutic areas were found, but the most common areas were infectious diseases (15%), endocrinology (13.5%), oncology (13%), neurology (11%), and cardiovascular diseases (10%). Examination of major clinical indications within these therapeutic areas showed some level of consistency in the species of choice for testing and the pediatric age that required support. Examination of juvenile animal study findings presented in product labels raises questions around how useful the data are to allow prescribing the drug to a child. It is hopeful that the new ICH S11 guideline "Nonclinical Safety Testing in Support of Development of Pediatric Medicines" currently in preparation will aid drug developers in clarifying the need for juvenile animal studies as well as in promoting a move away from toxicology studies with a conventional design. This would permit more focused testing to examine identified areas of toxicity or safety concerns and clarify the presentation/interpretation of juvenile animal study findings for proper risk assessment by a drug prescriber.

  14. A Tool for Predicting Regulatory Approval After Phase II Testing of New Oncology Compounds.

    Science.gov (United States)

    DiMasi, J A; Hermann, J C; Twyman, K; Kondru, R K; Stergiopoulos, S; Getz, K A; Rackoff, W

    2015-11-01

    We developed an algorithm (ANDI) for predicting regulatory marketing approval for new cancer drugs after phase II testing has been conducted, with the objective of providing a tool to improve drug portfolio decision-making. We examined 98 oncology drugs from the top 50 pharmaceutical companies (2006 sales) that first entered clinical development from 1999 to 2007, had been taken to at least phase II development, and had a known final outcome (research abandonment or regulatory marketing approval). Data on safety, efficacy, operational, market, and company characteristics were obtained from public sources. Logistic regression and machine-learning methods were used to provide an unbiased approach to assess overall predictability and to identify the most important individual predictors. We found that a simple four-factor model (activity, number of patients in the pivotal phase II trial, phase II duration, and a prevalence-related measure) had high sensitivity and specificity for predicting regulatory marketing approval. © 2015 American Society for Clinical Pharmacology and Therapeutics.

  15. 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

  16. 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

  17. 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

  18. [Regulatory radiation risks' for the population and natural objects within the Semipalatinsk Test Site].

    Science.gov (United States)

    Spiridonov, S I; Teten'kin, V L; Mukusheva, M K; Solomatin, V M

    2008-01-01

    Advisability of using risks as indicators for estimating radiation impacts on environmental objects and humans has been jusified. Results are presented from identification of dose burdens distribution to various cohorts of the population living within the Semipalatinsk Test Site (STS) and consuming contaminated farm products. Parameters of dose burden distributions are estimated for areas of livestock grazing and the most contaminated sectors within these areas. Dose distributions to meadow plants for the above areas have been found. Regulatory radiation risks for the STS population and meadow ecosystem components have been calculated. Based on the parameters estimated, levels of radiation exposure of the population and herbaceous plants have been compared.

  19. 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.

  20. Animal investigation program 1978 annual report: Nevada Test Site and vicinity

    International Nuclear Information System (INIS)

    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

  1. Non-animal assessment of skin sensitization hazard: Is an integrated testing strategy needed, and if so what should be integrated?

    Science.gov (United States)

    Roberts, David W; Patlewicz, Grace

    2018-01-01

    There is an expectation that to meet regulatory requirements, and avoid or minimize animal testing, integrated approaches to testing and assessment will be needed that rely on assays representing key events (KEs) in the skin sensitization adverse outcome pathway. Three non-animal assays have been formally validated and regulatory adopted: the direct peptide reactivity assay (DPRA), the KeratinoSens™ assay and the human cell line activation test (h-CLAT). There have been many efforts to develop integrated approaches to testing and assessment with the "two out of three" approach attracting much attention. Here a set of 271 chemicals with mouse, human and non-animal sensitization test data was evaluated to compare the predictive performances of the three individual non-animal assays, their binary combinations and the "two out of three" approach in predicting skin sensitization potential. The most predictive approach was to use both the DPRA and h-CLAT as follows: (1) perform DPRA - if positive, classify as sensitizing, and (2) if negative, perform h-CLAT - a positive outcome denotes a sensitizer, a negative, a non-sensitizer. With this approach, 85% (local lymph node assay) and 93% (human) of non-sensitizer predictions were correct, whereas the "two out of three" approach had 69% (local lymph node assay) and 79% (human) of non-sensitizer predictions correct. The findings are consistent with the argument, supported by published quantitative mechanistic models that only the first KE needs to be modeled. All three assays model this KE to an extent. The value of using more than one assay depends on how the different assays compensate for each other's technical limitations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Nucleic-acid testing, new platforms and nanotechnology for point-of-decision diagnosis of animal pathogens.

    Science.gov (United States)

    Teles, Fernando; Fonseca, Luís

    2015-01-01

    Accurate disease diagnosis in animals is crucial for animal well-being but also for preventing zoonosis transmission to humans. In particular, livestock diseases may constitute severe threats to humans due to the particularly high physical contact and exposure and, also, be the cause of important economic losses, even in non-endemic countries, where they often arise in the form of rapid and devastating epidemics. Rapid diagnostic tests have been used for a long time in field situations, particularly during outbreaks. However, they mostly rely on serological approaches, which may confirm the exposure to a particular pathogen but may be inappropriate for point-of-decision (point-of-care) settings when emergency responses supported on early and accurate diagnosis are required. Moreover, they often exhibit modest sensitivity and hence significantly depend on later result confirmation in central or reference laboratories. The impressive advances observed in recent years in materials sciences and in nanotechnology, as well as in nucleic-acid synthesis and engineering, have led to an outburst of new in-the-bench and prototype tests for nucleic-acid testing towards point-of-care diagnosis of genetic and infectious diseases. Manufacturing, commercial, regulatory, and technical nature issues for field applicability more likely have hindered their wider entrance into veterinary medicine and practice than have fundamental science gaps. This chapter begins by outlining the current situation, requirements, difficulties, and perspectives of point-of-care tests for diagnosing diseases of veterinary interest. Nucleic-acid testing, particularly for the point of care, is addressed subsequently. A range of valuable signal transduction mechanisms commonly employed in proof-of-concept schemes and techniques born on the analytical chemistry laboratories are also described. As the essential core of this chapter, sections dedicated to the principles and applications of microfluidics, lab

  3. 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

  4. 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.

  5. 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

    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...

  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. 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.

  8. 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

  9. 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...

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

    Science.gov (United States)

    Speit, Günter

    2009-08-01

    Animal experiments (in vivo tests) currently play a key role in genotoxicity testing. Results from in vivo tests are, in many cases, decisive for the assessment of a mutagenic potential of a test compound. The Seventh Amendment to the European Cosmetics Directive will, however, ban the European marketing of cosmetic/personal care products that contain ingredients that have been tested in animal experiments. If genotoxicity testing is solely based on the currently established in vitro tests, the attrition rate for chemicals used in cosmetic products will greatly increase due to irrelevant positive in vitro test results. There is urgent need for new and/or improved in vitro genotoxicity tests and for modified test strategies. Test strategies should consider all available information on chemistry of the test substance/the chemical class (e.g. SAR, metabolic activation and dermal adsorption). Test protocols for in vitro genotoxicity tests should be sensitive and robust enough to ensure that negative results can be accepted with confidence. It should be excluded that positive in vitro test results are due to high cytotoxicity or secondary genotoxic effects which may be thresholded and/or only occur under in vitro test conditions. Consequently, further research is needed to establish the nature of thresholds in in vitro assays and to determine the potential for incorporation of mode of action data into future risk assessments. New/improved tests have to be established and validated, considering the use of (metabolically competent) primary (skin) cells, 3D skin models and cells with defined capacity for metabolic activation (e.g. genetically engineered cell lines). The sensitivity and specificity of new and improved genotoxicity tests has to be determined by testing a battery of genotoxic and non-genotoxic chemicals. New or adapted international guidelines will be needed for these tests. The establishment of such a new genotoxicity testing strategy will take time and the

  11. A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements.

    Science.gov (United States)

    Giannakou, Christina; Park, Margriet Vdz; de Jong, Wim H; van Loveren, Henk; Vandebriel, Rob J; Geertsma, Robert E

    2016-01-01

    Nanomaterials (NMs) are attractive for biomedical and pharmaceutical applications because of their unique physicochemical and biological properties. A major application area of NMs is drug delivery. Many nanomedicinal products (NMPs) currently on the market or in clinical trials are most often based on liposomal products or polymer conjugates. NMPs can be designed to target specific tissues, eg, tumors. In virtually all cases, NMPs will eventually reach the immune system. It has been shown that most NMs end up in organs of the mononuclear phagocytic system, notably liver and spleen. Adverse immune effects, including allergy, hypersensitivity, and immunosuppression, have been reported after NMP administration. Interactions of NMPs with the immune system may therefore constitute important side effects. Currently, no regulatory documents are specifically dedicated to evaluate the immunotoxicity of NMs or NMPs. Their immunotoxicity assessment is performed based on existing guidelines for conventional substances or medicinal products. Due to the unique properties of NMPs when compared with conventional medicinal products, it is uncertain whether the currently prescribed set of tests provides sufficient information for an adequate evaluation of potential immunotoxicity of NMPs. The aim of this study was therefore, to compare the current regulatory immunotoxicity testing requirements with the accumulating knowledge on immunotoxic effects of NMPs in order to identify potential gaps in the safety assessment. This comparison showed that immunotoxic effects, such as complement activation-related pseudoallergy, myelosuppression, inflammasome activation, and hypersensitivity, are not readily detected by using current testing guidelines. Immunotoxicity of NMPs would be more accurately evaluated by an expanded testing strategy that is equipped to stratify applicable testing for the various types of NMPs.

  12. 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

  13. [Prediction of 137Cs accumulation in animal products in the territory of Semipalatinsk test site].

    Science.gov (United States)

    Spiridonov, S I; Gontarenko, I A; Mukusheva, M K; Fesenko, S V; Semioshkina, N A

    2005-01-01

    The paper describes mathematical models for 137Cs behavior in the organism of horses and sheep pasturing on the bording area to the testing area "Ground Zero" of the Semipalatinsk Test Site. The models are parameterized on the base of the data from an experiment with the breeds of animals now commonly encountered within the Semipalatinsk Test Site. The predictive calculations with the models devised have shown that 137Cs concentrations in milk of horses and sheep pasturingon the testing area to "Ground Zero" can exceed the adopted standards during a long period of time.

  14. 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

  15. 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.

  16. Patch test reactivity to metal allergens following regulatory interventions: a 33-year retrospective study

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Ross-Hansen, Katrine; Menné, Torkil

    2010-01-01

    Contact allergy epidemics to chromate and nickel were addressed in Denmark in 1983 and 1990 by regulatory interventions.......Contact allergy epidemics to chromate and nickel were addressed in Denmark in 1983 and 1990 by regulatory interventions....

  17. 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.

  18. Regulatory concerns for leakage testing of packagings with three O-ring closure seals

    International Nuclear Information System (INIS)

    Oras, J.J.; Towell, R.H.; Wangler, M.E.

    1997-01-01

    The American National Standard for Radioactive Materials--Leakage Tests on Packages for Shipment (ANSI N14.5) provides guidance for leakage rate testing to show that a particular packaging complies with regulatory requirements and also provides guidance in determining appropriate acceptance criteria. Recent radioactive packagings designs have incorporated three O-ring closure seals, the middle O-ring being the containment seal. These designs have the potential for false positive results of leakage rate tests. The volume between the containment O-ring and the inner O-ring is used for the helium gas required for the leakage rate tests to reduce both the amount of helium used and the time required to conduct the tests. A leak detector samples the evacuated volume between the outer O-ring and the containment O-ring. False positive results can be caused in two ways, a large leakage in the containment seal or leakage in the inner seal. This paper will describe the problem together with possible solutions/areas that need to be addressed in a Safety Analysis Report for Packagings before a particular packaging design can be certified for transport

  19. 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....

  20. NRC review of passive reactor design certification testing programs: Overview and regulatory perspective

    International Nuclear Information System (INIS)

    Levin, A.E.

    1993-01-01

    Reactor vendors are developing new designs for future deployment, including open-quotes passiveclose quotes light water reactors (LWRs), such as General Electric's (G.E.'s) simplified boiling water reactor (SBWR) and Westinghouse's AP600, which depend primarily on inherent processes, such as national convection and gravity feed, for safety injection and emergency core cooling. The U.S. Nuclear Regulatory Commission (NRC) has implemented a new process, certification of standardized reactor designs, for licensing these Plants. Part 52 of Title 10 of the Code of Federal Regulations (10CFR52) contains the requirements that vendors must meet for design certification. One important section, 10CFR52.47, reads open-quotes Certification of a standard design which . . . utilizes simplified, inherent, passive, or other innovative means to accomplish its safety functions will be granted only if: (1) The performance of each safety feature of the design has been demonstrated through either analysis, appropriate test programs, experience, or a combination thereof; (2) Interdependent effects among the safety features have been found acceptable by analysis, appropriate test programs, experience, or a combination thereof; and (3) Sufficient data exist on the safety features of the design to assess the analytical tools used for safety analyses. . . . The vendors have initiated programs to test innovative features of their designs and to develop data bases needed to validate their analytical codes, as required by the design certification rule. Accordingly, the NRC is reviewing and evaluating the vendors programs to ensure that they address adequately key issues concerning safety system performance. This paper provides an overview of the NRC's review process and regulatory perspective

  1. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. LncRNA, a new component of expanding RNA-protein regulatory network important for animal sperm development.

    Science.gov (United States)

    Zhang, Chenwang; Gao, Liuze; Xu, Eugene Yujun

    2016-11-01

    Spermatogenesis is one of the fundamental processes of sexual reproduction, present in almost all metazoan animals. Like many other reproductive traits, developmental features and traits of spermatogenesis are under strong selective pressure to change, both at morphological and underlying molecular levels. Yet evidence suggests that some fundamental features of spermatogenesis may be ancient and conserved among metazoan species. Identifying the underlying conserved molecular mechanisms could reveal core components of metazoan spermatogenic machinery and provide novel insight into causes of human infertility. Conserved RNA-binding proteins and their interacting RNA network emerge to be a common theme important for animal sperm development. We review research on the recent addition to the RNA family - Long non-coding RNA (lncRNA) and its roles in spermatogenesis in the context of the expanding RNA-protein network. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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...

  10. Pulmonary function testing of animals chronically exposed to diluted diesel exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Gross, K B

    1981-04-01

    The purpose of this work was to assess the potential effect that chronic inhalation of diesel exhaust may have on lung mechanics and lung volume. Noninvasive pulmonary function tests that produced data on lung air flows and volumes have been conducted repeatedly on 25 male Fischer-344 rats exposed to diesel exhaust at a particulate concentration of 1500 micrograms m-3, 20 h per day, 5 1/2 days per week, for 612 days. The same tests were conducted on 25 clean air control animals. When the data were normalized, the majority of tests did not reveal any significant deviation from the norm for the first year of exposure. In the second year, the functional residual capacity and its component volumes - expiratory reserve and residual volume, maximum expiratory flow at 40% of vital capacity, maximum expiratory flow at 20% of vital capacity and the forced expiratory volume in 0.1 s - were significantly greater in the diesel exposed animals. The data are inconsistent with known clinically significant adverse health effects. Although the lung volume changes in the diesel exposed animals could be indicative of emphysema or other forms of chronic obstructive lung disease, this interpretation is contradicted by the air flow data which suggest simultaneous lowering of the resistance of the smaller airways. The observations are not consistent with documented clinical lung disease in man.

  11. The organization structure and regulatory elements of Chlamydomonas histone genes reveal features linking plant and animal genes.

    Science.gov (United States)

    Fabry, S; Müller, K; Lindauer, A; Park, P B; Cornelius, T; Schmitt, R

    1995-09-01

    The genome of the green alga Chlamydomonas reinhardtii contains approximately 15 gene clusters of the nucleosomal (or core) histone H2A, H2B, H3 and H4 genes and at least one histone H1 gene. Seven non-allelic histone gene loci were isolated from a genomic library, physically mapped, and the nucleotide sequences of three isotypes of each core histone gene species and one linked H1 gene determined. The core histone genes are organized in clusters of H2A-H2B and H3-H4 pairs, in which each gene pair shows outwardly divergent transcription from a short (< 300 bp) intercistronic region. These intercistronic regions contain typically conserved promoter elements, namely a TATA-box and the three motifs TGGCCAG-G(G/C)-CGAG, CGTTGACC and CGGTTG. Different from the genes of higher plants, but like those of animals and the related alga Volvox, the 3' untranslated regions contain no poly A signal, but a palindromic sequence (3' palindrome) essential for mRNA processing is present. One single H1 gene was found in close linkage to a H2A-H2B pair. The H1 upstream region contains the octameric promoter element GGTTGACC (also found upstream of the core histone genes) and two specific sequence motifs that are shared only with the Volvox H1 promoters. This suggests differential transcription of the H1 and the core histone genes. The H1 gene is interrupted by two introns. Unlike Volvox H3 genes, the three sequenced H3 isoforms are intron-free. Primer-directed PCR of genomic DNA demonstrated, however, that at least 8 of the about 15 H3 genes do contain one intron at a conserved position. In synchronized C. reinhardtii cells, H4 mRNA levels (representative of all core histone mRNAs) peak during cell division, suggesting strict replication-dependent gene control. The derived peptide sequences place C. reinhardtii core histones closer to plants than to animals, except that the H2A histones are more animal-like. The peptide sequence of histone H1 is closely related to the V. carteri VH1-II

  12. Animal investigation program: Nevada test site and vicinity. Annual report, 1977

    International Nuclear Information System (INIS)

    Smith, D.D.; Crockett, A.B.; Bernhardt, D.E.; Giles, K.R.; Kinnison, R.R.

    1979-07-01

    Data are presented from the radioanalysis of tissues collected from cattle, mule deer, desert bighorn sheep, rabbits, feral horses, and other wildlife that resided on or near the Nevada Test Site. Routine activities and special investigations of the Animal Investigation Program are also discussed. Other than potassium-40, gamma-emitting radionuclides were detected infrequently. Strontium-90 concentrations in bones from deer, cattle, and desert bighorn sheep continued the downward trend of recent years. Tritium concentrations were generally within expected environmental limits with the exception of animals exposed to sources of contamination. Radionuclide tissue concentrations were generally higher in the tissues of animals residing in Area 15 than in other areas. Statistical analyses made of plutonium-239 levels reported in cattle tissue collected from 1971 through 1977 reveal that activity levels in lungs, liver, and bone are significantly related to age. Activity levels did not change significantly in the ingesta and lungs during this time but did tend to increase for bone and liver. Activity levels in the ingesta are significantly higher in the fall than in the spring. Hypothetical dose estimates to man were calculated on the basis of liver or muscle from animals that contained peak radionuclide levels. The highest postulated dose was 8.6 millirems for tritium in tissues from a mule deer. The movements of 17 mule deer were monitored on a weekly basis.During the winter months, all deer left their summer range on the mesas of the Nevada Test Site and migrated 40 to 60 kilometers south and west. A statistical estimate was made of the deer population in selected areas utilizing the marked deer as a basis for this estimate. No gross or microscopic lesions were found in necropsied animals that could be directly attributed to the effects of ionizing radiation

  13. The Revised Animal Preference Test: An Implicit Probe of Tendencies Toward Psychopathy.

    Science.gov (United States)

    Penzel, Ian B; Bair, Jessica; Liu, Tianwei; Robinson, Michael D

    2018-05-01

    At least some forms of interpersonal violence could follow from a vision of the self as a fierce, dominant creature. This should be particularly true when psychopathic (more proactive, less reactive) tendencies are involved. Possible relations of this type were examined in two studies (total N = 278) in which college student samples were presented with a new, structured version of an old projective test typically used in psychotherapy contexts. Participants were presented with predator-prey animal pairs (e.g., lion-zebra) that were not explicitly labeled as such. For each pair, the person was asked to choose the animal that they would more prefer to be. Participants who desired to be predator animals more often, on this Revised Animal Preference Test (RAPT), tended toward psychopathy to a greater extent. In Study 1, such relations were manifest in terms of correlations with psychopathic traits and with an interpersonal style marked by hostile dominance. Further analyses, though, revealed that predator self-identifications were more strongly related to primary psychopathy than secondary psychopathy. Study 2 replicated the interpersonal style correlates of the RAPT. In addition, photographs were taken of the participants in the second study and these photographs were rated for apparent hostility and dominance. As hypothesized, participants who wanted to be predator animals to a greater extent also appeared more hostile and dominant in their nonverbal behaviors. These studies suggest that projective preferences can be assessed in a reliable manner through the use of standardizing procedures. Furthermore, the studies point to some of the motivational factors that may contribute to psychopathy and interpersonal violence.

  14. 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.

  15. In Vitro Antimicrobial Susceptibility Testing of Animal Nocardia Isolated from Field Cases of Skin Diseases

    Directory of Open Access Journals (Sweden)

    M. A. Oyekunle

    2001-03-01

    Full Text Available In vitro antimicrobial tests were carried out on strains of Nocardia isolated from field cases of cutaneous nocardiosis in farm animals. Results with the disc diffusion test showed the multiresistant nature of the isolates, but 23.81 and 21.43% were sensitive to ciprofloxacin and gentamycin, respectively. The MIC mode and range for oxytetracycline were 12.5 and 3.12–25 μg/ml, respectively, while those of erythromycin were 3.12 and 0.78–6.25 μg/ml, respectively.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. Architecture optimization at IPEN animal facility in order to improve the welfare and the quality of the animals employed at radiopharmaceutical tests

    Energy Technology Data Exchange (ETDEWEB)

    Lainetti, Elizabeth Brigagao de Faria; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: eblainet@ipen.br; Passos, Luiz Augusto Correa [Universidade Estadual de Campinas, SP (Brazil). Centro Multidisciplinar para a Investigacao Biologica (CEMIB/UNICAMP)

    2009-07-01

    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{sup 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

  1. 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

  2. [Replacement of dogs as research animals for the approval testing of plant protection products].

    Science.gov (United States)

    Box, Rainer J

    2006-01-01

    The replacement of animal testing using dogs for the registration of plant protection products requires a long-term step-by-step procedure. The first goal should be to achieve international agreement on using only one single study in dogs. This would result in a significant short-term reduction of the use of dogs for this purpose. The competent working groups both in the EU and the United States EPA have declared this to be their intended aim. In this context, the 90-day study is to be the preferred study from the scientific as well as the animal welfare points of view. It is proposed to set up an international expert task force within the next 12 months, which should seek to initiate a process of international harmonization of the testing requirements following the example of the International Conference of Harmonization of Technical Requirements for Medical Products, ICH. The goal should be to achieve international agreement on only one single study with dogs within the next 2 to 3 years. In addition, other valid scientific procedures, with which the use of dogs for testing can be reduced, should be critically assessed. A complete replacement of the use of dogs for plant protection product testing is suggested to take place at a later stage. This may be achieved by either deriving safety threshold values by applying a safety factor to chronic NOAEL values obtained in studies using rats for those groups of substances, for which there is evidence that the dog is the more sensitive species, or by combining the chronic rat study with other animal tests stipulated for the registration of pesticides.

  3. [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.

  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. 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.

  6. 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.

  7. The adverse outcome pathway for skin sensitisation: Moving closer to replacing animal testing.

    Science.gov (United States)

    Schultz, Terry W; Dimitrova, Gergana; Dimitrov, Sabcho; Mekenyan, Ovanes G

    2016-10-01

    This article outlines the work of the Organisation for Economic Co-operation and Development (OECD) that led to being jointly awarded the 2015 Lush Black Box Prize. The award-winning work centred on the development of 'The Adverse Outcome Pathway for Skin Sensitisation Initiated by Covalent Binding to Proteins'. This Adverse Outcome Pathway (AOP) has provided the mechanistic basis for the integration of skin sensitisation-related information. Recent developments in integrated approaches to testing and assessment, based on the AOP, are summarised. The impact of the AOP on regulatory policy and on the Three Rs are discussed. An overview of the next generation of the skin sensitisation AOP module in the OECD QSAR Toolbox, based on more-recent work at the Laboratory of Mathematical Chemistry, is also presented. 2016 FRAME.

  8. From road to lab to math: the co-evolution of technological, regulatory, and organizational innovations for automotive crash testing.

    Science.gov (United States)

    Leonardi, Paul M

    2010-04-01

    Today, in the midst of economic crisis, senior executives at US automakers and influential industry analysts frequently reflect on the progression that safety testing has taken from the crude trials done on the road, to controlled laboratory experiments, and to today's complex math-based simulation models. They use stories of this seemingly linear and natural sequence to justify further investment in simulation technologies. The analysis presented in this paper shows that change in the structures of automakers' organizations co-evolved with regulations specifying who was at fault in vehicle impacts, how vehicles should be built to withstand the force of an impact, and how testing should be done to assure that vehicles met those requirements. Changes in the regulatory environment were bolstered by new theories about crash test dynamics and changing technologies with which to test those theories. Thus, as new technological and regulatory innovations co-evolved with innovations in organizational structuring, ideas about how to best conduct crash tests shifted and catalyzed new cycles of technological, regulatory, and organizational innovation. However, this co-evolutionary story tells us that the move from road to lab to math was not natural or linear as today's managerial rhetoric would have us believe. Rather, the logic of math-based simulation was the result of technological, regulatory and organizational changes that created an industry-wide ideology that supported the move toward math while making it appear natural within the shifting structure of the industry.

  9. 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.

  10. 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

  11. 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.

  12. The challenge of a ban on animal testing for the development of a regulated legal market for new psychoactive substances (NPS) ('legal highs') in New Zealand: Issues and options for resolution.

    Science.gov (United States)

    Rychert, Marta; Wilkins, Chris

    2015-12-01

    In mid-July 2013, New Zealand passed the Psychoactive Substances Act (PSA), which allowed 'low risk' psychoactive products ('legal highs') to be approved for legal sale. In early May 2014, following public protest, the Psychoactive Substances Amendment Act (PSAA) was passed banning animal testing of psychoactive products, potentially making the new regime unworkable. To investigate strategies to overcome the impasse created by the animal testing ban. Solutions to the impasse were investigated using 'scenario' and 'stakeholder' analysis. Legislation, parliamentary debates, and regulatory statements related to the PSA and animal testing were reviewed. Strategies to resolve the impasse were discussed with stakeholders including the Psychoactive Substances Regulatory Authority (PSRA) officials, health officials, a legal high industry lawyer, and a leading legal highs manufacturer. This process generated six possible scenarios and five decision-making criteria of key importance to major stakeholders. Scenarios were then evaluated based on feedback from the industry and regulators. The six scenarios were: (1) pragmatic modification of the animal testing ban; (2) waiting until new non-animal test models are internationally accepted; (3) use of non-validated replacement test methods; (4) judicial challenge of the animal testing ban; (5) 'creative compliance' by only presenting human clinical trial results; and (6) philosophical re-conceptualisation of the 'benefits' from psychoactive products. Options 1 and 5 appear to be the most attractive overall solutions. However, both rely on a new political consensus and astute framing of the issues by political communicators. Political decision makers may be happy to accept Scenario 2 which would impose significant delays. A 'failed' pharmaceutical product with psychoactive effects may have the test data required to be approved under Scenarios 1 and 5. Ultimately, the pleasurable benefits from psychoactive products may need to be

  13. [Radiobiological effects on plants and animals within Semipalatinsk Test Site (Kazakhstan)].

    Science.gov (United States)

    Mozolin, E M; Geras'kin, S A; Minkenova, K S

    2008-01-01

    The Semipalatinsk Test Site (STS) was the main place of nuclear devices tests in the former Soviet Union. From 1949 to 1989 about 460 nuclear explosions have been carried out at STS. Radioactive contamination of STS territory has the extremely non-uniform character. The main dose-forming radionuclides are 137Cs, 90Sr, 152Eu, as well as 154Eu, 60CO, 239,240Pu and 241Am. The greatest specific activity of 137Cs and 239,240Pu in ground are n x 10(3) kBk/kg, 152Eu - 96 kBk/kg, 154Eu - 10.4 kBk/kg, 60Co - 20.5 kBk/kg, 241Am - 15 kBk/kg. However, up to now, within STS sites exists where gamma-dose rate comes to 60 microGy/h, that is enough for induction reliable biological effects in animals and plants. Inhabiting territory of STS plants and animals are characterized by increased level of mutagenesis, changes of morpho-anatomic indices and parameters of peripheral blood, by the increase of asymmetry bilateral indices, change of composition and structure of communities.

  14. Animal investigation program, 1981 annual report: Nevada Test Site and vicinity

    International Nuclear Information System (INIS)

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

    1982-01-01

    Data are presented from the radioanalysis of tissues, collected from animals that resided on or near the Nevada Test Site (NTS). Other than naturally occurring potassium-40, cesium-137 was the only gamma-emitting radionuclide frequently detected and was within a narrow range of activity. For example, 12 of 14 cattle muscle samples contained 15 to 65 pCi of cesium-137 per kilogram. Strontium-90 and plutonium-238 or -239 tissue concentrations were similar to those of recent years. Nanocurie levels of tritium were found in tissue from two deer that drank contaminated water draining from the tunnel test areas. Annual dose estimates to man were calculated based on the daily consumption of 0.5 kg of tissue with peak radionuclide levels. The highest postulated dose was 45 millirems to the whole body from ingestion of deer muscle that drank from the tritium contaminated waters. This dose is about 9% of the radiation protection guide. Movement of deer on the NTS is discussed. In general, deer from Pahute Mesa winter in the Timber Mt. area with some movement off the NTS, while deer from Rainier Mesa winter in the Shoshone Mt. area. The sudden death of an offsite goat kid was investigated and death was attributed to enterotoxemia. No gross or microscopic lesions in necropsied animals were found that could be attributed to the effect of ionizing radiation

  15. 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.

  16. 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.

