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.

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

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.

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.

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...

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.

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.

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.

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...

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

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

Science.gov (United States)

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

2015-11-01

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

Replacement of serum with ocular fluid for cryopreservation of immature testes.

Science.gov (United States)

Pothana, Lavanya; Devi, Lalitha; Venna, Naresh Kumar; Pentakota, Niharika; Varma, Vivek Phani; Jose, Jedy; Goel, Sandeep

2016-12-01

Cryopreservation of immature testis is a feasible approach for germplasm preservation of male animals. Combinations of dimethyl sulfoxide (DMSO) and foetal bovine serum (FBS) are used for testis cryopreservation. However, an alternative to FBS is needed, because FBS is expensive. Buffalo ocular fluid (BuOF), a slaughter house by-product, could be an economical option. The objective of the present study was to assess whether BuOF can replace FBS for cryopreservation of immature mouse (Mus musculus), rat (Rattus norvegicus), and buffalo (Bubalus bubalis) testes. Results showed that rodent and buffalo testes frozen in DMSO (10% for rodents and 20% for buffalo) with 20% FBS or BuOF had similar numbers of viable and DNA-damaged cells (P > 0.05). The expression of cell proliferation- (PCNA) and apoptosis-specific proteins (Annexin V and BAX/BCL2 ratio) were also comparable in mouse and buffalo testes frozen in DMSO with FBS or BuOF (P > 0.05). Interestingly, rat testis frozen in DMSO with BuOF had lower expression of Annexin V protein than testis frozen in DMSO with FBS (P  0.05). These findings provide evidence that BuOF has potential to replace FBS for cryopreservation of immature rodent and buffalo testis. Further investigation is needed to explore whether BuOF can replace FBS for testis cryopreservation of other species. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

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

Full Text Available A avaliação da toxicidade de uma substância é realizada com o objetivo de predizer os efeitos nocivos que a mesma poderá desencadear quando da exposição humana pelas diversas vias. Para cumprir este propósito, o modelo animal é o mais utilizado nos estudos toxicológicos e requerido nos processos investigativos. Entretanto, a utilização de animais na pesquisa tem sido razão de diversas discussões em função do grande número necessário e do sofrimento causado, principalmente em relação aos estudos de toxicidade aguda. Existe uma tendência mundial para reavaliar a utilização de animais nos experimentos, concretizada a partir de um programa denominado de 3Rs (Reduction, Refinement, Replacement, que objetiva além de diminuir o número de animais, minimizar a dor e o desconforto e buscar alternativas para a substituição dos testes in vivo. Diversas metodologias alternativas já foram implantadas, sendo este um processo complexo que abrange desde o seu desenvolvimento até sua aceitação regulatória e adoção por diversas organizações. Sendo assim, o presente trabalho apresenta abordagem atualizada do Programa 3Rs, com ênfase na sua evolução histórica e nos processos de implantação e validação de métodos alternativos, principalmente aplicados no contexto da avaliação da toxicidade, enfatizando sua importância e utilidade frente à tendência global de harmonização.Toxicity assessment is the process of predicting the adverse effects that may be caused to an organism by exposuring it to a given chemical and, for regulation purposes, the most used model in toxicity testing is the animal. However, in today's society the use of animals has become a subject of much public health due to the large number of animals used as well as the pain and distress caused, mainly related to acute toxicity testing. The concept of the "Three Rs" - reduction, refinement, and replacement of animal use - emerged as a mean of removing

Replacement, Reduction, Refinement - Animal welfare progress in European Pharmacopoeia monographs: activities of the European Pharmacopoeia Commission from 2007 to 2017.

Science.gov (United States)

Lang, C; Kolaj-Robin, O; Cirefice, G; Taconet, L; Pel, E; Jouette, S; Buda, M; Milne, C; Charton, E

2018-01-01

Since the opening for signature of the European Convention for the Protection of Animals Used for Experimental and Other Scientific Purposes in 1986, the European Pharmacopoeia Commission and its experts have carried out a programme of work committed to Replacing, Reducing and Refining (3Rs) the use of animals for test purposes. While updates on achievements in the field of the 3Rs are regularly provided, this article summarises the activities of the Ph. Eur. Commission in this field within the last decade.

Replacement of harmful animal use in life science education: the approach and activities of InterNICHE.

Science.gov (United States)

Jukes, Nick

2004-06-01

Harmful animal use in undergraduate education is increasingly being replaced by alternatives, such as computer software, manikins and simulators, ethically sourced animal cadavers, apprentice work with animal patients, and student self-experimentation. Combinations of such alternatives can better meet teaching objectives, reduce costs and avoid the negative pedagogical and social impact of animal experimentation. Since 1988, the International Network for Humane Education (InterNICHE, formerly EuroNICHE) has been working with teachers to replace harmful animal use and has been supporting students' right to conscientious objection. This paper presents the approach, history and current activities of InterNICHE. With a vision of 100% replacement, the network aims for empowerment by networking information and providing support. It works with the belief that most teachers want investment in the best quality and most humane education possible. The forthcoming second edition of the InterNICHE book, from Guinea Pig to Computer Mouse,1 includes practical details of progressive teaching aids and approaches, as well as case studies from teachers who employ such alternatives. In 1999, InterNICHE produced the film Alternatives in Education, now available in 20 languages. Such resources are complemented by outreach trips and conferences and an Alternatives Loan System, which offers products for familiarisation and assessment. The InterNICHE website (www.interniche.org) was launched in 2001.

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.

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...

Testing of milk replacers for Mycobacterium avium subsp. paratuberculosis by PCR and bacterial culture as a possible source for Johne's disease (paratuberculosis) in calves.

Science.gov (United States)

Khol, Johannes Lorenz; Braun, Anna Lena; Slana, Iva; Kralik, Petr; Wittek, Thomas

2017-09-01

Johne's disease (paratuberculosis) is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and can lead to severe economic losses in the affected cattle herds. The transmission of the disease occurs mainly orally, by the ingestion of MAP, which is shed in the feces and milk of infected animals. Calves show a high susceptibility for the infection compared to adult animals. The use of milk replacers can, therefore, contribute to the prevention of the transmission of the disease to calves in MAP-positive herds by preventing the ingestion of the bacterium with milk from infected animals. The objective of this study was to test milk replacers for calves for the presence of MAP by bacteriological culture and PCR. Therefore, commercially available milk replacers for calves were purchased from 15 different companies. All of the products were tested for MAP by solid culture and real time quantitative PCR (qPCR) targeting IS900 and F57. During the present study, MAP could not be detected by qPCR or solid culture in commercially available milk replacers for calf rearing. The results of the present study underpins that the use of milk replacers for calf rearing might contribute to the reduction of MAP intake by calves in JD positive herds. Additional studies, including more products with a higher diversity, are needed to further elucidate the presence or absence of MAP in milk replacers for calves. Copyright © 2017 Elsevier B.V. All rights reserved.

Flow boiling test of GDP replacement coolants

International Nuclear Information System (INIS)

Park, S.H.

1995-01-01

The tests were part of the CFC replacement program to identify and test alternate coolants to replace CFC-114 being used in the uranium enrichment plants at Paducah and Portsmouth. The coolants tested, C 4 F 10 and C 4 F 8 , were selected based on their compatibility with the uranium hexafluoride process gas and how well the boiling temperature and vapor pressure matched that of CFC-114. However, the heat of vaporization of both coolants is lower than that of CFC-114 requiring larger coolant mass flow than CFC-114 to remove the same amount of heat. The vapor pressure of these coolants is higher than CFC-114 within the cascade operational range, and each coolant can be used as a replacement coolant with some limitation at 3,300 hp operation. The results of the CFC-114/C 4 F 10 mixture tests show boiling heat transfer coefficient degraded to a minimum value with about 25% C 4 F 10 weight mixture in CFC-114 and the degree of degradation is about 20% from that of CFC-114 boiling heat transfer coefficient. This report consists of the final reports from Cudo Technologies, Ltd

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

Science.gov (United States)

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

2013-01-01

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

Testing of Replacement Bag Material

International Nuclear Information System (INIS)

Laurinat, J.E.

1998-01-01

Recently, the FB-Line bagout material was changed to simplify the processing of sand, slag, and crucible.The results of the strength tests and the outgassing measurements and calculations demonstrate that the proposed replacement nylon bag materials (HRMP and orange anti-static material) are acceptable substitutes for LDPE and the original nylon with respect to mechanical properties

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.

Reliability tests for reactor internals replacement technology

International Nuclear Information System (INIS)

Fujimaki, K.; Uchiyama, J.; Ohtsubo, T.

2000-01-01

Structural damage due to aging degradation of LWR reactor internals has been reported in several nuclear plants. NUPEC has started a project to test the reliability of the technology for replacing reactor internals, which was directed at preventive maintenance before damage and repair after damage for the aging degradation. The project has been funded by the Ministry of International Trade and Industry (MITI) of Japan since 1995, and it follows the policy of a report that the MITI has formally issued in April 1996 summarizing the countermeasures to be considered for aging nuclear plants and equipment. This paper gives an outline of the whole test plans and the test results for the BWR reactor internals replacement methods; core shroud, ICM housing, and CRD Housing and stub tube. The test results have shown that the methods were reliable and the structural integrity was appropriate based on the evaluation. (author)

Replacement of animal protein with vegetable protein in the diets of Astyanax altiparanae

Directory of Open Access Journals (Sweden)

Fábio Rosa Sussel

2014-09-01

Full Text Available The aim of this study was to evaluate the effect of replacing animal protein with vegetable protein sources on the productive performance of Astyanax altiparanae (lambari-do-rabo-amarelo. Five experimental diets were formulated with increasing replacement levels of animal protein by vegetable protein. A total of 9000 individuals (initial mean weight 1.18 ± 0.12 g, initial mean length 2.1 ± 0.3 cm were distributed in 20 net cages (1 m3 with a density of 450 ind. m-3. Cages were randomly placed in a pond (180 m2, 1.5 m deep, 10% water renewal per day. After 63 days of cultivation, total count and individual biometrics from 20% of each experimental unit were taken. Mean weight, total length, survival, feed conversion, biomass weight gain and proximate body composition were evaluated. The experimental design was completely randomized with five treatments and four replications. The reduction in the formulation cost achieved by increasing levels of vegetable protein compensated the slight decrease in biomass gain. Besides that, inclusion of vegetable protein resulted in greater fat deposition, suggesting future exploration of A. altiparanae as a functional food.

Replacement of the Advanced Test Reactor control room

International Nuclear Information System (INIS)

Durney, J.L.; Klingler, W.B.

1989-01-01

The control room for the Advanced Test Reactor has been replaced to provide modern equipment utilizing current standards and meeting the current human factors requirements. The control room was designed in the early 1960 era and had not been significantly upgraded since the initial installation. The replacement did not change any of the safety circuits or equipment but did result in replacement of some of the recorders that display information from the safety systems. The replacement was completed in concert with the replacement of the control room simulator which provided important feedback on the design. The design successfully incorporates computer-based systems into the display of the plant variables. This improved design provides the operator with more information in a more usable form than was provided by the original design. The replacement was successfully completed within the scheduled time thereby minimizing the down time for the reactor. 1 fig., 1 tab

Replacement of the Advanced Test Reactor control room

International Nuclear Information System (INIS)

Durney, J.L.; Klingler, W.B.

1990-01-01

The control room for the Advanced Test Reactor has been replaced to provide modern equipment utilizing current standards and meeting the current human factors requirements. The control room was designed in the early 1960 era and had not been significantly upgraded since the initial installation. The replacement did not change any of the safety circuits or equipment but did result in replacement of some of the recorders that display information from the safety systems. The replacement was completed in concert with the replacement of the control room simulator which provided important feedback on the design. The design successfully incorporates computer-based systems into the display of the plant variables. This improved design provides the operator with more information in a more usable form than was provided by the original design. The replacement was successfully completed within the scheduled time thereby minimizing the down time for the reactor

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...

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.

Replacement of core components in the Advanced Test Reactor

International Nuclear Information System (INIS)

Durney, J.L.; Croucher, D.W.

1990-01-01

The core internals of the Advanced Test Reactor are subjected to very high neutron fluences resulting in significant aging. The most irradiated components have been replaced on several occasions as a result of the neutron damage. The surveillance program to monitor the aging developed the needed criteria to establish replacement schedules and maximize the use of the reactor. The methods to complete the replacements with minimum radiation exposures to workers have been developed using the experience gained from each replacement. The original design of the reactor core and associated components allows replacements to be completed without special equipment. The plant has operated for about 20 years and is expected to continue operation for at least and additional 25 years. Aging evaluations are in progress to address additional replacements that may be needed during this period

Replacement of core components in the Advanced Test Reactor

International Nuclear Information System (INIS)

Durney, J.L.; Croucher, D.W.

1989-01-01

The core internals of the Advanced Test Reactor are subjected to very high neutron fluences resulting in significant aging. The most irradiated components have been replaced on several occasions as a result of the neutron damage. The surveillance program to monitor the aging developed the needed criteria to establish replacement schedules and maximize the use of the reactor. Methods to complete the replacements with minimum radiation exposures to workers have been developed using the experience gained from each replacement. The original design of the reactor core and associated components allows replacements to be completed without special equipment. The plant has operated for about 20 years and will continue operation for perhaps another 20 years. Aging evaluations are in program to address additional replacements that may be needed during this extended time period. 3 figs

10 CFR 34.27 - Leak testing and replacement of sealed sources.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Leak testing and replacement of sealed sources. 34.27... SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Equipment § 34.27 Leak testing and replacement... radiographic exposure device and leak testing of any sealed source must be performed by persons authorized to...

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.

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

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.

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.

Fast Flux Test Facility replacement of a primary sodium pump

International Nuclear Information System (INIS)

Krieg, S.A.; Thomson, J.D.

1985-01-01

The Fast Flux Test Facility is a 400 MW Thermal Sodium Cooled Fast Reactor operated by Westinghouse Hanford Company for the US Department of Energy. During startup testing in 1979, the sodium level in one of the primary sodium pumps was inadvertently raised above the normal height. This resulted in distortion of the pump shaft. Pump replacement was carried out using special maintenance equipment. Nuclear radiation and contamination were not significant problems since replacement operations were carried out shortly after startup of the Fast Flux Test Facility

Acceptance test for 900 MWe PWR unit replacement steam generators

International Nuclear Information System (INIS)

Gourguechon, B.

1993-01-01

During the first half of 1994, the Gravelines 1 steam generators will be replaced (SG replacement procedure). The new SG's differ from the former components notably by the alloy used for the tube bundle, in this case, the high chromium content Inconel 690. So, from this standpoint, they are to be considered as PWR 900 replacement SG first models and their thermal efficiency has consequently to be assessed. This will provide an opportunity of ensuring that the performance of the components delivered is in compliance with requirements and of making the necessary provisions if significant deviations are observed. The EFMT branch, which has been in charge of the instrumentation and acceptance of the different SG first models since the first PWR plants were commissioned, will be responsible for the acceptance tests and the ultimate validation of a performance assessment procedure applicable to the future replacement steam generators. The methods and tests proposed for SG expert appraisal are based on consideration of the importance of primary measurement quality for satisfactory SG assessment and of the new test facilities with which the 900 and 1 300 PWR plants are gradually being equipped. These facilities provide an on-site computer environment for tests compatible with the tools (PATTERN, etc.) used at EFMT and in other departments. This test is the first of this kind performed by EFMT and the test facility of a nuclear power plant. (author). 6 figs

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

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

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.

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.

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.

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

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Science.gov (United States)

Viguiliouk, Effie; Stewart, Sarah E; Jayalath, Viranda H; Ng, Alena Praneet; Mirrahimi, Arash; de Souza, Russell J; Hanley, Anthony J; Bazinet, Richard P; Blanco Mejia, Sonia; Leiter, Lawrence A; Josse, Robert G; Kendall, Cyril W C; Jenkins, David J A; Sievenpiper, John L

2015-12-01

Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG), and fasting insulin (FI). Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I²-statistic). Thirteen RCTs (n = 280) met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = -0.15%; 95%-CI: -0.26, -0.05%), FG (MD = -0.53 mmol/L; 95%-CI: -0.92, -0.13 mmol/L) and FI (MD = -10.09 pmol/L; 95%-CI: -17.31, -2.86 pmol/L) compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. ClinicalTrials.gov registration number: NCT02037321.

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.

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...

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.

CALiPER Special Summary Report: Retail Replacement Lamp Testing

Energy Technology Data Exchange (ETDEWEB)

None

2011-04-01

CALiPER testing has evaluated many products for commercial lighting markets and found some excellent performers. However, many of these are not available on the retail market. This special testing was undertaken to identify and test solid-state lighting (SSL) replacement lamp products that are available to the general public through retail stores and websites.

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.

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Directory of Open Access Journals (Sweden)

Effie Viguiliouk

2015-12-01

Full Text Available Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG, and fasting insulin (FI. Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD with 95% confidence intervals (CIs. Heterogeneity was assessed (Cochran Q-statistic and quantified (I2-statistic. Thirteen RCTs (n = 280 met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = −0.15%; 95%-CI: −0.26, −0.05%, FG (MD = −0.53 mmol/L; 95%-CI: −0.92, −0.13 mmol/L and FI (MD = −10.09 pmol/L; 95%-CI: −17.31, −2.86 pmol/L compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. Trial Registration: ClinicalTrials.gov registration number: NCT02037321.