  17. Annular phased array transducer for preclinical testing of anti-cancer drug efficacy on small animals.

    Science.gov (United States)

    Kujawska, Tamara; Secomski, Wojciech; Byra, Michał; Postema, Michiel; Nowicki, Andrzej

    2017-04-01

    A technique using pulsed High Intensity Focused Ultrasound (HIFU) to destroy deep-seated solid tumors is a promising noninvasive therapeutic approach. A main purpose of this study was to design and test a HIFU transducer suitable for preclinical studies of efficacy of tested, anti-cancer drugs, activated by HIFU beams, in the treatment of a variety of solid tumors implanted to various organs of small animals at the depth of the order of 1-2cm under the skin. To allow focusing of the beam, generated by such transducer, within treated tissue at different depths, a spherical, 2-MHz, 29-mm diameter annular phased array transducer was designed and built. To prove its potential for preclinical studies on small animals, multiple thermal lesions were induced in a pork loin ex vivo by heating beams of the same: 6W, or 12W, or 18W acoustic power and 25mm, 30mm, and 35mm focal lengths. Time delay for each annulus was controlled electronically to provide beam focusing within tissue at the depths of 10mm, 15mm, and 20mm. The exposure time required to induce local necrosis was determined at different depths using thermocouples. Location and extent of thermal lesions determined from numerical simulations were compared with those measured using ultrasound and magnetic resonance imaging techniques and verified by a digital caliper after cutting the tested tissue samples. Quantitative analysis of the results showed that the location and extent of necrotic lesions on the magnetic resonance images are consistent with those predicted numerically and measured by caliper. The edges of lesions were clearly outlined although on ultrasound images they were fuzzy. This allows to conclude that the use of the transducer designed offers an effective noninvasive tool not only to induce local necrotic lesions within treated tissue without damaging the surrounding tissue structures but also to test various chemotherapeutics activated by the HIFU beams in preclinical studies on small animals

  18. 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…

  19. Genetic horoscopes: is it all in the genes? Points for regulatory control of direct-to-consumer genetic testing.

    Science.gov (United States)

    Patch, Christine; Sequeiros, Jorge; Cornel, Martina C

    2009-07-01

    The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and the appropriate regulatory and policy response. How these concerns are interpreted and addressed is an ongoing debate. If the possibility of using the discoveries from genomic science to improve health is to be realised without losing public confidence, then improvements in the evaluation and mechanisms for control of supply of tests may be as important as the science itself.

  20. 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.

  1. Strategic focus on 3R principles reveals major reductions in the use of animals in pharmaceutical toxicity testing.

    Directory of Open Access Journals (Sweden)

    Elin Törnqvist

    Full Text Available The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. Substantial reduction in animal use was achieved by different strategies, including improved study design, method development and project coordination. Major animal savings were shown in both regulatory and investigative safety studies. If a similar (i.e. 53% reduction had been achieved simultaneously within the twelve largest pharmaceutical companies, the equivalent reduction world-wide would be about 150,000 rats annually. The results point at the importance of a strong 3R culture, with scientific engagement, collaboration and a responsive management being vital components. A strong commitment in leadership for the 3R is recommended to be translated into cross-department and inter-profession involvement in projects for innovation, validation and implementation. Synergies between all the three Rs are observed and conclude that in silico-, in vitro- and in vivo-methods all hold the potential for applying the reduction R and should be consequently coordinated at a strategic level.

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

    OpenAIRE

    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 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 esp...

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Cigarette smoke induced genotoxicity and respiratory tract pathology: evidence to support reduced exposure time and animal numbers in tobacco product testing.

    Science.gov (United States)

    Dalrymple, Annette; Ordoñez, Patricia; Thorne, David; Walker, David; Camacho, Oscar M; Büttner, Ansgar; Dillon, Debbie; Meredith, Clive

    2016-06-01

    Many laboratories are working to develop in vitro models that will replace in vivo tests, but occasionally there remains a regulatory expectation of some in vivo testing. Historically, cigarettes have been tested in vivo for 90 days. Recently, methods to reduce and refine animal use have been explored. This study investigated the potential of reducing animal cigarette smoke (CS) exposure to 3 or 6 weeks, and the feasibility of separate lung lobes for histopathology or the Comet assay. Rats were exposed to sham air or CS (1 or 2 h) for 3 or 6 weeks. Respiratory tissues were processed for histopathological evaluation, and Alveolar type II cells (AEC II) isolated for the Comet assay. Blood was collected for Pig-a and micronucleus quantification. Histopathological analyses demonstrated exposure effects, which were generally dependent on CS dose (1 or 2 h, 5 days/week). Comet analysis identified that DNA damage increased in AEC II following 3 or 6 weeks CS exposure, and the level at 6 weeks was higher than 3 weeks. Pig-a mutation or micronucleus levels were not increased. In conclusion, this study showed that 3 weeks of CS exposure was sufficient to observe respiratory tract pathology and DNA damage in isolated AEC II. Differences between the 3 and 6 week data imply that DNA damage in the lung is cumulative. Reducing exposure time, plus analyzing separate lung lobes for DNA damage or histopathology, supports a strategy to reduce and refine animal use in tobacco product testing and is aligned to the 3Rs (replacement, reduction and refinement).

  9. The current state of inservice testing programs at U.S. Nuclear Power Plants - a regulatory overview

    International Nuclear Information System (INIS)

    Campbell, P.; Colaccino, J.

    1994-01-01

    Information is provided on inservice testing (IST) of pumps and valves at U.S. nuclear power plants to provide consistency in the implementation of regulatory requirements and to enhance communications among utility licensees who may have, like NSSS vendors, similar kinds and numbers of components or comparable IST programs. Documents discussed include the ASME Operation and Maintenance Standards Parts 6 and 10 (covering inservice testing of pumps and valves in light water reactor power plants), the draft NUREG-1482, Guidelines for Inservice Testing at Nuclear Power Plants (including review comments by Nuclear Management and Resource Council), and applicable Licensee Event Reports including summaries of several reports relating to IST

  10. Evaluation of testing strategies to identify infected animals at a single round of testing within dairy herds known to be infected with Mycobacterium avium ssp. paratuberculosis.

    Science.gov (United States)

    More, S J; Cameron, A R; Strain, S; Cashman, W; Ezanno, P; Kenny, K; Fourichon, C; Graham, D

    2015-08-01

    As part of a broader control strategy within herds known to be infected with Mycobacterium avium ssp. paratuberculosis (MAP), individual animal testing is generally conducted to identify infected animals for action, usually culling. Opportunities are now available to quantitatively compare different testing strategies (combinations of tests) in known infected herds. This study evaluates the effectiveness, cost, and cost-effectiveness of different testing strategies to identify infected animals at a single round of testing within dairy herds known to be MAP infected. A model was developed, taking account of both within-herd infection dynamics and test performance, to simulate the use of different tests at a single round of testing in a known infected herd. Model inputs included the number of animals at different stages of infection, the sensitivity and specificity of each test, and the costs of testing and culling. Testing strategies included either milk or serum ELISA alone or with fecal culture in series. Model outputs included effectiveness (detection fraction, the proportion of truly infected animals in the herd that are successfully detected by the testing strategy), cost, and cost-effectiveness (testing cost per true positive detected, total cost per true positive detected). Several assumptions were made: MAP was introduced with a single animal and no management interventions were implemented to limit within-herd transmission of MAP before this test. In medium herds, between 7 and 26% of infected animals are detected at a single round of testing, the former using the milk ELISA and fecal culture in series 5 yr after MAP introduction and the latter using fecal culture alone 15 yr after MAP introduction. The combined costs of testing and culling at a single round of testing increases with time since introduction of MAP infection, with culling costs being much greater than testing costs. The cost-effectiveness of testing varied by testing strategy. It was also

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. The Fragility of Individual-Based Explanations of Social Hierarchies: A Test Using Animal Pecking Orders

    Science.gov (United States)

    2016-01-01

    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. PMID:27410230

  16. 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

  17. 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.

  18. 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.

  19. An innovative approach to sampling complex industrial emissions for use in animal toxicity tests: application to iron casting operations.

    Science.gov (United States)

    Palmer, W G; Scholz, R C; Moorman, W J

    1983-03-01

    Sampling of complex mixtures of airborne contaminants for chronic animal toxicity tests often involves numerous sampling devices, requires extensive sampling time, and yields forms of collected materials unsuitable for administration to animals. A method is described which used a high volume, wet venturi scrubber for collection of respirable fractions of emissions from iron foundry casting operations. The construction and operation of the sampler are presented along with collection efficiency data and its application to the preparation of large quantities of samples to be administered to animals by intratracheal instillation.

  20. Dynamics of cytogenetic indexes of agriculture animals dwelling on the Semipalatinsk test site territory

    International Nuclear Information System (INIS)

    Mukusheva, M.K.; Sejsebaev, A.T.; Karabalin, B.K.; Tusupbaev, V.I.; Zhapbasov, R.Zh.

    2001-01-01

    Aim of the work is analysis of genetic processes taking place in the agricultural animal populations exposed to constant radiation due to increased radiation background in their dwelling places. By the cytogenetic methods the sheep, cattle and horses were examined. It was revealed cytogenetic effect manifested in form of a high genome genetic instability level for studied animals. It is suggested, that the effect is caused with low chronic ionizing radiation doses exposure on the agricultural animals somatic cells

  1. Prospective clinical testing of regulatory dendritic cells (DCreg) in organ transplantation

    OpenAIRE

    ANGUS W THOMSON; ALAN F ZAHORCHAK; Mohamed B. Ezzelarab; Lisa H. Butterfield; Fadi G. Lakkis; Diana M Metes

    2016-01-01

    Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

  2. Comparison of four microbiological inhibition tests for the screening of antimicrobial residues in the tissues of food-producing animals

    Directory of Open Access Journals (Sweden)

    Zuzana Gondová

    2014-10-01

    Full Text Available The study compares two existing microbiological inhibition tests, Screening Test for Antibiotic Residues (STAR and Premi®Test with two recently introduced tests, Nouws Antibiotic Test (NAT and Total Antibiotics for the screening of antimicrobial residues in the tissues of food-producing animals. In the negative or positive sample classification based on inhibition of the growth of test strain sensitive to many antibiotics and sulphonamides, out of 142 samples obtained from slaughterhouses and retail operations, 39 samples yielded a positive result in one or more tests: 4 samples in four tests, 14 samples in three tests, 13 samples in two tests, and 8 samples in one test. As for the numbers of observed positive samples, the descending sequence of tests was: STAR, Total Antibiotics, Premi®Test, NAT. The growth inhibition was observed in three out of seven test strains, namely Bacillus cereus ATCC 11778, Kocuria rhizophila ATCC 9341, and Bacillus stearothermophilus var. calidolactis. Considering the test strains sensitivity and no inhibition on the Bacillus pumilus NCIMB 10822 NAT test plates, our preliminary conclusion is that the animal samples are suspected for the presence of tetracycline, macrolide, and b-lactam antibiotics.

  3. The regulatory function of self-esteem: testing the epistemic and acceptance signaling systems.

    Science.gov (United States)

    Stinson, Danu Anthony; Logel, Christine; Holmes, John G; Wood, Joanne V; Forest, Amanda L; Gaucher, Danielle; Fitzsimons, Grainné M; Kath, Jennifer

    2010-12-01

    The authors draw on sociometer theory (e.g., Leary, 2004) and self-verification theory (e.g., Swann, 1997) to propose an expanded model of the regulatory function of self-esteem. The model suggests that people not only possess an acceptance signaling system that indicates whether relational value is high or low but also possess an epistemic signaling system that indicates whether social feedback is consistent or inconsistent with chronic perceived relational value (i.e., global self-esteem). One correlational study and 5 experiments, with diverse operationalizations of social feedback, demonstrated that the epistemic signaling system responds to self-esteem consistent or inconsistent relational-value feedback with increases or deceases in epistemic certainty. Moreover, Studies 3-6 demonstrated that the acceptance and epistemic signaling systems respond uniquely to social feedback. Finally, Studies 5 and 6 provide evidence that the epistemic signaling system is part of a broader self-regulatory system: Self-esteem inconsistent feedback caused cognitive efforts to decrease the discrepancy between self-views and feedback and caused depleted self-regulatory capacity on a subsequent self-control task. PsycINFO Database Record (c) 2010 APA, all rights reserved.

  4. 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.

  5. Whiteboard animation for knowledge mobilization: a test case from the Slave River and Delta, Canada.

    Science.gov (United States)

    Bradford, Lori E A; Bharadwaj, Lalita A

    2015-01-01

    To present the co-creation of a whiteboard animation video, an enhanced e-storytelling technique for relaying traditional knowledge interview results as narratives. We present a design for translating interview results into a script and accompanying series of figures, followed by technical steps to create a whiteboard animation product. Our project used content analysis and researcher triangulation, followed by a collaborative process to develop an animated video to disseminate research findings. A 13-minute long whiteboard animation video was produced from a research study about changing environments in northern Canadian communities and was distributed to local people. Three challenging issues in the video creation process including communication issues, technical difficulties and contextual debate were resolved among the supporting agencies and researchers. Dissemination of findings is a crucial step in the research process. Whiteboard animation video products may be a viable and culturally-appropriate form of relaying research results back to Indigenous communities in a storytelling format.

  6. Foundational Tests of the Need-Support Model: A Framework for Bridging Regulatory Focus Theory and Self-Determination Theory.

    Science.gov (United States)

    Vaughn, Leigh Ann

    2017-03-01

    This article introduces the need-support model, which proposes that regulatory focus can affect subjective support for the needs proposed by self-determination theory (autonomy, competence, and relatedness), and support of these needs can affect subjective labeling of experiences as promotion-focused and prevention-focused. Three studies tested these hypotheses ( N = 2,114). Study 1 found that people recall more need support in promotion-focused experiences than in prevention-focused experiences, and need support in their day yesterday (with no particular regulatory focus) fell in between. Study 2 found that experiences of higher need support were more likely to be labeled as promotion-focused rather than prevention-focused, and that each need accounted for distinct variance in the labeling of experiences. Study 3 varied regulatory focus within a performance task and found that participants in the promotion condition engaged in need-support inflation, whereas participants in the prevention condition engaged in need-support deflation. Directions for future research are discussed.

  7. Animal experimentation

    OpenAIRE

    Laz, Alak; Cholakova, Tanya Stefanova; Vrablova, Sofia; Arshad, Naverawaheed

    2016-01-01

    Animal experimentation is a crucial part of medical science. One of the ways to define it is any scientific experiment conducted for research purposes that cause any kind of pain or suffering to animals. Over the years, the new discovered drugs or treatments are first applied on animals to test their positive outcomes to be later used by humans. There is a debate about violating ethical considerations by exploiting animals for human benefits. However, different ethical theories have been made...

  8. Design standards for experimental and field studies to evaluate diagnostic accuracy of tests for infectious diseases in aquatic animals.

    Science.gov (United States)

    Laurin, E; Thakur, K K; Gardner, I A; Hick, P; Moody, N J G; Crane, M S J; Ernst, I

    2018-05-01

    Design and reporting quality of diagnostic accuracy studies (DAS) are important metrics for assessing utility of tests used in animal and human health. Following standards for designing DAS will assist in appropriate test selection for specific testing purposes and minimize the risk of reporting biased sensitivity and specificity estimates. To examine the benefits of recommending standards, design information from published DAS literature was assessed for 10 finfish, seven mollusc, nine crustacean and two amphibian diseases listed in the 2017 OIE Manual of Diagnostic Tests for Aquatic Animals. Of the 56 DAS identified, 41 were based on field testing, eight on experimental challenge studies and seven on both. Also, we adapted human and terrestrial-animal standards and guidelines for DAS structure for use in aquatic animal diagnostic research. Through this process, we identified and addressed important metrics for consideration at the design phase: study purpose, targeted disease state, selection of appropriate samples and specimens, laboratory analytical methods, statistical methods and data interpretation. These recommended design standards for DAS are presented as a checklist including risk-of-failure points and actions to mitigate bias at each critical step. Adherence to standards when designing DAS will also facilitate future systematic review and meta-analyses of DAS research literature. © 2018 John Wiley & Sons Ltd.

  9. Prospective clinical testing of regulatory dendritic cells (DCreg in organ transplantation

    Directory of Open Access Journals (Sweden)

    ANGUS W THOMSON

    2016-01-01

    Full Text Available Dendritic cells (DC are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

  10. The Hidden Costs of Sexier Lipstick: Animal Testing in the Cosmetic Industry

    OpenAIRE

    Davis, William L.

    1999-01-01

    This paper does not argue, as the opening paragraphs of this section may seem to suggest, that animals should be seen as devoid of rights. On the contrary, it is filled with strong arguments pointing the other way. Its final assertion, however, is that those seeking to secure protection for animals in cosmetic laboratories should not allow themselves to become entangled in the emotional side of this old and ongoing debate. To do so invites an ultimately inconclusory, and perhaps violent, disc...

  11. Tracing water sources of terrestrial animal populations with stable isotopes: laboratory tests with crickets and spiders.

    Directory of Open Access Journals (Sweden)

    Kevin E McCluney

    2010-12-01

    Full Text Available Fluxes of carbon, nitrogen, and water between ecosystem components and organisms have great impacts across levels of biological organization. Although much progress has been made in tracing carbon and nitrogen, difficulty remains in tracing water sources from the ecosystem to animals and among animals (the "water web". Naturally occurring, non-radioactive isotopes of hydrogen and oxygen in water provide a potential method for tracing water sources. However, using this approach for terrestrial animals is complicated by a change in water isotopes within the body due to differences in activity of heavy and light isotopes during cuticular and transpiratory water losses. Here we present a technique to use stable water isotopes to estimate the mean mix of water sources in a population by sampling a group of sympatric animals over time. Strong correlations between H and O isotopes in the body water of animals collected over time provide linear patterns of enrichment that can be used to predict a mean mix of water sources useful in standard mixing models to determine relative source contribution. Multiple temperature and humidity treatment levels do not greatly alter these relationships, thus having little effect on our ability to estimate this population-level mix of water sources. We show evidence for the validity of using multiple samples of animal body water, collected across time, to estimate the isotopic mix of water sources in a population and more accurately trace water sources. The ability to use isotopes to document patterns of animal water use should be a great asset to biologists globally, especially those studying drylands, droughts, streamside areas, irrigated landscapes, and the effects of climate change.

  12. Tracing water sources of terrestrial animal populations with stable isotopes: laboratory tests with crickets and spiders.

    Science.gov (United States)

    McCluney, Kevin E; Sabo, John L

    2010-12-31

    Fluxes of carbon, nitrogen, and water between ecosystem components and organisms have great impacts across levels of biological organization. Although much progress has been made in tracing carbon and nitrogen, difficulty remains in tracing water sources from the ecosystem to animals and among animals (the "water web"). Naturally occurring, non-radioactive isotopes of hydrogen and oxygen in water provide a potential method for tracing water sources. However, using this approach for terrestrial animals is complicated by a change in water isotopes within the body due to differences in activity of heavy and light isotopes during cuticular and transpiratory water losses. Here we present a technique to use stable water isotopes to estimate the mean mix of water sources in a population by sampling a group of sympatric animals over time. Strong correlations between H and O isotopes in the body water of animals collected over time provide linear patterns of enrichment that can be used to predict a mean mix of water sources useful in standard mixing models to determine relative source contribution. Multiple temperature and humidity treatment levels do not greatly alter these relationships, thus having little effect on our ability to estimate this population-level mix of water sources. We show evidence for the validity of using multiple samples of animal body water, collected across time, to estimate the isotopic mix of water sources in a population and more accurately trace water sources. The ability to use isotopes to document patterns of animal water use should be a great asset to biologists globally, especially those studying drylands, droughts, streamside areas, irrigated landscapes, and the effects of climate change.

  13. A TeGM6-4r antigen-based immunochromatographic test (ICT) for animal trypanosomosis.

    Science.gov (United States)

    Nguyen, Thu-Thuy; Ruttayaporn, Ngasaman; Goto, Yasuyuki; Kawazu, Shin-ichiro; Sakurai, Tatsuya; Inoue, Noboru

    2015-11-01

    Animal trypanosomosis is a disease that is distributed worldwide which results in huge economic losses due to reduced animal productivity. Endemic regions are often located in the countryside where laboratory diagnosis is costly or inaccessible. The establishment of simple, effective, and accurate field tests is therefore of great interest to the farming and veterinary sectors. Our study aimed to develop a simple, rapid, and sensitive immunochromatographic test (ICT) for animal trypanosomosis utilizing the recombinant tandem repeat antigen TeGM6-4r, which is conserved amongst salivarian trypanosome species. In the specificity analysis, TeGM6-4r/ICT detected all of Trypanosoma evansi-positive controls from experimentally infected water buffaloes. As expected, uninfected controls tested negative. All sera samples collected from Tanzanian and Ugandan cattle that were Trypanosoma congolense- and/or Trypanosoma vivax-positive by microscopic examination of the buffy coat were found to be positive by the newly developed TeGM6-4r/ICT, which was comparable to results from TeGM6-4r/ELISA (kappa coefficient [κ] = 0.78). TeGM6/ICT also showed substantial agreement with ELISA using Trypanosoma brucei brucei (κ = 0.64) and T. congolense (κ = 0.72) crude antigen, suggesting the high potential of TeGM6-4r/ICT as a field diagnostic test, both for research purposes and on-site diagnosis of animal trypanosomosis.

  14. Using a Graphics Turing Test to Evaluate the Effect of Frame Rate and Motion Blur on Telepresence of Animated Objects

    DEFF Research Database (Denmark)

    Borg, Mathias; Johansen, Stine Schmieg; Krog, Kim Srirat

    2013-01-01

    A limited Graphics Turing Test is used to determine the frame rate that is required to achieve telepresence of an animated object. For low object velocities of 2.25 and 4.5 degrees of visual angle per second at 60 frames per second a rotating object with no added motion blur is able to pass the t...

  15. 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

  16. 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.

  17. Developing the Frith-Happé animations: a quick and objective test of Theory of Mind for adults with autism.

    Science.gov (United States)

    White, Sarah J; Coniston, Devorah; Rogers, Rosannagh; Frith, Uta

    2011-04-01

    It is now widely accepted that individuals with autism have a Theory of Mind (ToM) or mentalizing deficit. This has traditionally been assessed with false-belief tasks and, more recently, with silent geometric animations, an on-line ToM task. In adults with milder forms of autism standard false-belief tests, originally devised for children, often prove insensitive, while the Frith-Happé animations have had rather better success at capturing the on-line ToM deficit in this population. However, analysis of participants' verbal descriptions of these animations, which span scenarios from "Random" to "Goal-Directed" and "ToM," is time consuming and subjective. In this study, we developed and established the feasibility of an objective method of response through a series of multiple-choice questions. Sixteen adults with autism and 15 typically developing adults took part, matched for age and intelligence. The adults with autism were less accurate as a group at categorizing the Frith-Happé animations by the presence or absence of mental and physical interactions. Furthermore, they were less able to select the correct emotions that are typically attributed to the triangles in the mental state animations. This new objective method for assessing the understanding of the animations succeeded in being as sensitive as the original subjective method in detecting the mentalizing difficulties in autism, as well as being quicker and easier to administer and analyze. Copyright © 2011, International Society for Autism Research, Wiley Periodicals, Inc.

  18. Putting theory to the test: which regulatory mechanisms can drive realistic growth of a root?

    Science.gov (United States)

    De Vos, Dirk; Vissenberg, Kris; Broeckhove, Jan; Beemster, Gerrit T S

    2014-10-01

    In recent years there has been a strong development of computational approaches to mechanistically understand organ growth regulation in plants. In this study, simulation methods were used to explore which regulatory mechanisms can lead to realistic output at the cell and whole organ scale and which other possibilities must be discarded as they result in cellular patterns and kinematic characteristics that are not consistent with experimental observations for the Arabidopsis thaliana primary root. To aid in this analysis, a 'Uniform Longitudinal Strain Rule' (ULSR) was formulated as a necessary condition for stable, unidirectional, symplastic growth. Our simulations indicate that symplastic structures are robust to differences in longitudinal strain rates along the growth axis only if these differences are small and short-lived. Whereas simple cell-autonomous regulatory rules based on counters and timers can produce stable growth, it was found that steady developmental zones and smooth transitions in cell lengths are not feasible. By introducing spatial cues into growth regulation, those inadequacies could be avoided and experimental data could be faithfully reproduced. Nevertheless, a root growth model based on previous polar auxin-transport mechanisms violates the proposed ULSR due to the presence of lateral gradients. Models with layer-specific regulation or layer-driven growth offer potential solutions. Alternatively, a model representing the known cross-talk between auxin, as the cell proliferation promoting factor, and cytokinin, as the cell differentiation promoting factor, predicts the effect of hormone-perturbations on meristem size. By down-regulating PIN-mediated transport through the transcription factor SHY2, cytokinin effectively flattens the lateral auxin gradient, at the basal boundary of the division zone, (thereby imposing the ULSR) to signal the exit of proliferation and start of elongation. This model exploration underlines the value of

  19. 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

  20. Whiteboard animation for knowledge mobilization: a test case from the Slave River and Delta, Canada

    Directory of Open Access Journals (Sweden)

    Lori E. A. Bradford

    2015-10-01

    Full Text Available Objective: To present the co-creation of a whiteboard animation video, an enhanced e-storytelling technique for relaying traditional knowledge interview results as narratives. Design: We present a design for translating interview results into a script and accompanying series of figures, followed by technical steps to create a whiteboard animation product. Method: Our project used content analysis and researcher triangulation, followed by a collaborative process to develop an animated video to disseminate research findings. A 13-minute long whiteboard animation video was produced from a research study about changing environments in northern Canadian communities and was distributed to local people. Three challenging issues in the video creation process including communication issues, technical difficulties and contextual debate were resolved among the supporting agencies and researchers. Conclusions: Dissemination of findings is a crucial step in the research process. Whiteboard animation video products may be a viable and culturally-appropriate form of relaying research results back to Indigenous communities in a storytelling format.

  1. Testing long-term memory in animal models of schizophrenia: suggestions from CNTRICS.

    Science.gov (United States)

    Bussey, Timothy J; Barch, Deanna M; Baxter, Mark G

    2013-11-01

    This paper reports the results of discussions at the fourth meeting of Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) meeting, held over two days in Washington, DC in April 2011. The meeting focused on animal paradigms for assessing the cognitive constructs relevant to schizophrenia identified in previous CNTRICS meetings. This report focuses on the outcome of discussions in the general area of long-term memory. A number of candidate animal paradigms were discussed. Two of these - one for rodents and one for non-human primates - were recommended as particularly promising for further development. Copyright © 2013 Elsevier Ltd. All rights reserved.

  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. 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

    , 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......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......, 4) existing measurement instruments, and 5) focus groups of patients. Test-retest reliability was assessed in 30/110 patients. In 110 patients correlations were calculated between AAQ and self-reported Hip disability and Knee injury Osteoarthritis Outcome ADL subscale (H/KOOS). In 45/110 patients...

  4. 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.

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

    NARCIS (Netherlands)

    Reisinger, K.; Hoffmann, S.; Alépée, N.; Ashikaga, T.; Barroso, J.; Elcombe, C.; Gellatly, N.; Galbiati, V.; Gibbs, S.; Groux, H.; Hibatallah, J.; Keller, D.; Kern, P.; Klaric, M.; Kolle, S.; Kuehnl, J.; Lambrechts, N.; Lindstedt, M.; Millet, M.; Martinozzi-Teissier, S.; Natsch, A.; Petersohn, D.; Pike, I.; Sakaguchi, H.; Schepky, A.; Tailhardat, M.; Templier, M.; van Vliet, E; Maxwell, G.

    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

  6. Numerical study of the SSME nozzle flow fields during transient operations: A comparison of the animated results with test

    Science.gov (United States)

    Wang, Ten-See; Dumas, Catherine

    1993-01-01

    A computational fluid dynamics (CFD) model has been applied to study the transient flow phenomena of the nozzle and exhaust plume of the Space Shuttle Main Engine (SSME), fired at sea level. The CFD model is a time accurate, pressure based, reactive flow solver. A six-species hydrogen/oxygen equilibrium chemistry is used to describe the chemical-thermodynamics. An adaptive upwinding scheme is employed for the spatial discretization, and a predictor, multiple corrector method is used for the temporal solution. Both engine start-up and shut-down processes were simulated. The elapse time is approximately five seconds for both cases. The computed results were animated and compared with the test. The images for the animation were created with PLOT3D and FAST and then animated with ABEKAS. The hysteresis effects, and the issues of free-shock separation, restricted-shock separation and the end-effects were addressed.

  7. The Belgian regulatory framework for NORM industries : test-case of a phosphate production plant

    International Nuclear Information System (INIS)

    Pepin, Stephane; Dehandschutter, Boris; Poffijn, Andre; Michel Sonck

    2008-01-01

    According to the Belgian radiation protection regulatory framework, some categories of NORM industries must register to the competent Belgian radiation protection authority (FANC, Federal Agency for Nuclear Control). The facilities must provide a set of information which allows the authority to assess the radiological impact of the industrial activity on the workers, the population and the environment. If the dose exceeds or is likely to exceed 1 mSv/y, corrective measures have to be implemented. FANC has issued a methodology in order to define more precisely the data needed to evaluate the radiological impact. The methodology lists also the exposure pathways which have to be taken into account and the relevant parameters for the evaluation of the doses. The case of a phosphate production plant is discussed in more details: although the exposure of the workers in the production process as such is rather limited, the specific activity of some residues (calcium fluoride sludge) reaches around 10 kBq/kg of Ra-226. This sludge is disposed off in a specific landfill for which a program of radiological monitoring has been implemented. It includes periodic measurements of dose rate and radon concentration on the landfill. (author)

  8. Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes

    DEFF Research Database (Denmark)

    Fritsche, Ellen; Grandjean, Philippe; Crofton, Kevin M

    2018-01-01

    in the environment, with high uncertainty concerning their developmental neurotoxicity (DNT) potential. Closing this data gap with the current test guideline approach is not feasible, because the in vivo bioassays are far too resource-intensive concerning time, money and number of animals. A variety of in vitro...... methods are now available, that have the potential to close this data gap by permitting mode-of-action-based DNT testing employing human stem cells-derived neuronal/glial models. In vitro DNT data together with in silico approaches will in the future allow development of predictive models for DNT effects...

  9. The use of Minilabs to improve the testing capacity of regulatory authorities in resource limited settings: Tanzanian experience.

    Science.gov (United States)

    Risha, Peter Gasper; Msuya, Zera; Clark, Malcolm; Johnson, Keith; Ndomondo-Sigonda, Margareth; Layloff, Thomas

    2008-08-01

    The Tanzania Food and Drugs Authority piloted the use of Minilab kits, a thin-layer-chromatographic based drug quality testing technique, in a two-tier quality assurance program. The program is intended to improve testing capacity with timely screening of the quality of medicines as they enter the market. After 1 week training of inspectors on Minilab screening techniques, they were stationed at key Ports-of-Entry (POE) to screen the quality of imported medicines. In addition, three non-Ports-of-Entry centres were established to screen samples collected during Post-Marketing-Surveillance. Standard operating procedures (SOPs) were developed to structure and standardize the implementation process. Over 1200 samples were tested using the Minilab outside the central quality control laboratory (QCL), almost doubling the previous testing capacity. The program contributed to increased regulatory reach and visibility of the Authority throughout the country, serving as a deterrent against entry of substandard medicines into market. The use of Minilab for quality screening was inexpensive and provided a high sample throughput. However, it suffers from the limitation that it can reliably detect only grossly substandard or wrong drug samples and therefore, it should not be used as an independent testing resource but in conjunction with a full-service quality control laboratory capable of auditing reported substandard results.

  10. Safety testing of VIROTECTO as a bio insecticide on animal health

    International Nuclear Information System (INIS)

    Ali, S.E.

    2007-01-01

    The purpose of the present study was to investigate the effect of viral uses as a bio insecticide on animal's health. Fifty-four male albino rats (100-110 g) were randomly divided into three equal groups, eighteen in each, the first group served as control, the second group fed on 50% normal concentrate and 50% normal potato and the third group fed on 50% normal concentrate and 50% potato sprayed with 0.15 g/kg potato virotecto. Blood samples were collected at fixed time intervals of 15, 35 and 45 days. Results of the present study showed that viral uses led to a significant decrease in final body weight and organs weight. Hematological (RBC, WBC, Hb, Ht, MCU, MCH and MCHC), biochemical (testosterone, lipid peroxide, total lipid, total protein and albumin) and histopathological examination of testis revealed that there were different disorders as a result of viral uses as a bio insecticide on animal health

  11. Potential for tumor therapy with tritiated tetracycline. Summary evaluation. [Animal tests

    Energy Technology Data Exchange (ETDEWEB)

    Davis, R.C.; Wood, P.; Wood, L.L.; Mendelsohn, M.L.

    1976-10-26

    Reports of tetracycline accumulation in human and animal tumors have led a number of investigators to postulate that this drug, if radio-labeled, might have potential as a therapeutic or diagnostic agent. This paper describes attempts to investigate this potential for tritiated tetracycling. The therapeutic studies demonstrated that while a significant reduction in the growth rates of transplanted tumors could be obtained by the administration of heavy doses of TTC relative to uninjected controls, similar reductions were observed in the growth rates of tumors in animals receiving unlabeled TC. In the localization studies in rodents, the concentrations of TTC in normal tissues and tumors were compared and were correlated with the corresponding concentrations of /sup 14/C-thymidine, a measure of proliferative activity.

  12. PEGDA hydrogels as a replacement for animal tissues in mucoadhesion testing.

    Science.gov (United States)

    Eshel-Green, Tal; Eliyahu, Shaked; Avidan-Shlomovich, Shlomit; Bianco-Peled, Havazelet

    2016-06-15

    Utilization of animal parts in ex-vivo mucoadhesion assays is a common approach that presents many difficulties due to animal rights issues and large variance between animals. This study examines the suitability of two PEGDA (poly(ethylene glycol) diacrylate) based hydrogels to serve as tissue mimetics for mucoadhesion evaluation. One hydrogel, termed PEGDA-QT, was composed of pentaerythritol tetrakis (3-mercaptopropionate) and PEG and contained free thiol groups mimicking those found in natural mucosa. The other hydrogel was formed by UV (ultraviolet) curing of PEGDA and mimicked the mechanical property of mucosa but not its chemical constitute. When ranking different first generation mucoadhesive polymers using a tensile assay, both hydrogels showed good agreement with the ranking achieved for porcine small intestine. However, only PEGDA-QT and porcine small intestine shared a similar displacement curve. The same ranking for PEGDA-QT and porcine small intestine was also observed when comparing a second-generation mucoadhesive polymer, thiolated alginate, to native alginate. Our findings suggest that PEGDA-QT could serve as a replacement for porcine small intestine in both mucoadhesion evaluations using a tensile machine and the flow-through method for first and second-generation mucoadhesive polymers. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Optimal energy efficiency policies and regulatory demand-side management tests: How well do they match?

    International Nuclear Information System (INIS)

    Brennan, Timothy J.

    2010-01-01

    Under conventional models, subsidizing energy efficiency requires electricity to be priced below marginal cost. Its benefits increase when electricity prices increase to finance the subsidy. With high prices, subsidies are counterproductive unless consumers fail to make efficiency investments when private benefits exceed costs. If the gain from adopting efficiency is only reduced electricity spending, capping revenues from energy sales may induce a utility to substitute efficiency for generation when the former is less costly. This goes beyond standard 'decoupling' of distribution revenues from sales, requiring complex energy price regulation. The models' results are used to evaluate tests in the 2002 California Standard Practice Manual for assessing demand-side management programs. Its 'Ratepayer Impact Measure' test best conforms to the condition that electricity price is too low. Its 'Total Resource Cost' and 'Societal Cost' tests resemble the condition for expanded decoupling. No test incorporates optimality conditions apart from consumer choice failure.

  14. 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.

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

    Science.gov (United States)

    2011-01-01

    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. PMID:21824406

  16. Pre-criticality testing of radiation monitors associated with protective and regulatory channels of PHWRs and related work

    International Nuclear Information System (INIS)

    Tripathi, S.M.; Rao, Suresh; Mahant, A.K.; Sathian, V.; Ghodke, Shobha; Satam, R.A.; Singh, Yashoda; Phadnis, U.V.; Shaha, V.V.

    2006-01-01

    The paper describes the various experiments that are regularly carried out for each PHWR since RAPS-2. The work involves performance evaluation of start-up counters and ion chambers used in Protective and Regulatory channels and start-up counters used both in-core and out of core. In addition, Radiation Safety Systems Division (RSSD) also carries out calibration of Delayed Neutron Monitors (DNM) and Self Powered Neutron Detectors (SPND). Except SPND, all other detectors are tested not only at BARC but also at reactor sites prior to initial flushing of heavy water, using the actual circuitry and control instruments at site. The performance evaluation of SPNDs is carried out at A-1 location of APSARA reactor core. Apart from these, RSSD also carries out calibration of zonal classification monitors and health physics related radiation monitors at BARC. (author)

  17. 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

  18. Design of a testing strategy using non-animal based test methods: lessons learnt from the ACuteTox project.

    Science.gov (United States)

    Kopp-Schneider, Annette; Prieto, Pilar; Kinsner-Ovaskainen, Agnieszka; Stanzel, Sven

    2013-06-01

    In the framework of toxicology, a testing strategy can be viewed as a series of steps which are taken to come to a final prediction about a characteristic of a compound under study. The testing strategy is performed as a single-step procedure, usually called a test battery, using simultaneously all information collected on different endpoints, or as tiered approach in which a decision tree is followed. Design of a testing strategy involves statistical considerations, such as the development of a statistical prediction model. During the EU FP6 ACuteTox project, several prediction models were proposed on the basis of statistical classification algorithms which we illustrate here. The final choice of testing strategies was not based on statistical considerations alone. However, without thorough statistical evaluations a testing strategy cannot be identified. We present here a number of observations made from the statistical viewpoint which relate to the development of testing strategies. The points we make were derived from problems we had to deal with during the evaluation of this large research project. A central issue during the development of a prediction model is the danger of overfitting. Procedures are presented to deal with this challenge. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. An experimental test on large animals of MCNP application for whole body counting

    International Nuclear Information System (INIS)

    Borisov, N.; Yatsenko, V.; Kochetkov, O.; Gusev, I.; Vlasov, P.; Kalistratova, V.; Nisimov, P.; Levochkin, F.; Borovkov, M.; Stolyarov, V.; Tsedish, S.; Tyurin, I.; Franck, D.; Carlan, L. de

    2005-01-01

    Measurements of actinide body burden using whole body counting spectrometry is hampered due to intensive absorption of γ-rays inside the patient's body, which depends on the anatomy of a patient. To establish the correspondence between pulse-height-spectra intensity and radionuclide activity, Monte Carlo calculations are widely used. For such calculations, the radiation transport geometry is usually described in terms of small rectangular boxes (voxels) retrieved from computed tomography or magnetic resonance images. The software for Monte Carlo-assisted calibration of whole body counting, which performs automatic creation of individual MCNP voxel phantoms, was checked in a quasi-in vivo experiment on large animals. During the experiment, pigs of 35-40 kg body mass were used as phantoms for measurement of actinides body burden. 241 Am was administered (via injection of a radioactive solution or via implantation of plastic capsules containing the radioactive material) into the lungs of pigs. The pigs were measured using the pure germanium low-energy γ-spectrometers. The images of animals were obtained using the computed tomography machine. On the base of these tomograms, MCNP4c2 calculations were done to obtain the pulse-height-spectra of the whole body counters. The experimental results were reproduced in calculations with error of less than 30% for 241 Am administered via injection and less than 10% for 241 Am administered inside the capsules. (authors)

  20. An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

    Science.gov (United States)

    Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

    2011-06-01

    Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

  1. Surra Sero K-SeT, a new immunochromatographic test for serodiagnosis of Trypanosoma evansi infection in domestic animals.

    Science.gov (United States)

    Birhanu, Hadush; Rogé, Stijn; Simon, Thomas; Baelmans, Rudy; Gebrehiwot, Tadesse; Goddeeris, Bruno Maria; Büscher, Philippe

    2015-07-30

    Trypanosoma evansi, the causative agent of surra, infects different domestic and wild animals and has a wide geographical distribution. It is mechanically transmitted mainly by haematophagous flies. Parasitological techniques are commonly used for the diagnosis of surra but have limited sensitivity. Therefore, serodiagnosis based on the detection of T. evansi specific antibodies is recommended by the World Organisation for Animal Health (OIE). Recently, we developed a new antibody detection test for the serodiagnosis of T. evansi infection, the Surra Sero K-SeT. Surra Sero K-SeT is an immunochromatographic test (ICT) that makes use of recombinant variant surface glycoprotein rVSG RoTat 1.2, produced in the yeast Pichia pastoris. In this study, we compared the diagnostic accuracy of the Surra Sero K-SeT and the Card Agglutination Test for T. evansi Trypanosomososis (CATT/T. evansi) with immune trypanolysis (TL) as reference test on a total of 806 sera from camels, water buffaloes, horses, bovines, sheep, dogs and alpacas. Test agreement was highest between Surra Sero K-SeT and TL (κ=0.91, 95% CI 0.841-0.979) and somewhat lower between CATT/T. evansi and TL (κ=0.85, 95% CI 0.785-0.922) and Surra Sero K-SeT and CATT/T. evansi (κ=0.81, 95% CI 0.742-0.878). The Surra Sero K-SeT displayed a somewhat lower overall specificity than CATT/T. evansi (94.8% versus 98.3%, χ(2)=13.37, p<0.001) but a considerably higher sensitivity (98.1% versus 84.4%, χ(2)=33.39, p<0.001). We conclude that the Surra Sero K-SeT may become an alternative for the CATT/T. evansi for sensitive detection of antibodies against T. evansi in domestic animals. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies.

    Science.gov (United States)

    Kuper, C Frieke; van Bilsen, Jolanda; Cnossen, Hilde; Houben, Geert; Garthoff, Jossie; Wolterbeek, Andre

    2016-09-01

    A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Design and testing of a 750MHz CW-EPR digital console for small animal imaging.

    Science.gov (United States)

    Sato-Akaba, Hideo; Emoto, Miho C; Hirata, Hiroshi; Fujii, Hirotada G

    2017-11-01

    This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Design and testing of a 750 MHz CW-EPR digital console for small animal imaging

    Science.gov (United States)

    Sato-Akaba, Hideo; Emoto, Miho C.; Hirata, Hiroshi; Fujii, Hirotada G.

    2017-11-01

    This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750 MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed.

  5. Opinion versus evidence for the need to move away from animal testing.

    Science.gov (United States)

    Hartung, Thomas

    2017-01-01

    Science is based on facts and their discourse. Willingly or unwillingly, facts are mixed with opinion, i.e., views or judgments formed, not necessarily based on fact or knowledge. This is often necessary, where we have controversial facts or no definitive evidence yet, because we need to take decisions or have to prioritize. Evidence-based approaches aim at identifying the facts and their quality objectively and transparently; they are now increasingly embraced in toxicology, especially by employing systematic reviews, meta-analyses, quality scoring, risk-of-bias tools, etc. These are core to Evidence-based Toxicology. Such approaches aim at minimizing opinion, the "eminence-based" part of science. Animal experiments are the basis of a lot of our textbook knowledge in the life sciences, have helped to develop desperately needed therapies, and have made this world a safer place. However, they represent only one of the many possible approaches to accomplish all these things. Like all approaches, they come with shortcomings, and their true contribution is often overrated. This article aims to summarize their limitations and challenges beside the ethical and economical concerns (i.e., costs and duration as well as costs following wrong decisions in product development): they include reproducibility, inadequate reporting, statistical under-powering, lack of inter-species predictivity, lack of reflection of human diversity and of real-life exposure. Each and every one of these increasingly discussed aspects of animal experiments can be amended, but this would require enormous additional resources. Together, they prompt a need to engineer a new paradigm to ensure the safety of patients and consumers, new products and therapies.

  6. Sensitivity, specificity and comparison of three commercially available immunological tests in the diagnosis of Cryptosporidium species in animals.

    Science.gov (United States)

    Danišová, Olga; Halánová, Monika; Valenčáková, Alexandra; Luptáková, Lenka

    The study was conducted to compare the specificity of immunological diagnostic methods used for the diagnosis of Cryptosporidium species capable of causing life-threatening infection in both immunosuppressed and immunocompetent patients. For the detection of Cryptosporidium species in 79 animals with diarrhoea, we used three Copro-antigen tests: RIDASCREEN ® Cryptosporidium test, Cryptosporidium 2nd Generation (ELISA) and RIDA ® QUICK Cryptosporidium. For immunoassays we used positive and negative samples detected by means of polymerase chain reaction and validated by sequencing and nested polymerase chain reaction to confirm the presence six different species of Cryptosporidium species. Prevalence of cryptosporidiosis in the entire group determined by enzyme immunoassay, enzyme linked immunosorbent assay, immuno-chromatographic test and polymerase chain reaction was 34.17%, 27.84%, 6.33% and 27.84%, respectively. Sensitivity of animal samples with enzyme immunoassay, enzyme linked immunosorbent assay, and immuno-chromatographic test was 63.6%, 40.9% and 22.7%, resp., when questionable samples were considered positive, whereas specificity of enzyme immunoassay, enzyme linked immunosorbent assay and immuno-chromatographic test was 75.9%, 78.9% and 100%, respectively. Positive predictive values and negative predictive values were different for all the tests. These differences results are controversial and therefore reliability and reproducibility of immunoassays as the only diagnostic method is questionable. The use of various Cryptosporidium species in diagnosis based on immunological testing and different results obtained by individual tests indicate potential differences in Copro-antigens produced by individual Cryptosporidium species. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

  7. Non-Animal Testing Approach to EPA Labeling for Eye Irritation

    Science.gov (United States)

    This document is an update to EPA’s 2013 published alternative testing approach (using in vitro/ex vivo assays) for determination of eye irritation potential in the pesticide program under EPA's classification and labeling system.

  8. STRATEGIES TO REDUCE OR REPLACE THE USE OF ANIMALS IN THE ENDOCRINE SCREENING AND TESTING PROGRAM.

    Science.gov (United States)

    Abstract: The US Environmental Protection Agency (EPA) is developing a screening and testing program for endocrine disrupting chemicals (EDCs) to detect alterations of hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen and thyroid hormone synthesis and androgen (AR...

  9. Design and testing of microfabricated surgical tools for large animal probe insertion

    Energy Technology Data Exchange (ETDEWEB)

    Jorgensen, Shelly [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-08-05

    Neural probes provide therapeutic stimulation for neuropsychiatric disorders or record neural activity to investigate the workings of the brain. Researchers utilize 6 mm long temporary silicon stiffeners attached with biodissolvable adhesive to insert flexible neural probes into rat brains, but increasing the probe length fivefold makes inserting large animal probes a significant challenge because of an increased potential for buckling. This study compared the insertion success rates of 6 mm and 30 mm long silicon stiffeners that were 80 μm wide and 30 μm thick, and ascertained the material thickness and modulus of elasticity that would provide successful insertion for a 30 mm probe. Using a microdrive, stiffeners were inserted into an agarose brain phantom at controlled insertion speeds while being video-recorded. Twenty-five percent of the 30 mm silicon stiffeners fully inserted at speeds approximately four times higher than the target rate of 0.13 mm/s, while 100 percent of the 6 mm silicon stiffeners inserted successfully at target speed. Critical buckling loads (Pcr) were calculated for the 6 mm and 30 mm silicon stiffeners, and for 30 mm diamond and tungsten stiffeners, with thicknesses varying from 30-80 μm. Increasing the thickness of the material by 10 μm, 20 μm and 30 μm improved the Pcr by 2.4, 4.7 and 8.2 times, respectively, independent of the material, and substituting diamond for silicon multiplied the buckling capacity by 5.0 times. Stiffeners made of silicon for large animal probe insertion are not strong enough to withstand buckling upon insertion without a significant increase in thickness. Replacing silicon with diamond and increasing the thickness of the stiffener to 50 μm would afford a stiffener with the same Pcr capacity as the 6 mm silicon stiffener that had a 100 percent insertion success rate. Experiments should continue with diamond to determine a minimum thickness that will ensure successful

  10. Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants.

    Science.gov (United States)

    Mezadri, T J; Batista, G M; Portes, A C; Marino-Neto, J; Lino-de-Oliveira, C

    2011-02-15

    The forced swim test (FST) is a pre-clinical test to short and long term treatment with antidepressant drugs (ADT), which requires between-subject designs. Herein a modified protocol of the FST using within-subject design (repeated rat-FST) was evaluated. Male Wistar rats were submitted to 15 min of swimming (Day 1: pretest) followed by three subsequent 5 min-swimming tests one week apart (Day 2: test, Day 7: retest 1, Day 14: retest 2). To determine the temporal and factorial characteristics of the variables scored in the repeated rat-FST, the protocol was carried out in untreated animals (E1). To validate the method, daily injections of Fluoxetine (FLX, 2.5mg/kg, i.p.) or saline were given over a 2-week period (E2). Tests and retests have been videotaped for further register of the latency, frequency and duration of behaviors. Over retesting the latency to immobility decreased whereas duration of immobility tended to increase. Factorial analysis revealed that the test, the retest 1 as well as the retest 2 have variables suitable to detection of antidepressant-like effects of ADT. Compared to saline, FLX chronically administrated reduced duration of immobility whereas increased duration of swimming in retest 2. The data suggest that repeated rat-FST detected the gradual increase in the efficacy of low doses of FLX over time. Therefore, repeated rat-FST seemed suitable to detect short and long term effects of selective serotonin reuptake inhibitors, or other ADT, thus reducing the number of animals used in the screenings of this type of compounds. © 2010 Elsevier B.V. All rights reserved.

  11. Estimating diagnostic test accuracies for Brachyspira hyodysenteriae accounting for the complexities of population structure in food animals.

    Directory of Open Access Journals (Sweden)

    Sonja Hartnack

    Full Text Available For swine dysentery, which is caused by Brachyspira hyodysenteriae infection and is an economically important disease in intensive pig production systems worldwide, a perfect or error-free diagnostic test ("gold standard" is not available. In the absence of a gold standard, Bayesian latent class modelling is a well-established methodology for robust diagnostic test evaluation. In contrast to risk factor studies in food animals, where adjustment for within group correlations is both usual and required for good statistical practice, diagnostic test evaluation studies rarely take such clustering aspects into account, which can result in misleading results. The aim of the present study was to estimate test accuracies of a PCR originally designed for use as a confirmatory test, displaying a high diagnostic specificity, and cultural examination for B. hyodysenteriae. This estimation was conducted based on results of 239 samples from 103 herds originating from routine diagnostic sampling. Using Bayesian latent class modelling comprising of a hierarchical beta-binomial approach (which allowed prevalence across individual herds to vary as herd level random effect, robust estimates for the sensitivities of PCR and culture, as well as for the specificity of PCR, were obtained. The estimated diagnostic sensitivity of PCR (95% CI and culture were 73.2% (62.3; 82.9 and 88.6% (74.9; 99.3, respectively. The estimated specificity of the PCR was 96.2% (90.9; 99.8. For test evaluation studies, a Bayesian latent class approach is well suited for addressing the considerable complexities of population structure in food animals.

  12. Testing complex animal cognition: Concept learning, proactive interference, and list memory.

    Science.gov (United States)

    Wright, Anthony A

    2018-01-01

    This article describes an approach for assessing and comparing complex cognition in rhesus monkeys and pigeons by training them in a sequence of synergistic tasks, each yielding a whole function for enhanced comparisons. These species were trained in similar same/different tasks with expanding training sets (8, 16, 32, 64, 128 … 1024 pictures) followed by novel-stimulus transfer eventually resulting in full abstract-concept learning. Concept-learning functions revealed better rhesus transfer throughout and full concept learning at the 128 set, versus pigeons at the 256 set. They were then tested in delayed same/different tasks for proactive interference by inserting occasional tests within trial-unique sessions where the test stimulus matched a previous sample stimulus (1, 2, 4, 8, 16 trials prior). Proactive-interference functions revealed time-based interference for pigeons (1, 10 s delays), but event-based interference for rhesus (no effect of 1, 10, 20 s delays). They were then tested in list-memory tasks by expanding the sample to four samples in trial-unique sessions (minimizing proactive interference). The four-item, list-memory functions revealed strong recency memory at short delays, gradually changing to strong primacy memory at long delays over 30 s for rhesus, and 10 s for pigeons. Other species comparisons and future directions are discussed. © 2018 Society for the Experimental Analysis of Behavior.

  13. The Cosmetics Europe strategy for animal-free genotoxicity testing: project status up-date.

    Science.gov (United States)

    Pfuhler, S; Fautz, R; Ouedraogo, G; Latil, A; Kenny, J; Moore, C; Diembeck, W; Hewitt, N J; Reisinger, K; Barroso, J

    2014-02-01

    The Cosmetics Europe (formerly COLIPA) Genotoxicity Task Force has driven and funded three projects to help address the high rate of misleading positives in in vitro genotoxicity tests: The completed "False Positives" project optimized current mammalian cell assays and showed that the predictive capacity of the in vitro micronucleus assay was improved dramatically by selecting more relevant cells and more sensitive toxicity measures. The on-going "3D skin model" project has been developed and is now validating the use of human reconstructed skin (RS) models in combination with the micronucleus (MN) and Comet assays. These models better reflect the in use conditions of dermally applied products, such as cosmetics. Both assays have demonstrated good inter- and intra-laboratory reproducibility and are entering validation stages. The completed "Metabolism" project investigated enzyme capacities of human skin and RS models. The RS models were shown to have comparable metabolic capacity to native human skin, confirming their usefulness for testing of compounds with dermal exposure. The program has already helped to improve the initial test battery predictivity and the RS projects have provided sound support for their use as a follow-up test in the assessment of the genotoxic hazard of cosmetic ingredients in the absence of in vivo data. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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...

  15. 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 ...

  16. 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.

  17. Study of the relative toxicity of anions, with Polycelis nigra as test animal

    Energy Technology Data Exchange (ETDEWEB)

    Jones, J R.E.

    1942-01-01

    A brief review is given of existing knowledge regarding the physiological effects of anions, and literature dealing with their relative toxicity. The degree of toxicity of twenty-seven anions to Polycelis nigra (Mueller) has been assessed, by determining in each case the molar concentration the animal survives for 48 hr. at 15-18/sup 0/C. On this basis their order of increasing toxicity is as follows; commas separate ions of similar degree of toxicity: Cl

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

    Science.gov (United States)

    1993-09-01

    diagnostic laboratory. After publishing a series of papers on bovine tetany and mastitis , he joined the Medical Research Laboratory at Edgewood Arsenal in...Viability (Simons, 1981). f. Bovine Red Blood Cell/Hemolysis (Shadduck et. al., 1987). g. Mouse L929 fNbroblasts-Erythrocin C Staining (Frazier, 1988). h...1983). 3. Bovine Cornea/Corneal Opacity (Muir, 1984). 4. Proposed Mouse Eye/Permeability Test (Maurice and Singh, 1986). IV. INFLAMMATION/IMMUNITY 1

  19. Engineering aspects of the experiment and results of animal tests. [Apollo 17 Biological Cosmic Ray Experiment

    Science.gov (United States)

    Look, B. C.; Tremor, J. W.; Barrows, W. F.; Zabower, H. R.; Suri, K.; Park, E. G., Jr.; Durso, J. A.; Leon, H. A.; Haymaker, W.; Lindberg, R. G.

    1975-01-01

    A closed passive system independent of support from the spacecraft or its crew was developed to house five pocket mice for their flight on Apollo XVII. The reaction of potassium superoxide with carbon dioxide and water vapor to produce oxygen provided a habitable atmosphere within the experiment package. The performance of the system and the ability of the mice to survive the key preflight tests gave reasonable assurance that the mice would also withstand the Apollo flight.-

  20. AFNOR validation of Premi Test, a microbiological-based screening tube-test for the detection of antimicrobial residues in animal muscle tissue.

    Science.gov (United States)

    Gaudin, Valerie; Juhel-Gaugain, Murielle; Morétain, Jean-Pierre; Sanders, Pascal

    2008-12-01

    Premi Test contains viable spores of a strain of Bacillus stearothermophilus which is sensitive to antimicrobial residues, such as beta-lactams, tetracyclines, macrolides and sulphonamides. The growth of the strain is inhibited by the presence of antimicrobial residues in muscle tissue samples. Premi Test was validated according to AFNOR rules (French Association for Normalisation). The AFNOR validation was based on the comparison of reference methods (French Official method, i.e. four plate test (FPT) and the STAR protocol (five plate test)) with the alternative method (Premi Test). A preliminary study was conducted in an expert laboratory (Community Reference Laboratory, CRL) on both spiked and incurred samples (field samples). Several method performance criteria (sensitivity, specificity, relative accuracy) were estimated and are discussed, in addition to detection capabilities. Adequate agreement was found between the alternative method and the reference methods. However, Premi Test was more sensitive to beta-lactams and sulphonamides than the FPT. Subsequently, a collaborative study with 11 laboratories was organised by the CRL. Blank and spiked meat juice samples were sent to participants. The expert laboratory (CRL) statistically analysed the results. It was concluded that Premi Test could be used for the routine determination of antimicrobial residues in muscle of different animal origin with acceptable analytical performance. The detection capabilities of Premi Test for beta-lactams (amoxicillin, ceftiofur), one macrolide (tylosin) and tetracycline were at the level of the respective maximum residue limits (MRL) in muscle samples or even lower.

  1. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Embry, Michelle R., E-mail: membry@ilsi.org [ILSI Health and Environmental Sciences Institute, 1156 15th Street, NW, Suite 200, Washington, DC 20005 (United States); Belanger, Scott E., E-mail: belanger.se@pg.com [Procter and Gamble, Central Product Safety, PO Box 538707, Miami Valley Innovation Center, Cincinnati, OH 45253-8707 (United States); Braunbeck, Thomas A., E-mail: braunbeck@zoo.uni-heidelberg.de [University of Heidelberg, Im Neuenheimer Feld 230, Heidelberg D -69120 (Germany); Galay-Burgos, Malyka, E-mail: malyka.galay-burgos@ecetoc.org [European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC), 4 Avenue E. Van Nieuwenhuyse B-1160, Brussels (Belgium); Halder, Marlies, E-mail: marlies.halder@jrc.ec.europa.eu [European Commission, Joint Research Centre, Institute for Health and Consumer Protection, In-Vitro Methods Unit TP-580 Ispra 21027 (Italy); Hinton, David E., E-mail: dhinton@duke.edu [Duke University, Nicholas School of the Environment, PO Box 90328, Durham, NC 27708, Unites States (United States); Leonard, Marc A., E-mail: mleonard@rd.loreal.com [L' Oreal Recherche Avancee, Unite d' Ecotoxicologie, 1 av. E. Schueller, 93601 Aulnay sous bois (France); Lillicrap, Adam, E-mail: Adam.lillicrap@niva.no [AstraZeneca, Freshwater Quarry, Brixham TQ5 8BA (United Kingdom); Norberg-King, Teresa, E-mail: norberg-king.teresa@epa.gov [U.S. EPA, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, MN 55804-1636 (United States); Whale, Graham, E-mail: graham.whale@shell.com [Shell Global Solutions, Analytical Technology, P.O. Box 1, Chester CH1 3SH (United Kingdom)

    2010-04-15

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

  3. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information.