Assessment of Replacement Bridge using Proof Load Test

Science.gov (United States)

Sundru, Saibabu

2017-11-01

This work begins with an overview of the condition assessment of old bridge and explained reasons for demolishing of the bridge. Briefly presented flexural analysis of two stage post-tensioned prestressed concrete girder, which will be replace the old (new bridge). Construction of I-girder and composite girder at first stage and second stage prestressing respectively is explained with figures. Assessment of the load-caring capacity of the one span of the replacement bridge with simple supports using proof load test is presented which is mandatory according to Indian standards. Weighted sand bags were used to load the bridge up to a predetermined service load with impact factor. Deflections of the I-girders of the bridge were measured at selected locations along and across the bridge span and compared with computed values. Linear response was observed during loading and unloading. Considering the load test results, theoretical estimation and criteria as stipulated in codes of practice, it can be inferred that prestressed concrete I-girder bridge span has adequate capacity to carry the loads and hence, deemed to have passed the test.

Replacement of the in vivo neutralisation test for efficacy demonstration of tetanus vaccines ad us. vet.

Science.gov (United States)

Rosskopf, Ute; Noeske, Kerstin; Werner, Esther

2005-01-01

antibody responses were recorded. The in vitro DAE method seems to be suitable to replace the mouse neutralisation test used for the detection of tetanus antitoxin in sera of target animal species. The comparison of some sera in the ELISA and the TNT showed good equivalence of results. Nevertheless, before an ELISA titre in horse and sheep sera indicating unambiguous protection against tetanus can be fixed, further comparative assays of low titre sera in the TNT and the DAE will have to be performed.

9 CFR 82.15 - Replacement birds and poultry.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Replacement birds and poultry. 82.15... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS EXOTIC NEWCASTLE DIS- EASE (END) AND CHLAMYDIOSIS Exotic Newcastle Disease (END) § 82.15 Replacement birds and poultry. Birds...

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.

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

[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.

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...

Testing of CFC replacement fluids for arc-induced toxic by-products

Energy Technology Data Exchange (ETDEWEB)

Cravey, W.R.; Goerz, D.A.; Hawley-Fedder, R.A.

1993-06-01

The authors have developed a unique test-stand for quantifying the generation of perfluoroisobutylene (PFIB) in chlorofluorocarbon (CFC) replacement fluids when they are subjected to high electrical stress/breakdown environments. PFIB is an extremely toxic gas with a threshold limit value of 10 ppbv as set by the American Conference of Governmental Industrial Hygienists. They have tested several new fluids from various manufacturers for their potential to generate PFIB. Their goal is to determine breakdown characteristics and quantify toxic by-products of these replacement fluids to determine a safe, usable alternative for present CFC`s.

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).

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.

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.

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.

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.

Innovative Solid State Lighting Replacements for Industrial and Test Facility Locations, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — The proposed innovation is the replacement of existing test stand and parking lot fixtures with current SSL LED technology. The replacement fixtures will reduce...

The role of inertial containment fusion in replacing nuclear tests

Energy Technology Data Exchange (ETDEWEB)

Schaper, Annette [Hessische Stiftung Friedens- und Konfliktforschung, Frankfurt am Main (Germany)

2008-07-01

Nuclear weapon physicists need to understand the process of a nuclear explosion, and their major experimental tools had been nuclear tests. Since a couple of years, the established nuclear weapon states observe a testing moratorium. Nevertheless, they still want to keep their nuclear arsenals, and consequently to ensure the reliability, safety, and security of their nuclear warheads. For this purpose, they use experimental tools that replace nuclear tests, among them ICF. ICF plays a central role in the so-called ''stockpile stewardship program'' that the U.S. has implemented when it participated in the negotiations on a Comprehensive Test Ban Treaty. Several questions arise and are discussed in the presentation: Does ICF allow to simulate the extreme conditions of a nuclear explosion? Which are the functions of nuclear testing that ICF can replace and which are beyond its capabilities? Would ICF be a useful tool for the design of new nuclear warheads? Why are so huge sums spent on ICF in a military context although the usefulness for nuclear weapons seems rather limited?.

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

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.

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.

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...

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...

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.

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.

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...

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.

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.

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.

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

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.

The influence of animal fat replacement with vegetable oils on sensorial perception of meat emulsified products

Directory of Open Access Journals (Sweden)

Cristian TUDOSE

2014-12-01

Full Text Available For the purpose of the present study, in an emulsified meat product the pork backfat was replaced with a vegetable oil pre-emulsion and its effect on quality attributes were investigated. In order to do so, a classic and a new meat products were manufactured. Extra virgin olive oil and palm oil pre-emulsion were added instead of animal fat in the new product. Texture and physiochemical properties were analyzed by instrumental measurements. It was observed that during storage moisture and pH decreased. Using vegetable oils determined substantial increase of TBA values. Texture was influenced mainly by storage time for both products, while replacement of pork backfat with vegetable oil pre-emulsion had no influence on sample firmness. The sensory properties of meat products were evaluated by a group of trained panelists using an analitycal sensory evaluation technique. Overall the new product presented good acceptability which recommends it like a new healthier meat product.

Utilization of fermented animal by-product blend as fishmeal replacer in the diet of Labeo rohita

Directory of Open Access Journals (Sweden)

Ayan Samaddar

2015-05-01

Full Text Available Experiments were carried out to evaluate efficiency of Labeo rohita to utilize fermented animal protein blend containing slaughter house blood (SHB and fish offal (FO as dietary fishmeal (FM replacer. Five isoproteic (30%, isolipidic (8% and isoenergitic (15.00 kJ g−1 feed were prepared by replacing 0 (T1, 25 (T2, 50 (T3, 75 (T4 and 100% (T5 FM protein with the fermented blend and fingerlings of L. rohita (mean weight 2.07 g were fed each of these feed in triplicate groups. The results showed that apparent digestibility coefficient (ADC of protein significantly increased in T3–T5, while ADC of lipid and total amino acid absorption rate increased in T2–T5 as compared to control (T1. Among the essential amino acids (EAA, arginine exhibited maximum absorption followed by histidine, phenylalanine, valine and lysine while aspartic acid showed a high absorption among the non-essential amino acids (NAA. Fish fed up to 75% of replacement level (T4 did not show any significant difference (P < 0.05 in weight gain (WG, specific growth rate (SGR, feed conversion ratio (FCR, protein efficiency ratio (PER and apparent net protein utilization (ANPU between the dietary groups (T1–T4. But FCR was increased and other growth parameters were significantly reduced in 100% replacement group (T5, while body muscle protein was significantly reduced in both T4 and T5. Deposition of EAA (except histidine and methionine in T4 and NAA (except cystine in both T4 and T5 in the muscle of fish were also significantly reduced as compared to control (T1. Multi-objective optimization programming technique was used to determine FM replacement level that optimized all the growth parameters (WG, SGR, FCR and PER simultaneously. By using Global Criterion method, it was obtained that 21.11% replacement of FM by the fermented blend was ideal for optimum growth of L. rohita.

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…

Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

International Nuclear Information System (INIS)

Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

1986-01-01

When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. An indirect effect of T via early stimulation of TSH may be partly responsible for the high incidence of irradiation-induced thyroid tumors in rats

Effects of replacing fishmeal with animal by-products meal supplementation in diets on the growth and nutrient utilization of mangrove red snapper

Science.gov (United States)

Jamil, Khalid; Abbas, Ghulam; Akhtar, Rukhsana; Lin, Hong; Li, Zhenxing

2007-07-01

A feeding trial was conducted for 75 d to evaluate the nutritive value of a mixture of animal by-products (MAB) as a possible protein source in diets for juvenile mangrove red snapper, Lutjanus argentimaculatus (mean initial body weight, 30 g). Fish were fed one of five isonitrogenous diets (40% crude protein) replacing 0, 25% (MAB25), 50% (MAB50), 75% (MAB75) and 100% (MAB100) of fish meal protein with similar percentages of MAB. The MAB consisted of 25% cow liver meal, 20% leather meal, 20% meat and bone meal, 15% blood meal, 10% APC (poultry feather meal), 8% poultry manure dried, 1.5% choline and 0.5% chromic oxide. After 75 d of feeding, fish fed with diets MAB50, MAB75 and MAB100 exhibited significantly lower growth performance than that of fish fed with control and MAB25 diets. The optimum level of MAB was estimated to be 23%. Replacement of fish meal by MAB23% showed the following performance: maximum weight gain, 510%; SGR, 2.39% and FCE, 2.83%. The MAB substitution up to 75% of fish meal protein in diets did not show differences in apparent protein digestibility (83.6% for MAB25, 79.2% for MAB50, 78.7% for MAB75) compared with control (83.4%), whereas in MAB100 group digestibility (65.3%) was significantly lower than in other groups. The apparent phosphorus absorption of test diet groups was significantly higher (37.1% for MAB25, 28.5% for MAB50, 55.6% for MAB75 and 54.5% for MAB100) than that of control (11.2%). The levels of protein and ash in the whole body, carcass and viscera increased as MAB substitution in diets increased, whereas lipids and moisture remained consistent among all treatment groups. These results showed that approximately 23% of fish meal protein could be replaced by a mixture of animal by-products for juvenile snapper growing from 30 g to 167 g in 75 d without compromising growth performance and feed efficiency.

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...

EXPERIMENTAL RESEARCH OF REGENERATIVE FEATURES IN BONE TISSUES AROUND IMPLANTS AFTER ONE-STAGE BILATERAL TOTAL HIP REPLACEMENT

Directory of Open Access Journals (Sweden)

V. M. Mashkov

2012-01-01

Full Text Available Objective: to research the specific features of regenerative processes of bone tissue around implants after one-stage bilateral total hip replacement in experiment. Material and methods: 27 total hip replacement operations have been performed in 18 rabbits of breed "chinchilla" to which bipolar femoral endoprosthesis made of titanic alloy PT-38, one type-size, with friction pair metal-on-metal and neck-shaft angle 165 degrees have been implanted: total unilateral hip replacement operations have been performed in 9 animals (control group, one-stage bilateral total hip replacement operations have been performed in 9 animals (experimental group. During research they have been on radiological and clinical checking-up. After the experiment the animals had histological tests of the tissues around endoprosthesis components. Results and conclusions: After one-stage bilateral total hip replacement in early terms of research more expressed changes of bone tissue in the form of its thinning and decompaction were found around implants. One-stage bilateral total hip replacement did not essentially influence on the speed of osteogenesis around endoprothesis components in comparison with unilateral total hip replacement, so in late terms of observation in both groups the fixing of endoprothesis components did not differ.

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

OpenAIRE

Kim, Seung Won; Kim, Bae-Hwan

2016-01-01

Animal testing was used traditionally in the cosmetics industry to confirm product safety, but has begun to be banned; alternative methods to replace animal experiments are either in development, or are being validated, worldwide. Research data related to test substances are critical for developing novel alternative tests. Moreover, safety information on cosmetic materials has neither been collected in a database nor shared among researchers. Therefore, it is imperative to build and share a d...

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.

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.

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.

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...

78 FR 76059 - New Animal Drugs for Use in Animal Feeds; Bambermycins

Science.gov (United States)

2013-12-16

.... FDA-2012-N-0002] New Animal Drugs for Use in Animal Feeds; Bambermycins AGENCY: Food and Drug... amending the animal drug regulations to remove dairy replacement heifers from the pasture cattle class for....gov . SUPPLEMENTARY INFORMATION: FDA has noticed that the animal drug regulations for bambermycins...

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

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.

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

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...

Animal-free toxicology

DEFF Research Database (Denmark)

Knudsen, Lisbeth E

2013-01-01

Human data on exposure and adverse effects are the most appropriate for human risk assessment, and modern toxicology focuses on human pathway analysis and the development of human biomarkers. Human biomonitoring and human placental transport studies provide necessary information for human risk...... assessment, in accordance with the legislation on chemical, medicine and food safety. Toxicology studies based on human mechanistic and exposure information can replace animal studies. These animal-free approaches can be further supplemented by new in silico methods and chemical structure......-activity relationships. The inclusion of replacement expertise in the international Three Rs centres, the ongoing exploration of alternatives to animal research, and the improvement of conditions for research animals, all imply the beginning of a paradigm shift in toxicology research toward the use of human data....

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

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 .

[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.

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.

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

The teratology testing of cosmetics.

Science.gov (United States)

Spézia, François; Barrow, Paul C

2013-01-01

In Europe, the developmental toxicity testing (including teratogenicity) of new cosmetic ingredients is performed according to the Cosmetics Directive 76/768/EEC: only alternatives leading to full replacement of animal experiments should be used. This chapter presents the three scientifically validated animal alternative methods for the assessment of embryotoxicity: the embryonic stem cell test (EST), the micromass (MM) assay, and the whole embryo culture (WEC) assay.

A new machine for continuous renal replacement therapy: from development to clinical testing.

Science.gov (United States)

Ricci, Zaccaria; Salvatori, Gabriella; Bonello, Monica; Ratanarat, Ranistha; Andrikos, Emilios; Dan, Maurizio; Piccinni, Pasquale; Ronco, Claudio

2005-01-01

A new continuous renal replacement therapy machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called Prismaflex and it is the natural evolution of the PRISMA machine that has been utilized worldwide for continuous renal replacement therapy in the last 10 years. The authors performed a preliminary alpha-trial to establish the usability, flexibility and reliability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities during 62 treatments. This article will describe our first experience with this new device and touch upon the historic and technologic background leading to its development.

The state of animal welfare in the context of refinement.

Science.gov (United States)

Zurlo, Joanne; Hutchinson, Eric

2014-01-01

The ultimate goal of the Three Rs is the full replacement of animals used in biomedical research and testing. However, replacement is unlikely to occur in the near future; therefore the scientific community as a whole must continue to devote considerable effort to ensure optimal animal welfare for the benefit of the science and the animals, i.e., the R of refinement. Laws governing the care and use of laboratory animals have recently been revised in Europe and the US and these place greater emphasis on promoting the well-being of the animals in addition to minimizing pain and distress. Social housing for social species is now the default condition, which can present a challenge in certain experimental settings and for certain species. The practice of positive reinforcement training of laboratory animals, particularly non-human primates, is gathering momentum but is not yet universally employed. Enhanced consideration of refinement extends to rodents, particularly mice, whose use is still increasing as more genetically modified models are generated. The wastage of extraneous mice and the method of their euthanasia are refinement issues that still need to be addressed. An international, concerted effort into defining the needs of laboratory animals is still necessary to improve the quality of the animal models used as well as their welfare.

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

[Recent developments on the European ban on animal experiments for cosmetics].

Science.gov (United States)

Ruhdel, I W

2001-01-01

For the second time the European Commission has postponed the sales ban on cosmetics products that have been developed and tested in animal experiments now until 2002. In the meantime the Commission wants to adopt the Seventh Amendment of the EU Cosmetics Directive. In its draft the Commission proposes to scrap the sales ban and replace it with an animal testing ban. This change would avoid possible conflicts with the WTO, however, from the animal welfare point of view would result in animal testing moving into third countries instead of avoiding them. This is because cosmetics products tested on animals outside the EU could be sold in the EU without any restrictions. As a consequence this measure would take the pressure from authorities and industry to further develop and adopt alternative methods. Other proposed measures are not acceptable from the animal welfare point of view, e.g. because they contradict Directive 86/609 and would result in a delay of the application of validated alternative methods. The Deutscher Tierschutzbund therefore still demands an immediate and complete sales ban in connection with an animal testing ban within the EU.

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.

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.

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…

78 FR 79299 - New Animal Drugs for Use in Animal Feeds; Bambermycins; Correction

Science.gov (United States)

2013-12-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 [Docket No. FDA-2013-N-0002] New Animal Drugs for Use in Animal Feeds; Bambermycins; Correction AGENCY: Food and... amended the animal drug regulations to remove dairy replacement heifers from the pasture cattle class for...

Vibration test of spherical shell structure and replacing method into mathematical model

International Nuclear Information System (INIS)

Takayanagi, M.; Suzuki, S.; Okamura, T.; Haas, E.E.; Krutzik, N.J.

1989-01-01

To verify the beam-type and oval-type vibratory characteristics of a spherical shell structure, two test specimens were made and vibration tests were carried out. Results of these tests are compared with results of detailed analyses using 3-D FEM and 2-D axisymmetric FEM models. The analytical results of overall vibratory characteristics are in good agreement with the test results, has been found that the effect of the attached mass should be considered in evaluating local vibration. The replacing method into equivalent beam model is proposed

Innovative Solid State Lighting Replacements for Industrial and Test Facility Locations, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The proposed effort will develop a solid-state LED replacement lamp for rocket engine test stand lighting and more general hazardous-location lighting. The LED...

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

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.

Appropriate statistical methods are required to assess diagnostic tests for replacement, add-on, and triage

NARCIS (Netherlands)

Hayen, Andrew; Macaskill, Petra; Irwig, Les; Bossuyt, Patrick

2010-01-01

To explain which measures of accuracy and which statistical methods should be used in studies to assess the value of a new binary test as a replacement test, an add-on test, or a triage test. Selection and explanation of statistical methods, illustrated with examples. Statistical methods for

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)

Cassava dreg as replacement of corn in goat kid diets.

Science.gov (United States)

Ferraz, Lucíola Vilarim; Guim, Adriana; Véras, Robson Magno Liberal; de Carvalho, Francisco Fernando Ramos; de Freitas, Marciela Thais Dino

2018-02-01

The effects of corn replacement by cassava dreg in diets of crossbred goat kids were evaluated. We tested the impacts of 0, 33, 66 and 100% replacement on intake, digestibility, feeding behaviour, performance and carcass characteristics. Thirty-six goat kids, aged between 4 and 5 months and with initial body weights of 17.61 ± 1.98 kg, were used in a completely randomised design. Analysis of regression revealed a negative linear effect on neutral detergent fibre (NDF) intake and a positive linear effect on non-fibrous carbohydrates (NFC) and hydrocyanic acids (HCN) intake. Cassava dreg use had a positive linear effect on organic matter digestibility and non-fibrous carbohydrates. Based on our results, cassava dreg use did not negatively impact animal performance, feeding behaviour and carcass characteristics, suggesting that it may replace corn up to 100% in the diets of confined goat kids.

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.

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.

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.

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

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

A mucosa-mimetic material for the mucoadhesion testing of thermogelling semi-solids.

Science.gov (United States)

da Silva, Jéssica Bassi; Khutoryanskiy, Vitaliy V; Bruschi, Marcos L; Cook, Michael T

2017-08-07

Mucosa-mimetic materials are synthetic substrates which aim to replace animal tissue in mucoadhesion experiments. One potential mucosa-mimetic material is a hydrogel comprised of N-acryloyl-d-glucosamine and 2-hydroxyethylmethacrylate, which has been investigated as a surrogate for animal mucosae in the mucoadhesion testing of tablets and solution formulations. This study aims to investigate the efficacy of this mucosa-mimetic material in the testing of thermogelling semi-solid formulations, which transition from solution to gel upon warming. Two methods for assessing mucoadhesion have been used; tensile testing and a flow-through system, which allow for investigation under dramatically different conditions. It was found that the mucosa-mimetic material was a good surrogate for buccal mucosa using both testing methods. This material may be used to replace animal tissue in these experiments, potentially reducing the number of laboratory animals used in studies of this type. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

[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.

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.

Evolution of high tooth replacement rates in sauropod dinosaurs.

Science.gov (United States)

D'Emic, Michael D; Whitlock, John A; Smith, Kathlyn M; Fisher, Daniel C; Wilson, Jeffrey A

2013-01-01

Tooth replacement rate can be calculated in extinct animals by counting incremental lines of deposition in tooth dentin. Calculating this rate in several taxa allows for the study of the evolution of tooth replacement rate. Sauropod dinosaurs, the largest terrestrial animals that ever evolved, exhibited a diversity of tooth sizes and shapes, but little is known about their tooth replacement rates. We present tooth replacement rate, formation time, crown volume, total dentition volume, and enamel thickness for two coexisting but distantly related and morphologically disparate sauropod dinosaurs Camarasaurus and Diplodocus. Individual tooth formation time was determined by counting daily incremental lines in dentin. Tooth replacement rate is calculated as the difference between the number of days recorded in successive replacement teeth. Each tooth family in Camarasaurus has a maximum of three replacement teeth, whereas each Diplodocus tooth family has up to five. Tooth formation times are about 1.7 times longer in Camarasaurus than in Diplodocus (315 vs. 185 days). Average tooth replacement rate in Camarasaurus is about one tooth every 62 days versus about one tooth every 35 days in Diplodocus. Despite slower tooth replacement rates in Camarasaurus, the volumetric rate of Camarasaurus tooth replacement is 10 times faster than in Diplodocus because of its substantially greater tooth volumes. A novel method to estimate replacement rate was developed and applied to several other sauropodomorphs that we were not able to thin section. Differences in tooth replacement rate among sauropodomorphs likely reflect disparate feeding strategies and/or food choices, which would have facilitated the coexistence of these gigantic herbivores in one ecosystem. Early neosauropods are characterized by high tooth replacement rates (despite their large tooth size), and derived titanosaurs and diplodocoids independently evolved the highest known tooth replacement rates among archosaurs.

Evolution of high tooth replacement rates in sauropod dinosaurs.

Directory of Open Access Journals (Sweden)

Michael D D'Emic

Full Text Available BACKGROUND: Tooth replacement rate can be calculated in extinct animals by counting incremental lines of deposition in tooth dentin. Calculating this rate in several taxa allows for the study of the evolution of tooth replacement rate. Sauropod dinosaurs, the largest terrestrial animals that ever evolved, exhibited a diversity of tooth sizes and shapes, but little is known about their tooth replacement rates. METHODOLOGY/PRINCIPAL FINDINGS: We present tooth replacement rate, formation time, crown volume, total dentition volume, and enamel thickness for two coexisting but distantly related and morphologically disparate sauropod dinosaurs Camarasaurus and Diplodocus. Individual tooth formation time was determined by counting daily incremental lines in dentin. Tooth replacement rate is calculated as the difference between the number of days recorded in successive replacement teeth. Each tooth family in Camarasaurus has a maximum of three replacement teeth, whereas each Diplodocus tooth family has up to five. Tooth formation times are about 1.7 times longer in Camarasaurus than in Diplodocus (315 vs. 185 days. Average tooth replacement rate in Camarasaurus is about one tooth every 62 days versus about one tooth every 35 days in Diplodocus. Despite slower tooth replacement rates in Camarasaurus, the volumetric rate of Camarasaurus tooth replacement is 10 times faster than in Diplodocus because of its substantially greater tooth volumes. A novel method to estimate replacement rate was developed and applied to several other sauropodomorphs that we were not able to thin section. CONCLUSIONS/SIGNIFICANCE: Differences in tooth replacement rate among sauropodomorphs likely reflect disparate feeding strategies and/or food choices, which would have facilitated the coexistence of these gigantic herbivores in one ecosystem. Early neosauropods are characterized by high tooth replacement rates (despite their large tooth size, and derived titanosaurs and

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.

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.

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

The Effect of Root Coating with Titanium on Prevention of Root Resorption in Avulsed Teeth: An Animal Study

Science.gov (United States)

Heydari, Azar; Tahmasbi, Soodeh; Badiee, Mohammadreza; Izadi, SeyedSadra; Mashhadi Abbas, Fatemeh; Mokhtari, Sepideh

2016-01-01

Introduction: Tooth avulsion is a real dental emergency. If immediate replantation is not performed, the avulsed tooth may be lost due to inflammatory or replacement resorption. This animal study aimed to evaluate the bone response to the titanium coating of the root surface as an artificial barrier, and prevention of resorption of avulsed teeth. Methods and Materials: This experimental study was conducted on four male dogs. The dogs were randomly divided into two groups for assessment at two and eight weeks. Four teeth were extracted in each animal. The root surfaces of the test group were coated with a titanium layer using the Electron Beam Deposition system. After 24 h, replantation of the teeth was performed. Two animals were sacrificed after two weeks and the remaining dogs were killed after eight weeks. The presence of inflammation, inflammatory resorption, replacement resorption, periodontal regeneration, periapical granuloma and ankylosis were evaluated through histological analyses. Results: Inflammatory root resorption was not present in any tooth except one tooth in the coated group after eight weeks. Replacement resorption was noted just in three of the non-coated teeth after two weeks and two teeth after eight weeks. The McNemar's test revealed that the frequency of replacement resorption in the non-coated group was significantly higher than the coated group (P=0.031). Conclusion: Based on the results of this study, it seems that coating the root surfaces of avulsed teeth with titanium may control the replacement root resorption. PMID:27790261

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. ...

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.

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...

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...

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.

Animal Models of Hemophilia and Related Bleeding Disorders

Science.gov (United States)

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

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.

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

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.

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.

How single nucleotide polymorphism chips will advance our knowledge of factors controlling puberty and aid in selecting replacement beef females

Science.gov (United States)

The promise of genomic selection is accurate prediction of animals' genetic potential from their genotypes. Simple DNA tests might replace low accuracy predictions for expensive or lowly heritable measures of puberty and fertility based on performance and pedigree. Knowing which DNA variants affec...

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 ...

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.

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.

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

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

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.

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

OpenAIRE

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

2017-01-01

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

Refining animal experiments: the first Brazilian regulation on animal experimentation.

Science.gov (United States)

de A e Tréz, Thales

2010-06-01

The very first law on animal experimentation has been approved recently in Brazil, and now is part of a set of the legal instruments that profile the Brazilian government's attitude toward the use of animals in experiments. Law 11794/08 establishes a new legal instrument that will guide new methods of conduct for ethics committees, researchers and representatives of animal protection societies. This comment aims to analyse critically the implications that this law brings to Brazilian reality. The link between it and the Russell and Burch's Three Rs concept is defined, and certain problems are identified. The conclusion is that the body of the law emphasises the refinement of animal experiments, but gives little importance to the principles of reduction and replacement.

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...

Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

DEFF Research Database (Denmark)

Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

2004-01-01

We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

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.

Safety evaluations under the proposed US Safe Cosmetics and Personal Care Products Act of 2013: animal use and cost estimates.

Science.gov (United States)

Knight, Jean; Rovida, Costanca

2014-01-01

The proposed Safe Cosmetics and Personal Care Products Act of 2013 calls for a new evaluation program for cosmetic ingredients in the US, with the new assessments initially dependent on expanded animal testing. This paper considers possible testing scenarios under the proposed Act and estimates the number of test animals and cost under each scenario. It focuses on the impact for the first 10 years of testing, the period of greatest impact on animals and costs. The analysis suggests the first 10 years of testing under the Act could evaluate, at most, about 50% of ingredients used in cosmetics. Testing during this period would cost about $ 1.7-$ 9 billion and 1-11.5 million animals. By test year 10, alternative, high-throughput test methods under development are expected to be available, replacing animal testing and allowing rapid evaluation of all ingredients. Given the high cost in dollars and animal lives of the first 10 years for only about half of ingredients, a better choice may be to accelerate development of high-throughput methods. This would allow evaluation of 100% of cosmetic ingredients before year 10 at lower cost and without animal testing.

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

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

Science.gov (United States)

Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

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

Can spectroscopy in combination with chemometrics replace minks in digestibility tests?

DEFF Research Database (Denmark)

Dahl, P.L.; Christensen, B.M.; Munck, L.

2000-01-01

One of the most relevant but expensive methods of assessing the quality of fish meal is the physiological digestibility test with minks. The purpose of this study was to determine whether spectroscopic and chemical analyses evaluated with chemometrics can replace minks in digestibility tests....... The spectroscopic methods used were the two complementary techniques of fluorescence emission and near-infrared reflectance. The investigation included 54 samples of high-quality fish meal ranging from 89.6 to 93.9 on the mink digestibility index. The investigation also included determination of seven quality...... parameters in the fish meal to substantiate the spectroscopic models on the mink digestibility. These quality parameters include the content of protein, oil, water, water-soluble protein, ash and the biogenic substance cadaverine as well as the titration value. The study demonstrates that the mink...

The era of 3Rs implementation in developmental and reproductive toxicity (DART) testing: Current overview and future perspectives.

Science.gov (United States)

Beekhuijzen, Manon

2017-09-01

Since adoption of the first globally implemented guidelines for developmental and reproductive toxicity (DART) testing for pharmaceuticals, industrial chemicals and agrochemicals, many years passed without major updates. However in recent years, significant changes in these guidelines have been made or are being implemented. These changes have been guided by the ethical drive to reduce, refine and replace (3R) animal testing, as well as the addition of endocrine disruptor relevant endpoints. Recent applied improvements have focused on reduction and refinement. Ongoing scientific and technical innovations will provide the means for replacement of animal testing in the future and will improve predictivity in humans. The aim of this review is to provide an overview of ongoing global DART endeavors in respect to the 3Rs, with an outlook towards future advances in DART testing aspiring to reduce animal testing to a minimum and the supreme ambition towards animal-free hazard and risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

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....

Efficient immunoglobulin gene disruption and targeted replacement in rabbit using zinc finger nucleases.

Directory of Open Access Journals (Sweden)

Tatiana Flisikowska

Full Text Available Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM(+ and IgG(+ B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields.

Respondent-Driven Sampling – Testing Assumptions: Sampling with Replacement

Directory of Open Access Journals (Sweden)

Barash Vladimir D.

2016-03-01

Full Text Available Classical Respondent-Driven Sampling (RDS estimators are based on a Markov Process model in which sampling occurs with replacement. Given that respondents generally cannot be interviewed more than once, this assumption is counterfactual. We join recent work by Gile and Handcock in exploring the implications of the sampling-with-replacement assumption for bias of RDS estimators. We differ from previous studies in examining a wider range of sampling fractions and in using not only simulations but also formal proofs. One key finding is that RDS estimates are surprisingly stable even in the presence of substantial sampling fractions. Our analyses show that the sampling-with-replacement assumption is a minor contributor to bias for sampling fractions under 40%, and bias is negligible for the 20% or smaller sampling fractions typical of field applications of RDS.

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

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

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

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 ...

Complete replacement of fish meal by other animal protein sources on growth performance of Clarias gariepinus fingerlings

Directory of Open Access Journals (Sweden)

Arnauld S. M. Djissou

2016-10-01

Full Text Available Abstract To completely replace the fish meal by a mixture of earthworm and maggot meals, experimental diets were tested during 42 days on Clarias gariepinus fingerlings. Five isoproteic and isoenergetic diets (40 % crude protein and 17.9 ± 0.3 kJ g−1 including the control diet (D1 based on fish meal, were formulated. All these diets satisfied the essential amino acids requirements of C. gariepinus fingerlings. These diets were tested on triplicate groups of 50 fishes (initial body weight: 3 ± 0.1 g bred in tank (0.5 m3. The approximate ratios 2:5; 1:4; 1:12 and 0:1 between the earthworm meal and the maggot meal were used, respectively, to formulate four diets D2, D3, D4 and D5 without fish meal. After the feeding period, significant differences (P < 0.05 were observed on growth, feed utilization between control diet (D1 and test diets (D2–D5. Fish fed earthworm- and maggot-based diets were grown better than those fed the control diet. Survival and feed utilization were not significantly affected by the ratio between earthworm meal and maggot meal in the test diets. Lipid content was higher in carcass and fillet of fishes fed earthworm- and maggot meals-based diets than that of those fed fish meal-based diet. This study indicates that when the ratio 2:5 between the earthworm meal and the maggot meal is used to entirely replace fish meal and the ratio lysine/arginine of the diet is inferior to 1, the growth performances and feed utilization of Clarias gariepinus fingerlings are improved.

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

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

Design and adjustment on test bed of replacing subassembly machine control system for China experimental fast reactor

International Nuclear Information System (INIS)

Dong Shengguo; Ma Hongsheng; Zhao Lixia

2008-01-01

The present research concerns in the design and adjustment of replacing sub- assembly machine control system of China Experimental Fast Reactor. The design of replacing subassembly machine control system adopts some electric equipments, such as programmable controllers, digital DC drivers. The designed control system was adjusted on the test bed. The results indicate that the operation of the control system is steady and reliable, and designed control system can meet the needs of the design specification. (authors)

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.

Can vaccinia virus be replaced by MVA virus for testing virucidal activity of chemical disinfectants?

Directory of Open Access Journals (Sweden)

Rapp Ingrid

2010-06-01

Full Text Available Abstract Background Vaccinia virus strain Lister Elstree (VACV is a test virus in the DVV/RKI guidelines as representative of the stable enveloped viruses. Since the potential risk of laboratory-acquired infections with VACV persists and since the adverse effects of vaccination with VACV are described, the replacement of VACV by the modified vaccinia Ankara strain (MVA was studied by testing the activity of different chemical biocides in three German laboratories. Methods The inactivating properties of different chemical biocides (peracetic acid, aldehydes and alcohols were tested in a quantitative suspension test according to the DVV/RKI guideline. All tests were performed with a protein load of 10% fetal calf serum with both viruses in parallel using different concentrations and contact times. Residual virus was determined by endpoint dilution method. Results The chemical biocides exhibited similar virucidal activity against VACV and MVA. In three cases intra-laboratory differences were determined between VACV and MVA - 40% (v/v ethanol and 30% (v/v isopropanol are more active against MVA, whereas MVA seems more stable than VACV when testing with 0.05% glutardialdehyde. Test accuracy across the three participating laboratories was high. Remarkably inter-laboratory differences in the reduction factor were only observed in two cases. Conclusions Our data provide valuable information for the replacement of VACV by MVA for testing chemical biocides and disinfectants. Because MVA does not replicate in humans this would eliminate the potential risk of inadvertent inoculation with vaccinia virus and disease in non-vaccinated laboratory workers.