  4. Experimental study on L-[1-13C] phenylalanine breath test for quantitative assessment of liver function with animal

    International Nuclear Information System (INIS)

    Yan Weili; Fudan Univ., Shanghai; Lin Xiangtong; Sun Dayu; Jiang Yibin; Sun Xu; Rong Lan; Liang Qi

    2006-01-01

    Objective: Using a small animal breath test model we designed and L-[1- 13 C] phenylalanine breath test ( 13 C-PheBT) of rats, the authors investigated its feasibility and validity and determined effective parameter of the test. Methods: Twenty male Sprague-Dawley (SD) weighting 280-290 g rats randomized into two groups acute hepatitis rats (n=10) and control rats (n=10). Hepatitis was induced by carbon tetrachloride (CCl 4 ) olive oil administration through intragastric gavage. PheBT was assisted by small mechanical ventilator improved and air samples were collected discontinuously, 20 mg/kg body weight L-[1- 13 C] phenylalanine ( 13 C-Phe) was administered intravenously. Twenty-nine breath samples were taken before and different intervals within sixty minutes after administration. 13 Cenrichment was measured by isotope ratio mass spectrometer. Results: All time phase curves of 13 C enrichment in rat breath reached a peak almost at 2 min after the intravenous administration of 13 C-Phe. The PheBT parameters, 13 C excretion rate constant (PheBT-K), of CCl 4 hepatitis rats were significantly lower than that of normal control rats [(2.45 ± 0.25) x 10 -2 min -1 vs (2.98 ± 0.19) x 10 -2 min -1 , t = 5.40, P 13 C fast phase disposition constant did not statistically differ between the two groups (t=0.58, P>0.05). PheBT-K had significant negative cor-relation with serum ALT, AKP, TBA and total bilirum TBIL (the correlation coefficient r is -0.74, -0.73, -0.82 and -0.67 respectively, P 0.05). Conclusions: It was indicated that the small animal breath test model we designed was a virtual tool to use in experimental study on breath test and PheBT-K was a sensitive index. (authors)

  5. Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo.

    Science.gov (United States)

    Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

    2015-05-07

    The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ∼21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.

  6. Canine Food Preference Assessment of Animal and Vegetable Ingredient-Based Diets Using Single-Pan Tests and Behavioral Observation

    Directory of Open Access Journals (Sweden)

    Meghan C. Callon

    2017-10-01

    Full Text Available Knowledge of canine food selection is critical for both the pet food industry and dog owners, since owners want quality foods that are palatable, while fulfilling their pet’s nutritional requirements. There are two common methods for assessing canine food preference: the two-pan test and the one-pan test. Neither test fully accounts for the complexity of the canine feeding experience nor do they provide applicable representations of canine feeding behavior in the home. The objectives of this study were to (1 determine whether dogs display a preference for animal ingredient-based diets when compared with vegetable ingredient-based diets and (2 examine whether dogs experience neophobia when presented with a novel diet. Eight adult Beagles (average age = 24 months, weighing 8–12 kg were individually fed each of four novel diets in a 4 × 4 replicated Latin square design, with 10-d treatment periods and four dietary treatments. Data were analyzed using a mixed model with repeated measures and significance was declared when p < 0.05. The diets were: animal and vegetable ingredient-based diets, and animal- and vegetable-based ingredients diluted with anhydrous α-d-glucose. The diluted diets were used for a larger study to determine true mineral digestibility. Dogs were fed twice per day (0800 and 1300 h. Behavioral observations were made by video on the first, and last 2 days of each 10-day treatment period of both a.m. and p.m. feedings. Time to consume feed, distraction, hesitation, level of anticipation pre-consumption, and interest post-consumption were recorded. Dogs experienced initial disruptive (neophobic effects of a novel diet. Neophobia was demonstrated by a decreased (slower rate of consumption, increased distraction during consumption of the diet, and increased hesitation on the first day of each new diet (p < 0.05. The level of interest post-consumption was highest when dogs consumed the animal

  7. Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

    Science.gov (United States)

    Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

    2016-07-01

    Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Equivalence testing using existing reference data: An example with genetically modified and conventional crops in animal feeding studies.

    Science.gov (United States)

    van der Voet, Hilko; Goedhart, Paul W; Schmidt, Kerstin

    2017-11-01

    An equivalence testing method is described to assess the safety of regulated products using relevant data obtained in historical studies with assumedly safe reference products. The method is illustrated using data from a series of animal feeding studies with genetically modified and reference maize varieties. Several criteria for quantifying equivalence are discussed, and study-corrected distribution-wise equivalence is selected as being appropriate for the example case study. An equivalence test is proposed based on a high probability of declaring equivalence in a simplified situation, where there is no between-group variation, where the historical and current studies have the same residual variance, and where the current study is assumed to have a sample size as set by a regulator. The method makes use of generalized fiducial inference methods to integrate uncertainties from both the historical and the current data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Science.gov (United States)

    Curren, Rodger

    2009-12-01

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

  10. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  11. Vertebral osteoporosis: perfused animal cadaver model for testing new vertebroplastic agents.

    Science.gov (United States)

    Hoell, Thomas; Huschak, Gerald; Beier, Andre; Holzhausen, Hans-Juergen; Meisel, Hans-Joerg; Emmrich, Frank

    2010-12-01

    Experimental study. It was aimed to establish a cadaver model to imitate osteoporotic perfused vertebral bone and to allow for transpedicular transfer of bone cement and various new materials into vertebrae. The model was perfused to simulate vertebroplasty in the presence of transvertebral blood flow. The injection of bone cement into vertebrae bears the risk of irreversible discharge of material into the venous system of the spinal canal. The bovine cadaver model studied allows visual studies of material distribution in a vertebral bone, the potential spill-out of material, and quantification of washout and disintegration phenomena. Thoracic and lumbar vertebrae from 1-year-old calves were cut transversally into 5 mm slices, macerated, and decalcified. The softened bone slices were compressed between 2 transparent plastic discs. A standard vertebroplasty cannula (outer diameter 3.5 mm, inner diameter 2.5 mm) was inserted into the vertebral body via the pedicle to transfer the different vertebroplasty materials. Arterial blood flow was simulated by means of liquid irrigation via 2 needles in the ventral part of the vertebral body slice. Metal powder was mixed with the solution to indicate the blood flow in the bone. The model was evaluated with the vertebroplasty cement polymethylmethacrylate. The model permitted visualization of the insertion and distribution of vertebroplasty materials. Liquid bone cement was effused into the spinal canal as in the clinical situation. Higher modulus cement acted in the same way as in clinical vertebroplasty. Rigid vertebroplasty agents led to trabecular fractures and stable mechanical interactions with the bone and eventually moved dorsal bone fragments into the spinal canal. Sedimentation of the metal powder indicated regions of perfusion. The model simulated the clinical behavior of liquid and higher modulus vertebroplasty agents in the presence of blood flow. It enabled safe ex vivo testing of the mechanical and physical

  12. A cable-driven soft robot surgical system for cardiothoracic endoscopic surgery: preclinical tests in animals.

    Science.gov (United States)

    Wang, Hesheng; Zhang, Runxi; Chen, Weidong; Wang, Xiaozhou; Pfeifer, Rolf

    2017-08-01

    Minimally invasive surgery attracts more and more attention because of the advantages of minimal trauma, less bleeding and pain and low complication rate. However, minimally invasive surgery for beating hearts is still a challenge. Our goal is to develop a soft robot surgical system for single-port minimally invasive surgery on a beating heart. The soft robot described in this paper is inspired by the octopus arm. Although the octopus arm is soft and has more degrees of freedom (DOFs), it can be controlled flexibly. The soft robot is driven by cables that are embedded into the soft robot manipulator and can control the direction of the end and middle of the soft robot manipulator. The forward, backward and rotation movement of the soft robot is driven by a propulsion plant. The soft robot can move freely by properly controlling the cables and the propulsion plant. The soft surgical robot system can perform different thoracic operations by changing surgical instruments. To evaluate the flexibility, controllability and reachability of the designed soft robot surgical system, some testing experiments have been conducted in vivo on a swine. Through the subxiphoid, the soft robot manipulator could enter into the thoracic cavity and pericardial cavity smoothly and perform some operations such as biopsy, ligation and ablation. The operations were performed successfully and did not cause any damage to the surrounding soft tissues. From the experiments, the flexibility, controllability and reachability of the soft robot surgical system have been verified. Also, it has been shown that this system can be used in the thoracic and pericardial cavity for different operations. Compared with other endoscopy robots, the soft robot surgical system is safer, has more DOFs and is more flexible for control. When performing operations in a beating heart, this system maybe more suitable than traditional endoscopy robots.

  13. Current status and perspectives of neurobehavioral approaches in guideline—oriented animal testing

    Institute of Scientific and Technical Information of China (English)

    TakaH

    2002-01-01

    This presentation aims to overview the current status and perspective of behavioral approaches used in guideline-oriented toxicological studies for agricultural chemicals.Guidelines revised recently (MAFF,OECD,EPA) require sytematic observation of non-learning behavior using defined scales.The observational endpoints are organized into a battery (e.g.functional observational battery,FOB) and inculde home-cage and open-field observation of behavior reactivity to various stimuli(e.g.auditory,tactile,visual),grip strength,and motor activity under a novel environment.The outline of FOB will be illustrated and discussed in the first half of the presentation.One social concern in neurotoxicology is the impact of chemical exposure on cnognitive functions such as learning and memory as well as non-learning behavior.Guidelines describe the necessity of learning and memory tests when other data suggest potential effects on brain function,even though little information regarding cognitive status other than brain pathology can be obtained with FOB.This discrepancy arises from the lack of a simple method compatible with regular studies.One candidate method is fear-induced freezing of rats conditioned to context and auditory cue(Kim & Fanselow,1992).In order to evaluate this paradigm as a screening method,the effects of trimethyltin chloride (TMT) have been studied.Prior to the study,it has been characterized that oral administration of TMT to rats produces excitatory clinical signs and massive neural cell death in the hippocampal CA1 and CA3 regions at lethal dose(8mg·kg-1),but not any abnormalities at sub-lethal doses (4mg·kg-1 or less).Oral administration of TMT at a sub-lethal dose produced a significant decrease in freezing time to the context (hippocampal-dependent measure),but not to the auditory cue.Administration of TMT at a sublethal dose significantly inhibited long-term potentiation in the CA1,but not in the dentate gyrus.These results suggest that the model can be

  14. LLNA variability: An essential ingredient for a comprehensive assessment of non-animal skin sensitization test methods and strategies.

    Science.gov (United States)

    Hoffmann, Sebastian

    2015-01-01

    The development of non-animal skin sensitization test methods and strategies is quickly progressing. Either individually or in combination, the predictive capacity is usually described in comparison to local lymph node assay (LLNA) results. In this process the important lesson from other endpoints, such as skin or eye irritation, to account for variability reference test results - here the LLNA - has not yet been fully acknowledged. In order to provide assessors as well as method and strategy developers with appropriate estimates, we investigated the variability of EC3 values from repeated substance testing using the publicly available NICEATM (NTP Interagency Center for the Evaluation of Alternative Toxicological Methods) LLNA database. Repeat experiments for more than 60 substances were analyzed - once taking the vehicle into account and once combining data over all vehicles. In general, variability was higher when different vehicles were used. In terms of skin sensitization potential, i.e., discriminating sensitizer from non-sensitizers, the false positive rate ranged from 14-20%, while the false negative rate was 4-5%. In terms of skin sensitization potency, the rate to assign a substance to the next higher or next lower potency class was approx.10-15%. In addition, general estimates for EC3 variability are provided that can be used for modelling purposes. With our analysis we stress the importance of considering the LLNA variability in the assessment of skin sensitization test methods and strategies and provide estimates thereof.

  15. Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma?

    Science.gov (United States)

    Tournoy, K G; Hove, C; Grooten, J; Moerloose, K; Brusselle, G G; Joos, G F

    2006-01-01

    Non-specific anti-inflammatory medication is actually the treatment of choice for controlling the T-helper type 2 (Th-2) cell-driven airway inflammation in asthma. The induction of counterbalancing Th-1 cell clones, long considered a promising approach for immunotherapy, has failed to fulfil its promise because of potentially detrimental side-effects. This is therefore probably not a valid option for the treatment of asthma. With the increasing awareness that active immune mechanisms exist to control inflammatory responses, interest rises to investigate whether these can be exploited to control allergen-induced airway disease. The induction of antigen-specific T cells with suppressive characteristics (regulatory T cells) is therefore a potentially interesting approach. These regulatory T cells mediate tolerance in healthy, non-atopic individuals and have the potential of becoming an effective means of preventing allergen-induced airway inflammation and possibly of suppressing ongoing allergic immune responses. Here we review the available knowledge about allergen-induced suppressive immunity obtained from animal models taking into account the different developmental stages of allergic airway disease.

  16. Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.

    Directory of Open Access Journals (Sweden)

    Dammy Pinheiro

    Full Text Available The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL, proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3(+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01 and overall survival (hazard ratio 1.61; p = 0.01 when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.

  17. Risk mitigation for children exposed to drugs during gestation: A critical role for animal preclinical behavioral testing.

    Science.gov (United States)

    Zucker, Irving

    2017-06-01

    Many drugs with unknown safety profiles are administered to pregnant women, placing their offspring at risk. I assessed whether behavioral outcomes for children exposed during gestation to antidepressants, anxiolytics, anti-seizure, analgesic, anti-nausea and sedative medications can be predicted by more extensive animal studies than are part of the FDA approval process. Human plus rodent data were available for only 8 of 33 CNS-active drugs examined. Similar behavioral and cognitive deficits, including autism and ADHD emerged in human offspring and in animal models of these disorders after exposure to fluoxetine, valproic acid, carbamazepine, phenytoin, phenobarbital and acetaminophen. Rodent data helpful in identifying and predicting adverse effects of prenatal drug exposure in children were first generated many years after drugs were FDA-approved and administered to pregnant women. I recommend that enhanced behavioral testing of rodent offspring exposed to drugs prenatally should begin during preclinical drug evaluation and continue during Phase I clinical trials, with findings communicated to physicians and patients in drug labels. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-06-01

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

  19. High concentrations of protein test substances may have non-toxic effects on Daphnia magna: implications for regulatory study designs and ecological risk assessments for GM crops.

    Science.gov (United States)

    Raybould, Alan; Burns, Andrea; Hamer, Mick

    2014-01-01

    Laboratory testing for possible adverse effects of insecticidal proteins on non-target organisms (NTOs) is an important part of many ecological risk assessments for regulatory decision-making about the cultivation of insect-resistant genetically modified (IRGM) crops. To increase confidence in the risk assessments, regulatory guidelines for effects testing specify that representative surrogate species for NTOs are exposed to concentrations of insecticidal proteins that are in excess of worst-case predicted exposures in the field. High concentrations in effects tests are achieved by using protein test substances produced in microbes, such as Escherichia coli. In a study that exposed Daphnia magna to a single high concentration of a microbial test substance containing Vip3Aa20, the insecticidal protein in MIR162 maize, small reductions in growth were observed. These effects were surprising as many other studies strongly suggest that the activity of Vip3Aa20 is limited to Lepidoptera. A plausible explanation for the effect on growth is that high concentrations of test substance have a non-toxic effect on Daphnia, perhaps by reducing its feeding rate. A follow-up study tested that hypothesis by exposing D. magna to several concentrations of Vip3Aa20, and a high concentration of a non-toxic protein, bovine serum albumin (BSA). Vip3Aa20 and BSA had sporadic effects on the reproduction and growth of D. magna. The pattern of the effects suggests that they result from non-toxic effects of high concentrations of protein, and not from toxicity. The implications of these results for regulatory NTO effects testing and ERA of IRGM crops are discussed.

  20. Animal radiographs

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    This chapter presents historical x rays of a wide variety of animals taken within 5 years of the discovery of x radiation. Such photos were used as tests or as illustrations for radiographic publications. Numerous historical photographs are included. 10 refs

  1. Regulatory Physiology

    Science.gov (United States)

    Lane, Helen W.; Whitson, Peggy A.; Putcha, Lakshmi; Baker, Ellen; Smith, Scott M.; Stewart, Karen; Gretebeck, Randall; Nimmagudda, R. R.; Schoeller, Dale A.; Davis-Street, Janis

    1999-01-01

    As noted elsewhere in this report, a central goal of the Extended Duration Orbiter Medical Project (EDOMP) was to ensure that cardiovascular and muscle function were adequate to perform an emergency egress after 16 days of spaceflight. The goals of the Regulatory Physiology component of the EDOMP were to identify and subsequently ameliorate those biochemical and nutritional factors that deplete physiological reserves or increase risk for disease, and to facilitate the development of effective muscle, exercise, and cardiovascular countermeasures. The component investigations designed to meet these goals focused on biochemical and physiological aspects of nutrition and metabolism, the risk of renal (kidney) stone formation, gastrointestinal function, and sleep in space. Investigations involved both ground-based protocols to validate proposed methods and flight studies to test those methods. Two hardware tests were also completed.

  2. The effects of cutting parameters on cutting forces and heat generation when drilling animal bone and biomechanical test materials.

    Science.gov (United States)

    Cseke, Akos; Heinemann, Robert

    2018-01-01

    The research presented in this paper investigated the effects of spindle speed and feed rate on the resultant cutting forces (thrust force and torque) and temperatures while drilling SawBones ® biomechanical test materials and cadaveric cortical bone (bovine and porcine femur) specimens. It also investigated cortical bone anisotropy on the cutting forces, when drilling in axial and radial directions. The cutting forces are only affected by the feed rate, whereas the cutting temperature in contrast is affected by both spindle speed and feed rate. The temperature distribution indicates friction as the primary heat source, which is caused by the rubbing of the tool margins and the already cut chips over the borehole wall. Cutting forces were considerably higher when drilling animal cortical bone, in comparison to cortical test material. Drilling direction, and therewith anisotropy, appears to have a negligible effect on the cutting forces. The results suggest that this can be attributed to the osteons being cut at an angle rather than in purely axial or radial direction, as a result of a twist drill's point angle. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  3. Regulatory Acceptance of Alternative Methods in the Development and Approval of Pharmaceuticals.

    Science.gov (United States)

    Beken, Sonja; Kasper, Peter; van der Laan, Jan-Willem

    Animal studies may be carried out to support first administration of a new medicinal product to either humans or the target animal species, or before performing clinical trials in even larger populations, or before marketing authorisation, or to control quality during production. Ethical and animal welfare considerations require that animal use is limited as much as possible. Directive 2010/63/EU on the protection of animals used for scientific purposes unambiguously fosters the application of the principle of the 3Rs when considering the choice of methods to be used.As such, today, the 3Rs are embedded in the relevant regulatory guidance both at the European (European Medicines Agency (EMA)) and (Veterinary) International Conference on Harmonization ((V)ICH) levels. With respect to non-clinical testing requirements for human medicinal products, reduction and replacement of animal testing has been achieved by the regulatory acceptance of new in vitro methods, either as pivotal, supportive or exploratory mechanistic studies. Whilst replacement of animal studies remains the ultimate goal, approaches aimed at reducing or refining animal studies have also been routinely implemented in regulatory guidelines, where applicable. The chapter provides an overview of the implementation of 3Rs in the drafting of non-clinical testing guidelines for human medicinal products at the level of the ICH. In addition, the revision of the ICH S2 guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use is discussed as a case study.In October 2010, the EMA established a Joint ad hoc Expert Group (JEG 3Rs) with the mandate to improve and foster the application of 3Rs principles to the regulatory testing of medicinal products throughout their lifecycle. As such, a Guideline on regulatory acceptance of 3R testing approaches was drafted that defines regulatory acceptance and provides guidance on the scientific and technical criteria for regulatory

  4. Evaluation of non-Animal methods for assessing skin Sensitisation hazard

    NARCIS (Netherlands)

    Leontaridou, Maria; Gabbert, Silke; Ierland, van Ekko C.; Worth, Andrew P.; Landsiedel, Robert

    2016-01-01

    This paper offers a Bayesian Value-of-Information (VOI) analysis for guiding the development of non-Animal testing strategies, balancing information gains from testing with the expected social gains and costs from the adoption of regulatory decisions. Testing is assumed to have value, if, and

  5. Development and implementation of EPID-based quality assurance tests for the small animal radiation research platform (SARRP).

    Science.gov (United States)

    Anvari, Akbar; Poirier, Yannick; Sawant, Amit

    2018-04-28

    Although small animal image-guided radiotherapy (SA-IGRT) systems are used increasingly in preclinical research, tools for performing routine quality assurance (QA) have not been optimized and are not readily available. Robust, efficient, and reliable QA tools are needed to ensure the accuracy and reproducibility of SA-IGRT systems. Several investigators have reported custom-made phantoms and protocols for SA-IGRT systems QA. These are typically time and resource intensive and are therefore not well suited to the preclinical radiotherapy environment, in which physics support is limited and routine QA is performed by technical staff. We investigated the use of the inbuilt electronic portal imaging device (EPID) to develop and validate routine QA tests and procedures. In this work, we focus on the Xstrahl Small Animal Radiation Research Platform (SARRP) EPID. However, the methodology and tests developed here are applicable to any SA-IGRT system that incorporates an EPID. We performed a comprehensive characterization of the dosimetric properties of the camera-based EPID at kilovoltage energies over a 11-month period, including detector warm-up time, radiation dose history effect, stability and short- and long-term reproducibility, gantry angle dependency, output factor, and linearity of the EPID response. We developed a test to measure the constancy of beam quality in terms of half-value layer and tube peak potential using the EPID. We verified the SARRP daily output and beam profile constancy using the imager. We investigated the use of the imager to monitor beam-targeting accuracy at various gantry and couch angles. The EPID response was stable and reproducible, exhibiting maximum variations of ≤0.3% and ≤1.9% for short and long terms, respectively. The detector showed no dependence on response at different gantry angles, with a maximum variation ≤0.5%. We found close agreement in output factor measurement between the portal imager and reference dosimeters

  6. Pilot-scale fluidized-bed combustor testing cofiring animal-tissue biomass with coal as a carcass disposal option

    Energy Technology Data Exchange (ETDEWEB)

    Bruce G. Miller; Sharon Falcone Miller; Elizabeth M. Fedorowicz; David W. Harlan; Linda A. Detwiler; Michelle L. Rossman [Pennsylvania State University, University Park, PA (United States). Energy Institute

    2006-10-15

    This study was performed to demonstrate the technical viability of cofiring animal-tissue biomass (ATB) in a coal-fired fluidized-bed combustor (FBC) as an option for disposing of specified risk materials (SRMs) and carcasses. The purpose of this study was to assess the technical issues of feeding/combusting ATB and not to investigate prion deactivation/pathogen destruction. Overall, the project successfully demonstrated that carcasses and SRMs can be cofired with coal in a bubbling FBC. Feeding ATB into the FBC did, however, present several challenges. Specifically, handling/feeding issues resulting from the small scale of the equipment and the extremely heterogeneous nature of the ATB were encountered during the testing. Feeder modifications and an overbed firing system were necessary. Through statistical analysis, it was shown that the ATB feed location had a greater effect on CO emissions, which were used as an indication of combustion performance, than the fuel type due to the feeding difficulties. Baseline coal tests and tests cofiring ATB into the bed were statistically indistinguishable. Fuel feeding issues would not be expected at the full scale since full-scale units routinely handle low-quality fuels. In a full-scale unit, the disproportionate ratio of feed line size to unit diameter would be eliminated thereby eliminating feed slugging. Also, the ATB would either be injected into the bed, thereby ensuring uniform mixing and complete combustion, or be injected directly above the bed with overfire air ports used to ensure complete combustion. Therefore, it is anticipated that a demonstration at the full scale, which is the next activity in demonstrating this concept, should be successful. As the statistical analysis shows, emissions cofiring ATB with coal would be expected to be similar to that when firing coal only. 14 refs., 5 figs., 6 tabs.

  7. 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...... industry sectors....

  8. 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

  9. Diagnostic informative value of gastroduodenal regulatory peptides of the blood serum on an empty stomach and after test breakfasts of various compositions

    International Nuclear Information System (INIS)

    Ablyazov, A.A.; Korot'ko, G.F.

    1992-01-01

    Gastrin, secretin and cholecystokinin were determined by a radioimmunoassay in healthy persons (19) and in patients with peptic ulcer (13) on an empty stomach and after test breakfasts with different nutrients. In the healthy persons the blood concentration of regulatory peptides was lower than in the patients. Breakfasts increased the concentrations of gastrin, secretin and cholecystokinin in the patients much more than in the controls. Some differences in changes of the blood concentration of peptides were noted with regard to a type of test breakfast. However differentiated reactions of the endocrine apparatus of the gastroduodenal complex in response to the breakfasts were not a reliable functional and diagnostic criterion

  10. Validation of innovative technologies and strategies for regulatory safety assessment methods: challenges and opportunities.

    Science.gov (United States)

    Stokes, William S; Wind, Marilyn

    2010-01-01

    Advances in science and innovative technologies are providing new opportunities to develop test methods and strategies that may improve safety assessments and reduce animal use for safety testing. These include high throughput screening and other approaches that can rapidly measure or predict various molecular, genetic, and cellular perturbations caused by test substances. Integrated testing and decision strategies that consider multiple types of information and data are also being developed. Prior to their use for regulatory decision-making, new methods and strategies must undergo appropriate validation studies to determine the extent that their use can provide equivalent or improved protection compared to existing methods and to determine the extent that reproducible results can be obtained in different laboratories. Comprehensive and optimal validation study designs are expected to expedite the validation and regulatory acceptance of new test methods and strategies that will support improved safety assessments and reduced animal use for regulatory testing.

  11. Antidepressant-like effects of Gan-Mai-Dazao-Tang via monoamine regulatory pathways on forced swimming test in rats.

    Science.gov (United States)

    Huang, Hsiang-Ling; Lim, Swee-Ling; Lu, Kuan-Hung; Sheen, Lee-Yan

    2018-01-01

    Depression is a highly prevalent and recurrent mental disorder that impacts all aspects of human life. Undesirable effects of the antidepressant drugs led to the development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (, gān mài dà zǎo tang) is a traditional herbal formula commonly used for the treatment of depression, but lack of scientific proof on its mechanism. It consisted of Glycyrrhiza uralensis Fisch. (licorice), Triticum aestivum L. (wheat) and Zizphus jujuba Mill. (jujube). The objective of this study is to investigate the antidepressant effects of Gan-Mai-Dazao-Tang and its ingredients in rats exposed to forced swimming test (FST). The 72 of male Nerl: Wistar rats (8 weeks old) were randomized into control (10 mL/kg bw H 2 O), licorice (0.4 g/kg bw), wheat (1.6 g/kg bw), jujube (0.5 g/kg bw), Gan-Mai-Da-Zao-Tang (2.5 g/kg bw of licorice: wheat: jujube in ratio of 5:20:6) and Prozac (18 mg/kg bw) groups. Samples were administered by oral gavage for 21 days. FST was performed on 21st day, with 15 min for pretest followed by 5 min for real test. Then, the animals were sacrificed and brain tissues were collected for monoamines analyses. The Gan-Mai-Da-Zao-Tang (LWJ) showed significantly down-regulation of immobility time, 3,4-dihydroxyphenylacetic acid (DOPAC) and DOPAC/dopamine (DA) turnover rates, and also enhanced the concentration of serotonin (5-HT) and DA in brain tissues, as compared with the control. The LWJ stated the potent antidepressant-like effect by modulating these monoamines concentration, while the licorice, wheat and jujube did not reported significant results as compared with control group. The positive control (Prozac) was noted with significantly reduction in body weight and appetite. In conclusion, the antidepressant-like effects of LWJ might be mediated by the regulation of monoamine neurotransmitters. Thus, it could beneficial in depression treatment as a complementary approach.

  12. Antidepressant-like effects of Gan-Mai-Dazao-Tang via monoamine regulatory pathways on forced swimming test in rats

    Directory of Open Access Journals (Sweden)

    Hsiang-Ling Huang

    2018-01-01

    Full Text Available Depression is a highly prevalent and recurrent mental disorder that impacts all aspects of human life. Undesirable effects of the antidepressant drugs led to the development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (甘麥大棗湯, gān mài dà zǎo tang is a traditional herbal formula commonly used for the treatment of depression, but lack of scientific proof on its mechanism. It consisted of Glycyrrhiza uralensis Fisch. (licorice, Triticum aestivum L. (wheat and Zizphus jujuba Mill. (jujube. The objective of this study is to investigate the antidepressant effects of Gan-Mai-Dazao-Tang and its ingredients in rats exposed to forced swimming test (FST. The 72 of male Nerl: Wistar rats (8 weeks old were randomized into control (10 mL/kg bw H2O, licorice (0.4 g/kg bw, wheat (1.6 g/kg bw, jujube (0.5 g/kg bw, Gan-Mai-Da-Zao-Tang (2.5 g/kg bw of licorice: wheat: jujube in ratio of 5:20:6 and Prozac (18 mg/kg bw groups. Samples were administered by oral gavage for 21 days. FST was performed on 21st day, with 15 min for pretest followed by 5 min for real test. Then, the animals were sacrificed and brain tissues were collected for monoamines analyses. The Gan-Mai-Da-Zao-Tang (LWJ showed significantly down-regulation of immobility time, 3,4-dihydroxyphenylacetic acid (DOPAC and DOPAC/dopamine (DA turnover rates, and also enhanced the concentration of serotonin (5-HT and DA in brain tissues, as compared with the control. The LWJ stated the potent antidepressant-like effect by modulating these monoamines concentration, while the licorice, wheat and jujube did not reported significant results as compared with control group. The positive control (Prozac was noted with significantly reduction in body weight and appetite. In conclusion, the antidepressant-like effects of LWJ might be mediated by the regulation of monoamine neurotransmitters. Thus, it could beneficial in depression treatment as a complementary approach.

  13. Testing a key assumption in animal communication: between-individual variation in female visual systems alters perception of male signals

    Directory of Open Access Journals (Sweden)

    Kelly L. Ronald

    2017-12-01

    Full Text Available Variation in male signal production has been extensively studied because of its relevance to animal communication and sexual selection. Although we now know much about the mechanisms that can lead to variation between males in the properties of their signals, there is still a general assumption that there is little variation in terms of how females process these male signals. Variation between females in signal processing may lead to variation between females in how they rank individual males, meaning that one single signal may not be universally attractive to all females. We tested this assumption in a group of female wild-caught brown-headed cowbirds (Molothrus ater, a species that uses a male visual signal (e.g. a wingspread display to make its mate-choice decisions. We found that females varied in two key parameters of their visual sensory systems related to chromatic and achromatic vision: cone densities (both total and proportions and cone oil droplet absorbance. Using visual chromatic and achromatic contrast modeling, we then found that this between-individual variation in visual physiology leads to significant between-individual differences in how females perceive chromatic and achromatic male signals. These differences may lead to variation in female preferences for male visual signals, which would provide a potential mechanism for explaining individual differences in mate-choice behavior.

  14. Tumor implantation model for rapid testing of lymphatic dye uptake from paw to node in small animals

    Science.gov (United States)

    DSouza, Alisha V.; Elliott, Jonathan T.; Gunn, Jason R.; Barth, Richard J.; Samkoe, Kimberley S.; Tichauer, Kenneth M.; Pogue, Brian W.

    2015-03-01

    Morbidity and complexity involved in lymph node staging via surgical resection and biopsy calls for staging techniques that are less invasive. While visible blue dyes are commonly used in locating sentinel lymph nodes, since they follow tumor-draining lymphatic vessels, they do not provide a metric to evaluate presence of cancer. An area of active research is to use fluorescent dyes to assess tumor burden of sentinel and secondary lymph nodes. The goal of this work was to successfully deploy and test an intra-nodal cancer-cell injection model to enable planar fluorescence imaging of a clinically relevant blue dye, specifically methylene blue - used in the sentinel lymph node procedure - in normal and tumor-bearing animals, and subsequently segregate tumor-bearing from normal lymph nodes. This direct-injection based tumor model was employed in athymic rats (6 normal, 4 controls, 6 cancer-bearing), where luciferase-expressing breast cancer cells were injected into axillary lymph nodes. Tumor presence in nodes was confirmed by bioluminescence imaging before and after fluorescence imaging. Lymphatic uptake from the injection site (intradermal on forepaw) to lymph node was imaged at approximately 2 frames/minute. Large variability was observed within each cohort.

  15. Testing a key assumption in animal communication: between-individual variation in female visual systems alters perception of male signals.

    Science.gov (United States)

    Ronald, Kelly L; Ensminger, Amanda L; Shawkey, Matthew D; Lucas, Jeffrey R; Fernández-Juricic, Esteban

    2017-12-15

    Variation in male signal production has been extensively studied because of its relevance to animal communication and sexual selection. Although we now know much about the mechanisms that can lead to variation between males in the properties of their signals, there is still a general assumption that there is little variation in terms of how females process these male signals. Variation between females in signal processing may lead to variation between females in how they rank individual males, meaning that one single signal may not be universally attractive to all females. We tested this assumption in a group of female wild-caught brown-headed cowbirds ( Molothrus ater ), a species that uses a male visual signal (e.g. a wingspread display) to make its mate-choice decisions. We found that females varied in two key parameters of their visual sensory systems related to chromatic and achromatic vision: cone densities (both total and proportions) and cone oil droplet absorbance. Using visual chromatic and achromatic contrast modeling, we then found that this between-individual variation in visual physiology leads to significant between-individual differences in how females perceive chromatic and achromatic male signals. These differences may lead to variation in female preferences for male visual signals, which would provide a potential mechanism for explaining individual differences in mate-choice behavior. © 2017. Published by The Company of Biologists Ltd.

  16. Effects of musicality and motivational orientation on auditory category learning: a test of a regulatory-fit hypothesis.

    Science.gov (United States)

    McAuley, J Devin; Henry, Molly J; Wedd, Alan; Pleskac, Timothy J; Cesario, Joseph

    2012-02-01

    Two experiments investigated the effects of musicality and motivational orientation on auditory category learning. In both experiments, participants learned to classify tone stimuli that varied in frequency and duration according to an initially unknown disjunctive rule; feedback involved gaining points for correct responses (a gains reward structure) or losing points for incorrect responses (a losses reward structure). For Experiment 1, participants were told at the start that musicians typically outperform nonmusicians on the task, and then they were asked to identify themselves as either a "musician" or a "nonmusician." For Experiment 2, participants were given either a promotion focus prime (a performance-based opportunity to gain entry into a raffle) or a prevention focus prime (a performance-based criterion that needed to be maintained to avoid losing an entry into a raffle) at the start of the experiment. Consistent with a regulatory-fit hypothesis, self-identified musicians and promotion-primed participants given a gains reward structure made more correct tone classifications and were more likely to discover the optimal disjunctive rule than were musicians and promotion-primed participants experiencing losses. Reward structure (gains vs. losses) had inconsistent effects on the performance of nonmusicians, and a weaker regulatory-fit effect was found for the prevention focus prime. Overall, the findings from this study demonstrate a regulatory-fit effect in the domain of auditory category learning and show that motivational orientation may contribute to musician performance advantages in auditory perception.

  17. Regulatory acceptance and use of 3R models for pharmaceuticals and chemicals: Expert opinions on the state of affairs and the way forward

    NARCIS (Netherlands)

    Schiffelers, M.J.W.A.; Blaauboer, B.J.; Bakker, W.E.; Beken, S.; Hendriksen, C.F.M.; Koeter, H.; Krul, C.A.M.

    2014-01-01

    Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these

  18. U.S. Unit Opens Way to Patent Animals; Humans Seen Likely to Be Next Test Case.

    Science.gov (United States)

    Wheeler, David L.

    1987-01-01

    With a decision on an oyster developed at the University of Washington, the federal Board of Patent Appeals and Interferences has opened the way to granting patents for animals and animal improvements developed through genetic engineering and other scientific methods. (MSE)

  19. Testing the direct, indirect, and moderated effects of childhood animal cruelty on future aggressive and non-aggressive offending.

    Science.gov (United States)

    Walters, Glenn D

    2014-01-01

    The relationship between childhood cruelty toward animals and subsequent aggressive offending was explored in 1,336 (1,154 male, 182 female) participants from the 11-wave Pathways to Desistance study (Mulvey, 2013). Aggressive and income offending at Waves 1 through 10 were regressed onto a dichotomous measure of prior involvement in animal cruelty and four control variables (age, race, sex, early onset behavior problems) assessed at Wave 0 (baseline). Results indicated that childhood animal cruelty was equally predictive of aggressive and non-aggressive (income) offending, a finding inconsistent with the hypothesis that cruelty toward animals desensitizes a person to future interpersonal aggression or in some way prepares the individual for interpersonal violence toward humans. Whereas a significant sex by animal cruelty interaction was predicted, there was no evidence that sex or any of the other demographic variables included in this study (age, race) consistently moderated the animal cruelty-subsequent offending relationship. On the other hand, two cognitive-personality measures (interpersonal hostility, callousness/unemotionality) were found to successfully mediate the animal cruelty-subsequent offending relationship. Outcomes from this study imply that a causal nexus-partially or fully mediated by hostility, callousness/unemotionality, and other cognitive-personality variables-may exist between childhood animal cruelty and subsequent offending, although the effect is not specific to violence. © 2013 Wiley Periodicals, Inc.

  20. Critically appraised topic on adverse food reactions of companion animals (4): can we diagnose adverse food reactions in dogs and cats with in vivo or in vitro tests?

    Science.gov (United States)

    Mueller, Ralf S; Olivry, Thierry

    2017-08-30

    The gold standard to diagnose adverse food reactions (AFRs) in the dog and cat is currently an elimination diet with subsequent provocation trials. However, those trials are inconvenient and client compliance can be low. Our objective was to systematically review the literature to evaluate in vivo and in vitro tests used to diagnose AFR in small animals. We searched three databases (CAB Abstracts, MEDLINE and Web of Science) for pertinent references on September 16, 2016. Among 71, 544 and 41 articles found in the CAB Abstract, MEDLINE and Web of Science databases, respectively, we selected 22 articles and abstracts from conference proceedings that reported data usable for evaluation of tests for AFR. Serum tests for food-specific IgE and IgG, intradermal testing with food antigens, lymphocyte proliferation tests, fecal food-specific IgE, patch, gastroscopic, and colonoscopic testing were evaluated. Testing for serum food-specific IgE and IgG showed low repeatability and, in dogs, a highly variable accuracy. In cats, the accuracy of testing for food-specific IgE was low. Lymphocyte proliferation tests were more frequently positive and more accurate in animals with AFR, but, as they are more difficult to perform, they remain currently a research tool. All other reported tests were only evaluated by individual studies with small numbers of animals. Negative patch test reactions have a very high negative predictability in dogs and could enable a choice of ingredients for the elimination diet in selected patients. Gastroscopic and colonoscopic testing as well as food-specific fecal IgE or food-specific serum IgG measurements appear less useful. Currently, the best diagnostic procedure to identify AFRs in small animals remains an elimination diet with subsequent provocation trials.

  1. Regulatory Guide 1.131: Qualification tests of electric cables, field splices, and connections for light-water-cooled nuclear power plants

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    Criterion III, ''Design Control,'' of Appendix B, ''Quality Assurance Criteria for Nuclear Power Plants and Fuel Reprocessing Plant,'' to 10 CFR Part 50, ''Licensing of Production and Utilization Facilities,'' requires that, where a test program is used to verify the adequacy of a specific design feature, it include suitable qualification testing of a prototype unit under the most adverse design conditions. This regulatory guide describes a method acceptable to the NRC staff for complying with the Commission's regulations with regard to qualification testing of electric cables, field splices, and connections for service in light-water-cooled nuclear power plants to ensure that the cables, field splices, and connections can perform their safety-related functions. The fire test provisions of this guide do not apply to qualification for an installed configuration

  2. Redução, refinamento e substituição do uso de animais em estudos toxicológicos: uma abordagem atual Reduction, refinement and replacement of animal use in toxicity testing: an overview

    Directory of Open Access Journals (Sweden)

    Karen Cristine Ceroni Cazarin

    2004-09-01

    inhumanity from animal experimentation and aiming to lower the number of animals used, in order to decrease the incidence or severity of inhumane procedures and to find alternative procedures to replace in vivo testing. Many alternative toxicological tests have already been implemented, even knowing that this process is very complex and need to be extensively validated and accepted by regulatory bodies. This paper presents an overview on several aspects of the "Three Rs", including historical evolution and implementation and validation of alternative methods, emphasizing its application on toxicity testing and in global harmonization.

  3. 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.

  4. 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.

  5. Testing an integrated PDA-GPS system to collect standardized animal carcass removal data on Virginia roadways.

    Science.gov (United States)

    2008-01-01

    Animal-vehicle collisions (AVCs) have a growing impact in the United States in terms of safety, economic loss, and species conservation. According to estimates from insurance claims, Virginia has consistently ranked as one of the top seven states for...

  6. 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.

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

    Science.gov (United States)

    1977-01-01

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

  8. Lateral flow test strip based on colloidal selenium immunoassay for rapid detection of melamine in milk, milk powder, and animal feed

    Directory of Open Access Journals (Sweden)

    Wang ZZ

    2014-04-01

    Full Text Available Zhizeng Wang,1 Dejuan Zhi,2 Yang Zhao,1 Hailong Zhang,2 Xin Wang,2 Yi Ru,1 Hongyu Li1,2 1MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China; 2Institute of Microbiology and Biochemical Pharmacy, School of Pharmaceutics, Lanzhou University, Lanzhou, People's Republic of China Abstract: Although high melamine (MEL intake has been proven to cause serious health problems, MEL is sometimes illegally added to milk products and animal feed, arousing serious food safety concerns. A satisfactory method of detecting MEL in onsite or in-home testing is in urgent need of development. This work aimed to explore a rapid, convenient, and cost-effective method of identifying MEL in milk products or other food by colloidal selenium-based lateral flow immunoassay. Colloidal selenium was synthesized by L-ascorbic acid to reduce seleninic acid at room temperature. After conjugation with a monoclonal antibody anti-MEL, a test strip was successfully prepared. The detection limit of the test strip reached 150 µg/kg, 1,000 µg/kg, and 800 µg/kg in liquid milk, milk powder, and animal feed, respectively. No cross-reactions with homologues cyanuric acid, cyanurodiamide, or ammelide were found. Moreover, the MEL test strip can remain stable after storage for 1 year at room temperature. Our results demonstrate that the colloidal selenium MEL test strip can detect MEL in adulterated milk products or animal feed conveniently, rapidly, and sensitively. In contrast with a colloidal gold MEL test strip, the colloidal selenium MEL test strip was easy to prepare and more cost-efficient. Keywords: melamine, selenium nanoparticles, test strip, milk, animal feed, dairy food

  9. Control of Trypanosoma evansi in buffalo in Indonesia: Identification of infected animals by Ag- and Ab-ELISA tests and treatment with diminazene aceturate

    International Nuclear Information System (INIS)

    Luckins, A.G.

    2000-01-01

    In order to control effectively infections with Trypanosoma evansi it is necessary to identify all infected individuals, including not only animals with patent infections but also those with non-patent infections. In order to provide a reliable means of diagnosing infected individuals, a combination of Ab-ELISA, Ag-ELISA and parasitological tests were used to identify for treatment groups of buffalo from Central Java, Indonesia in an area in which trypanosomosis caused by T. evansi is endemic. The animals were divided into four groups, Group A comprised animals positive by both Ab- and Ag-ELISA and/or parasitological examination. Group B consisted of animals positive by Ag-ELISA and Group C by Ab-ELISA only. Group D was a control group of animals that were negative by both serological and parasitological tests. All of Group A were treated with diminazene aceturate and the prevalence and incidence of infection in the four groups determined over approximately 12 months. The prevalence of infection declined in Group A declined from 100% to <25% in four months and remained at this low level until the end of the study. In the other groups, the serological prevalence increased up to 50%, although in Group D, the initially uninfected group, the increase was lower. Although treatment was effective in reducing the prevalence of infection, the cumulative incidence in the four groups was found to be similar. (author)

  10. Measurable Changes in Pre-Post Test Scores in Iraqi 4-H Leader’s Knowledge of Animal Science Production Principles

    Directory of Open Access Journals (Sweden)

    Justen O. Smith

    2015-06-01

    Full Text Available The 4-H volunteer program is a new concept to the people of Iraq, for decades the country has been closed to western ideas. Iraqi culture and the Arabic customs have not embraced the volunteer concept and even more the concept of scientific animal production technologies designed to increase profitability for producers. In 2011 the USAID-Inma Agribusiness program teamed with the Iraq 4-H program to create youth and community entrepreneurship opportunities for widowed families. Iraq 4-H provided the youth members and adult volunteers and Inma provided the financial capital (livestock and the animal science training program for the volunteers. The purpose of this study was to measure the knowledge level gained through intensive animal science training for Iraqi 4-H volunteers. Researchers designed and implemented a pre and post test to measure the knowledge of fifteen volunteers who participated in the three day course. The pretest exposed a general lack of animal science knowledge of all volunteers; over 80% of the participants incorrectly answered the questions. However, the post-test indicated positive change in the participants understanding of animal science production principles.

  11. An overview of tests for animal tissues in feeds applied in response to public health concerns regarding bovine spongiform encephalopathy.

    Science.gov (United States)

    Gizzi, G; van Raamsdonk, L W D; Baeten, V; Murray, I; Berben, G; Brambilla, G; von Holst, C

    2003-04-01

    Enforcing the ban on meat-and-bone meal in feed for farmed animals, and especially ruminants, is considered an important measure to prevent the spread of bovine spongiform encephalopathy. The authors describe current analytical methods for the detection and identification of animal tissues in feed. In addition, recently approved requirements, such as the ban of intra-species recycling (practice of feeding an animal species with proteins derived from the bodies, or parts of bodies, of the same species) are described. In principle, four different approaches are currently applied, i.e. microscopic analysis, polymerase chain reaction, immunoassay analysis and near infrared spectroscopy or microscopy. The principal performance characteristics of these methods are presented and compared, and their specific advantages and disadvantages described. Special emphasis is also placed on the impact of rendering conditions, particularly high temperatures and on the use of molecular biology techniques.

  12. Labelled T{sub 3}, T{sub 4} and TBP for In Vitro Testing of Thyroid Function in Man and Animals

    Energy Technology Data Exchange (ETDEWEB)

    Czerniak, P.; Boruchowski, Sabina; Shomron, I. [Dept. of Radiotherapy and Isotopes, Tel-Hashomer Hospital, Tel-Aviv University Medical School, Faculty of Continuing Medical Education, Tel-Aviv (Israel)

    1970-02-15

    Iodothyronines are bound to determined electrophoretic fractions of serum proteins - TBP (TBG, TBA, TBPA). Radioiodine labelled T{sub 3} and T{sub 4} complex the free TBP fractions until saturation. The excess of added in vitro thyronines is then absorbed by the RBC. The changes described can be detected and quantitatively determined by radioisotope tests: radioelectrophoresis - T{sub 3/4} BP test, and RBC - {sup 125}I T{sub 3} test (Hamolsky test). The in vitro tests of the thyroid function can be clinically reliable if the protein fractions are normal, and they may be altered without thyroid pathology if the TBG fractions are abnormal. The electrophoretic fractions vary quantitatively and qualitatively in animals of different classes and orders. We chose these features to study the correlation between iodothyronines, plasma proteins and the above-mentioned thyroid tests. Twenty-two animal species (arranged according to the increasing percentage of the Hamolsky test) were examined: goat (8.6%, cow, lamb, calf, man, camel, goose, hamster, rat, turkey, marmot, duck, horse, donkey, hen, dog, pigeon, rabbit, guinea-pig, mouse, fish and frog (91.5%). The following additional parameters were examined: PBI, serum quantitative electrophoresis, T{sub 3} BP studies. All the tests were performed under identical technical conditions. Results and conclusions: (1) The Hamolsky test in the examined animals ranges from 9% to 92%. It is highest in the poicolothermics, in which much prealbumin and few glubulins are found on electrophoresis. The T{sub 3} BP is low, and about a half of the added {sup 125}I T{sub 3} remains unbound. (2) T{sub 3} and T{sub 4} are complexed with T{sub 3} BP and T{sub 4} BP fractions, which correspond to prealbumin, albumin, alpha 1-2, beta and exceptionally gamma globulin. The fractions are variable but characteristic for each animal species. T{sub 3} BP does not correlate exactly with T{sub 4} BP, and seems to be distributed over more fractions

  13. Animal cloning: problems and prospects.

    Science.gov (United States)

    Wells, D N

    2005-04-01

    An efficient animal cloning technology would provide many new opportunities for livestock agriculture, human medicine, and animal conservation. Nuclear cloning involves the production of animals that are genetically identical to the donor cells used in a technique known as nuclear transfer (NT). However, at present it is an inefficient process: in cattle, only around 6% of the embryos transferred to the reproductive tracts of recipient cows result in healthy, longterm surviving clones. Of concern are the high losses throughout gestation, during birth and in the post-natal period through to adulthood. Many of the pregnancy losses relate to failure of the placenta to develop and function correctly. Placental dysfunction may also have an adverse influence on postnatal health. These anomalies are probably due to incorrect epigenetic reprogramming of the donor genome following NT, leading to inappropriate patterns of gene expression during the development of clones. Whilst some physiological tests on surviving clones suggest normality, other reports indicate a variety of post-natal clone-associated abnormalities. This variability in outcome may reflect species-specific and/or cloning methodological differences. Importantly, to date it appears that these clone-associated phenotypes are not transmitted to offspring following sexual reproduction. This indicates that they represent epigenetic errors, rather than genetic errors, which are corrected during gametogenesis. Whilst this needs confirmation at the molecular level, it provides initial confidence in the first application of NT in agriculture, namely, the production of small numbers of cloned sires from genetically elite bulls, for natural mating, to effectively disseminate genetic gain. In addition to the animal welfare concerns with the technology, the underlying health of the animals and the consequential effect on food safety are critical aspects that require investigation to gain regulatory and consumer

  14. 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.

  15. Genetic horoscopes: is it all in the genes? Points for regulatory control of direct-to-consumer genetic testing

    NARCIS (Netherlands)

    Patch, C.; Sequeiros, J.; Cornel, M.C.

    2009-01-01

    The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and

  16. The dose-response relationship between the patch test and ROAT and the potential use for regulatory purposes

    DEFF Research Database (Denmark)

    Fischer, Louise Arup; Voelund, Aage; Andersen, Klaus Ejner

    2009-01-01

    Background: Allergic contact dermatitis is common and can be prevented. The relationship between thresholds for patch tests and the repeated open application test (ROAT) is unclear. It would be desirable if patch test and ROAT data from already sensitized individuals could be used in prevention. ...

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

    Science.gov (United States)

    The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December ...

  18. Closure Strategy for a Waste Disposal Facility with Multiple Waste Types and Regulatory Drivers at the Nevada Test Site - 8422

    International Nuclear Information System (INIS)

    D Wieland; V Yucel; L Desotell; G Shott; J Wrapp

    2008-01-01

    The U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office (NNSA/NSO) plans to close the waste and classified material storage cells in the southeast quadrant of the Area 5 Radioactive Waste Management Site (RWMS), informally known as the '92-Acre Area', by 2011. The 25 shallow trenches and pits and the 13 Greater Confinement Disposal (GCD) borings contain various waste streams including low-level waste (LLW), low-level mixed waste (LLMW), transuranic (TRU), mixed transuranic (MTRU), and high specific activity LLW. The cells are managed under several regulatory and permit programs by the U.S. Department of Energy (DOE) and the Nevada Division of Environmental Protection (NDEP). Although the specific closure requirements for each cell vary, 37 closely spaced cells will be closed under a single integrated monolayer evapotranspirative (ET) final cover. One cell will be closed under a separate cover concurrently. The site setting and climate constrain transport pathways and are factors in the technical approach to closure and performance assessment. Successful implementation of the integrated closure plan requires excellent communication and coordination between NNSA/NSO and the regulators

  19. Does positive selection drive transcription factor binding site turnover? A test with Drosophila cis-regulatory modules.

    Directory of Open Access Journals (Sweden)

    Bin Z He

    2011-04-01

    Full Text Available Transcription factor binding site(s (TFBS gain and loss (i.e., turnover is a well-documented feature of cis-regulatory module (CRM evolution, yet little attention has been paid to the evolutionary force(s driving this turnover process. The predominant view, motivated by its widespread occurrence, emphasizes the importance of compensatory mutation and genetic drift. Positive selection, in contrast, although it has been invoked in specific instances of adaptive gene expression evolution, has not been considered as a general alternative to neutral compensatory evolution. In this study we evaluate the two hypotheses by analyzing patterns of single nucleotide polymorphism in the TFBS of well-characterized CRM in two closely related Drosophila species, Drosophila melanogaster and Drosophila simulans. An important feature of the analysis is classification of TFBS mutations according to the direction of their predicted effect on binding affinity, which allows gains and losses to be evaluated independently along the two phylogenetic lineages. The observed patterns of polymorphism and divergence are not compatible with neutral evolution for either class of mutations. Instead, multiple lines of evidence are consistent with contributions of positive selection to TFBS gain and loss as well as purifying selection in its maintenance. In discussion, we propose a model to reconcile the finding of selection driving TFBS turnover with constrained CRM function over long evolutionary time.

  20. In vitro metabolism and bioavailability tests for endocrine active substances: What is needed next for regulatory purposes?

    Science.gov (United States)

    Legistation and prospective legislative proposals internationally (may) require that chemicals be tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive in vitro are considered to be endocrine active substances (EAS) and may be puta...

  1. Regulatory ecotoxicity testing of nanomaterials – proposed modifications of OECD test guidelines based on laboratory experience with silver and titanium dioxide nanoparticles

    DEFF Research Database (Denmark)

    Hund-Rinke, Kerstin; Baun, Anders; Cupi, Denisa

    2016-01-01

    of the sediment-living worm Lumbriculus variegatus (TG 225), activity of soil microflora (TGs 216, 217), and reproduction of the invertebrates (Enchytraeus crypticus, Eisenia fetida, TGs 220, 222). Additionally, test descriptions for two further test systems (root elongation of plants in hydroponic culture; test...

  2. Animal research

    DEFF Research Database (Denmark)

    Olsson, I.A.S.; Sandøe, Peter

    2012-01-01

    This article presents the ethical issues in animal research using a combined approach of ethical theory and analysis of scientific findings with bearing on the ethical analysis. The article opens with a general discussion of the moral acceptability of animal use in research. The use of animals...... in research is analyzed from the viewpoint of three distinct ethical approaches: contractarianism, utilitarianism, and animal rights view. On a contractarian view, research on animals is only an ethical issue to the extent that other humans as parties to the social contract care about how research animals...... are faring. From the utilitarian perspective, the use of sentient animals in research that may harm them is an ethical issue, but harm done to animals can be balanced by benefit generated for humans and other animals. The animal rights view, when thoroughgoing, is abolitionist as regards the use of animals...

  3. Including Bioconcentration Kinetics for the Prioritization and Interpretation of Regulatory Aquatic Toxicity Tests of Highly Hydrophobic Chemicals

    DEFF Research Database (Denmark)

    Kwon, Jung-Hwan; Lee, So-Young; Kang, Hyun-Joong

    2016-01-01

    experiments. In this work, internal concentrations of highly hydrophobic chemicals were predicted for standard acute ecotoxicity tests at three trophic levels, algae, invertebrate, and fish. As demonstrated by comparison with maximum aqueous concentrations at water solubility, chemicals with an octanol...

  4. The use and interpretation of in vitro data in regulatory toxicology: cosmetics, toiletries and household products.

    Science.gov (United States)

    Indans, Ian

    2002-02-28

    There is currently a drive to eliminate animal testing for cosmetics, toiletries and household products; indeed, the European Union Cosmetics Directive aims to prohibit the use of experimental animals for the testing of finished cosmetic products after 2002. At present, national prohibitions are in place in the UK, Germany, Austria and the Netherlands, for the testing of finished cosmetic products and cosmetic ingredients. In the USA animal testing for certain types of finished products is mandatory. Against this background, the currently available regulatory in vitro tests comprise methods for eye irritation, skin corrosivity, genotoxicity, dermal penetration and photoirritation. The draft updates to the Organisation for Economic Co-operation and Development guidelines for eye and skin irritation advocate the use of in vitro or ex vivo methods prior to the commencement of animal studies. At present, testing for these endpoints cannot be completed in vitro, but potentially corrosive substances and products can be classified without the need for animal studies. Regulatory genotoxicity testing can be completed using only in vitro methods, provided that a clear negative outcome is obtained for each test. Data from dermal penetration studies may be used to refine risk assessments. Current developments in areas such as skin sensitisation and skin irritation promise that in the reasonably near future such information may be generated without the use of animals.

  5. Innovative non-animal testing strategies for reproductive toxicology: the contribution of Italian partners within the EU project ReProTect

    Directory of Open Access Journals (Sweden)

    Stefano Lorenzetti

    2011-12-01

    Full Text Available Reproductive toxicity, with its many targets and mechanisms, is a complex area of toxicology; thus, the screening and identification of reproductive toxicants is a main scientific challenge for the safety assessment of chemicals, including the European Regulation on Chemicals (REACH. Regulatory agencies recommend the implementation of the 3Rs principle (refinement, reduction, replacement as well as of intelligent testing strategies, through the development of in vitro methods and the use of mechanistic information in the hazard identification and characterization steps of the risk assessment process. The EU Integrated Project ReProTect (6th Framework Programme implemented an array of in vitro tests to study different building blocks of the mammalian reproductive cycle: methodological developments and results on male and female germ cells, prostate and placenta are presented.

  6. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo

    DEFF Research Database (Denmark)

    Verhagen, H.; Aruoma, O.I.; van Delft, J.H.M.

    2003-01-01

    There is increasing evidence that chemicals/test substances cannot only have adverse effects, but that there are many substances that can (also) have a beneficial effect on health. As this journal regularly publishes papers in this area and has every intention in continuing to do so in the near......, provided they can be justified on scientific grounds. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo concern the following areas: (1) Hypothesis-driven study design; (2......) The nature of the test substance; (3) Valid and invalid test systems; (4) The selection of dose levels and gender; (5) Reversal of the effects induced by oxidants, carcinogens and mutagens; (6) Route of administration; (7) Number and validity of test variables; (8) Repeatability and reproducibility; (9...

  7. A multi-analyte biosensor for the simultaneous label-free detection of pathogens and biomarkers in point-of-need animal testing.

    Science.gov (United States)

    Ewald, Melanie; Fechner, Peter; Gauglitz, Günter

    2015-05-01

    For the first time, a multi-analyte biosensor platform has been developed using the label-free 1-lambda-reflectometry technique. This platform is the first, which does not use imaging techniques, but is able to perform multi-analyte measurements. It is designed to be portable and cost-effective and therefore allows for point-of-need testing or on-site field-testing with possible applications in diagnostics. This work highlights the application possibilities of this platform in the field of animal testing, but is also relevant and transferable to human diagnostics. The performance of the platform has been evaluated using relevant reference systems like biomarker (C-reactive protein) and serology (anti-Salmonella antibodies) as well as a panel of real samples (animal sera). The comparison of the working range and limit of detection shows no loss of performance transferring the separate assays to the multi-analyte setup. Moreover, the new multi-analyte platform allows for discrimination between sera of animals infected with different Salmonella subtypes.

  8. Assuring safety without animal testing: Unilever's ongoing research programme to deliver novel ways to assure consumer safety.