Development and validation of the small punch test for UHMWPE used in total joint replacements

Energy Technology Data Exchange (ETDEWEB)

Edidin, A.A. [Drexel Univ., Philadelphia, PA (United States). School of Biomedical Engineering, Science and Health Systems; Howmedica Osteonics Corp., Allendale, NJ (United States); Kurtz, S.M. [Drexel Univ., Philadelphia, PA (United States). School of Biomedical Engineering, Science and Health Systems; Thomas Jefferson Univ., Philadelphia, PA (United States). Dept. of Orthopaedic Surgery; Exponent, Inc., Philadelphia, PA (United States)

2001-07-01

In order to better understand the mechanical effects of oxidative degradation, improved oxidative stability and crosslinking on ultra-high molecular weight polyethylene (UHMWPE), a unique miniature specimen mechanical testing technique, known as the small punch test, was developed for evaluating total joint replacement components. The small punch test involves deforming a disk-shaped specimen having a thickness of 0.5 mm and a diameter of 6.4 mm. In addition to its small specimen size, the small punch test differs from conventional testing in that deformation of the UHMWPE specimen occurs under multiaxial loading conditions. Using the small punch test, we have traced the evolution of mechanical behavior in UHMWPE after natural (shelf-storage) and accelerated aging conditions. In addition, we have determined relationships between the mechanical behavior of UHMWPE and the biologically relevant wear debris volume generated in total hip replacements. The small punch test has also been used to investigate the effects of radiation crosslinking which has been shown to improve the wear performance in an in vitro hip simulator. However, the crosslinking and subsequent thermal processes used to improve the wear behavior may compromise the native mechanical behavior by changing the ductility and toughness of the UHMWPE bearing. The primary objective of this study was to investigate which tradeoffs exist related to the mechanical behavior associated with various clinically available types of highly crosslinked and thermally treated UHMWPE. We also review the development and validation of the small punch disk bend test and highlight its application to problems of clinical relevance in both hip and knee arthroplasty. (orig.)

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.

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

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

REPLACEMENT IN RABBIT HERDS: A REVIEW

Directory of Open Access Journals (Sweden)

Ibrahim F.M. Marai

2010-08-01

Full Text Available Doe rabbit's replacement constitutes the annual renewal rate of new breeders that must be incorporated into the production stock. Criterion for culling non-productive animals differs significantly among fryer production colonies, foundation stocks and a colony with continuous enzootic disease or continuous malnourishment. In commercial rabbit production, good management improves the health and productivity of the entire herd, by reducing the all-time high replacement rates and improving economic viability. In the present article, a comprehensive review of numerous experiences in the rabbit production field of different countries, was presented. Basic recommendations for professional breeders were highlighted, covering critical issues such as the need for continuously upgrading the health status of the colony, the positive effect of   genetic selection and the nutritional conditioning and special treatment of young does being groomed as future replacements.

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

Science.gov (United States)

Pasupuleti, Mohan Kumar; Molahally, Subramanya Shetty; Salwaji, Supraja

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Mohan Kumar Pasupuleti

2016-01-01

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

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

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.

Is animal experimentation fundamental?

Science.gov (United States)

d'Acampora, Armando José; Rossi, Lucas Félix; Ely, Jorge Bins; de Vasconcellos, Zulmar Acciolli

2009-01-01

The understanding about the utilization of experimental animals in scientific research and in teaching is many times a complex issue. Special attention needs to be paid to attain the understanding by the general public of the importance of animal experimentation in experimental research and in undergraduate medical teaching. Experimental teaching and research based on the availability of animals for experimentation is important and necessary for the personal and scientific development of the physician-to-be. The technological arsenal which intends to mimic experimentation animals and thus fully replace their use many times does not prove to be compatible with the reality of the living animal. The purpose of this paper is to discuss aspects concerning this topic, bringing up an issue which is complex and likely to arouse in-depth reflections.

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.

Experimental animal modelling for TB vaccine development

Directory of Open Access Journals (Sweden)

Pere-Joan Cardona

2017-03-01

Full Text Available Research for a novel vaccine to prevent tuberculosis is an urgent medical need. The current vaccine, BCG, has demonstrated a non-homogenous efficacy in humans, but still is the gold standard to be improved upon. In general, the main indicator for testing the potency of new candidates in animal models is the reduction of the bacillary load in the lungs at the acute phase of the infection. Usually, this reduction is similar to that induced by BCG, although in some cases a weak but significant improvement can be detected, but none of candidates are able to prevent establishment of infection. The main characteristics of several laboratory animals are reviewed, reflecting that none are able to simulate the whole characteristics of human tuberculosis. As, so far, no surrogate of protection has been found, it is important to test new candidates in several models in order to generate convincing evidence of efficacy that might be better than that of BCG in humans. It is also important to investigate the use of “in silico” and “ex vivo” models to better understand experimental data and also to try to replace, or at least reduce and refine experimental models in animals.

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…

Guiding principles for the implementation of non-animal safety assessment approaches for cosmetics: skin sensitisation.

Science.gov (United States)

Goebel, Carsten; Aeby, Pierre; Ade, Nadège; Alépée, Nathalie; Aptula, Aynur; Araki, Daisuke; Dufour, Eric; Gilmour, Nicola; Hibatallah, Jalila; Keller, Detlef; Kern, Petra; Kirst, Annette; Marrec-Fairley, Monique; Maxwell, Gavin; Rowland, Joanna; Safford, Bob; Schellauf, Florian; Schepky, Andreas; Seaman, Chris; Teichert, Thomas; Tessier, Nicolas; Teissier, Silvia; Weltzien, Hans Ulrich; Winkler, Petra; Scheel, Julia

2012-06-01

Characterisation of skin sensitisation potential is a key endpoint for the safety assessment of cosmetic ingredients especially when significant dermal exposure to an ingredient is expected. At present the mouse local lymph node assay (LLNA) remains the 'gold standard' test method for this purpose however non-animal test methods are under development that aim to replace the need for new animal test data. COLIPA (the European Cosmetics Association) funds an extensive programme of skin sensitisation research, method development and method evaluation and helped coordinate the early evaluation of the three test methods currently undergoing pre-validation. In May 2010, a COLIPA scientific meeting was held to analyse to what extent skin sensitisation safety assessments for cosmetic ingredients can be made in the absence of animal data. In order to propose guiding principles for the application and further development of non-animal safety assessment strategies it was evaluated how and when non-animal test methods, predictions based on physico-chemical properties (including in silico tools), threshold concepts and weight-of-evidence based hazard characterisation could be used to enable safety decisions. Generation and assessment of potency information from alternative tools which at present is predominantly derived from the LLNA is considered the future key research area. Copyright © 2012 Elsevier Inc. All rights reserved.

Working in partnership to advance the 3Rs in toxicity testing

International Nuclear Information System (INIS)

Holmes, Anthony M.; Creton, Stuart; Chapman, Kathryn

2010-01-01

Toxicological assessment of pharmaceutical and non-pharmaceutical chemicals is a regulatory requirement to ensure all compounds likely to be exposed to humans or the environment are safe. These studies rely on the use of large numbers of animals and involve a number of assumptions and extrapolations that remain controversial in assuring consumer safety. The UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has taken a collaborative approach to identify opportunities for implementation of the 3Rs principles (Replacement, Reduction and Refinement) to drive innovation and support animal welfare in toxicity testing. This review highlights the mechanisms by which the NC3Rs is working with the pharmaceutical and chemical industries and regulatory authorities to achieve these goals.

Acceptance test procedure for SY Tank Farm replacement exhauster unit

Energy Technology Data Exchange (ETDEWEB)

Becken, G.W.

1994-12-16

The proper functioning of a new 241-SY Tank Farm replacement exhauster will be acceptance tested, to establish operability and to provide an operational baseline for the equipment. During this test, a verification of all of the alarm and control circuits associated with the exhaust, which provide operating controls and/or signals to local and remote alarm/annunciator panels, shall be performed. Test signals for sensors that provide alarms, warnings, and/or interlocks will be applied to verify that alarm, warning, and interlock setpoints are correct. Alarm and warning lights, controls, and local and remote readouts for the exhauster will be verified to be adequate for proper operation of the exhauster. Testing per this procedure shall be conducted in two phases. The first phase of testing, to verify alarm, warning, and interlock setpoints primarily, will be performed in the MO-566 Fab Shop. The second phase of testing, to verify proper operation and acceptable interface with other tank farm systems, will be conducted after the exhauster and all associated support and monitoring equipment have been installed in the SY Tank Farm. The exhauster, which is mounted on a skid and which will eventually be located in the SY tank farm, receives input signals from a variety of sensors mounted on the skid and associated equipment. These sensors provide information such as: exhauster system inlet vacuum pressure; prefilter and HEPA filter differential pressures; exhaust stack sampler status; exhaust fan status; system status (running/shut down); and radiation monitoring systems status. The output of these sensors is transmitted to the exhauster annunciator panel where the signals are displayed and monitored for out-of-specification conditions.

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.

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

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

Optimization of station battery replacement

International Nuclear Information System (INIS)

Jancauskas, J.R.; Shook, D.A.

1994-01-01

During a loss of ac power at a nuclear generating station (including diesel generators), batteries provide the source of power which is required to operate safety-related components. Because traditional lead-acid batteries have a qualified life of 20 years, the batteries must be replaced a minimum of once during a station's lifetime, twice if license extension is pursued, and more often depending on actual in-service dates and the results of surveillance tests. Replacement of batteries often occurs prior to 20 years as a result of systems changes caused by factors such as Station Blackout Regulations, control system upgrades, incremental load growth, and changes in the operating times of existing equipment. Many of these replacement decisions are based on the predictive capabilities of manual design basis calculations. The inherent conservatism of manual calculations may result in battery replacements occurring before actually required. Computerized analysis of batteries can aid in optimizing the timing of replacements as well as in interpreting service test data. Computerized analysis also provides large benefits in maintaining the as-configured load profile and corresponding design margins, while also providing the capability of quickly analyze proposed modifications and response to internal and external audits

Animal experimentation in forensic sciences: How far have we come?

Science.gov (United States)

Cattaneo, C; Maderna, E; Rendinelli, A; Gibelli, D

2015-09-01

In the third millennium where ethical, ethological and cultural evolution seem to be leading more and more towards an inter-species society, the issue of animal experimentation is a moral dilemma. Speaking from a self-interested human perspective, avoiding all animal testing where human disease and therapy are concerned may be very difficult or even impossible; such testing may not be so easily justifiable when suffering-or killing-of non human animals is inflicted for forensic research. In order to verify how forensic scientists are evolving in this ethical issue, we undertook a systematic review of the current literature. We investigated the frequency of animal experimentation in forensic studies in the past 15 years and trends in publication in the main forensic science journals. Types of species, lesions inflicted, manner of sedation or anesthesia and euthanasia were examined in a total of 404 articles reviewed, among which 279 (69.1%) concerned studies involving animals sacrificed exclusively for the sake of the experiment. Killing still frequently includes painful methods such as blunt trauma, electrocution, mechanical asphyxia, hypothermia, and even exsanguination; of all these animals, apparently only 60.8% were anesthetized. The most recent call for a severe reduction if not a total halt to the use of animals in forensic sciences was made by Bernard Knight in 1992. In fact the principle of reduction and replacement, frequently respected in clinical research, must be considered the basis for forensic science research needing animals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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

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....

Tracheal replacement by autogenous aorta.

Science.gov (United States)

Anoosh, Farhad; Hodjati, Hossain; Dehghani, Seifollah; Tanideh, Nader; Kumar, Perikala V

2009-06-09

Tracheal defects may occur after trauma or prolonged intubation. Resection of tracheal tumors also poses a major challenge for substitution. In an effort to solve this problem, different techniques have been tried with little success. We report on a new animal model which showed acceptable results with fewer complications. We replaced 5 cm of cervical trachea in 10 dogs with harvested infra-renal aorta and repaired the aortic defect with Dacron graft. Necropsy of the grafted aorta and anastomotic site revealed well healed anastomosis in all animals together with ciliated columnar epithelium coverage of grafted aorta and neovascularization of aortic wall. Aortic graft is preferable to other substitutes because of less antigenicity, less vascularity, and no mucous secretions or peristalsis.

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

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

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

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

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.

Gaps in US Animal Welfare Law for Laboratory Animals: Perspectives From an Animal Law Attorney.

Science.gov (United States)

Frasch, Pamela D

2016-05-01

The use of animals in biomedical, toxicological, and basic research has been common practice, and a tool for scientists and researchers, for many years. And yet, serious conflict continues to exist between those who believe that the use of animals in research will yield scientific results that benefit humans and those who believe such practices are unethical regardless of use or outcome. High-profile undercover cases have further raised public awareness and have put the entire industry under pressure to be transparent, accountable, and aggressive in its adoption of reduction, refinement, and replacement (3R) principles. Many animal law attorneys are deeply frustrated by what they see as weak US laws that are unevenly enforced, especially when compared with legal advances in other countries and regions. This article (1) explores those gaps in US animal welfare laws with an emphasis on the Animal Welfare Act, (2) argues in favor of stronger laws and rigorous enforcement, and (3) suggests steps to advance these goals. These steps include (1) expanding the definition of "animal" in the Animal Welfare Act (AWA), (2) improving and expanding minimum care requirements in USDA regulations, (3) instituting mandatory reporting requirements, improving Institutional Animal Care and Use Committees, and allowing easier accessibility to laboratory reports and plans, (4) adding a citizen suit provision to the AWA, and (5) continuing education about the emotional and social capacities of animals and a stronger commitment to 3R principles. © The Author 2017. 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.

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....

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

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.

78 FR 15753 - Maintenance, Testing, and Replacement of Vented Lead-Acid Storage Batteries for Nuclear Power Plants

Science.gov (United States)

2013-03-12

...-Acid Storage Batteries for Nuclear Power Plants AGENCY: Nuclear Regulatory Commission. ACTION: Draft...-Acid Storage Batteries for Nuclear Power Plants.'' The draft guide describes methods that the NRC staff..., testing, and replacement of vented lead-acid storage batteries in nuclear power plants. DATES: Submit...

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

Acceptance test for 900 MWe PWR unit replacement steam generators; Essai de reception des generateurs de vapeur de remplacement des tranches REP 900

Energy Technology Data Exchange (ETDEWEB)

Gourguechon, B.

1993-12-31

During the first half of 1994, the Gravelines 1 steam generators will be replaced (SG replacement procedure). The new SG`s differ from the former components notably by the alloy used for the tube bundle, in this case, the high chromium content Inconel 690. So, from this standpoint, they are to be considered as PWR 900 replacement SG first models and their thermal efficiency has consequently to be assessed. This will provide an opportunity of ensuring that the performance of the components delivered is in compliance with requirements and of making the necessary provisions if significant deviations are observed. The EFMT branch, which has been in charge of the instrumentation and acceptance of the different SG first models since the first PWR plants were commissioned, will be responsible for the acceptance tests and the ultimate validation of a performance assessment procedure applicable to the future replacement steam generators. The methods and tests proposed for SG expert appraisal are based on consideration of the importance of primary measurement quality for satisfactory SG assessment and of the new test facilities with which the 900 and 1 300 PWR plants are gradually being equipped. These facilities provide an on-site computer environment for tests compatible with the tools (PATTERN, etc.) used at EFMT and in other departments. This test is the first of this kind performed by EFMT and the test facility of a nuclear power plant. (author). 6 figs.

The replacement of fishmeal by plant proteins in piglet production

Directory of Open Access Journals (Sweden)

G. Martelli

2010-01-01

Full Text Available According to EC Commission Decision 9/2001 on BSE protection (OJEC, 2001, feedstuffs containing fishmeal can be produced only in establishments manufacturing animal feed which do not prepare feedstuffs for ruminant animals and which are authorised for this purpose by the competent authority. This fact, leading to a reduction of the productive capacity of small establishments, and the increasing aversion of consumers towards the use of animal protein in feedstuffs justify the studies about the possibility of excluding fishmeal from young animal formulations. The aim of the present work was to evaluate the effect of the total replacement of fishmeal by some vegetable protein sources in piglet diets.

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

Tracheal replacement by autogenous aorta

Directory of Open Access Journals (Sweden)

Anoosh Farhad

2009-06-01

Full Text Available Abstract Background Tracheal defects may occur after trauma or prolonged intubation. Resection of tracheal tumors also poses a major challenge for substitution. In an effort to solve this problem, different techniques have been tried with little success. We report on a new animal model which showed acceptable results with fewer complications. Methods We replaced 5 cm of cervical trachea in 10 dogs with harvested infra-renal aorta and repaired the aortic defect with Dacron graft. Results Necropsy of the grafted aorta and anastomotic site revealed well healed anastomosis in all animals together with ciliated columnar epithelium coverage of grafted aorta and neovascularization of aortic wall. Conclusion Aortic graft is preferable to other substitutes because of less antigenicity, less vascularity, and no mucous secretions or peristalsis

A replaceable reflective film for solar concentrators

Energy Technology Data Exchange (ETDEWEB)

1991-09-01

The 3M Company manufactures a silvered acrylic film called ECP-305 that is regarded as the preferred reflective film for use on stretched-membrane heliostats. However, ECP-305 will degrade in time, due to both corrosion of the silver layer and delamination at the film's silver-to-acrylic interface, and will eventually need to be replaced. 3M uses a very aggressive adhesive on this film, and once it is laminated, replacement is very difficult. The purpose of this investigation was the development of a replaceable reflector, a reflective film that can be easily removed and replaced. A replaceable reflector was successfully configured by laminating ECP-305 to the top surface of a smooth, dimensionally stable polymer film, with a removable adhesive applied to the underside of the polymer film. Several stages of screening and testing led to the selection of a 0.010-inch thick polycarbonate (GE 8030) as the best polymer film and a medium tack tape (3M Y-9425) was selected as the best removable adhesive. To demonstrate the feasibility of the replaceable reflector concept and to provide a real-time field test, the chosen construction was successfully applied to the 50-m{sup 2} SKI heliostat at the Central Receiver Test Facility at Sandia National Laboratories in Albuquerque. 4 refs., 13 figs., 7 tabs.