    Science.gov (United States)

    Westmoreland, Carl; Carmichael, Paul; Dent, Matt; Fentem, Julia; MacKay, Cameron; Maxwell, Gavin; Pease, Camilla; Reynolds, Fiona

    2010-01-01

    Assuring consumer safety without the generation of new animal data is currently a considerable challenge. However, through the application of new technologies and the further development of risk-based approaches for safety assessment, we remain confident it is ultimately achievable. For many complex, multi-organ consumer safety endpoints, the development, evaluation and application of new, non-animal approaches is hampered by a lack of biological understanding of the underlying mechanistic processes involved. The enormity of this scientific challenge should not be underestimated. To tackle this challenge a substantial research programme was initiated by Unilever in 2004 to critically evaluate the feasibility of a new conceptual approach based upon the following key components: 1.Developing new, exposure-driven risk assessment approaches. 2.Developing new biological (in vitro) and computer-based (in silico) predictive models. 3.Evaluating the applicability of new technologies for generating data (e.g. "omics", informatics) and for integrating new types of data (e.g. systems approaches) for risk-based safety assessment. Our research efforts are focussed in the priority areas of skin allergy, cancer and general toxicity (including inhaled toxicity). In all of these areas, a long-term investment is essential to increase the scientific understanding of the underlying biology and molecular mechanisms that we believe will ultimately form a sound basis for novel risk assessment approaches. Our research programme in these priority areas consists of in-house research as well as Unilever-sponsored academic research, involvement in EU-funded projects (e.g. Sens-it-iv, Carcinogenomics), participation in cross-industry collaborative research (e.g. Colipa, EPAA) and ongoing involvement with other scientific initiatives on non-animal approaches to risk assessment (e.g. UK NC3Rs, US "Human Toxicology Project" consortium).

  9. A critical appraisal of the process of regulatory implementation of novel in vivo and in vitro methods for chemical hazard and risk assessment.

    Science.gov (United States)

    Piersma, Aldert H; Ezendam, Janine; Luijten, Mirjam; Muller, J J Andre; Rorije, Emiel; van der Ven, Leo T M; van Benthem, Jan

    2014-11-01

    Regulatory toxicology urgently needs applicable alternative test systems that reduce animal use, testing time, and cost. European regulation on cosmetic ingredients has already banned animal experimentation for hazard identification, and public awareness drives toward additional restrictions in other regulatory frameworks as well. In addition, scientific progress stimulates a more mechanistic approach of hazard identification. Nevertheless, the implementation of alternative methods is lagging far behind their development. In search for general bottlenecks for the implementation of alternative methods, this manuscript reviews the state of the art as to the development and implementation of 10 diverse test systems in various areas of toxicological hazard assessment. They vary widely in complexity and regulatory acceptance status. The assays are reviewed as to parameters assessed, biological system involved, standardization, interpretation of results, extrapolation to human hazard, position in testing strategies, and current regulatory acceptance status. Given the diversity of alternative methods in many aspects, no common bottlenecks could be identified that hamper implementation of individual alternative assays in general. However, specific issues for the regulatory acceptance and application were identified for each assay. Acceptance of one-in-one replacement of complex in vivo tests by relatively simple in vitro assays is not feasible. Rather, innovative approaches using test batteries are required together with metabolic information and in vitro to in vivo dose extrapolation to convincingly provide the same level of information of current in vivo tests. A mechanistically based alternative approach using the Adverse Outcome Pathway concept could stimulate further (regulatory) acceptance of non-animal tests.

  10. A test of the embodied simulation theory of object perception: potentiation of responses to artifacts and animals.

    Science.gov (United States)

    Matheson, Heath E; White, Nicole C; McMullen, Patricia A

    2014-07-01

    Theories of embodied object representation predict a tight association between sensorimotor processes and visual processing of manipulable objects. Previous research has shown that object handles can 'potentiate' a manual response (i.e., button press) to a congruent location. This potentiation effect is taken as evidence that objects automatically evoke sensorimotor simulations in response to the visual presentation of manipulable objects. In the present series of experiments, we investigated a critical prediction of the theory of embodied object representations that potentiation effects should be observed with manipulable artifacts but not non-manipulable animals. In four experiments we show that (a) potentiation effects are observed with animals and artifacts; (b) potentiation effects depend on the absolute size of the objects and (c) task context influences the presence/absence of potentiation effects. We conclude that potentiation effects do not provide evidence for embodied object representations, but are suggestive of a more general stimulus-response compatibility effect that may depend on the distribution of attention to different object features.

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

    Science.gov (United States)

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

    2014-05-01

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

  13. Emerging Resistance, New Antimicrobial Agents  …  but No Tests! The Challenge of Antimicrobial Susceptibility Testing in the Current US Regulatory Landscape.

    Science.gov (United States)

    Humphries, R M; Hindler, J A

    2016-07-01

    Accurate and timely performance of antimicrobial susceptibility testing (AST) by the clinical laboratory is paramount to combating antimicrobial resistance. The ability of laboratories in the United States to effectively perform ASTs is challenged by several factors. Some, such as new resistance mechanisms and the associated evolution of testing recommendations and breakpoints, are inevitable. Others are entirely man-made. These include unnecessarily strict US Food and Drug Administration (FDA) limitations on how commercial AST systems can be used for diagnostic testing, the absence of up-to-date performance data on these systems, and the lack of commercially available FDA-cleared tests for newer antimicrobial agents or for older agents with updated breakpoints. This viewpoint will highlight contemporary AST challenges faced by the clinical laboratory, and propose some solutions. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  14. 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

  15. Estimation of body surface area in the musk shrew ( Suncus murinus): a small animal for testing chemotherapy-induced emesis.

    Science.gov (United States)

    Eiseman, Julie L; Sciullo, Michael; Wang, Hong; Beumer, Jan H; Horn, Charles C

    2017-10-01

    Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K m ) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.

  16. Preclinical Testing of Antihuman CD28 Fab' Antibody in a Novel Nonhuman Primate Small Animal Rodent Model of Xenogenic Graft-Versus-Host Disease.

    Science.gov (United States)

    Hippen, Keli L; Watkins, Benjamin; Tkachev, Victor; Lemire, Amanda M; Lehnen, Charles; Riddle, Megan J; Singh, Karnail; Panoskaltsis-Mortari, Angela; Vanhove, Bernard; Tolar, Jakub; Kean, Leslie S; Blazar, Bruce R

    2016-12-01

    Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation. Current therapies to prevent alloreactive T cell activation largely cause generalized immunosuppression and may result in adverse drug, antileukemia and antipathogen responses. Recently, several immunomodulatory therapeutics have been developed that show efficacy in maintaining antileukemia responses while inhibiting GVHD in murine models. To analyze efficacy and better understand immunological tolerance, escape mechanisms, and side effects of clinical reagents, testing of species cross-reactive human agents in large animal GVHD models is critical. We have previously developed and refined a nonhuman primate (NHP) large animal GVHD model. However, this model is not readily amenable to semi-high throughput screening of candidate clinical reagents. Here, we report a novel, optimized NHP xenogeneic GVHD (xeno-GVHD) small animal model that recapitulates many aspects of NHP and human GVHD. This model was validated using a clinically available blocking, monovalent anti-CD28 antibody (FR104) whose effects in a human xeno-GVHD rodent model are known. Because human-reactive reagents may not be fully cross-reactive or effective in vivo on NHP immune cells, this NHP xeno-GVHD model provides immunological insights and direct testing on NHP-induced GVHD before committing to the intensive NHP studies that are being increasingly used for detailed evaluation of new immune therapeutic strategies before human trials.

  17. Animal Investigation Program (AIP), A.I.P. summary report on and around the Nevada Test Site from 1982--1995

    International Nuclear Information System (INIS)

    Giles, K.R.

    1997-04-01

    This report describes the Animal Investigation Program conducted from 1982--1995 by the Environmental Protection Agency's (EPA's), Radiation and Indoor Environments National Laboratory (R and IE), formerly Radiation Sciences Laboratory-Las Vegas. This laboratory operates an environmental radiation monitoring program in the region surrounding the Nevada Test Site. The surveillance program was designed to measure levels and trends of radionuclides in animals on and around the Nevada Test Site to ascertain whether world-wide fallout, current radiation levels, and associated doses, to the general public were in compliance with existing radiation protection standards. The surveillance program additionally had the responsibility to take action to protect the health and well-being of the public in the event of any accidental release of radioactive contaminants. Comparison of the measurements and sample analysis results indicated that no significant amounts of biological radionuclides had been detected in the near offsite areas or on the NTS, except in animals drinking water that drains from tunnels in Area 12

  18. Large Dataset of Acute Oral Toxicity Data Created for Testing in Silico Models (ASCCT meeting)

    Science.gov (United States)

    Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are ...

  19. Evaluation of a Community's Risk for Canine Parvovirus and Distemper Using Antibody Testing and GIS Mapping of Animal Shelter Intakes.

    Science.gov (United States)

    Spindel, Miranda E; Krecic, Matthew R; Slater, Margaret R; Vigil, Nicole

    2018-03-20

    This cross-sectional study aimed to identify where dogs with negative antibody tests to canine parvovirus (CPV) and canine distemper virus (CDV) originated when entering a community shelter, using a commercially available ELISA antibody test and Geographic Information Systems mapping. Of 2745 canines entering during a three-month period, 1056 test results were obtained. Dogs or puppies weighing over 2 lb were eligible if they could be humanely, nonchemically restrained for phlebotomy. Age and minor health issues weren't exclusions. Dogs were excluded if trained personnel were concerned health would be compromised by phlebotomy. Blood samples were collected within 24 hours of entry. Four hundred and twenty-seven (40%) dogs had positive antibody test results for both viruses, 422 (40%) were positive for CPV, 37 (4%) were positive for CDV, and 170 (16%) were negative for both. Mapping revealed geographic patterns for dogs with negative antibody tests. This shelter admitted dogs with negative CPV and/or CDV antibody tests from defined community areas. Targeting vaccination efforts in communities to areas where dogs with negative antibody tests originate could be an effective wellness strategy.

  20. Foundational Tests of the Need-Support Model: A Framework for Bridging Regulatory Focus Theory and Self-Determination Theory

    Directory of Open Access Journals (Sweden)

    Leigh Ann Vaughn

    2017-04-01

    Full Text Available This dataset includes data from the three studies reported in my paper on Foundational Tests of the Need-Support Model [6]. I collected these data in 2014, 2015, and 2016 from over 2,100 Amazon Mechanical Turk workers in the United States and Canada. The dataset contains the measures described in the paper, as well as participants’ writing about the experiences they brought to mind in these studies. The data are stored on the Open Science Framework, and they could be used for exploratory research, meta-analyses, and research on replication. I also welcome collaborative research involving re-analyses of these data.

  1. Bovine and Caprine Brucellosis in Bangladesh: Bayesian evaluation of four serological tests, true prevalence, and associated risk factors in household animals.

    Science.gov (United States)

    Ahasan, Md Shamim; Rahman, Md Siddiqur; Rahman, A K M Anisur; Berkvens, Dirk

    2017-01-01

    A cross-sectional study was carried out to estimate the true prevalence of Brucella spp. and identify allied risk factors/indicators associated with brucellosis in the Dinajpur and Mymensingh districts of Bangladesh. A total 320 stratified random blood samples were collected and tested in parallel for Brucella antibodies using Rose Bengal (RBT), slow agglutination (SAT), and indirect and competitive ELISA. In addition, a structured questionnaire was administered to each household herd owner to gather information regarding potential risk factors. Both univariate and multivariate logistic regression analyses were used to identify potential risk factors or indicators at animal level. A Bayesian approach was used to estimate the true prevalence of brucellosis along with the test performances (Se and Sp). The estimated animal level true prevalence in cattle was 9.70 % (95 % CPI 5.0-16 %) and in goat 6.3 % (95 % CPI 2.8-11.0 %). The highest sensitivity was achieved by SAT ranges from 69.6 to 78.9 %, and iELISA was found to be more specific (97.4 to 98.8 %) in comparison with other tests. On the other hand, a significant level of (P tests can be recommended to apply alone for the diagnosis of bovine and caprine brucellosis.

  2. 9 CFR 116.6 - Animal records.

    Science.gov (United States)

    2010-01-01

    .... Complete records shall be kept for all animals at a licensed establishment. Results of tests performed... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Animal records. 116.6 Section 116.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES...

  3. Animal Bites

    Science.gov (United States)

    Wild animals usually avoid people. They might attack, however, if they feel threatened, are sick, or are protecting their ... or territory. Attacks by pets are more common. Animal bites rarely are life-threatening, but if they ...

  4. Comparison between two commercially available serological tests and polymerase chain reaction in the diagnosis of Cryptosporidium in animals and diarrhoeic children.

    Science.gov (United States)

    Helmy, Yosra A; Krücken, Jürgen; Nöckler, Karsten; von Samson-Himmelstjerna, Georg; Zessin, Karl-H

    2014-01-01

    For the detection of Cryptosporidium species in 804 animals and 165 diarrhoeic children (tests, the RIDASCREEN® Cryptosporidium test [enzyme immunoassay (EIA)] and the RIDA®QUICK Cryptosporidium/Giardia Combi [immuno-chromatographic test (ICT)] as well as polymerase chain reaction (PCR) were used. Prevalence of Cryptosporidium was 15.0, 19.5 and 32.3% in animals and 2.4, 6.7 and 49.1% in children using EIA, ICT and PCR, respectively.Using PCR as reference method, animal samples sensitivity (Se) of the EIA was 46.5% when questionable samples were considered positive, whereas specificity (Sp) was 100%. Se of the ICT was 60.4% while Sp was 100%. Positive predictive values (PPVs) for both EIA and ICT test were 100%, and negative predictive values (NPVs) for EIA were 79.7 and 84.1% for ICT. For the children samples, the Se of EIA was 5%, Sp was 100%, PPV was 100% and NPV was 52.2%, while the Se of ICT was 13.6%, Sp was 100%, PPV was 100% and NPV was 54.6%.The Kappa score of agreement between PCR and ICT was 67.4%, 54.1% between PCR and EIA and 84.4% between ICT and EIA. Until the second serial dilution of the EIA and ICT test, 9 × 10(3) oocysts/μl of Cryptosporidia was detected, whereas in PCR, they were detected until the sixth serial dilution. Copro-antigen tests were easy to perform and less time-consuming but less sensitive compared to PCR. They obviously are best applicable for screening and epidemiological studies of large numbers of subjects, for batch specimen processing and in isolated or rural areas where reliable tests like PCR are unfeasible. When in children, a single stool sample is used for the diagnosis of clinical cases; better results can be obtained when non-standardized PCR due low specificity is coupled with copro-antigen tests.

  5. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

    This article proposes the term “safety logics” to understand attempts within the European Union (EU) to harmonize member state legislation to ensure a safe and stable supply of human biological material for transplants and transfusions. With safety logics, I refer to assemblages of discourses, le...... they arise. In short, I expose the regulatory anatomy of the policy landscape....

  6. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

    Regulatory governance frameworks have become essential building blocks of world society. From supply chains to the regimes surrounding international organizations, extensive governance frameworks have emerged which structure and channel a variety of social exchanges, including economic, political...... by the International Transitional Administrations (ITAs) in Kosovo and Iraq as well as global supply chains and their impact on the garment industry in Bangladesh....

  7. Disrupting self-assembly and toxicity of amyloidogenic protein oligomers by "molecular tweezers" - from the test tube to animal models.

    Science.gov (United States)

    Attar, Aida; Bitan, Gal

    2014-01-01

    Despite decades of research, therapy for diseases caused by abnormal protein folding and aggregation (amyloidoses) is limited to treatment of symptoms and provides only temporary and moderate relief to sufferers. The failure in developing successful disease-modifying drugs for amyloidoses stems from the nature of the targets for such drugs - primarily oligomers of amyloidogenic proteins, which are distinct from traditional targets, such as enzymes or receptors. The oligomers are metastable, do not have well-defined structures, and exist in dynamically changing mixtures. Therefore, inhibiting the formation and toxicity of these oligomers likely will require out-of-the-box thinking and novel strategies. We review here the development of a strategy based on targeting the combination of hydrophobic and electrostatic interactions that are key to the assembly and toxicity of amyloidogenic proteins using lysine (K)-specific "molecular tweezers" (MTs). Our discussion includes a survey of the literature demonstrating the important role of K residues in the assembly and toxicity of amyloidogenic proteins and the development of a lead MT derivative called CLR01, from an inhibitor of protein aggregation in vitro to a drug candidate showing effective amelioration of disease symptoms in animal models of Alzheimer's and Parkinson's diseases.

  8. Animal models

    DEFF Research Database (Denmark)

    Gøtze, Jens Peter; Krentz, Andrew

    2014-01-01

    In this issue of Cardiovascular Endocrinology, we are proud to present a broad and dedicated spectrum of reviews on animal models in cardiovascular disease. The reviews cover most aspects of animal models in science from basic differences and similarities between small animals and the human...

  9. Animal Deliberation

    NARCIS (Netherlands)

    Driessen, C.P.G.

    2014-01-01

    While much has been written on environmental politics on the one hand, and animal ethics and welfare on the other, animal politics, as the interface of the two, is underexamined. There are key political implications in the increase of animal protection laws, the rights of nature, and political

  10. 75 FR 12804 - Withdrawal of Regulatory Guide 8.6

    Science.gov (United States)

    2010-03-17

    ... ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.6, ``Standard Test Procedure for Geiger-M...

  11. Optimization and evaluation of Flexicult(®) Vet for detection, identification and antimicrobial susceptibility testing of bacterial uropathogens in small animal veterinary practice

    DEFF Research Database (Denmark)

    Guardabassi, Luca; Hedberg, Sandra; Jessen, Lisbeth Rem

    2015-01-01

    BACKGROUND: Urinary tract infection (UTI) is a common reason for antimicrobial prescription in dogs and cats. The objective of this study was to optimize and evaluate a culture-based point-of-care test for detection, identification and antimicrobial susceptibility testing of bacterial uro......-pathogens in veterinary practice. METHODS: Seventy-two urine samples from dogs and cats with suspected UTI presenting to seven veterinary facilities were used by clinical staff and an investigator to estimate sensitivity and specificity of Flexicult Vet A compared to laboratory reference standards for culture...... B (commercial name Flexicult(®) Vet) is a time- and cost-effective point-of-care test to guide antimicrobial choice and facilitate implementation of antimicrobial use guidelines for treatment of UTIs in small animals, provided that clinical staff is adequately trained to interpret the results...

  12. Implementation challenges for designing Integrated In Vitro Testing Strategies (ITS) aiming at reducing and replacing animal experimentation

    NARCIS (Netherlands)

    Wever, B.de; Fuchs, H.W.; Gaca, M.; Krul, C.A.M.; Mikulowski, S.; Poth, A.; Roggen, E.L.; Vilà, M.R.

    2012-01-01

    At the IVTIP (In Vitro Testing Industrial Platform) meeting of November 26th 2009 entitled 'Toxicology in the 21st century ('21C') - working our way towards a visionary reality' all delegates endorsed the emerging concept of the '21C' vision as the way forward to enable a thorough, reliable and

  13. Studies into laboratory animals for clearance rate of 32P-labelled Brucellae, using antigen elimination test after biotechnological treatment

    International Nuclear Information System (INIS)

    Lusky, K.; Hoffmann, A.; Bache, K.; Mueller, M.; Zwies, G.

    1988-01-01

    Studies were performed for the purpose of assessment of the immune status of mice, with regard to literature data and taking into consideration the large-scale use of veterinary pharmaceuticals for biotechnological control of reproduction. The antigen elimination test with Brucellae was applied to ICR mice but no influence on the immune status of 6 consecutive generations could be demonstrated. (author)

  14. 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.

  15. 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.

  16. 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.

  17. Prevalence and risk factors for cats testing positive for feline immunodeficiency virus and feline leukaemia virus infection in cats entering an animal shelter in New Zealand.

    Science.gov (United States)

    Gates, M C; Vigeant, S; Dale, A

    2017-11-01

    AIMS To estimate the prevalence of cats testing positive for antibodies to feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) antigens in domestic cats entering a New Zealand animal shelter, based on a commercial point-of-care ELISA, to identify risk factors associated with cats testing positive, and to compare the results obtained from the ELISA with those obtained using PCR-based testing. METHOD A cross-sectional study was performed on 388 cats entering the Royal New Zealand Society for the Prevention of Cruelty to Animals animal shelter in Auckland, New Zealand between 7 February 2014 and 30 May 2014. Whole blood samples were collected from each cat and tested for FIV antibody and FeLV antigen using a commercial point-of-care ELISA. Information on the signalment and health status of the cat at the time of entry was also recorded. Blood and saliva samples from a subset of cats were tested for FIV and FeLV proviral DNA using a real-time PCR assay. RESULTS Of the 388 cats in the study sample, 146 (37.6%) had been relinquished by owners, 237 (62.4%) were strays, and 5 (1.3%) were of unknown origin. Overall, 53/388 (13.7%) cats tested positive for FIV antibodies and 4/388 (1.0%) were positive for FeLV antigen. Stray cats had a higher FIV seroprevalence than relinquished cats (42/237 (17.8%) vs. 11/146 (7.5%); p=0.008). Of 53 cats that were FIV-seropositive, 51 (96%) tested positive for FIV proviral DNA using PCR testing of blood. Of these 51 cats, 28 (55%) were positive by PCR testing of saliva. Of the four cats that were FeLV antigen-positive by ELISA, two (50%) were positive for FeLV proviral DNA by PCR testing of blood. The odds of a cat being seropositive for FIV were greater for intact compared to desexed cats (OR=3.3; 95% CI=1.6-7.4) and for male compared to female cats (OR=6.5; 95% CI=3.2-14.0). CONCLUSIONS AND CLINICAL RELEVANCE The seroprevalence for FIV was 14% among cats entering an animal shelter in Auckland, whereas the prevalence of

  18. Design and testing of a controlled electromagnetic spinal cord impactor for use in large animal models of acute traumatic spinal cord injury.

    Science.gov (United States)

    Petteys, Rory J; Spitz, Steven M; Syed, Hasan; Rice, R Andrew; Sarabia-Estrada, Rachel; Goodwin, C Rory; Sciubba, Daniel M; Freedman, Brett A

    2017-09-01

    Spinal cord injury (SCI) causes debilitating neurological dysfunction and has been observed in warfighters injured in IED blasts. Clinical benefit of SCI treatment remains elusive and better large animal models are needed to assess treatment options. Here, we describe a controlled electromagnetic spinal cord impactor for use in large animal models of SCI. A custom spinal cord impactor and platform were fabricated for large animals (e.g., pig, sheep, dog, etc.). Impacts were generated by a voice coil actuator; force and displacement were measured with a load cell and potentiometer respectively. Labview (National Instruments, Austin, TX) software was used to control the impact cycle and import force and displacement data. Software finite impulse response (FIR) filtering was employed for all input data. Silicon tubing was used a surrogate for spinal cord in order to test the device; repeated impacts were performed at 15, 25, and 40 Newtons. Repeated impacts demonstrated predictable results at each target force. The average duration of impact was 71.2 ±6.1ms. At a target force of 40N, the output force was 41.5 ±0.7N. With a target of 25N, the output force was 23.5 ±0.6N; a target of 15Newtons revealed an output force of 15.2 ±1.4N. The calculated acceleration range was 12.5-21.2m/s 2 . This custom spinal cord impactor reliably delivers precise impacts to the spinal cord and will be utilized in future research to study acute traumatic SCI in a large animal. Published by Elsevier Ltd.

  19. Effect of the presence of two commercial adsorbents in animal feed on Aflatoxin B1 determination by ELISA kit test

    Directory of Open Access Journals (Sweden)

    Francesco Masoero

    2010-01-01

    Full Text Available A rapid AFB1 detection method by ELISA kit test was used on feedstuff samples, and compared to an HPLC method, to verify if the presence of clay-adsorbent (SA could cause erroneous quantification of the toxin. Samples were obtained using two AFB1-contaminated feedstuffs (7.92 and 17.58 µg/kg for low and high contaminated feeds; LC and HC respectively, added either one of two commercial SAs (Atox® and Myco AD and three different inclusion doses (0, 10 and 20 g/kg, respectively for CTR, 1% and 2% doses. The HPLC and ELISA data were compared in CTR samples with a paired t-test. The AFB1 recoveries, performed with ELISA, were analysed as a completely randomized design using a 2×2×3 factorial arrangement. The ELISA method tended to underestimate the AFB1 concentrations with respect to the HPLC method, both in HC (P=0.050 and in LC (P<0.001 feedstuffs. A more drastic reduction (P<0.001 was observed when SAs were included in the two feedstuffs. In particular, Atox® determined an AFB1 recovery of 15,5% in HC and 7,6% in LC (1% dose and of 11,1% in HC and 8,4% in LC (2% dose. Less severe penalisation were observed when Myco AD was added to feeds.

  20. 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.

  1. Cocombustion of animal meal

    International Nuclear Information System (INIS)

    Roggen, M.

    2001-01-01

    The electricity production companies are prepared to co-fire animal meal in their coal-fired power stations. Tests conducted at the Maasvlakte power station, Netherlands, demonstrate that adding animal meal to the coal has no negative influence on human beings, the environment, the plant or the fly ash quality

  2. Dynamic loads on human and animal surrogates at different test locations in compressed-gas-driven shock tubes

    Science.gov (United States)

    Alay, E.; Skotak, M.; Misistia, A.; Chandra, N.

    2018-01-01

    Dynamic loads on specimens in live-fire conditions as well as at different locations within and outside compressed-gas-driven shock tubes are determined by both static and total blast overpressure-time pressure pulses. The biomechanical loading on the specimen is determined by surface pressures that combine the effects of static, dynamic, and reflected pressures and specimen geometry. Surface pressure is both space and time dependent; it varies as a function of size, shape, and external contour of the specimens. In this work, we used two sets of specimens: (1) anthropometric dummy head and (2) a surrogate rodent headform instrumented with pressure sensors and subjected them to blast waves in the interior and at the exit of the shock tube. We demonstrate in this work that while inside the shock tube the biomechanical loading as determined by various pressure measures closely aligns with live-fire data and shock wave theory, significant deviations are found when tests are performed outside.

  3. The relationship between anxiety and depression in animal models: a study using the forced swimming test and elevated plus-maze

    Directory of Open Access Journals (Sweden)

    R. Andreatini

    1999-09-01

    Full Text Available The present study evaluated the correlation between the behavior of mice in the forced swimming test (FST and in the elevated plus-maze (PM. The effect of the order of the experiments, i.e., the influence of the first test (FST or PM on mouse behavior in the second test (PM or FST, respectively was compared to handled animals (HAND. The execution of FST one week before the plus-maze (FST-PM, N = 10, in comparison to mice that were only handled (HAND-PM, N = 10 in week 1, decreased % open entries (HAND-PM: 33.6 ± 2.9; FST-PM: 20.0 ± 3.9; mean ± SEM; P0.10. A prior test in the plus-maze (PM-FST did not change % immobility time in the FST when compared to the HAND-FST group (HAND-FST: 57.7 ± 3.9; PM-FST: 65.7 ± 3.2; mean ± SEM; P>0.10. Since these data suggest that there is an order effect, the correlation was evaluated separately with each test sequence: FST-PM (N = 20 and PM-FST (N = 18. There was no significant correlation between % immobility time in the FST and plus-maze indexes (% time and entries in open arms in any test sequence (r: -0.07 to 0.18. These data suggest that mouse behavior in the elevated plus-maze is not related to behavior in the forced swimming test and that a forced swimming test before the plus-maze has an anxiogenic effect even after a one-week interval.

  4. Do black-furred animals compensate for high solar absorption with smaller hairs? A test with a polymorphic squirrel species

    Directory of Open Access Journals (Sweden)

    Melanie A. FRATTO, Andrew K. DAVIS

    2011-12-01

    Full Text Available In polymorphic mammalian species that display multiple color forms, those with dark, or melanic pelage would be prone to overheating, especially if they live in warm climates, because their fur absorbs solar energy at a higher rate. However, experimental studies indicate that certain physical properties of fur of dark individuals appear to prevent, or minimize heat stress, although it is not clear what properties do so. Here, we tested the possibility that black-furred individuals simply have shorter or thinner hair fibers, which would create a lighter (in terms of weight coat or one that allows greater air flow for evaporative coo- ling. We examined museum specimens of eastern fox squirrels Sciurus niger, a species native to the United States and one that displays brown, grey or all-black pelage color, and used image analysis procedures to quantify hairs from the dorsal surface and tail. From examination of 43 specimens (19 brown, 9 black and 15 grey, and 1,720 hairs, we found no significant difference in hair lengths across color morphs, but significant differences in hair fiber widths. Black squirrels had thinner body hairs than other forms (7% thinner, but thicker tail hairs (9% thicker than the others. Given that the dorsal surface would be directly exposed to solar radiation, we interpret this to be an adaptation to prevent heat stress during the day. The thicker tail hairs may be an adaptation for nighttime thermoregulation, since squirrels sleep with their tails wrapped around their bodies. These results add to a growing literature body of the functional significance of mammalian pelage [Current Zoology 57 (6: 731–736, 2011].

  5. Laboratory Animal Management: Wild Birds.

    Science.gov (United States)

    National Academy of Sciences - National Research Council, Washington, DC. Inst. of Lab. Animal Resources.

    This is a report on the care and use of wild birds in captivity as research animals. Chapters are presented on procurement and identification, housing, nutrition, health of birds and personnel, reproduction in confinement, and surgical procedures. Also included are addresses of federal, state, and provencial regulatory agencies concerned with wild…

  6. Animated Asphalt

    DEFF Research Database (Denmark)

    Paldam, Camilla Skovbjerg

    2015-01-01

    to be understood? How does animation differ in different media? And in particular by focusing on and questioning the gender positions inherent in Mitchell’s theory. Animation has an erotic component of seduction and desire, and what pictures want, becomes for Mitchell, what women want. There is of course no simple...

  7. Animal magic

    Science.gov (United States)

    Denny, Mark

    2017-11-01

    Writing a popular-science book about animal biophysics is hard work. Authors must read through hundreds of research papers as the subject is so multidisciplinary. On both counts of research and writing, Matin Durrani and Liz Kalaugher have done a good to excellent job with their book Furry Logic: the Physics of Animal Life

  8. Animal ethics

    DEFF Research Database (Denmark)

    Palmer, Clare; Sandøe, Peter

    2011-01-01

    This chapter describes and discusses different views concerning our duties towards animals. First, we explain why it is necessary to engage in thinking about animal ethics and why it is not enough to rely on feelings alone. Secondly, we present and discuss five different kinds of views about...

  9. ANIMAL code

    International Nuclear Information System (INIS)

    Lindemuth, I.R.

    1979-01-01

    This report describes ANIMAL, a two-dimensional Eulerian magnetohydrodynamic computer code. ANIMAL's physical model also appears. Formulated are temporal and spatial finite-difference equations in a manner that facilitates implementation of the algorithm. Outlined are the functions of the algorithm's FORTRAN subroutines and variables

  10. Animal Detectives

    Science.gov (United States)

    Mulvey, Bridget; Warnock, Carly

    2015-01-01

    During a two-week inquiry-based 5E learning cycle unit, children made observations and inferences to guide their explorations of animal traits and habitats (Bybee 2014). The children became "animal detectives" by studying a live-feed webcam and digital images of wolves in their natural habitat, reading books and online sources about…

  11. Comparison of gross anatomy test scores using traditional specimens vs. QuickTime Virtual Reality animated specimens

    Science.gov (United States)

    Maza, Paul Sadiri

    movie modules. The comparison of the two sample group means of the examinations show that there was no difference in results between using QTVR movie modules to test gross anatomy knowledge versus using physical specimens. The results of this study are discussed to explain the benefits of using such computer based anatomy resources in gross anatomy assessments.

  12. Animation & Neurocinematics*

    DEFF Research Database (Denmark)

    Carpe Pérez, Inmaculada Concepción

    2015-01-01

    , indeed, can be considered a social/ emotional learning media, which goes beyond the limitations of live action movies. This is due to the diversity of techniques, and its visual plasticity that constructs the impossible. Animators are not real actors but more like the midwife who brings the anima...... into aliveness, which requires knowing how emotions work. Ed Hooks as an expert in training animators and actors, always remarks: “emotions tend to lead to action”. In this paper we want to argue that by producing animated films, as we watch them, cause a stronger effect, not only in our brains, but also in our...... bodies. By using animation as a learning tool we can explore the world of emotions and question beliefs, feelings and actions in order to express our voices and enhance our communication, and well-being, both, internally and with others. Animation can be the visual expression of the emotions in movement...

  13. Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

    Science.gov (United States)

    Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

    Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

  14. Yarrowia lipolytica Lipase 2 Is Stable and Highly Active in Test Meals and Increases Fat Absorption in an Animal Model of Pancreatic Exocrine Insufficiency.

    Science.gov (United States)

    Aloulou, Ahmed; Schué, Mathieu; Puccinelli, Delphine; Milano, Stéphane; Delchambre, Chantal; Leblond, Yves; Laugier, René; Carrière, Frédéric

    2015-12-01

    Pancreatic exocrine insufficiency (PEI) reduces pancreatic secretion of digestive enzymes, including lipases. Oral pancreatic enzyme replacement therapy (PERT) with pancreatin produces unsatisfactory results. The lipase 2 produced by the yeast Yarrowia lipolytica (YLLIP2; GenBank: AJ012632) might be used in PERT. We investigated its ability to digest triglycerides in a test meal and its efficacy in reducing fecal fat in an animal model of PEI. YLLIP2 was produced by genetically engineered Y lipolytica and purified from culture media. YLLIP2 or other gastric (LIPF) and pancreatic (PNLIPD) lipases were added to a meal paste containing dietary triglycerides, at a range of pH values (pH 2-7), with and without pepsin or human bile and incubated at 37°C. We collected samples at various time points and measured lipase activities and stabilities. To create an animal model of PEI, steatorrhea was induced by embolization of the exocrine pancreas gland and pancreatic duct ligation in minipigs. The animals were given YLLIP2 (1, 4, 8, 40, or 80 mg/d) or pancreatin (100,000 US Pharmacopeia lipase units/d, controls) for 9 days. We then collected stool samples, measured fat levels, and calculated coefficient of fat absorption (CFA) values. YLLIP2 was highly stable and poorly degraded by pepsin, and had the highest activity of all lipases tested on meal triglyceride at pH 4-7 (pH 6 with bile: 94 ± 34 U/mg; pH 4 without bile: 43 ± 13 U/mg). Only gastric lipase was active and stable at pH 3, whereas YLLIP2 was sensitive to pepsin hydrolysis after pH inactivation. From in vitro test meal experiments, the lipase activity of YLLIP2 (10 mg) was estimated to be equivalent to that of pancreatin (1200 mg; 100,000 US Pharmacopeia units) at pH 6. In PEI minipigs, CFA values increased from 60.1% ± 9.3% before surgery to 90.5% ± 3.2% after administration of 1200 mg pancreatin (P meal triglycerides in a large pH range, with and without bile. Oral administration of milligram amounts of

  15. Application of omics data in regulatory toxicology: report of an international BfR expert workshop.

    Science.gov (United States)

    Marx-Stoelting, P; Braeuning, A; Buhrke, T; Lampen, A; Niemann, L; Oelgeschlaeger, M; Rieke, S; Schmidt, F; Heise, T; Pfeil, R; Solecki, R

    2015-11-01

    Advances in omics techniques and molecular toxicology are necessary to provide new perspectives for regulatory toxicology. By the application of modern molecular techniques, more mechanistic information should be gained to support standard toxicity studies and to contribute to a reduction and refinement of animal experiments required for certain regulatory purposes. The relevance and applicability of data obtained by omics methods to regulatory purposes such as grouping of chemicals, mode of action analysis or classification and labelling needs further improvement, defined validation and cautious expert judgment. Based on the results of an international expert workshop organized 2014 by the Federal Institute for Risk Assessment in Berlin, this paper is aimed to provide a critical overview of the regulatory relevance and reliability of omics methods, basic requirements on data quality and validation, as well as regulatory criteria to decide which effects observed by omics methods should be considered adverse or non-adverse. As a way forward, it was concluded that the inclusion of omics data can facilitate a more flexible approach for regulatory risk assessment and may help to reduce or refine animal testing.

  16. Animal Transports

    Directory of Open Access Journals (Sweden)

    Diana Ludrovcová

    2016-08-01

    Full Text Available Purpose and Originality: The research is aimed to the animal transports issue, from two points of view – first is the animal cruelty and second is the policy and economic consideration. The goal is to acquaint the readers with the transports risks and its cruelty and evaluation of the economic, political aspects for he involved countries. The study is oriented on more points of view, what is rare in works with a similar theme. Method: This paper examines many issues and examinations from different authors and subsequently summarized the findings with authors own knowledge to one expanded unit. Results: Results proves, that livestock transports have negative impact on animal´s health, environment. Number of transported animals is rising every year. Society: Research familiarize the society with the animal transports, cruelty against animals during them, and influence of transports on some countries, their economy, policy. People get better informed and can form their own opinion on this topic. They may start acting, undertaking some steps to improve the present situation, what could help a lot to animals and environment. Limitations / further research: Future research could show progress and improvement of transports, quality of food supply and economics.

  17. Iodine metabolism and thyroid functions in various species of domestic animals and poultry birds. I - Species difference in thyroid status as reflected by triiodothyronine 131I uptake test

    International Nuclear Information System (INIS)

    Setia, M.S.; Parshad, Omkar; Varman, P.N.

    1974-01-01

    In vitro triiodothyronine- 131 I uptake, by red blood cells was studied in buffaloes, buffaloe calves, cross-bred calves, rams, goats, piglets and also in pure white leg horn and cross-bred birds. Results revealed that buffalo calves have the lowest uptake values, whereas piglets appeared to have the highest values as compared to other species. Distinct differences in the uptake of T 3 - 131 I by the erythrocytes were observed to exist within as well as amongst the species of farm animals and poultry birds studied. Cross-breds exhibited higher degree of T 3 - 131 I uptake as compared to pure-breds. This test offers promise where more tedious methods may not be possible for conducting the survey on the thyroid status and iodine metabolism on large population of live-stock. (author)

  18. A novel semi-automatic snake robot for natural orifice transluminal endoscopic surgery: preclinical tests in animal and human cadaver models (with video).

    Science.gov (United States)

    Son, Jaebum; Cho, Chang Nho; Kim, Kwang Gi; Chang, Tae Young; Jung, Hyunchul; Kim, Sung Chun; Kim, Min-Tae; Yang, Nari; Kim, Tae-Yun; Sohn, Dae Kyung

    2015-06-01

    Natural orifice transluminal endoscopic surgery (NOTES) is an emerging surgical technique. We aimed to design, create, and evaluate a new semi-automatic snake robot for NOTES. The snake robot employs the characteristics of both a manual endoscope and a multi-segment snake robot. This robot is inserted and retracted manually, like a classical endoscope, while its shape is controlled using embedded robot technology. The feasibility of a prototype robot for NOTES was evaluated in animals and human cadavers. The transverse stiffness and maneuverability of the snake robot appeared satisfactory. It could be advanced through the anus as far as the peritoneal cavity without any injury to adjacent organs. Preclinical tests showed that the device could navigate the peritoneal cavity. The snake robot has advantages of high transverse force and intuitive control. This new robot may be clinically superior to conventional tools for transanal NOTES.

  19. Resíduos e contaminantes químicos em alimentos de origem animal no Brasil: histórico, legislação e atuação da vigilância sanitária e demais sistemas regulatórios Chemical residues and contaminants in food of animal origin in Brazil: history, legislation and actions of sanitary surveillance and other regulatory systems

    Directory of Open Access Journals (Sweden)

    Bernardete Ferraz Spisso

    2009-12-01

    , besides those on measures to control veterinary medicinal products and additives for use in animal nutrition. The chronological presentation of the legal basis intends to facilitate the interpretation of the acts inside respective political and economics scenarios. The actions proposed from the different agents involved into the regulatory systems are discussed from the public health point of view.

  20. Animal welfare and use of silkworm as a model animal.

    Science.gov (United States)

    Sekimizu, N; Paudel, A; Hamamoto, H

    2012-08-01

    Sacrificing model animals is required for developing effective drugs before being used in human beings. In Japan today, at least 4,210,000 mice and other mammals are sacrificed to a total of 6,140,000 per year for the purpose of medical studies. All the animals treated in Japan, including test animals, are managed under control of "Act on Welfare and Management of Animals". Under the principle of this Act, no person shall kill, injure, or inflict cruelty on animals without due cause. "Animal" addressed in the Act can be defined as a "vertebrate animal". If we can make use of invertebrate animals in testing instead of vertebrate ones, that would be a remarkable solution for the issue of animal welfare. Furthermore, there are numerous advantages of using invertebrate animal models: less space and small equipment are enough for taking care of a large number of animals and thus are cost-effective, they can be easily handled, and many biological processes and genes are conserved between mammals and invertebrates. Today, many invertebrates have been used as animal models, but silkworms have many beneficial traits compared to mammals as well as other insects. In a Genome Pharmaceutical Institute's study, we were able to achieve a lot making use of silkworms as model animals. We would like to suggest that pharmaceutical companies and institutes consider the use of the silkworm as a model animal which is efficacious both for financial value by cost cutting and ethical aspects in animals' welfare.

  1. Validation of the Explorer® 2.0 test coupled to e-Reader® for the screening of antimicrobials in muscle from different animal species.

    Science.gov (United States)

    Mata, Luis; Sanz, David; Razquin, Pedro

    2014-01-01

    The Explorer(®) 2.0 tube test is a microbial inhibition test for the screening of antimicrobial residues in food samples. The new e-Reader(®) device coupled to Explorer(®) 2.0 operates by incubation at a selected temperature, determination of the endpoint of the assay and interpretation to generate results. This system was validated for muscle samples according to the European Commission Decision 2002/657/EC. Sensitivity towards 25 substances from several groups of antimicrobials was investigated in a first step. Detection capabilities for six substances representing the six major antimicrobial groups were also determined in bovine muscle. The detection capabilities for amoxicillin (10 µg l(-1)), cefalexin (200 µg l(-1)), doxycyclin (100 µg l(-1)), sulfamethazine (100 µg l(-1)), tylosin (100 µg l(-1)) and neomycin (200 µg l(-1)) were in all cases at or below the maximum residue limit (MRL). Specificity and applicability of the test were demonstrated with muscle samples from four animal species (bovine, porcine, ovine and poultry) and results were found to be satisfactory. Ruggedness was evaluated on negative and spiked samples with sulfamethazine as a representative antimicrobial. Neither false-positives nor false-negatives were detected when varying the sample volume, the time of pre-incubation, the temperature of incubation and the batch of the test. These results prove that Explorer(®) 2.0 coupled to e-Reader(®) is a valuable tool for the screening of a broad range of antimicrobials in muscle. This new methodology simplifies the analysis and increases the accuracy of interpretation of the test results since the endpoint of the assay is automatically determined and results are interpreted objectively.

  2. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  3. Mentalizing animals

    DEFF Research Database (Denmark)

    Kasperbauer, Tyler Joshua

    2017-01-01

    Ethicists have tended to treat the psychology of attributing mental states to animals as an entirely separate issue from the moral importance of animals’ mental states. In this paper I bring these two issues together. I argue for two theses, one descriptive and one normative. The descriptive thesis...... holds that ordinary human agents use what are generally called phenomenal mental states (e.g., pain and other emotions) to assign moral considerability to animals. I examine recent empirical research on the attribution of phenomenal states and agential states (e.g., memory and intelligence) to argue...... that phenomenal mental states are the primary factor, psychologically, for judging an animal to be morally considerable. I further argue that, given the role of phenomenal states in assigning moral considerability, certain theories in animal ethics will meet significant psychological resistance. The normative...

  4. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of bench-marking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  5. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

    Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators. The appli......Benchmarking methods, and in particular Data Envelopment Analysis (DEA), have become well-established and informative tools for economic regulation. DEA is now routinely used by European regulators to set reasonable revenue caps for energy transmission and distribution system operators....... The application of benchmarking in regulation, however, requires specific steps in terms of data validation, model specification and outlier detection that are not systematically documented in open publications, leading to discussions about regulatory stability and economic feasibility of these techniques...

  6. Implementing nuclear non-proliferation in Finland. Regulatory control, international cooperation and the Comprehensive Nuclear-Test-Ban Treaty. Annual report 2011

    Energy Technology Data Exchange (ETDEWEB)

    Okko, O [ed.

    2012-07-01

    The regulatory control of nuclear materials (i.e. nuclear safeguards) is a prerequisite for the peaceful use of nuclear energy in Finland. Safeguards are required for Finland to comply with international agreements on nuclear non-proliferation - mainly the Non-Proliferation Treaty (NPT). This regulatory control is exercised by the Nuclear Materials Section of the Finnish Radiation and Nuclear Safety Authority (STUK). The results of STUK's nuclear safeguards inspection activities in 2011 continued to demonstrate that the Finnish licence holders take good care of their nuclear materials. There were no indications of undeclared nuclear materials or activities and the inspected materials and activities were in accordance with the licence holders' declarations.

  7. Optimization and evaluation of Flexicult® Vet for detection, identification and antimicrobial susceptibility testing of bacterial uropathogens in small animal veterinary practice.

    Science.gov (United States)

    Guardabassi, Luca; Hedberg, Sandra; Jessen, Lisbeth Rem; Damborg, Peter

    2015-10-26

    shortcomings regarding species identification by clinical staff and β-lactam susceptibility testing of E. coli, Flexicult Vet B (commercial name Flexicult(®) Vet) is a time- and cost-effective point-of-care test to guide antimicrobial choice and facilitate implementation of antimicrobial use guidelines for treatment of UTIs in small animals, provided that clinical staff is adequately trained to interpret the results and that clinics meet minimum standards to operate in-house culture.

  8. Animated Reconstruction of Forensic Animation

    OpenAIRE

    Hala, Albert; Unver, Ertu

    1998-01-01

    An animated accident display in court can be significant evidentiary tool. Computer graphics animation reconstructions which can be shown in court are cost effective, save valuable time and illustrate complex and technical issues, are realistic and can prove or disprove arguments or theories with reference to the perplexing newtonian physics involved in many accidents: this technology may well revolutionise accident reconstruction, thus enabling prosecution and defence to be more effective in...

  9. [Animal Health Law-- the National Animal Health Act and the European Animal Health Law].

    Science.gov (United States)

    Bätza, Hans-Joachim; Mettenleiter, Thomas

    2013-01-01

    The Animal Health Act that replaces the Animal Disease Act, which is currently in force, creates a regulatory framework in order to not only, as has been the case so far, control animal diseases that had already broken out, but in order to already prevent in advance possible outbreaks of animal diseases by means of preventive measures. The instruments to this effect are described here. At European level, too, the idea of prevention is set to play a greater role in the future, with the draft EU legal instrument on animal health, that has to date only been discussed at Commission level, also contributing to a simplification and easier implementation by the persons subject to law by harmonising the currently fragmented Community law. It remains to be seen when the deliberations in the Council and European Parliament will begin.

  10. Animal toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Amdur, M.

    1996-12-31

    The chapter evaluates results of toxicological studies on experimental animals to investigate health effects of air pollutants and examines the animal data have predicted the response to human subject. Data are presented on the comparative toxicity of sulfur dioxide and sulfuric acid. The animal data obtained by measurement of airway resistance in guinea pigs and of bronchial clearance of particles in donkeys predicted clearly that sulfuric acid was more irritant than sulfur dioxide. Data obtained on human subjects confirmed this prediction. These acute studies also correctly predicted the comparative toxicity of the two compounds in two year studies of monkeys. Such chronic studies are not possible in human subjects but it is a reasonable to assume that sulfuric acid would be more toxic than sulfur dioxide. Current findings in epidemiological studies certainly support this assumption.

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

    DEFF Research Database (Denmark)

    Meyer, Otto A.

    2003-01-01

    The object of toxicological testing is to predict possible adverse effect in humans when exposed to chemicals whether used as industrial chemicals, pharmaceuticals or pesticides. Animal models are predominantly used in identifying potential hazards of chemicals. The use of laboratory animals raises...... 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...... 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...

  12. Animal evolution

    DEFF Research Database (Denmark)

    Nielsen, Claus

    This book provides a comprehensive analysis of evolution in the animal kingdom. It reviews the classical, morphological information from structure and embryology, as well as the new data gained from studies using immune stainings of nerves and muscles and blastomere markings, which makes it possi......This book provides a comprehensive analysis of evolution in the animal kingdom. It reviews the classical, morphological information from structure and embryology, as well as the new data gained from studies using immune stainings of nerves and muscles and blastomere markings, which makes...

  13. SIMULATED ANIMAL EXPERIMENTS IN TEACHING AND RESEARCH

    Directory of Open Access Journals (Sweden)

    Chirag B. Mistry, Shreya M. Shah, Jagatkumar D. Bhatt

    2015-07-01

    Full Text Available Animal experiments are of paramount importance in the pre-clinical screening of new chemical entity. On the other hand, various regulatory guidelines for animal experiments are becoming more stringent in the face of worldwide protests by animal rights activists. Moreover, simulated animal experiments’ softwares are being developed and they can be implemented in the postgraduate and graduate students’ curriculum for demonstration of standard physiological and pharmacological principles compared to real time animal experiments. In fact, implementation of virtual experiment will decrease hand on experience of animal experiments among medical students, but after medical graduation, animal experiment is lest utilized during their day to day clinical practice. Similarly, in case of postgraduate pharmacology curriculum, computer based virtual animal experiments can facilitate teaching and learning in a short span of time with various protocols, without sacrificing any animal for already established experimental outcomes.

  14. Whole bone testing in small animals: systematic characterization of the mechanical properties of different rodent bones available for rat fracture models.

    Science.gov (United States)

    Prodinger, Peter M; Foehr, Peter; Bürklein, Dominik; Bissinger, Oliver; Pilge, Hakan; Kreutzer, Kilian; von Eisenhart-Rothe, Rüdiger; Tischer, Thomas

    2018-02-14

    animals, light animals showed good consistency in failure loads of the humeri (CV% 7.7). Most consistent results of both sides (left vs. right) in failure loads were provided by the femurs of light animals (mean difference 4.0 ± 2.8%); concerning stiffness, humeri of heavy animals were most consistent (mean difference of 6.2 ± 5%). In general, the failure loads showed strong correlations to the BMC (R 2  = 0.85-0.88) whereas stiffness correlated only moderate, except for the humerus (BMC vs. stiffness: R 2  = 0.79). Altogether, the rat's femur of mature specimens showed the most accurate and consistent radiological and biomechanical results. In synopsis with the common experimental use enabling comparison among different studies, this bone offers ideal biomechanical conditions for three point bending experiments. This can be explained by the combination of a superior aspect ratio and a round and long, straight morphology, which satisfies the beam criteria more than other bones tested.

  15. Animal Science.

    Science.gov (United States)

    VanCleave, Janice

    2001-01-01

    Presents a set of hands-on, outdoor science experiments designed to teach elementary school students about animal adaptation. The experiments focus on: how color camouflage affects an insect population; how spiderlings find a home; and how chameleons camouflage themselves by changing color. (SM)

  16. Animal impacts

    Science.gov (United States)

    Norbert V. DeByle

    1985-01-01

    The aspen ecosystem is rich in number and species of animals, especially in comparison to associated coniferous forest types. This natural species diversity and richness has been both increased and influenced by the introduction of domestic livestock. The high value of the aspen type as a forage resource for livestock and as forage and cover for wildlife makes the...

  17. Animated symbols

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth

    2008-01-01

    an analytic working model called Animated Symbols concerning critical reflection in a dialogic learning process. The model shows dialogue as interactions that involve two types of transformation: inner ‘learning processes' and outer signs and symbols. The classroom-based research study is part of a Ph...

  18. A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

    Science.gov (United States)

    Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

    2018-06-01

    Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Principles of animal extrapolation

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, E.J.

    1991-01-01

    Animal Extrapolation presents a comprehensive examination of the scientific issues involved in extrapolating results of animal experiments to human response. This text attempts to present a comprehensive synthesis and analysis of the host of biomedical and toxicological studies of interspecies extrapolation. Calabrese's work presents not only the conceptual basis of interspecies extrapolation, but also illustrates how these principles may be better used in selection of animal experimentation models and in the interpretation of animal experimental results. The book's theme centers around four types of extrapolation: (1) from average animal model to the average human; (2) from small animals to large ones; (3) from high-risk animal to the high risk human; and (4) from high doses of exposure to lower, more realistic, doses. Calabrese attacks the issues of interspecies extrapolation by dealing individually with the factors which contribute to interspecies variability: differences in absorption, intestinal flora, tissue distribution, metabolism, repair mechanisms, and excretion. From this foundation, Calabrese then discusses the heterogeneticity of these same factors in the human population in an attempt to evaluate the representativeness of various animal models in light of interindividual variations. In addition to discussing the question of suitable animal models for specific high-risk groups and specific toxicological endpoints, the author also examines extrapolation questions related to the use of short-term tests to predict long-term human carcinogenicity and birth defects. The book is comprehensive in scope and specific in detail; for those environmental health professions seeking to understand the toxicological models which underlay health risk assessments, Animal Extrapolation is a valuable information source.

  20. Biotecnologia animal

    Directory of Open Access Journals (Sweden)

    Luiz Lehmann Coutinho

    2010-01-01

    Full Text Available A biotecnologia animal tem fornecido novas ferramentas para os programas de melhoramento e, dessa forma, contribuído para melhorar a eficiência da produção dos produtos de origem animal. No entanto, os avanços têm sido mais lentos do que antecipados, especialmente em razão da dificuldade na identificação dos genes responsáveis pelas características fenotípicas de interesse zootécnico. Três estratégias principais têm sido utilizadas para identificar esses genes - mapeamento de QTL, genes candidatos e sequenciamento de DNA e mRNA - e cada uma tem suas vantagens e limitações. O mapeamento de QTL permite determinar as regiões genômicas que contêm genes, mas o intervalo de confiança do QTL pode ser grande e conter muitos genes. A estratégia de genes candidatos é limitada por causa do conhecimento ainda restrito das funções de todos os genes. Os sequenciamentos de genomas e de sequências expressas podem auxiliar na identificação da posição de genes e de vias metabólicas associadas à característica de interesse. A integração dessas estratégias por meio do desenvolvimento de programas de bioinformática permitirá a identificação de novos genes de interesse zootécnico. Assim, os programas de melhoramento genético se beneficiarão pela inclusão da informação obtida diretamente do DNA na avaliação do mérito genético dos plantéis disponíveis.Animal biotechnology is providing new tools for animal breeding and genetics and thus contributing to advances in production efficiency and quality of animal products. However, the progress is slower than anticipated, mainly because of the difficulty involved in identifying genes that control phenotypic characteristics of importance to the animal industry. Three main strategies: QTL mapping, candidate genes and DNA and mRNA sequencing have been used to identify genes of economic interest to animal breeding and each has advantages and disadvantages. QTL mapping allows

  1. Implementing nuclear non-proliferation in Finland. Regulatory control, international cooperation and the Comprehensive Nuclear-Test-Ban Treaty. Annual report 2011

    Energy Technology Data Exchange (ETDEWEB)

    Okko, O. (ed.)

    2012-07-01

    The regulatory control of nuclear materials (i.e. nuclear safeguards) is a prerequisite for the peaceful use of nuclear energy in Finland. Safeguards are required for Finland to comply with international agreements on nuclear non-proliferation - mainly the Non-Proliferation Treaty (NPT). This regulatory control is exercised by the Nuclear Materials Section of the Finnish Radiation and Nuclear Safety Authority (STUK). The results of STUK's nuclear safeguards inspection activities in 2011 continued to demonstrate that the Finnish licence holders take good care of their nuclear materials. There were no indications of undeclared nuclear materials or activities and the inspected materials and activities were in accordance with the licence holders' declarations.

  2. Animal facilities

    International Nuclear Information System (INIS)

    Fritz, T.E.; Angerman, J.M.; Keenan, W.G.; Linsley, J.G.; Poole, C.M.; Sallese, A.; Simkins, R.C.; Tolle, D.

    1981-01-01

    The animal facilities in the Division are described. They consist of kennels, animal rooms, service areas, and technical areas (examining rooms, operating rooms, pathology labs, x-ray rooms, and 60 Co exposure facilities). The computer support facility is also described. The advent of the Conversational Monitor System at Argonne has launched a new effort to set up conversational computing and graphics software for users. The existing LS-11 data acquisition systems have been further enhanced and expanded. The divisional radiation facilities include a number of gamma, neutron, and x-ray radiation sources with accompanying areas for related equipment. There are five 60 Co irradiation facilities; a research reactor, Janus, is a source for fission-spectrum neutrons; two other neutron sources in the Chicago area are also available to the staff for cell biology studies. The electron microscope facilities are also described

  3. Animal Locomotion

    CERN Document Server

    Taylor, Graham K; Tropea, Cameron

    2010-01-01

    This book provides a wide-ranging snapshot of the state-of-the-art in experimental research on the physics of swimming and flying animals. The resulting picture reflects not only upon the questions that are of interest in current pure and applied research, but also upon the experimental techniques that are available to answer them. Doubtless, many new questions will present themselves as the scope and performance of our experimental toolbox develops over the coming years.

  4. Recent progress and future directions for reduction, refinement, and replacement of animal use in veterinary vaccine potency and safety testing: a report from the 2010 NICEATM-ICCVAM International Vaccine Workshop.

    Science.gov (United States)

    Stokes, W S; Kulpa-Eddy, J; Brown, K; Srinivas, G; McFarland, R

    2012-01-01

    Veterinary vaccines contribute to improved animal and human health and welfare by preventing infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing, and to identify priority activities to advance new and improved methods that can further reduce, refine and replace animal use. Rabies, Clostridium sp., and Leptospira sp. vaccines were identified as the highest priorities, while tests requiring live viruses and bacteria hazardous to laboratory workers, livestock, pets, and wildlife were also considered high priorities. Priority research, development and validation activities to address critical knowledge and data gaps were identified, including opportunities to apply new science and technology. Enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers were recommended to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will benefit animal welfare and ensure continued and improved protection of human and animal health.

  5. Regulatory difficulties in a developing country

    International Nuclear Information System (INIS)

    Jacobs, W.R. Jr.

    1978-01-01

    The regulatory agency assigned the task of regulating the initial entry into the field of nuclear power generation by a developing country has a very difficult job. Based on the authors' experience during the start-up and initial operation of Ko-Ri Unit I, the first power reactor in the Republic of Korea, observations on regulatory difficulties and recommendations for improved regulatory effectiveness are offered. The problem areas can be loosely grouped into three general categories: (1) Lack of adequate technical knowledge which is the basis for all effective regulation; (2) Difficulties with understanding and utilization of the required regulatory documentation; (3) Failure to establish the proper regulatory environment. Examples are cited from actual experience during the Ko-Ri Unit I start-up to demonstrate the impact that regulatory activities can have on a plant construction and testing programme. The problems encountered are not unique to developing countries but also exist in the United States of America. Recommendations are offered which should be beneficial to either newly formed regulatory agencies or agencies wishing to improve their abilities and effectiveness. These include: (1) Additional training of regulatory inspectors in plant operations; (2) Additional experience gained by participation in regulatory activities in other countries; (3) Increased attention given to regulatory documents, especially plant technical specifications; (4) Establishment of formal lines of communication between the utility and the regulatory agency; (5) Clear definition of regulatory responsibilities to avoid areas of overlapping jurisdiction; (6) Active participation by the regulatory staff very early in the project. It is hoped that these and other recommendations offered will greatly improve regulatory effectiveness and at the same time demonstrate that when the decision is made to 'go nuclear', a strong commitment must be made to develop and support a technically

  6. Application and Comparative Evaluation of Fluorescent Antibody, Immunohistochemistry and Reverse Transcription Polymerase Chain Reaction Tests for the Detection of Rabies Virus Antigen or Nucleic Acid in Brain Samples of Animals Suspected of Rabies in India

    Directory of Open Access Journals (Sweden)

    K. Nithin Prabhu

    2018-02-01

    Full Text Available Accurate and early diagnosis of animal rabies is critical for undertaking public health measures. Whereas the direct fluorescent antibody (DFA technique is the recommended test, the more convenient, direct rapid immunochemistry test (dRIT, as well as the more sensitive, reverse transcription polymerase chain reaction (RT-PCR, have recently been employed for the laboratory diagnosis of rabies. We compared the three methods on brain samples from domestic (dog, cat, cattle, buffalo, horse, pig and goat and wild (leopard, wolf and jackal animals from various parts of India. Of the 257 samples tested, 167 were positive by all the three tests; in addition, 35 of the 36 decomposed samples were positive by RT-PCR. This is the first study in which such large number of animal samples have been subjected to the three tests simultaneously. The results confirm 100% corroboration between DFA and dRIT, buttress the applicability of dRIT in the simple and rapid diagnosis of rabies in animals, and reaffirm the suitability of RT-PCR for samples unfit for testing either by DFA or dRIT.