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

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.

The Three Rs of Animal Research: What they Mean for the Institutional Animal Care and Use Committee and Why.

Science.gov (United States)

Curzer, Howard J; Perry, Gad; Wallace, Mark C; Perry, Dan

2016-04-01

The Institutional Animal Care and Use Committee (IACUC) is entrusted with assessing the ethics of proposed projects prior to approval of animal research. The role of the IACUC is detailed in legislation and binding rules, which are in turn inspired by the Three Rs: the principles of Replacement, Reduction, and Refinement. However, these principles are poorly defined. Although this provides the IACUC leeway in assessing a proposed project, it also affords little guidance. Our goal is to provide procedural and philosophical clarity to the IACUC without mandating a particular outcome. To do this, we analyze the underlying logic of the Three Rs and conclude that the Three Rs accord animals moral standing, though not necessarily "rights" in the philosophical sense. We suggest that the Rs are hierarchical, such that Replacement, which can totally eliminate harm, should be considered prior to Reduction, which decreases the number of animals harmed, with Refinement being considered last. We also identify the need for a hitherto implicit fourth R: Reject, which allows the IACUC to refuse permission for a project which does not promise sufficient benefit to offset the pain and distress likely to be caused by the proposed research.

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...

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

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.

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....

Can experiments on animals constitute a criminal offence of cruelty to animals?

Directory of Open Access Journals (Sweden)

Ristivojevic Branislav

2014-01-01

Full Text Available The criminal offence “killing and torturing animals” under Article 269 of the Criminal Code says that it can be committed only “contrary to regulations”. The regulations governing the treatment of experimental animals are the Animal Welfare Law from 2009 and the Law on the Ratification of the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes amended by the Protocol of amendment to the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes from 2010. The first one imposes numerous obligations and introduces numerous prohibitions in the treatment of experimental animals, which at first sight make the possibilities of committing this criminal offence greater. The other law does not contain most of the prohibitions and restrictions that are included in the Animal Welfare Law. Thanks to a legal rule which says that a later law regulating the same subject replaces the former one (lex posterior derogate legi priori and the aforementioned unconstitutionality of many provisions of the Animal Welfare Law, researchers and teachers in Serbia are not in particular danger of criminal prosecution. [Projekat Ministarstva nauke Republike Srbije, br. 179079: Biomedicine, Environmental Protection and the Law

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.

High flux testing reactor Petten. Replacement of the reactor vessel and connected components. Overall report

International Nuclear Information System (INIS)

Chrysochoides, N.G.; Cundy, M.R.; Von der Hardt, P.; Husmann, K.; Swanenburg de Veye, R.J.; Tas, A.

1985-01-01

The project of replacing the HFR originated in 1974 when results of several research programmes confirmed severe neutron embrittlement of aluminium alloys suggesting a limited life of the existing facility. This report contains the detailed chronology of events concerning preparation and execution of the replacement. After a 14 months' outage the reactor resumed routine operation on 14th February, 1985. At the end of several years of planning and preparation the reconstruction proceded in the following steps: unloading of the old core, decay of short-lived radioactivity in December 1983, removal of the old tank and of its peripheral equipment in January-February 1984, segmentation and waste disposal of the removed components in March-April, decontamination of the pools, bottom penetration overhauling in May-June, installation of the new tank and other new components in July-September, testing and commissioning, including minor modifications in October-December, and, trials runs and start-up preparation in January-February 1985. The new HFR Petten features increased and improved experimental facilities. Among others the obsolete thermal columns was replaced by two high flux beam tubes. Moreover the new plant has been designed for future increases of reactor power and neutron fluxes. For the next three to four years the reactor has to cope with a large irradiation programme, claiming its capacity to nearly 100%

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.

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...

Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

Directory of Open Access Journals (Sweden)

Tai-Chi Lin

2017-01-01

Full Text Available Dysfunction and death of retinal pigment epithelium (RPE and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula. Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.

[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.

Cadmium plating replacements

Energy Technology Data Exchange (ETDEWEB)

Nelson, M.J.; Groshart, E.C.

1995-03-01

The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

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

Science.gov (United States)

Kim, Seung Won; Kim, Bae-Hwan

2016-07-01

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

Patellofemoral Joint Replacement and Nickel Allergy: An Unusual Presentation

Directory of Open Access Journals (Sweden)

Farhan Syed

2015-01-01

Full Text Available Metal allergy is an unusual complication of joint replacement that may cause aseptic loosening and necessitate joint revision surgery. We present the case of nickel allergy causing aseptic loosening following patellofemoral joint replacement (PFJR in a 54-year-old male. Joint revision surgery to a nickel-free total knee replacement was performed with good results. Our literature review shows that there is no evidence to guide the management of metal allergy in PFJR. The evidence from studies of total knee replacement is limited to retrospective case series and case reports and gives contradictory recommendations. The optimal management strategy for metal allergy in PFJR is not clear. We recommend allergy testing in patients with history of metal allergy and use of an allergen-free implant in those with positive tests. As there is no gold standard test to establish metal allergy, the choice of test should be guided by availability and recommendation from the local unit of dermatology and allergy testing. We recommend investigation for metal allergy in patients with implant loosening where other causes have been excluded.

BC Hydro's integrated approach on replacing underground feeder cables

Energy Technology Data Exchange (ETDEWEB)

Tarampi, D. [BC Hydro, Burnaby, BC (Canada)

2008-07-01

BC Hydro's integrated approach on replacing underground feeder cables was discussed. The feeder cables were all in ducts encased in concrete and splices were identified in concrete manholes. The feeder cables averaged 35 to 40 failures per year, with a large majority of failures occurring in manholes or near terminations. The age of the cables was not known. A graphical representation of a condition assessment was presented with reference to an electrical test, metallurgical test, hardness test, and dye penetrating test. Prioritization steps were also listed, including a condition index and replacement threshold. Steps in prioritizing the condition index included determining the insulation index based on electrical test results; determining the manhole condition based on metallurgical test results; determining the customer importance factor and feeder load factor; and calculating the overall condition index based on the indices. A process flowchart was also illustrated. A replacement strategy was then discussed and a cost comparison of two options was described. Option 1 was to replace only the unjacketed cables while option two involved selective replacement. tabs., figs.

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.

Animal Models in Forensic Science Research: Justified Use or Ethical Exploitation?

Science.gov (United States)

Mole, Calvin Gerald; Heyns, Marise

2018-05-01

A moral dilemma exists in biomedical research relating to the use of animal or human tissue when conducting scientific research. In human ethics, researchers need to justify why the use of humans is necessary should suitable models exist. Conversely, in animal ethics, a researcher must justify why research cannot be carried out on suitable alternatives. In the case of medical procedures or therapeutics testing, the use of animal models is often justified. However, in forensic research, the justification may be less evident, particularly when research involves the infliction of trauma on living animals. To determine how the forensic science community is dealing with this dilemma, a review of literature within major forensic science journals was conducted. The frequency and trends of the use of animals in forensic science research was investigated for the period 1 January 2012-31 December 2016. The review revealed 204 original articles utilizing 5050 animals in various forms as analogues for human tissue. The most common specimens utilized were various species of rats (35.3%), pigs (29.3%), mice (17.7%), and rabbits (8.2%) although different specimens were favored in different study themes. The majority of studies (58%) were conducted on post-mortem specimens. It is, however, evident that more needs to be done to uphold the basic ethical principles of reduction, refinement and replacement in the use of animals for research purposes.

The welfare implications of using exotic tortoises as ecological replacements.

Science.gov (United States)

Griffiths, Christine J; Zuël, Nicolas; Tatayah, Vikash; Jones, Carl G; Griffiths, Owen; Harris, Stephen

2012-01-01

Ecological replacement involves the introduction of non-native species to habitats beyond their historical range, a factor identified as increasing the risk of failure for translocations. Yet the effectiveness and success of ecological replacement rely in part on the ability of translocatees to adapt, survive and potentially reproduce in a novel environment. We discuss the welfare aspects of translocating captive-reared non-native tortoises, Aldabrachelys gigantea and Astrochelys radiata, to two offshore Mauritian islands, and the costs and success of the projects to date. Because tortoises are long-lived, late-maturing reptiles, we assessed the progress of the translocation by monitoring the survival, health, growth, and breeding by the founders. Between 2000 and 2011, a total of 26 A. gigantea were introduced to Ile aux Aigrettes, and in 2007 twelve sexually immature A. gigantea and twelve male A. radiata were introduced to Round Island, Mauritius. Annual mortality rates were low, with most animals either maintaining or gaining weight. A minimum of 529 hatchlings were produced on Ile aux Aigrettes in 11 years; there was no potential for breeding on Round Island. Project costs were low. We attribute the success of these introductions to the tortoises' generalist diet, habitat requirements, and innate behaviour. Feasibility analyses for ecological replacement and assisted colonisation projects should consider the candidate species' welfare during translocation and in its recipient environment. Our study provides a useful model for how this should be done. In addition to serving as ecological replacements for extinct Mauritian tortoises, we found that releasing small numbers of captive-reared A. gigantea and A. radiata is cost-effective and successful in the short term. The ability to release small numbers of animals is a particularly important attribute for ecological replacement projects since it reduces the potential risk and controversy associated with

The welfare implications of using exotic tortoises as ecological replacements.

Directory of Open Access Journals (Sweden)

Christine J Griffiths

Full Text Available Ecological replacement involves the introduction of non-native species to habitats beyond their historical range, a factor identified as increasing the risk of failure for translocations. Yet the effectiveness and success of ecological replacement rely in part on the ability of translocatees to adapt, survive and potentially reproduce in a novel environment. We discuss the welfare aspects of translocating captive-reared non-native tortoises, Aldabrachelys gigantea and Astrochelys radiata, to two offshore Mauritian islands, and the costs and success of the projects to date.Because tortoises are long-lived, late-maturing reptiles, we assessed the progress of the translocation by monitoring the survival, health, growth, and breeding by the founders. Between 2000 and 2011, a total of 26 A. gigantea were introduced to Ile aux Aigrettes, and in 2007 twelve sexually immature A. gigantea and twelve male A. radiata were introduced to Round Island, Mauritius. Annual mortality rates were low, with most animals either maintaining or gaining weight. A minimum of 529 hatchlings were produced on Ile aux Aigrettes in 11 years; there was no potential for breeding on Round Island. Project costs were low. We attribute the success of these introductions to the tortoises' generalist diet, habitat requirements, and innate behaviour.Feasibility analyses for ecological replacement and assisted colonisation projects should consider the candidate species' welfare during translocation and in its recipient environment. Our study provides a useful model for how this should be done. In addition to serving as ecological replacements for extinct Mauritian tortoises, we found that releasing small numbers of captive-reared A. gigantea and A. radiata is cost-effective and successful in the short term. The ability to release small numbers of animals is a particularly important attribute for ecological replacement projects since it reduces the potential risk and controversy

Testosterone Replacement, Muscle Strength, and Physical Function

Directory of Open Access Journals (Sweden)

You-Seon Nam

2018-05-01

Full Text Available Muscle strength and physical function decrease in older men, as do testosterone levels. Nonetheless, the effects of testosterone replacement therapy on muscle strength and physical function remain inconclusive and equivocal. We conducted a rapid systematic review, the results of which showed that testosterone replacement does not affect muscle strength (measured by hand grip strength and leg muscle strength, although it may increase physical function (measured by the 6-minute walk test, Physical Activity Scale for the Elderly score, and other physical performance tests. However, most of the studies were conducted in the United States or Europe and did not include participants from Asian or other ethnic backgrounds; therefore, further studies are needed to evaluate the effects of testosterone replacement in a broader population.

9 CFR 442.3 - Scale requirements for accurate weights, repairs, adjustments, and replacements after inspection.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Scale requirements for accurate... PROCEDURES AND REQUIREMENTS FOR ACCURATE WEIGHTS § 442.3 Scale requirements for accurate weights, repairs, adjustments, and replacements after inspection. (a) All scales used to determine the net weight of meat and...

The opportunity cost of animal based diets exceeds all food losses.

Science.gov (United States)

Shepon, Alon; Eshel, Gidon; Noor, Elad; Milo, Ron

2018-04-10

Food loss is widely recognized as undermining food security and environmental sustainability. However, consumption of resource-intensive food items instead of more efficient, equally nutritious alternatives can also be considered as an effective food loss. Here we define and quantify these opportunity food losses as the food loss associated with consuming resource-intensive animal-based items instead of plant-based alternatives which are nutritionally comparable, e.g., in terms of protein content. We consider replacements that minimize cropland use for each of the main US animal-based food categories. We find that although the characteristic conventional retail-to-consumer food losses are ≈30% for plant and animal products, the opportunity food losses of beef, pork, dairy, poultry, and eggs are 96%, 90%, 75%, 50%, and 40%, respectively. This arises because plant-based replacement diets can produce 20-fold and twofold more nutritionally similar food per cropland than beef and eggs, the most and least resource-intensive animal categories, respectively. Although conventional and opportunity food losses are both targets for improvement, the high opportunity food losses highlight the large potential savings beyond conventionally defined food losses. Concurrently replacing all animal-based items in the US diet with plant-based alternatives will add enough food to feed, in full, 350 million additional people, well above the expected benefits of eliminating all supply chain food waste. These results highlight the importance of dietary shifts to improving food availability and security. Copyright © 2018 the Author(s). Published by PNAS.

On-line PWR RHR pump performance testing following motor and impeller replacement

International Nuclear Information System (INIS)

DiMarzo, J.T.

1996-01-01

On-line maintenance and replacement of safety-related pumps requires the performance of an inservice test to determine and confirm the operational readiness of the pumps. In 1995, major maintenance was performed on two Pressurized Water Reactor (PWR) Residual Heat Removal (RHR) Pumps. A refurbished spare motor was overhauled with a new mechanical seal, new motor bearings and equipped with pump's 'B' impeller. The spare was installed into the 'B' train. The motor had never been run in the system before. A pump performance test was developed to verify it's operational readiness and determine the in-situ pump performance curve. Since the unit was operating, emphasis was placed on conducting a highly accurate pump performance test that would ensure that it satisfied the NSSS vendors accident analysis minimum acceptance curve. The design of the RHR System allowed testing of one train while the other was aligned for normal operation. A test flow path was established from the Refueling Water Storage Tank (RWST) through the pump (under test) and back to the RWST. This allowed staff to conduct a full flow range pump performance test. Each train was analyzed and an expression developed that included an error vector term for the TDH (ft), pressure (psig), and flow rate (gpm) using the variance error vector methodology. This method allowed the engineers to select a test instrumentation system that would yield accurate readings and minimal measurement errors, for data taken in the measurement of TDH (P,Q) versus Pump Flow Rate (Q). Test results for the 'B' Train showed performance well in excess of the minimum required. The motor that was originally in the 'B' train was similarly overhauled and equipped with 'A' pump's original impeller, re-installed in the 'A' train, and tested. Analysis of the 'A' train results indicate that the RHR pump's performance was also well in excess of the vendors requirements

On-line PWR RHR pump performance testing following motor and impeller replacement

Energy Technology Data Exchange (ETDEWEB)

DiMarzo, J.T.

1996-12-01

On-line maintenance and replacement of safety-related pumps requires the performance of an inservice test to determine and confirm the operational readiness of the pumps. In 1995, major maintenance was performed on two Pressurized Water Reactor (PWR) Residual Heat Removal (RHR) Pumps. A refurbished spare motor was overhauled with a new mechanical seal, new motor bearings and equipped with pump`s `B` impeller. The spare was installed into the `B` train. The motor had never been run in the system before. A pump performance test was developed to verify it`s operational readiness and determine the in-situ pump performance curve. Since the unit was operating, emphasis was placed on conducting a highly accurate pump performance test that would ensure that it satisfied the NSSS vendors accident analysis minimum acceptance curve. The design of the RHR System allowed testing of one train while the other was aligned for normal operation. A test flow path was established from the Refueling Water Storage Tank (RWST) through the pump (under test) and back to the RWST. This allowed staff to conduct a full flow range pump performance test. Each train was analyzed and an expression developed that included an error vector term for the TDH (ft), pressure (psig), and flow rate (gpm) using the variance error vector methodology. This method allowed the engineers to select a test instrumentation system that would yield accurate readings and minimal measurement errors, for data taken in the measurement of TDH (P,Q) versus Pump Flow Rate (Q). Test results for the `B` Train showed performance well in excess of the minimum required. The motor that was originally in the `B` train was similarly overhauled and equipped with `A` pump`s original impeller, re-installed in the `A` train, and tested. Analysis of the `A` train results indicate that the RHR pump`s performance was also well in excess of the vendors requirements.

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.

Halide test agent replacement study

Energy Technology Data Exchange (ETDEWEB)

Banks, E.M.; Freeman, W.P.; Kovach, B.J. [and others

1995-02-01

The intended phaseout of the chlorofluorocarbons (CFCs) from commercial use required the evaluation of substitute materials for the testing for leak paths through both individual adsorbers and installed adsorbent banks. The American Society of Mechanical Engineers (ASME) Committee on Nuclear Air and Gas Treatment (CONAGT) is in charge of maintaining the standards and codes specifying adsorbent leak test methods for the nuclear safety related air cleaning systems. The currently published standards and codes cite the use of R-11, R-12 and R-112 for leak path test agents. All of these compounds are CFCs. There are other agencies and organizations (USDOE, USDOD and USNRC) also specifying testing for leak paths or in some cases for special life tests using the above compounds. The CONAGT has recently developed criteria for the suitability evaluation of substitute test agents. On the basis of these criteria, several compounds were evaluated for their acceptability as adsorbent bed leak and life test agents. The ASME CONAGT Test Agent Qualification Criteria. The test agent qualification is based on the following parameters: (1) Similar retention times on activated carbons at the same concentration levels as one of the following: R-11, R-12, R-112 or R-112a. (2) Similar lower detection limit sensitivity and precision in the concentration range of use as R-11, R-12, R-112 and R-112a. (3) Gives the same in-place leak test results as R-11, R-12, R-112, or R-112a. (4) Chemical and radiological stability under the use conditions. (5) Causes no degradation of the carbon and its impregnant or of the other NATS components under the use conditions. (6) Is listed in the USEPA Toxic Substances Control Act (TSCA) inventory for commercial use.

Animal Rights as a Mainstream Phenomenon

Directory of Open Access Journals (Sweden)

Bernard E. Rollin

2011-01-01

Full Text Available Businesses and professions must stay in accord with social ethics, or risk losing their autonomy.A major social ethical issue that has emerged in the past four decades is the treatment of animals in various areas of human use. Society’s moral concern has outgrown the traditional ethic of animal cruelty that began in biblical times and is encoded in the laws of all civilized societies. There are five major reasons for this new social concern, most importantly, the replacement of husbandry-based agriculture with industrial agriculture. This loss of husbandry to industry has threatened the traditional fair contract between humans and animals, and resulted in significant amounts of animal suffering arising on four different fronts. Because such suffering is not occasioned by cruelty, a new ethic for animals was required to express social concerns. Since ethics proceed from preexisting ethics rather than ex nihilo, society has looked to its ethic for humans, appropriately modified, to find moral categories applicable to animals. This concept of legally encoded rights for animals has emerged as a plausible vehicle for reform.

Animal Rights as a Mainstream Phenomenon.

Science.gov (United States)

Rollin, Bernard E

2011-01-19

Businesses and professions must stay in accord with social ethics, or risk losing their autonomy.A major social ethical issue that has emerged in the past four decades is the treatment of animals in various areas of human use. Society's moral concern has outgrown the traditional ethic of animal cruelty that began in biblical times and is encoded in the laws of all civilized societies. There are five major reasons for this new social concern, most importantly, the replacement of husbandry-based agriculture with industrial agriculture. This loss of husbandry to industry has threatened the traditional fair contract between humans and animals, and resulted in significant amounts of animal suffering arising on four different fronts. Because such suffering is not occasioned by cruelty, a new ethic for animals was required to express social concerns. Since ethics proceed from preexisting ethics rather than ex nihilo, society has looked to its ethic for humans, appropriately modified, to find moral categories applicable to animals. This concept of legally encoded rights for animals has emerged as a plausible vehicle for reform.

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...

Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats

NARCIS (Netherlands)

Jonge, P.K.J.D. de; Sloff, M.; Janke, H.P.; Kortmann, B.B.M.; Gier, R.P.E. de; Geutjes, P.J.; Oosterwijk, E.; Feitz, W.F.J.

2017-01-01

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats.

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.

Restart Testing Program for piping following steam generator replacement at North Anna Unit 1

International Nuclear Information System (INIS)

Bain, R.A.; Bayer, R.K.

1993-01-01

In order to provide assurance that the effects of performing steam generator replacement (SGR) at North Anna unit 1 had no adverse impact on plant piping systems, a cold functional verification restart testing program was developed. This restart testing program was implemented in lieu of a hot functional testing program normally used during the initial startup of a nuclear plant. A review of North Anna plant-specific and generic U.S. Nuclear Regulatory Commission requirements for restart testing was performed to ensure that no mandatory hot functional testing was required. This was determined to be the case, and the development of a cold functional test program was initiated. The cold functional test had inherent advantages as compared to the hot functional testing, while still providing assurance of piping system adequacy. The advantages of the cold verification program included reducing risk to personnel from hot piping, increasing the accuracy of measurements with the improvement in work conditions, eliminating engineering activities during the heatup process, and being able to record measurements as construction work was completed allowing for rework or repair of components if required. To ensure the effectiveness of the cold verification program, a project procedure was generated to identify the personnel, equipment, and measurement requirements. An engineering calculation was issued to document the scope of the restart test program, and an additional calculation was developed to provide acceptance criteria for the critical commodity measurements

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

Science.gov (United States)

Cheluvappa, Rajkumar; Scowen, Paul; Eri, Rajaraman

2017-08-01

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

[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.

Estimating the shear strength of concrete with coarse aggregate replacement

OpenAIRE

Folagbade Olusoga Peter ORIOLA; George MOSES; Jacob Oyeniyi AFOLAYAN; John Engbonye SANI

2017-01-01

For economic, environmental and practical reasons, it is desirable to replace the constituents of concrete with wastes and cheaper alternative materials. However, it is best when such replacements are done at optimum replacement levels. In view of this, a laboratory investigative test was carried out to evaluate the shear strength of concrete with coarse aggregate replacement by Coconut Shell and by Waste Rubber Tyre. The coarse aggregate replacement was done at recommended optimum proportion...

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.

The fabrication of bioresorbable implants for bone defects replacement using computer tomogram and 3D printing

Science.gov (United States)

Kuznetsov, P. G.; Tverdokhlebov, S. I.; Goreninskii, S. I.; Bolbasov, E. N.; Popkov, A. V.; Kulbakin, D. E.; Grigoryev, E. G.; Cherdyntseva, N. V.; Choinzonov, E. L.

2017-09-01

The present work demonstrates the possibility of production of personalized implants from bioresorbable polymers designed for replacement of bone defects. The stages of creating a personalized implant are described, which include the obtaining of 3D model from a computer tomogram, development of the model with respect to shape of bone fitment bore using Autodesk Meshmixer software, and 3D printing process from bioresorbable polymers. The results of bioresorbable polymer scaffolds implantation in pre-clinical tests on laboratory animals are shown. The biological properties of new bioresorbable polymers based on poly(lactic acid) were studied during their subcutaneous, intramuscular, bone and intraosseous implantation in laboratory animals. In all cases, there was a lack of a fibrous capsule formation around the bioresorbable polymer over time. Also, during the performed study, conclusions were made on osteogenesis intensity depending on the initial state of bone tissue.

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...

CAD-CAM-generated hydroxyapatite scaffold to replace the mandibular condyle in sheep: preliminary results.

Science.gov (United States)

Ciocca, Leonardo; Donati, Davide; Fantini, Massimiliano; Landi, Elena; Piattelli, Adriano; Iezzi, Giovanna; Tampieri, Anna; Spadari, Alessandro; Romagnoli, Noemi; Scotti, Roberto

2013-08-01

In this study, rapid CAD-CAM prototyping of pure hydroxyapatite to replace temporomandibular joint condyles was tested in sheep. Three adult animals were implanted with CAD-CAM-designed porous hydroxyapatite scaffolds as condyle substitutes. The desired scaffold shape was achieved by subtractive automated milling machining (block reduction). Custom-made surgical guides were created by direct metal laser sintering and were used to export the virtual planning of the bone cut lines into the surgical environment. Using the same technique, fixation plates were created and applied to the scaffold pre-operatively to firmly secure the condyles to the bone and to assure primary stability of the hydroxyapatite scaffolds during masticatory function. Four months post-surgery, the sheep were sacrificed. The hydroxyapatite scaffolds were explanted, and histological specimens were prepared. Different histological tissues penetrating the scaffold macropores, the sequence of bone remodeling, new apposition of bone and/or cartilage as a consequence of the different functional anatomic role, and osseointegration at the interface between the scaffold and bone were documented. This animal model was found to be appropriate for testing CAD-CAM customization and the biomechanical properties of porous, pure hydroxyapatite scaffolds used as joint prostheses.

Integrated testing strategy (ITS) for bioaccumulation assessment under REACH

DEFF Research Database (Denmark)

Lombardo, Anna; Roncaglioni, Alessandra; Benfentati, Emilio

2014-01-01

in a dossier. REACH promotes the use of alternative methods to replace, refine and reduce the use of animal (eco)toxicity testing. Within the EU OSIRIS project, integrated testing strategies (ITSs) have been developed for the rational use of non-animal testing approaches in chemical hazard assessment. Here we......REACH (registration, evaluation, authorisation and restriction of chemicals) regulation requires that all the chemicals produced or imported in Europe above 1 tonne/year are registered. To register a chemical, physicochemical, toxicological and ecotoxicological information needs to be reported...... present an ITS for evaluating the bioaccumulation potential of organic chemicals. The scheme includes the use of all available data (also the non-optimal ones), waiving schemes, analysis of physicochemical properties related to the end point and alternative methods (both in silico and in vitro). In vivo...

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.

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

Guide to optimized replacement of equipment seals

International Nuclear Information System (INIS)

Gleason, J.F.

1990-03-01

A reevaluation of current scheduled replacement intervals of polymeric seals in plant equipment can achieve significant benefits. Information is provided which has the potential for increasing replacement intervals based on better information on how seals have performed through unique nuclear industry tests to qualify equipment, improved elastomers and increased knowledge of the failure mechanisms and related performance. The research was performed by reviewing applications of elastomeric seals in nuclear plants and practice associated with defining seal replacement intervals in the nuclear power and other industries. Performance indicators and how they predict degradation of seals were evaluated. Guidelines and a flow chart for reevaluating seal replacement intervals are provided. 29 refs., 38 figs., 8 tabs

Toxicity testing of polymer materials for dialysis equipment: reconsidering in vivo testing.

Science.gov (United States)

Sauer, U G; Liebsch, M; Kolar, R

2000-01-01

In fulfilment of the aims of the European Union Biocidal Directive (Directive 98/8/EC), Technical Guidance Documents are currently being compiled. Part I of these Technical Guidance Documents covers data requirements for active substances and biocidal products. The Three Rs principle has been applied in certain parts of the toxicity and ecotoxicity testing scheme for pesticides, such as testing for acute oral toxicity, skin and eye irritation, skin sensitisation, and dermal absorption. Further recommendations on how to proceed with regard to the continuing replacement, reduction and refinement of animal experiments in this field of regulatory testing are included for consideration. In this context, besides stressing the necessity to validate and accept further alternatives, emphasis is placed on providing the possibility of waiving unnecessary tests and on the continuous evaluation of whether certain tests are needed at all. 2000 FRAME.

Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats.

Science.gov (United States)

de Jonge, Paul K J D; Sloff, Marije; Janke, Heinz P; Kortmann, Barbara B M; de Gier, Robert P E; Geutjes, Paul J; Oosterwijk, Egbert; Feitz, Wout F J

2017-10-01

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats. Similarly to a previous study in pigs, the ureteral J-stent was blindly inserted until some resistance was met. During evaluation of the goats after three months, perforation of the renal cortex by the stent was observed in four out of seven animals. These results indicated that blind stent placement was not possible in goats. In four new goats, clinical protocols were followed using X-ray and iodinated contrast fluids to visualize the kidney and stent during stent placement. With this adaptation the stents were successfully placed in the kidneys of these four new goats with minimal additional effort. It is likely that other groups in other fields ran into similar problems that could have been avoided by following clinical protocols. Therefore, we would like to stress the importance of following clinical protocols when using medical devices in animals to prevent unnecessary suffering and to reduce the number of animals needed.

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)

The secondary hypothyroidism after radioiodine therapy and the replacement treatment

International Nuclear Information System (INIS)

Xu Ying; Xu Xiaohui

2004-01-01

The secondary hypothyroidism is the most important intercurrent disease after radioiodine therapy. The early hypothyroidism and the late hypothyroidism are incompletely different in pathogenesis. It needs researching further. there has not yet been an affirmable answer to choose the distillates from animal hypothyroid extract or complex preparation of levo-thyroxine in replacement treatment. (authors)

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...

Using web-based animations to teach histology.

Science.gov (United States)

Brisbourne, Marc A S; Chin, Susan S-L; Melnyk, Erica; Begg, David A

2002-02-15

We have been experimenting with the use of animations to teach histology as part of an interactive multimedia program we are developing to replace the traditional lecture/laboratory-based histology course in our medical and dental curricula. This program, called HistoQuest, uses animations to illustrate basic histologic principles, explain dynamic processes, integrate histologic structure with physiological function, and assist students in forming mental models with which to organize and integrate new information into their learning. With this article, we first briefly discuss the theory of mental modeling, principles of visual presentation, and how mental modeling and visual presentation can be integrated to create effective animations. We then discuss the major Web-based animation technologies that are currently available and their suitability for different visual styles and navigational structures. Finally, we describe the process we use to produce animations for our program. The approach described in this study can be used by other developers to create animations for delivery over the Internet for the teaching of histology.

Animal suffering should not trump environmental stewardship.

Science.gov (United States)

Vantassel, Stephen M

2010-01-01

Andrew Linzey contends that our treatment of children should act as a model for our treatment of animals: just as we use our power to prevent the suffering of children, so should we restrict our behavior to protect animals from human-originated suffering. While not ignoring the role theology and emotion play in his ethical view, Linzey endeavors to provide a rational argument for the moral consideration of animals. In addition, Linzey explains how humans have created institutions to help them justify the continuance of animal suffering, followed by a plan to replace those institutions with animal-friendly ones. Linzey then applies his thinking to three contemporary institutions he believes cause animal suffering in an unjustifiable manner, namely hunting with dogs, fur farming, and commercial sealing. This review offers a detailed account of several significant weaknesses of Linzey's argument, ranging from the theological to the scientific, that should be considered before adopting his views.

Bony vibration stimulation test combined with magnetic resonance imaging. Can discography be replaced?

Science.gov (United States)

Yrjämä, M; Tervonen, O; Kurunlahti, M; Vanharanta, H

1997-04-01

The results of two noninvasive methods, magnetic resonance imaging and a bony vibration test, were compared with discographic pain provocation findings. To evaluate whether the combination of magnetic resonance imaging and vibration pain provocation tests could be used to replace discography in low back pain diagnostics. Magnetic resonance imaging gives a wealth of visual information on anatomic changes of the spine with often unknown clinical significance. Discographic examination of the spine is still the only widely accepted diagnostic method that can relate the pathoanatomic changes to the patient's clinical pain. Internal anular rupture has been shown to be one of the sources of back pain. The bony vibration test of the spinal processes has been shown correlate well with discographic pain provocation tests in cases of internal anular rupture. The three lowest lumbar discs of 33 patients with back pain were examined by means of magnetic resonance imaging and a bony vibration stimulation test, and the results were compared with those from computed tomography-discography. In cases of intradiscal magnetic resonance imaging findings, the vibration provocation test showed a sensitivity of 0.88 and a specificity of 0.50 compared with the discographic pain provocation test. If the patients with previous back surgery were excluded, the specificity was 0.75. In the cases of total anular rupture, the sensitivity was 0.50, and the specificity was 0.33. The combination of the two noninvasive methods, vibration stimulation and magnetic resonance imaging, gives more information on the origin of the back pain than magnetic resonance imaging alone. The pathoanatomic changes seen in magnetic resonance imaging can be correlated with the patient's disorder more reliably using the vibration provocation test in the cases of partial anular ruptures. The use of discography can be limited mostly to cases with total anular ruptures detected by magnetic resonance imaging.

Thermal-hydraulic design calculations for the annular fuel element with replaceable test bundles (TOAST) on the test zone position 205 of KNK II/3

International Nuclear Information System (INIS)

Norajitra, P.

1984-10-01

Annular fuel elements are foreseen in KNK II as carrier elements for irradiation inserts and test bundles. For the third core a reloadable annular element on position 205 is foreseen, in which replaceable 19-pin test bundles (TOAST) shall be irradiated. The present report deals with the thermal-hydraulic design of the annular carrier element and the test bundle, whereby the test bundle required additional optimization. The code CIA has been used for the calculations. Start of irradiation of the subassembly is planned at the beginning of the third core operation. After optimization of the pin-spacer geometry in the test bundle, design calculations for both bundles were performed, whereby thermal coupling between both was taken into account. The calculated mass-flows and temperature distributions are given for the nominal and the eccentric element configuration. The calculated bundle pressure losses have been corrected according to experimental results [de

Molecular evolution of cyclin proteins in animals and fungi

Directory of Open Access Journals (Sweden)

Afonnikov Dmitry A

2011-07-01

Full Text Available Abstract Background The passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi. Results We constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution. Conclusions The results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events.