  7. Application and Comparative Evaluation of Fluorescent Antibody, Immunohistochemistry and Reverse Transcription Polymerase Chain Reaction Tests for the Detection of Rabies Virus Antigen or Nucleic Acid in Brain Samples of Animals Suspected of Rabies in India.

    Science.gov (United States)

    Prabhu, K Nithin; Isloor, Shrikrishna; Veeresh, B Hanchinal; Rathnamma, Doddamane; Sharada, R; Das, Lekshmi J; Satyanarayana, M L; Hegde, Nagendra R; Rahman, Sira Abdul

    2018-02-28

    Accurate and early diagnosis of animal rabies is critical for undertaking public health measures. Whereas the direct fluorescent antibody (DFA) technique is the recommended test, the more convenient, direct rapid immunochemistry test (dRIT), as well as the more sensitive, reverse transcription polymerase chain reaction (RT-PCR), have recently been employed for the laboratory diagnosis of rabies. We compared the three methods on brain samples from domestic (dog, cat, cattle, buffalo, horse, pig and goat) and wild (leopard, wolf and jackal) animals from various parts of India. Of the 257 samples tested, 167 were positive by all the three tests; in addition, 35 of the 36 decomposed samples were positive by RT-PCR. This is the first study in which such large number of animal samples have been subjected to the three tests simultaneously. The results confirm 100% corroboration between DFA and dRIT, buttress the applicability of dRIT in the simple and rapid diagnosis of rabies in animals, and reaffirm the suitability of RT-PCR for samples unfit for testing either by DFA or dRIT.

  8. Animation of Antimicrobial Resistance

    Science.gov (United States)

    ... Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin ...

  9. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Cosmetics Tobacco Products Animal & Veterinary Home Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin ...

  10. Ethical implications of using the minipig in regulatory toxicology studies.

    Science.gov (United States)

    Webster, John; Bollen, Peter; Grimm, Herwig; Jennings, Maggy

    2010-01-01

    Two key questions are addressed in this article. What are the potential harms to minipigs relative to the harms for dogs and non-human primates and can these harms be reduced more easily in minipigs than in other species? Are there potential benefits resulting from the use of minipigs relative to dogs and non-human primates? In considering the answers to these questions, we present an ethical framework which was developed taking into account the viewpoint of all concerned parties. This ethical matrix provides a framework upon which to identify and explore issues raised by the moral imperative to seek a fair compromise between the differing needs of different interest groups, which includes both the moral agents and the moral patients. The moral agents are the different groups of human stakeholders including society at large, regulatory bodies, industrialists and animal care staff. The moral patients are the laboratory animals, both breeding stock held by the animal supplier, and experimental animals in laboratories. In considering these animals it cannot be assumed that dogs, monkeys and minipigs differ with regard to the pain and suffering that they may experience and undergo when treated in studies designed for safety assessment. On this basis we rejected the argument that minipigs are more acceptable experimental animals than dogs or monkeys despite the fact that their use may prove less offensive to some groups within society at large. Species selection must be made on a case-by-case basis where the benefits are assessed by weighing the scientific evidence relating to the predictivity of the animal model, against the harm that may accrue to the animals both from the test procedures and their lifetime experience within the laboratory environment. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Investigations of multiresistance to antibiotics and chemotherapeutics and extended spectrum beta: Lactamase effect (ESBL test in strains E.coli and salmonella originating from domestic animals

    Directory of Open Access Journals (Sweden)

    Mišić Dušan

    2006-01-01

    Full Text Available The presence of multiresistance to the effects of antibiotics and chemotherapeutics and extended spectrum beta-lactamase were examined in 45 strains of E. coli and 35 strains of Salmonella. The strains of E. coli originated from several species of domestic animals: dogs, cats, poultry, and cattle, and 30 strains of Salmonella originated from poultry, 4 strains from cattle, and 1 strain from swine. The presence of the following serovarieties was established using serological examinations: Salmonella Enteritidis 17 strains, Salmonella Gallinarum 1 strain, Salmonella Hartford 5 strains, Salmonella Anatum 1 strain, Salmonella Typhimurium 4 strains, Salmonella Agona 1 strain, Salmonella Infantis 1 strain, Salmonella Thompson var. Berlin 1 strain, Salmonella Tennessee 1 strain, Salmonella Senftenberg 1 strain, Salmonella Glostrup 1 strain, and Salmonella Hadar 1 strain. In the examinations of the listed strains we used antibiogram discs of ampicillin, amoxicillin with clavulanic acid, cephalexin, cephtriaxon, cephotaxim, cephtazidime, aztreonam, gentamycin, chloramphenicol, tetracycline, cyprofloxacine, and a combination of sulphamethoxasole and trimethoprim. The lowest prevalence of multiresistance in E. Coli strains to 3 or more antibiotics was established in dogs 20%, and the highest in 60% strains originating from swine. In 62.88% strains of Salmonella we established sensitivity to all applied antibiotics. Resistance was also established in a small number of the examined strains to ampicillin (11 strains, to tetracycline (5 strains, to amoxicillin with clavulanic acid (5 strains, to sulphamethoxasole with trimethoprim (5 strains, to gentamycin (3 strains, and to cloramphenicol (1 strain. Of all the examined strains of Salmonella, 6 strains originating from poultry exhibited multiresistence. The presence of extended spectrum beta-lactamase effects examined using the ESBL test, was not established in strains of E. coli and Salmonella strains.

  12. Animated war

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth

    2012-01-01

    in production: Gzim Rewind (Sweden, 2011) by Knutte Wester, and In-World War (USA, expected 2011) by DJ Bad Vegan. These films have themes of war and include film scenes that are ‘machinima’ (real-time animation made in 3D graphic environments) within live action film scenes. Machinima harnesses...... DIY multimedia storytellers explore new ways to tell and to ‘animate’ stories. The article contains four parts: introduction to machinima and the notions of resemiosis and authorial practice, presentation of DIY filmmaking as a practice that intertwines with new networked economics, analysis...

  13. As to achieve regulatory action, regulatory approaches

    International Nuclear Information System (INIS)

    Cid, R.; Encinas, D.

    2014-01-01

    The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

  14. Technical note: Test of a low-cost and animal-friendly system for measuring methane emissions from dairy cows

    DEFF Research Database (Denmark)

    Hellwing, Anne Louise Frydendahl; Lund, Peter; Weisbjerg, Martin Riis

    2012-01-01

    the animals in chambers, as dry matter intake before and during chamber stay were similar. It was concluded that the system delivers reliable values, and the transparent construction in combination with the location in the barn environment prevent negative impact on animal welfare and, thereby, data quality.......Methane is a greenhouse gas with a significant anthropogenic contribution from cattle production. A demand exists for techniques that facilitate evaluation of mitigation strategies for dairy cows. Therefore, a low-cost system facilitating the highest possible animal welfare was constructed...... and validated. The system uses the same principles as systems for open-circuit indirect calorimetry, but to lower the costs, the chamber construction and air-conditioning system were simpler than described for other open-circuit systems. To secure the highest possible animal welfare, the system is located...

  15. 75 FR 16001 - New Animal Drugs; Removal of Obsolete and Redundant Regulations

    Science.gov (United States)

    2010-03-31

    ... drug-resistant bacteria associated with these animals, was obsolete as FDA had a new strategy and... on any approved new animal drugs, or to cause any approved new animal drug to lose its marketing ability or experience a loss of sales. C. Regulatory Flexibility Analysis The Regulatory Flexibility Act...

  16. Animal models.

    Science.gov (United States)

    Walker, Ellen A

    2010-01-01

    As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

  17. ANIMAL MODELS FOR IMMUNOTOXICITY

    Science.gov (United States)

    Greater susceptibility to infection is a hallmark of compromised immune function in humans and animals, and is often considered the benchmark against which the predictive value of immune function tests are compared. This focus of this paper is resistance to infection with the pa...

  18. The economics of animal welfare.

    Science.gov (United States)

    Gibson, T J; Jackson, E L

    2017-04-01

    This paper examines four examples of animal welfare issues, demonstrating the interactions between welfare and economic principles. Welfare issues associated with purebred companion animals are examined in terms of predicted inherited diseases, highlighting the power of supply and demand in perpetuating traits in pets that compromise their well-being. The livestock industry is presented from the point of view of pig production and the impact that a major disease (pleurisy) has on production and the animals' welfare. The authors investigate the conflicting and complementary demands of animal welfare and economic gains during the transport and slaughter of livestock and poultry. Finally, wildlife species are considered in terms of their prevalence as pests, and the different types of economic analysis that have been conducted to understand the losses caused by these organisms. Also included in this example are decisions made about cost effectiveness and opportunity costs, and regulatory and financial barriers to the development of humane control agents. In conclusion, animal welfare is illustrated as a central factor in the benefits that humans enjoy from the role played by animals in society. There are, however, tradeoffs between optimal animal welfare and meeting the needs of modern human society.

  19. Implementing nuclear non-proliferation in Finland. Regulatory control, international cooperation and the comprehensive nuclear-test-ban treaty. Annual report 2007

    International Nuclear Information System (INIS)

    Haemaelaeinen, M.; Karhu, P.

    2008-04-01

    Regulatory control of nuclear materials (nuclear safeguards) is a prerequisite for the peaceful use of nuclear energy in Finland. In order to uphold our part of the international agreements on nuclear non-proliferation - mainly the Non-Proliferation Treaty (NPT). This regulatory control is exercised by the Nuclear Materials Section of the Finnish Radiation and Nuclear Safety Authority (STUK). Nuclear safeguards are applied to all materials and activities that can lead to the proliferation of nuclear weapons or sensitive nuclear technology. These safeguards include nuclear materials accountancy, control, security and reporting. The results of STUK's nuclear safeguards inspection activities in 2007 continued to demonstrate that Finnish licence holders take good care of their nuclear materials. There were no indications of undeclared nuclear materials or activities and the inspected materials and activities were in accordance with the licence holders' declarations. STUK remarked on the nuclear safeguards systems of two licence holders in 2007, setting required actions for them to correct their reporting and to update the descriptions of their procedures. Neither the IAEA nor the European Commission made any remarks nor did they present any required actions based on their inspections. By their nuclear materials accountancy and control systems, all licence holders enabled STUK to fulfil its own obligations under the international agreements relevant to nuclear safeguards

  20. The regulatory framework in the UK

    International Nuclear Information System (INIS)

    O'Sullivan, R.

    1984-01-01

    The subject is covered in sections, headed: basic regulatory requirements covering the transport of radioactive material in the UK; responsibility for safety (competent authority; provision of regulations; implementation of regulations (international and national); design of transport flask; safety case; testing; assessment; approval certificate; compliance assurance; administration); advice and information on the regulatory safety standards. (U.K.)

  1. Animal and plant remains in a tomb in test-pit 1/05, outside the fortified imperial palace Felix Romuliana

    Directory of Open Access Journals (Sweden)

    Dimitrijević Vesna

    2007-01-01

    Full Text Available During the excavations of a tomb located outside the defence walls of the imperial palace, Felix Romuliana, animal and plant remains were collected the analysis of which is the subject of the present study. The faunal remains include the bones and teeth of domestic animals - mule (Equus caballus x Equus asinus, domestic ox (Bos taurus, sheep (Ovis aries, sheep or goat (Ovis/Capra, pig (Sus domesticus and dog (Canis familiaris, a few remains of wild animals - red deer (Cervus elaphus and fox (Vulpes vulpes, and bone of a bird. Until now, no remains of mule have been discovered on sites originating from the classical period at the territory of Serbia. As for plant remains, pieces of carbonized oak wood (Quercus and maple wood (Acer were found, as well as a carbonized seed of a cultivated grapevine (Vitis vinifera vinifera and a tiny fruit of goosegrass (Galium aparine.

  2. Bioethical Problems: Animal Welfare, Animal Rights.

    Science.gov (United States)

    March, B. E.

    1984-01-01

    Discusses various bioethical issues and problems related to animal welfare and animal rights. Areas examined include: Aristotelian views; animal welfare legislation; Darwin and evolutionary theory; animal and human behavior; and vegetarianism. A 14-point universal declaration of the rights of animals is included. (JN)

  3. The use of mice as animal model for testing acute toxicity (LD-50 of toxic shock syndrome toxin Utilização de camundongos como modelo animal para a verificação da toxicidade aguda da toxina-1 da síndrome do choque tóxico

    Directory of Open Access Journals (Sweden)

    R.S. Dias

    2009-02-01

    Full Text Available Acute toxicity test (LD-50 using toxic shock syndrome toxin (TSST-1 was tested in BALB/c, C57BL/6 and Swiss mice. Animals (n = 10 were intraperitoneally injected with TSST-1 (0.01-10.0µg/mouse followed 4h later by potentiating dose of lipopolysaccharide (75.0µg of LPS - E. coli O111:B4 and cumulative mortality was recorded over 72h. Control animals received either TSST-1 or LPS alone. The data were submitted to qui-Square test and acute toxicity test was calculated by probit analysis (confidence limits expressed as µg toxin/kg. BALB/c mice was the most sensitive (20.0µg/kg, 95% confidence limits: 9.0-92.0 followed by C57BL/6 (38.5µg/kg, 95% confidence limits: 9.11- 401.6. Data from Swiss mice was not conclusive, indicating only low sensitivity. Selection of the animal model and standardization of the experiment are fundamental for the development of serum neutralization tests used for final quality control of vaccine production.A toxicidade aguda (DL-50 da toxina da síndrome do choque tóxico (TSST-1 foi testada em linhagens de camundongos BALB/c, C57BL/6 e Suíça. Os animais (n=10 inoculados intraperitoneal com doses crescentes de toxina (0,01 - 10,0µg/animal receberam 4h após 75µg de LPS (E. coli O111: B4. A toxicidade aguda (DL50 foi observada por um período de 72h e os dados submetidos ao teste de qui- quadrado. Os resultados e os limites de confiança foram expressos em µg de toxina/kg. A linhagem BALB/c apresentou maior sensibilidade (20µg/kg - limite de confiança a 95% entre 9,0- 92,0, seguida da C57BL/6 (38,5µg/kg - limite de confiança a 95% entre 9,11 - 401,6. A amplitude dos limites de confiança deve-se à natureza da toxina, ao mecanismo de ação, a via de inoculação e ao animal utilizado. A seleção do modelo animal e a padronização do experimento são fundamentais para o desenvolvimento de testes de soro neutralização para fins de controle de qualidade do processo de produção de vacinas.

  4. Regulatory BC1 RNA in Cognitive Control

    Science.gov (United States)

    Iacoangeli, Anna; Dosunmu, Aderemi; Eom, Taesun; Stefanov, Dimitre G.; Tiedge, Henri

    2017-01-01

    Dendritic regulatory BC1 RNA is a non-protein-coding (npc) RNA that operates in the translational control of gene expression. The absence of BC1 RNA in BC1 knockout (KO) animals causes translational dysregulation that entails neuronal phenotypic alterations including prolonged epileptiform discharges, audiogenic seizure activity in vivo, and…

  5. Reproduction of post-weaning multi-systemic wasting syndrome in an animal disease model as a tool for vaccine testing under controlled conditions.

    Science.gov (United States)

    McKillen, John; McNair, Irene; Lagan, Paula; McKay, Karen; McClintock, Julie; Casement, Veronica; Charreyre, Catherine; Allan, Gordon

    2016-04-01

    Snatch farrowed, colostrum deprived piglets were inoculated with different combinations of porcine circovirus 2, porcine parvovirus and Erysipelothrix rhusiopathiae candidate vaccines. 10 piglets were mock-vaccinated. Following virus challenge with a combined porcine circovirus 2/porcine parvovirus inoculum, all animals were monitored and samples taken for serology, immunohistochemistry and qPCR. At 24 dpc all non-vaccinated animals remaining were exhibiting signs of post-weaning multi-systemic wasting syndrome which was confirmed by laboratory analysis. Details of the study, analysis of samples and performance of the candidate vaccines are described. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. LESSONS FROM A RETROSPECTIVE ANALYSIS OF A 5-YR PERIOD OF QUARANTINE AT SAN DIEGO ZOO: A RISK-BASED APPROACH TO QUARANTINE ISOLATION AND TESTING MAY BENEFIT ANIMAL WELFARE.

    Science.gov (United States)

    Wallace, Chelsea; Marinkovich, Matt; Morris, Pat J; Rideout, Bruce; Pye, Geoffrey W

    2016-03-01

    Quarantine is designed primarily to prevent the introduction of transmissible diseases to zoological collections. Improvements in preventive medicine, disease eradication, and comprehensive pathology programs call into question current industry quarantine standards. Disease risk analysis was used at the San Diego Zoo (SDZ) and the SDZ Safari Park to eliminate quarantine isolation and transmissible disease testing for animals transferred between the two institutions. To determine if a risk-based approach might be valid between other institutions and SDZ, we reviewed quarantine data for animals arriving at SDZ from 81 Association of Zoos and Aquariums (AZA)-accredited and 124 other sources (e.g., non-AZA-accredited institutions, private breeders, private dealers, governmental bodies) over a 5-yr period (2009-2013). No mammal or herptile failed quarantine due to transmissible diseases of concern. Approximately 2.5% of incoming birds failed quarantine due to transmissible disease; however, all 14 failed individuals were obtained from three nonaccredited sources (private breeders, confiscation). The results of our study suggest that a risk-based approach could be used to minimize or eliminate quarantine for the transfer of animals from institutions with comprehensive disease surveillance programs and/or preshipment testing practices. Quarantine isolation with testing remains an essential defense against introducing transmissible diseases of concern when there is a lack of health knowledge about the animals being received.

  7. Professional and Regulatory Search

    Science.gov (United States)

    Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

  8. Animal welfare: an animal science approach.

    Science.gov (United States)

    Koknaroglu, H; Akunal, T

    2013-12-01

    Increasing world population and demand for animal-derived protein puts pressure on animal production to meet this demand. For this purpose animal breeding efforts were conducted to obtain the maximum yield that the genetic makeup of the animals permits. Under the influence of economics which is the driving force behind animal production, animal farming became more concentrated and controlled which resulted in rearing animals under confinement. Since more attention was given on economics and yield per animal, animal welfare and behavior were neglected. Animal welfare which can be defined as providing environmental conditions in which animals can display all their natural behaviors in nature started gaining importance in recent years. This does not necessarily mean that animals provided with good management practices would have better welfare conditions as some animals may be distressed even though they are in good environmental conditions. Consumers are willing to pay more for welfare-friendly products (e.g.: free range vs caged egg) and this will change the animal production practices in the future. Thus animal scientists will have to adapt themselves for the changing animal welfare rules and regulations that differ for farm animal species and countries. In this review paper, animal welfare is discussed from an animal science standpoint. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  9. Animal models of sarcoidosis.

    Science.gov (United States)

    Hu, Yijie; Yibrehu, Betel; Zabini, Diana; Kuebler, Wolfgang M

    2017-03-01

    Sarcoidosis is a debilitating, inflammatory, multiorgan, granulomatous disease of unknown cause, commonly affecting the lung. In contrast to other chronic lung diseases such as interstitial pulmonary fibrosis or pulmonary arterial hypertension, there is so far no widely accepted or implemented animal model for this disease. This has hampered our insights into the etiology of sarcoidosis, the mechanisms of its pathogenesis, the identification of new biomarkers and diagnostic tools and, last not least, the development and implementation of novel treatment strategies. Over past years, however, a number of new animal models have been described that may provide useful tools to fill these critical knowledge gaps. In this review, we therefore outline the present status quo for animal models of sarcoidosis, comparing their pros and cons with respect to their ability to mimic the etiological, clinical and histological hallmarks of human disease and discuss their applicability for future research. Overall, the recent surge in animal models has markedly expanded our options for translational research; however, given the relative early stage of most animal models for sarcoidosis, appropriate replication of etiological and histological features of clinical disease, reproducibility and usefulness in terms of identification of new therapeutic targets and biomarkers, and testing of new treatments should be prioritized when considering the refinement of existing or the development of new models.

  10. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

    In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

  11. Elaboration and quality control of the inoculum of the experimental vaccine Brucella S19-tn7-GFP for use in white animals and associated serological test for the detection of anti-GFP antibodies

    International Nuclear Information System (INIS)

    Salas Alfaro, Dariana

    2014-01-01

    The preparation of the inoculum of the experimental vaccine Brucella S19-Tn7-GFP is optimized for application in white animals. An associated serological test has allowed differentiating infected animals from those vaccinated with the experimental strain. The same bacteriological and biological properties of the B. abortus S19-Tn7-GFP strain have maintained in the parental vaccine strain S19 and is stable over time. A protocol for the inoculums of strain S19-Tn7-GFP is established for its preparation and use in white animals and quality control. The inoculum stability is evaluated through the simulation of conditions that can be presented in the transportation and application process in the field. An enzyme immunoassay ELISA is optimized for the detection of anti-GFP antibodies in cattle [es

  12. The Dessau workshop on bioaccumulation: state of the art, challenges and regulatory implications.

    Science.gov (United States)

    Treu, Gabriele; Drost, Wiebke; Jöhncke, Ulrich; Rauert, Caren; Schlechtriem, Christian

    2015-01-01

    Bioaccumulation plays a vital role in understanding the fate of a substance in the environment and is key to the regulation of chemicals in several jurisdictions. The current assessment approaches commonly use the octanol-water partition coefficient (log K OW ) as an indicator for bioaccumulation and the bioconcentration factor (BCF) as a standard criterion to identify bioaccumulative substances show limitations. The log K OW does not take into account active transport phenomena or special structural properties (e.g., amphiphilic substances or dissociating substances) and therefore additional screening criteria are required. Regulatory BCF studies are so far restricted to fish and uptake through the gills. Studies on (terrestrial) air-breathing organisms are missing. Though there are alternative tests such as the dietary exposure bioaccumulation fish test described in the recently revised OECD test guideline 305, it still remains unclear how to deal with results of alternative tests in regulatory decision-making processes. A substantial number of bioaccumulation fish tests are required in regulation. The development of improved test systems following the 3R principles, namely to replace, reduce and refine animal testing, is thus required. All these aspects stress the importance to further develop the assessment of bioaccumulation. The Dessau Workshop on Bioaccumulation which was held from June 26th to 27th 2014, in Dessau, Germany, provided a comprehensive overview of the state of the art of bioaccumulation assessment, provided insights into the problems and challenges addressed by the regulatory authorities and described new research concepts and their regulatory implications. The event was organised by UBA (Dessau, Germany) and Fraunhofer IME (Schmallenberg, Germany). About 50 participants from industry, regulatory bodies and academia listened to 14 lectures on selected topics and joined the plenary discussions.

  13. Alberta Energy and Utilities Board, regulatory highlights for 1998

    International Nuclear Information System (INIS)

    1999-01-01

    This new publication informs readers about what the Alberta Energy and Utilities Board (EUB) did in the past year, including important regulatory issues, trends and initiatives. The EUB is an agency of the provincial government, established to regulate Alberta's energy resource and utility sectors. It is part of the Alberta Ministry of Energy. The four main functions of the Board are regulatory initiatives, license applications, enforcement and information. This publication summarized the EUB's position regarding flaring (both solution gas flaring and well test flaring), and Board activities in the areas of animal health concerns, the gas over bitumen controversy, the deregulation of the electric industry and what it means to the EUB, improvements in data quality as a result of improved industry compliance in reporting, and a variety of issues related to the oil sands and the negotiated settlement process. Also, the Board has been proactive in the area of oilfield waste management guidelines, proliferation policies for gas processing facilities, sulphur recovery guidelines, and the expansion of the orphan well program to include facilities and pipelines. As a measure of the success of the EUB, a recent survey of 19 randomly selected focus groups praised EUB for its impartiality, fair and equitable enforcement and independence. It was also praised for its technically competent and experienced staff, its access to quality information and the clarity of its mandate, regulatory requirements and processes. The Board's efforts in the area of timely stakeholder consultation was highlighted. tabs., figs

  14. Alberta Energy and Utilities Board, regulatory highlights for 1998

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-08-01

    This new publication informs readers about what the Alberta Energy and Utilities Board (EUB) did in the past year, including important regulatory issues, trends and initiatives. The EUB is an agency of the provincial government, established to regulate Alberta`s energy resource and utility sectors. It is part of the Alberta Ministry of Energy. The four main functions of the Board are regulatory initiatives, license applications, enforcement and information. This publication summarized the EUB`s position regarding flaring (both solution gas flaring and well test flaring), and Board activities in the areas of animal health concerns, the gas over bitumen controversy, the deregulation of the electric industry and what it means to the EUB, improvements in data quality as a result of improved industry compliance in reporting, and a variety of issues related to the oil sands and the negotiated settlement process. Also, the Board has been proactive in the area of oilfield waste management guidelines, proliferation policies for gas processing facilities, sulphur recovery guidelines, and the expansion of the orphan well program to include facilities and pipelines. As a measure of the success of the EUB, a recent survey of 19 randomly selected focus groups praised EUB for its impartiality, fair and equitable enforcement and independence. It was also praised for its technically competent and experienced staff, its access to quality information and the clarity of its mandate, regulatory requirements and processes. The Board`s efforts in the area of timely stakeholder consultation was highlighted. tabs., figs.

  15. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... video) Animation of Antimicrobial Resistance (text version) Arabic Translation of Animation of Antimicrobial Resistance Chinese Translation of Animation of Antimicrobial Resistance French Translation of ...

  16. A Study on Improvement of Test Method of Nuclear Power Plant ESF ACS by applying Regulatory Guide 1.52 (Rev.3)

    International Nuclear Information System (INIS)

    Lee, Sook Kyung; Kim, Kwang Sin; Sohn, Soon Hwan; Song, Kyu Min; Lee, Kae Woo; Cho, Byoung Ho; Park, Jeong Seo; Yoo, Byeang Jea; Hong, Soon Joon; Kang, Sun Haeng

    2010-01-01

    U. S. NRC Regulation Guide 1.52 regulating ESF ACS in nuclear power plants has been revised to revision 3. To apply reduction of operability test time, allowance of alternative challenge agents for in-place leak test of HEPA filters, and upgrade of Methyl Iodide penetration acceptance criterion in activated carbon performance test suggested in Reg. Guide 1.52(Rev.3) on Yonggwang units 5 and 6 ESF ACSes, technical feasibility study was carried out with on-site experiments as well as experiments with a lab-scale model. It was confirmed that the moisture in the system returned to the level before the test in 1 or 4 days even though the moisture was removed during the operability test lasting more than 10 hours. Therefore, it is appropriate to perform monthly operability test in 15 minutes just long enough to check the operability of equipment. To change challenge material for in-place HEPA filter leak test, size of aerosol, production rate, and leak detection capability were compared for DOP and PAO. It was concluded that PAO can be substituted for DOP in nuclear power plants. The upgrade of Methyl Iodide penetration acceptance criterion from 0.175 % to 0.5 % in active carbon filter bed deeper than 4 inches was to conform to the change of activated carbon performance test method to ASTM D3803(1989). It was confirmed that Methyl Iodide penetration acceptance criterion of 0.5 % under 30 .deg. C

  17. Averrhoa carambola L., Syzygium cumini (L. Skeels and Cissus sicyoides L.: medicinal herbal tea effects on vegetal and animal test systems Averrhoa carambola L., Syzygium cumini (L. Skeels e Cissus sicyoides L.: efeitos dos chás de plantas medicinais sobre os sistemas-teste vegetal e animal

    Directory of Open Access Journals (Sweden)

    Mario Sergio Mantovani

    2001-05-01

    Full Text Available Since folk medicine has been greatly appreciated for centuries, many researchers decided to study more deeply the curative qualities of plants. In the present study, meristematic cells of Allium cepa L. were used as vegetal test system and bone marrow cells of Wistar rats as animal test system. Both were treated in vivo to evaluate whether the plants Averrhoa carambola L., Syzygium cumini (L. Skeels and Cissus sicyoides L. presented cytotoxic and mutagenic effects and whether they resulted in cell alterations in their morphology, chromosomes or cell cycle division. Herbal teas were prepared as normally done by the population, albeit in two different concentrations, the usual concentration and a concentration ten times higher. Rats were treated with only one concentration of teas. Results showed that teas did not alter the cell cycle of Allium cepa L., with the exception of the 24 hours analysis after suspension of treatment (recovery of treatments, with a lower concentration of Averrhoa carambola. The latter had a low mitotic index when compared to control and to the post-treatment analysis, showing an inhibition of cell division. The three herbal teas neither induced an increase in the number of chromosomal damage in bone marrow cells of Wistar rats nor altered the cell division cycle. Results are important in so far as these plants are used as therapeutic agentsAs plantas medicinais têm sido muito estudadas devido aos seus efeitos curativos. Neste estudo foram utilizados o sistema teste vegetal em células meristemáticas de Allium cepa L. e o sistema teste animal em células da medula óssea de ratos Wistar tratados in vivo para avaliação dos efeitos citotóxicos e mutagênicos das plantas Averrhoa carambola L., Syzygium cumini (L. Skeels e Cissus sicyoides L., analisando-se o ciclo de divisão celular, morfologia e cromossomos. Os chás das plantas foram preparados da maneira usada pela população e em duas diferentes concentrações, a

  18. Animated construction of line drawings

    KAUST Repository

    Fu, Hongbo; Zhou, Shizhe; Liu, Ligang; Mitra, Niloy J.

    2011-01-01

    system produces plausible animated constructions of input line drawings, with no or little user intervention. We test our algorithm on a range of input sketches, with varying degree of complexity and structure, and evaluate the results via a user study