Digestibility of animal and vegetable protein ingredients by pirarucu juveniles, Arapaima gigas

Directory of Open Access Journals (Sweden)

Filipe dos Santos Cipriano

Full Text Available ABSTRACT The objective of this study was to determine the apparent digestibility coefficients of energy, protein, and amino acids in protein ingredients by pirarucu juveniles. A test was conducted with six protein ingredients: meat and bone meal, fish meal, hydrolyzed feather meal, poultry by-product meal, soybean meal, and corn gluten meal. Three repetitions were used for each tested ingredient. A reference feed was used with 430 g kg−1 crude protein and 19.63 kJ g−1 gross energy. The test feeds consisted of the replacement of 30% of the reference feeds with the test ingredients. Chromium oxide was added to the feeds at 1 g kg−1 as an external marker. Eighteen juveniles with an average weight of 235±36 g were used. The best apparent digestibility coefficients of protein were found for fish meal, followed by the poultry by-product meal and meat and bone meal. However, except for gluten, all the tested ingredients presented protein digestibilities above 0.70. The crude energy apparent digestibility coefficient was higher for animal ingredients, above 0.75, than for vegetable ingredients, which presented values below 0.60. Pirarucu efficiently uses the protein from the tested ingredients, regardless of origin. However, it has a preferential ability to use the energy from animal ingredients.

In vitro versus in vivo concordance: a case study of the replacement of an animal potency test with an immunochemical assay.

Science.gov (United States)

Schofield, T

2002-01-01

Early in its development, the potency of Merck's recombinant hepatitis B vaccine, RECOMBIVAX HB, was monitored using an assay performed in mice. A specification was determined to be the lowest potency which induced acceptable response in clinical trials. As a post-licensing commitment, Merck was asked to replace its mouse potency assay with an in vitro procedure for product release in the US market. Early studies with a commercial enzyme immunoassay (EIA) yielded highly variable results. That assay, combined with a sample pretreatment step, proved more dependable and predictive of potency in the mouse assay. Based on measurements made on manufactured materials, combined with experiments contrived to yield a wide range of reactivity in the two assays, concordance was established between the EIA and the mouse potency assay. This concordance was used to calibrate a specification for the in vitro assay that is predictive of a satisfactory response in vivo. Data from clinical trials established a correspondence between human immunogenicity and these potency markers.

A small punch test technique for characterizing the elastic modulus and fracture behavior of PMMA bone cement used in total joint replacement.

Science.gov (United States)

Giddings, V L; Kurtz, S M; Jewett, C W; Foulds, J R; Edidin, A A

2001-07-01

Polymethylmethacrylate (PMMA) bone cement is used in total joint replacements to anchor implants to the underlying bone. Establishing and maintaining the integrity of bone cement is thus of critical importance to the long-term outcome of joint replacement surgery. The goal of the present study was to evaluate the suitability of a novel testing technique, the small punch or miniaturized disk bend test, to characterize the elastic modulus and fracture behavior of PMMA. We investigated the hypothesis that the crack initiation behavior of PMMA during the small punch test was sensitive to the test temperature. Miniature disk-shaped specimens, 0.5 mm thick and 6.4 mm in diameter, were prepared from PMMA and Simplex-P bone cement according to manufacturers' instructions. Testing was conducted at ambient and body temperatures, and the effect of test temperature on the elastic modulus and fracture behavior was statistically evaluated using analysis of variance. For both PMMA materials, the test temperature had a significant effect on elastic modulus and crack initiation behavior. At body temperature, the specimens exhibited "ductile" crack initiation, whereas at room temperature "brittle" crack initiation was observed. The small punch test was found to be a sensitive and repeatable test method for evaluating the mechanical behavior of PMMA. In light of the results of this study, future small punch testing should be conducted at body temperature.

Five times sit-to-stand test in subjects with total knee replacement: Reliability and relationship with functional mobility tests.

Science.gov (United States)

Medina-Mirapeix, Francesc; Vivo-Fernández, Iván; López-Cañizares, Juan; García-Vidal, José A; Benítez-Martínez, Josep Carles; Del Baño-Aledo, María Elena

2018-01-01

The objective was to determine the inter-observer and test/retest reliability of the "Five-repetition sit-to-stand" (5STS) test in patients with total knee replacement (TKR). To explore correlation between 5STS and two mobility tests. A reliability study was conducted among 24 (mean age 72.13, S.D. 10.67; 50% were women) outpatients with TKR. They were recruited from a traumatology unit of a public hospital via convenience sampling. A physiotherapist and trauma physician assessed each patient at the same time. The same physiotherapist realized a 5STS second measurement 45-60min after the first one. Reliability was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots. Pearson coefficient was calculated to assess the correlation between 5STS, time up to go test (TUG) and four meters gait speed (4MGS). ICC for inter-observer and test-retest reliability of the 5STS were 0.998 (95% confidence interval [CI], 0.995-0.999) and 0.982 (95% CI, 0.959-0.992). Bland-Altman plot inter-observer showed limits between -0.82 and 1.06 with a mean of 0.11 and no heteroscedasticity within the data. Bland-Altman plot for test-retest showed the limits between 1.76 and 4.16, a mean of 1.20 and heteroscedasticity within the data. Pearson correlation coefficient revealed significant correlation between 5STS and TUG (r=0.7, ptest-retest reliability when it is used in people with TKR, and also significant correlation with other functional mobility tests. These findings support the use of 5STS as outcome measure in TKR population. Copyright © 2017 Elsevier B.V. All rights reserved.

Replacing soybean meal for cottonseed meal on performance of lactating dairy cows.

Science.gov (United States)

Imaizumi, Hugo; De Souza, Jonas; Batistel, Fernanda; Santos, Flávio Augusto Portela

2016-01-01

Cottonseed meal (CSM) is an alternative source of protein, and previous studies have been shown that it can replace soybean meal (SBM) without decrease animal performance. However, Brazilian CSM has a different chemical composition compared with the usual CSM reported in the literature. The objective of this experiment was to evaluate the effects of replacing SBM for Brazilian CSM on performance and energy balance of mid-lactating dairy cows. Forty-two Holstein cows were used in a replicate 3 × 3 Latin square design. Increasing contents of CSM (0, 15, and 30% of dry matter (DM)) were fed in diets to replace SBM. Milk yield and feed efficiency were linearly reduced with the replacement of CSM for SBM (P = 0.001). Milk fat content tended to increase quadratically (P = 0.07) with CSM addition. Replacing SBM for CSM affected milk protein content quadratically (P = 0.05). Milk urea nitrogen and plasma urea nitrogen (PUN) tended to respond quadratically (P = 0.06 and 0.10) when CSM replaced SBM to the diets. Variation in body weight (BW) also responded quadratically as CSM replaced SBM (P = 0.05). Altogether, the findings suggest better performance when cows receive SBM diet compared with the Brazilian CSM diet.

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.

Experimental replacement of esophagus with a short segment of trachea.

Science.gov (United States)

Abbasidezfouli, Azizollah; Ansari, Damoon; Sheikhy, Kambiz; Abarkar, Mohammad; Sadeghbeigi, Farahnaz; Abbasidezfouli, Sepehr; Sharifi, Davood

2016-03-01

Segmental resection of esophagus with primary anastomosis is prohibited because of the risk of dehiscence. We previously have shown that replacement of a segment of cervical esophagus with a tracheal segment of the same length could successfully be performed in a canine model. In this study, we sought to assess the feasibility of replacement of the esophageal defect with a shorter segment of trachea. In five mongrel dogs weighting 20-30 kg, under general anesthesia and after a cervical incision, 8 cm of the cervical esophagus was resected and replaced by a 4-cm segment of the adjacent trachea. The animals were evaluated clinically for signs and symptoms of stenosis and dehiscence and then euthanized after 2 mo of follow-up. All dogs recovered from surgery and started regular diet on the seventh postoperative day. No clinical or endoscopic sign of stenosis or voice change was seen. Squamous metaplasia and atrophy of mucosal glands and cartilage were detected in the histopathologic examination of the replaced segments. Replacement of a cervical esophageal defect with a shorter segment of trachea can be performed successfully in dogs. This procedure can be potentially used for the treatment of cervical esophageal lesions in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Development and validation of a quantitative competitive ELISA for potency testing of equine anti rabies sera with other potential use.

Science.gov (United States)

Korimbocus, Jehanara; Dehay, Nicolas; Tordo, Noël; Cano, François; Morgeaux, Sylvie

2016-06-14

In case of a bite by a rabies infected animal, the World Health Organisation recommends a prophylactic treatment including the administration of Human Rabies Immunoglobulins (HRIGs) or highly purified F(ab')2 fragments produced from Equine Rabies Immunoglobulin (F(ab')2 - ERIGs). According to international regulation, quality control of F(ab')2 - ERIGs lots requires potency testing by the in vivo Mouse Neutralisation Test (MNT) prior marketing. However, the strategy of the 3Rs (Reduce, Refine, Replace) for animal testing required by the European Directive encourages the replacement of the in vivo potency test by an in vitro assay. In this context, a competitive ELISA method (c-ELISA) has been developed by the Agence Nationale de Sécurité du Médicament et des Produits de Santé where F(ab')2 - ERIGs are in competition with a monoclonal antibody recognizing the trimeric native form of the rabies glycoprotein. After a full validation study, the c-ELISA has been applied to commercial batches of F(ab')2 - ERIGs. A correlation study with the MNT demonstrated a similarity between the two methods (r=0.751). Moreover, the c-ELISA method which does not need any species specific reagent has been applied to HRIGs potency testing as an alternative method to Rapid Fluorescent Focus Inhibition Test (RFFIT), thus avoiding the handling of live rabies virus in BSL3 containment. In conclusion, the c-ELISA has shown its potential to replace MNT and possibly RFFIT for the quantification of rabies immunoglobulin. After optimisation it may be used for the quantification of rabies immunoglobulin in any animal species, notably for rabies immunogenicity assay in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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...

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.

Innovative in cellulo method as an alternative to in vivo neurovirulence test for the characterization and quality control of human live Yellow Fever virus vaccines: A pilot study.

Science.gov (United States)

da Costa, Anaelle; Prehaud, Christophe; Khou, Cecile; Pardigon, Nathalie; Saulnier, Aure; Nougarede, Nolwenn; Lafon, Monique

2018-05-01

Live attenuated vaccines have proved to be mostly valuable in the prevention of infectious diseases in humans, especially in developing countries. The safety and potency of vaccine, and the consistency of vaccine batch-to-batch manufacturing, must be proven before being administrated to humans. For now, the tests used to control vaccine safety largely involve animal testing. For live viral vaccines, regulations require suppliers to demonstrate the absence of neurovirulence in animals, principally in non-human primates and mice. In a search to reduce the use of animals and embracing the 3Rs principles (Replacement, Reduction, Refinement in the use of laboratory animals), we developed a new Blood-Brain Barrier Minibrain (BBB-Minibrain) in cellulo device to evaluate the neuroinvasiveness/neurovirulence of live Yellow Fever virus (YFV) vaccines. A pilot study was performed using the features of two distinct YFV strains, with the ultimate goal of proposing a companion test to characterize YFV neurovirulence. Here, we demonstrate that the BBB-Minibrain model is a promising alternative to consider for future replacement of YFV vaccine in vivo neurovirulence testing (see graphical abstract). Copyright © 2018. Published by Elsevier Ltd.

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

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,…

Research perspectives for pre-screening alternatives to animal experimentation

International Nuclear Information System (INIS)

Walum, Erik; Hedander, Jan; Garberg, Per

2005-01-01

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

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...

Glutamatergic Tuning of Hyperactive Striatal Projection Neurons Controls the Motor Response to Dopamine Replacement in Parkinsonian Primates.

Science.gov (United States)

Singh, Arun; Jenkins, Meagan A; Burke, Kenneth J; Beck, Goichi; Jenkins, Andrew; Scimemi, Annalisa; Traynelis, Stephen F; Papa, Stella M

2018-01-23

Dopamine (DA) loss in Parkinson's disease (PD) alters the function of striatal projection neurons (SPNs) and causes motor deficits, but DA replacement can induce further abnormalities. A key pathological change in animal models and patients is SPN hyperactivity; however, the role of glutamate in altered DA responses remains elusive. We tested the effect of locally applied AMPAR or NMDAR antagonists on glutamatergic signaling in SPNs of parkinsonian primates. Following a reduction in basal hyperactivity by antagonists at either receptor, DA inputs induced SPN firing changes that were stable during the entire motor response, in clear contrast with the typically unstable effects. The SPN activity reduction over an extended putamenal area controlled the release of involuntary movements in the "on" state and therefore improved motor responses to DA replacement. These results demonstrate the pathophysiological role of upregulated SPN activity and support strategies to reduce striatal glutamate signaling for PD therapy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Food-grade double emulsions as effective fat replacers in meat systems

NARCIS (Netherlands)

Eisinaite, Viktorija; Juraite, Dovile; Schroën, Karin; Leskauskaite, Daiva

2017-01-01

Double emulsions were used to not only replace 7 and 11% of animal fat in meat products, but also as a way to enhance the product colour. The coarse emulsion containing native beetroot juice as inner water phase, sunflower oil as oil phase and 0.5% whey protein isolate as outer water phase was

Stress Testing of the Philips 60W Replacement Lamp L Prize Entry

Energy Technology Data Exchange (ETDEWEB)

Poplawski, Michael E.; Ledbetter, Marc R.; Smith, Mark

2012-04-24

The Pacific Northwest National Laboratory, operated by Battelle for the U.S. Department of Energy, worked with Intertek to develop a procedure for stress testing medium screw-base light sources. This procedure, composed of alternating stress cycles and performance evaluation, was used to qualitatively compare and contrast the durability and reliability of the Philips 60W replacement lamp L Prize entry with market-proven compact fluorescent lamps (CFLs) with comparable light output and functionality. The stress cycles applied simultaneous combinations of electrical, thermal, vibration, and humidity stresses of increasing magnitude. Performance evaluations measured relative illuminance, x chromaticity and y chromaticity shifts after each stress cycle. The Philips L Prize entry lamps appear to be appreciably more durable than the incumbent energy-efficient technology, as represented by the evaluated CFLs, and with respect to the applied stresses. Through the course of testing, all 15 CFL samples permanently ceased to function as a result of the applied stresses, while only 1 Philips L Prize entry lamp exhibited a failure, the nature of which was minor, non-destructive, and a consequence of a known (and resolved) subcontractor issue. Given that current CFL technology appears to be moderately mature and no Philips L Prize entry failures could be produced within the stress envelope causing 100 percent failure of the benchmark CFLs, it seems that, in this particular implementation, light-emitting diode (LED) technology would be much more durable in the field than current CFL technology. However, the Philips L Prize entry lamps used for testing were carefully designed and built for the competition, while the benchmark CFLs were mass produced for retail sale—a distinction that should be taken into consideration. Further reliability testing on final production samples would be necessary to judge the extent to which the results of this analysis apply to production versions

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.

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.

Hip joint replacement

Science.gov (United States)

Hip arthroplasty; Total hip replacement; Hip hemiarthroplasty; Arthritis - hip replacement; Osteoarthritis - hip replacement ... Your hip joint is made up of 2 major parts. One or both parts may be replaced during surgery: ...

The use of the cardiopulmonary flow index to detect cardiac defects in man and animal

International Nuclear Information System (INIS)

Cilliers, G.D.

1982-01-01

The efficiency of the cardiopulmonary flow index (CPFI) to detect cardiac defects and to evaluate therapy in man and animal is tested. The CPFI seems to be sensitive enough to evaluate vasodilator and inotropic therapy during cardiac failure with 'gousiekte' sheep. Pulmonary emboli in sheep is induced by injecting coagulated blood into the pulmonary circulation. These pulmonary emboli caused a decrease in the CPFI. CPFI recordings were made on patients, before and after aorta- and mitralvalve replacements. The CPFI is sensitive enough to detect the valve inefficiency and also to detect the improvement in the pump efficiency of the heart after the double valve replacement. The results obtained prove that the CPFI could have a proper place in modern cardiology to evaluate therapy (clinical and surgical) and also to distinguish between cardiac defects and pulmonary emboli

Optimal replacement time estimation for machines and equipment based on cost function

Directory of Open Access Journals (Sweden)

J. Šebo

2013-01-01

Full Text Available The article deals with a multidisciplinary issue of estimating the optimal replacement time for the machines. Considered categories of machines, for which the optimization method is usable, are of the metallurgical and engineering production. Different models of cost function are considered (both with one and two variables. Parameters of the models were calculated through the least squares method. Models testing show that all are good enough, so for estimation of optimal replacement time is sufficient to use simpler models. In addition to the testing of models we developed the method (tested on selected simple model which enable us in actual real time (with limited data set to indicate the optimal replacement time. The indicated time moment is close enough to the optimal replacement time t*.

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.

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.

Design verification for reactor head replacement

International Nuclear Information System (INIS)

Dwivedy, K.K.; Whitt, M.S.; Lee, R.

2005-01-01

This paper outlines the challenges of design verification for reactor head replacement for PWR plants and the program for qualification from the prospective of the utility design engineering group. This paper is based on the experience with the design confirmation of four reactor head replacements for two plants, and their interfacing components, parts, appurtenances, and support structures. The reactor head replacement falls under the jurisdiction of the applicable edition of the ASME Section XI code, with particular reference to repair/replacement activities. Under any repair/replacement activities, demands may be encountered in the development of program and plan for replacement due to the vintage of the original design/construction Code and the design reports governing the component qualifications. Because of the obvious importance of the reactor vessel, these challenges take on an added significance. Additional complexities are introduced to the project, when the replacement components are fabricated by vendors different from the original vendor. Specific attention is needed with respect to compatibility with the original design and construction of the part and interfacing components. The program for reactor head replacement requires evaluation of welding procedures, applicable examination, test, and acceptance criteria for material, welds, and the components. Also, the design needs to take into consideration the life of the replacement components with respect to the extended period of operation of the plant after license renewal and other plant improvements. Thus, the verification of acceptability of reactor head replacement provides challenges for development and maintenance of a program and plan, design specification, design report, manufacturer's data report and material certification, and a report of reconciliation. The technical need may also be compounded by other challenges such as widely scattered global activities and organizational barriers, which

[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.

Fault Sample Generation for Virtual Testability Demonstration Test Subject to Minimal Maintenance and Scheduled Replacement

Directory of Open Access Journals (Sweden)

Yong Zhang

2015-01-01

Full Text Available Virtual testability demonstration test brings new requirements to the fault sample generation. First, fault occurrence process is described by stochastic process theory. It is discussed that fault occurrence process subject to minimal repair is nonhomogeneous Poisson process (NHPP. Second, the interarrival time distribution function of the next fault event is proposed and three typical kinds of parameterized NHPP are discussed. Third, the procedure of fault sample generation is put forward with the assumptions of minimal maintenance and scheduled replacement. The fault modes and their occurrence time subject to specified conditions and time period can be obtained. Finally, an antenna driving subsystem in automatic pointing and tracking platform is taken as a case to illustrate the proposed method. Results indicate that both the size and structure of the fault samples generated by the proposed method are reasonable and effective. The proposed method can be applied to virtual testability demonstration test well.

Machine Learned Replacement of N-Labels for Basecalled Sequences in DNA Barcoding.

Science.gov (United States)

Ma, Eddie Y T; Ratnasingham, Sujeevan; Kremer, Stefan C

2018-01-01

This study presents a machine learning method that increases the number of identified bases in Sanger Sequencing. The system post-processes a KB basecalled chromatogram. It selects a recoverable subset of N-labels in the KB-called chromatogram to replace with basecalls (A,C,G,T). An N-label correction is defined given an additional read of the same sequence, and a human finished sequence. Corrections are added to the dataset when an alignment determines the additional read and human agree on the identity of the N-label. KB must also rate the replacement with quality value of in the additional read. Corrections are only available during system training. Developing the system, nearly 850,000 N-labels are obtained from Barcode of Life Datasystems, the premier database of genetic markers called DNA Barcodes. Increasing the number of correct bases improves reference sequence reliability, increases sequence identification accuracy, and assures analysis correctness. Keeping with barcoding standards, our system maintains an error rate of percent. Our system only applies corrections when it estimates low rate of error. Tested on this data, our automation selects and recovers: 79 percent of N-labels from COI (animal barcode); 80 percent from matK and rbcL (plant barcodes); and 58 percent from non-protein-coding sequences (across eukaryotes).

Results of the Test Program for Replacement of AK-225G Solvent for Cleaning NASA Propulsion Oxygen Systems

Science.gov (United States)

Lowrey, Nikki M.; Mitchell, Mark A.

2016-01-01

Since the 1990's, when the Class I Ozone Depleting Substance (ODS) chlorofluorocarbon-113 (CFC-113) was banned, NASA's propulsion test facilities at Marshall Space Flight Center (MSFC) and Stennis Space Center (SSC) have relied upon the solvent AsahiKlin AK-225 (hydrochlorofluorocarbon-225ca/cb or HCFC-225ca/cb) and, more recently AK-225G (the single isomer form, HCFC-225cb) to safely clean and verify the cleanliness of large scale propulsion oxygen systems. Effective January 1, 2015, the production, import, export, and new use of Class II Ozone Depleting Substances, including AK-225G, was prohibited in the United States by the Clean Air Act. In 2012 through 2014, NASA test labs at MSFC, SSC, and Johnson Space Center's White Sands Test Facility (WSTF) collaborated to seek out, test, and qualify a solvent replacement for AK-225G that is both an effective cleaner and safe for use with oxygen systems. This paper summarizes the tests performed, results, and lessons learned.

Get the lead out: Wildlife advocates file suit to replace toxic ammo ...

African Journals Online (AJOL)

2007-03-02

Mar 2, 2007 ... Get the lead out: Wildlife advocates file suit to replace toxic ammo with safer alternatives. Simple, practical ... who eats game, which often contains shot or small metal fragments. Lead is an extremely toxic ... eating meat from animals taken with lead ammunition often have unhealthy lead levels in their own ...

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

The replacement of an electromagnetic primary sodium sampling pump in the Fast Flux Test Facility

International Nuclear Information System (INIS)

Grygiel, M.L.; McCargar, C.G.

1985-01-01

On November 16, 1984 a leak was discovered in one of the Fast Flux Test Facility (FFTF) Primary Sodium Sampling System electromagnetic pumps. The leak was discovered in the course of routine cell entry to investigate a shorted trace heat element. The purpose of this paper is to describe the circumstances surrounding the occurrence of the leak, the actions taken to replace the damaged pump and the additional steps which were necessary to return the plant to power. In addition, the processes involved in producing the leak are described briefly. The relative ease of recovery from this incident is indicative of the overall feasibility of the Liquid Metal Reactor (LMR) operational concept

Biological X-ray irradiator characterization for use with small animals and cells.

Science.gov (United States)

Bruno, A Colello; Mazaro, S J; Amaral, L L; Rego, E M; Oliveira, H F; Pavoni, J F

2017-03-02

This study presents the characterization of an X-ray irradiator through dosimetric tests, which confirms the actual dose rate that small animals and cells will be exposed to during radiobiological experiments. We evaluated the linearity, consistency, repeatability, and dose distribution in the positions in which the animals or cells are placed during irradiation. In addition, we evaluated the performance of the X-ray tube (voltage and tube operating current), the radiometric survey (leakage radiation) and safety devices. The irradiator default setting was established as 160 kV and 25 mA. Tests showed that the dose rate was linear overtime (R2=1) and remained stable for long (constant) and short (repeatability) intervals between readings. The mean dose rate inside the animal cages was 1.27±0.06 Gy/min with a uniform beam of 95.40% (above the minimum threshold guaranteed by the manufacturer). The mean dose rate inside the cell plates was 0.92±0.19 Gy/min. The dose rate dependence with tube voltage and current presented a quadratic and linear relationship, respectively. There was no observed mechanical failure during evaluation of the irradiator safety devices and the radiometric survey obtained a maximum ambient equivalent dose rate of 0.26 mSv/h, which exempts it from the radiological protection requirements of the International Atomic Energy Agency. The irradiator characterization enables us to perform radiobiological experiments, and assists or even replaces traditional therapy equipment (e.g., linear accelerators) for cells and small animal irradiation, especially in early research stages.

Biological X-ray irradiator characterization for use with small animals and cells

Directory of Open Access Journals (Sweden)

A. Colello Bruno

Full Text Available This study presents the characterization of an X-ray irradiator through dosimetric tests, which confirms the actual dose rate that small animals and cells will be exposed to during radiobiological experiments. We evaluated the linearity, consistency, repeatability, and dose distribution in the positions in which the animals or cells are placed during irradiation. In addition, we evaluated the performance of the X-ray tube (voltage and tube operating current, the radiometric survey (leakage radiation and safety devices. The irradiator default setting was established as 160 kV and 25 mA. Tests showed that the dose rate was linear overtime (R2=1 and remained stable for long (constant and short (repeatability intervals between readings. The mean dose rate inside the animal cages was 1.27±0.06 Gy/min with a uniform beam of 95.40% (above the minimum threshold guaranteed by the manufacturer. The mean dose rate inside the cell plates was 0.92±0.19 Gy/min. The dose rate dependence with tube voltage and current presented a quadratic and linear relationship, respectively. There was no observed mechanical failure during evaluation of the irradiator safety devices and the radiometric survey obtained a maximum ambient equivalent dose rate of 0.26 mSv/h, which exempts it from the radiological protection requirements of the International Atomic Energy Agency. The irradiator characterization enables us to perform radiobiological experiments, and assists or even replaces traditional therapy equipment (e.g., linear accelerators for cells and small animal irradiation, especially in early research stages.

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

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…

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.

Diagnosis of animal diseases using nuclear and related techniques: Developments and trends

International Nuclear Information System (INIS)

Anderson, J.; McKay, J.A.

1991-01-01

Nuclear techniques such as radioimmune precipitation, radioimmunoassay, DNA cloning and amino acid sequencing have led to a greater understanding of protein structure and function, antigenic variation and the immune response to infection. Knowledge gained from the use of this technology has led to the development of improved diagnostic assays. Although radioimmunoassay has been used for animal disease diagnosis for many years, more recently it has been replaced by the enzyme linked immunosorbent assay (ELISA). The ELISA offers advantages in speed of reading and longer reagent shelf life and obviates the use of radiochemicals. This is particularly important in developing countries, which may have no facilities for storage, handling and disposal of radioactive materials. In the case of rinderpest diagnosis, taken as an example, the virus neutralization test was replaced by a simple indirect ELISA for seromonitoring throughout the Pan-African Rinderpest Campaign. In the near future, this will be replaced by a competitive ELISA using a rinderpest specific monoclonal antibody, which will offer significant advantages in sensitivity and specificity. In the future it may be possible to replace the rinderpest antigen with vector expressed proteins or synthetic polypeptides. More recent developments such as the 'amplified' ELISA and the use of fluorogenic and bioluminescent substrates may further improve disease diagnosis. The knowledge gained from the use of modern technology is essential to the development of improved diagnostic assays which in turn will lead to improved disease diagnosis and control. (author). 9 refs

The Reliable Replacement Warhead Program: Background and Current Developments

National Research Council Canada - National Science Library

Medalia, Jonathan

2008-01-01

...), part of a larger Stockpile Stewardship Program (SSP), replaces components. Modifying some components would require a nuclear test, but the United States has observed a test moratorium since 1992...

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...

Shoulder replacement - discharge

Science.gov (United States)

Total shoulder arthroplasty - discharge; Endoprosthetic shoulder replacement - discharge; Partial shoulder replacement - discharge; Partial shoulder arthroplasty - discharge; Replacement - shoulder - discharge; Arthroplasty - shoulder - discharge

Replacing penalties

Directory of Open Access Journals (Sweden)

Vitaly Stepashin

2017-01-01

Full Text Available УДК 343.24The subject. The article deals with the problem of the use of "substitute" penalties.The purpose of the article is to identify criminal and legal criteria for: selecting the replacement punishment; proportionality replacement leave punishment to others (the formalization of replacement; actually increasing the punishment (worsening of legal situation of the convicted.Methodology.The author uses the method of analysis and synthesis, formal legal method.Results. Replacing the punishment more severe as a result of malicious evasion from serving accused designated penalty requires the optimization of the following areas: 1 the selection of a substitute punishment; 2 replacement of proportionality is serving a sentence other (formalization of replacement; 3 ensuring the actual toughening penalties (deterioration of the legal status of the convict. It is important that the first two requirements pro-vide savings of repression in the implementation of the replacement of one form of punishment to others.Replacement of punishment on their own do not have any specifics. However, it is necessary to compare them with the contents of the punishment, which the convict from serving maliciously evaded. First, substitute the punishment should assume a more significant range of restrictions and deprivation of certain rights of the convict. Second, the perfor-mance characteristics of order substitute the punishment should assume guarantee imple-mentation of the new measures.With regard to replacing all forms of punishment are set significant limitations in the application that, in some cases, eliminates the possibility of replacement of the sentence, from serving where there has been willful evasion, a stricter measure of state coercion. It is important in the context of the topic and the possibility of a sentence of imprisonment as a substitute punishment in cases where the original purpose of the strict measures excluded. It is noteworthy that the

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.

Role of Nano-Mineral as A Feed Additive to Enhance Animal Productivity and Quality of Animal Products

Directory of Open Access Journals (Sweden)

Frans Kurnia

2012-12-01

Full Text Available A development of nanotechnology today has penetrated almost all areas of life. Utilization in improving livestock production can be done by replacing commonly used conventional mineral by nanoparticles-mineral. Application of chromium (Cr, selenium (Se, silver (Ag and copper (Cu nanoparticles are reported to improve livestock production. However, the potential risk of the application such as mineral deposit in the body of animal itself and to people as consumers of livestock product has to be evaluated. Nanoparticle-minerals that have smaller size are easier to penetrate the cells and it is suspected that it may give more negative risk. Analysis evaluation of nanoparticle-minerals in the animal including people are still being developed.

Utilization of noodle waste as replacement for maize in the diets of ...

African Journals Online (AJOL)

Maize is a major source of energy. It is expensive because of competition between man, animal and a strong demand for it by the manufacturing/industrial sector. Noodle waste (NW) (a by-product from the wheat noodle processing industry) which attracts little/ almost zero cost was used to replace the maize fraction of the ...

Mechanical Properties of Lightweight Concrete Using Recycled Cement-Sand Brick as Coarse Aggregates Replacement

Science.gov (United States)

Joohari, Ilya; Farhani Ishak, Nor; Amin, Norliyati Mohd

2018-03-01

This paper presents the result of replacing natural course aggregate with recycled cement-sand brick (CSB) towards the mechanical properties of concrete. Natural aggregates were used in this study as a control sample to compare with recycled coarse aggregates. This study was also carried to determine the optimum proportion of coarse aggregates replacement to produce lightweight concrete. Besides, this study was conducted to observe the crack and its behaviour development during the mechanical testing. Through this study, four types of concrete mixed were prepared, which were the control sample, 25%, 50% and 75% replacement of CSB. The test conducted to determine the effectiveness of recycled CSB as coarse aggregates replacement in this study were slump test, density measurement, compression test, and flexural test and. The strength of concrete was tested at 7 days and 28 days of curing. From the results obtained, the optimum proportion which produced the highest strength is 25% replacement of recycled CSB. The compressive and flexural strength has decreased by 10%-12% and 4%-34% respectively compared to the control sample. The presence of recycled coarse aggregates in sample has decreased the density of concrete by 0.8%-3% compared to the control sample.

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.

Teste de um sucedâneo na produção de vitelos Test of a milk replacer for veal calves

Directory of Open Access Journals (Sweden)

Pedro Afonso Moreira Alves

2001-06-01

difference among treatments for calves daily weight gain (NS, age at slaughter (P=.06701 and carcass rate (P=0,21527; however, calves on treatment III showed higher dry matter feed intake (P=.00055 and, consequently lower feed efficiency (P=.00021. There was no significant difference among treatments for scours (P>.05 and nasal flow. The utilization of the tested milk replacer would be economically feasible if the price of 1kg of de product (powder would be lower than 6.4 times the price of 1kg of whole milk.

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.

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.

Platelet lysate: a replacement for fetal bovine serum in animal cell culture?

OpenAIRE

Johansson, Liselott; Klinth, Jeanna; Holmqvist, Olov; Ohlson, Sten

2003-01-01

A new cell culture supplement, platelet lysate, was evaluated with reference to fetal bovine serum (FBS), an established industrial medium for animal cell culture. Chemical and bacteriological profiles were conducted including the presence of platelet-derived growth factor (PDGF). PDGF was detected in the platelet lysate but it was not present in FBS. The platelet lysate medium demonstrated lack of microorganisms, mycoplasma and endotoxins. The platelet lysate was investigated in culture stud...

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 (P_cr) 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 P_cr 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 P_cr 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

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.

From beef to beans: Eating motives and the replacement of animal proteins with plant proteins among Finnish consumers.

Science.gov (United States)

Vainio, Annukka; Niva, Mari; Jallinoja, Piia; Latvala, Terhi

2016-11-01

A better understanding of the motives underlying the adoption of sustainable and healthy diets is needed for designing more effective policies. The aim of the study was to examine how eating motives were associated with self-reported changes in the consumption of beef, beans, and soy products, i.e., changes related to reducing animal and increasing plant proteins. The study analysed a survey of an adult population living in Finland (N = 1048). The eating motives were measured with the Eating Motivation Survey (TEMS), which distinguishes between 15 eating motives. Six clusters of consumers based on self-reported changes in food choices were identified with latent class analysis (LCA). Four clusters had established food consumption patterns ("Beef only", "Beef and beans", "Beef, beans, and soy products", and "No beef"), one was undergoing a change, and one had attempted a change earlier. ANOVA with planned contrasts revealed that the motives relating to natural concerns, health, and weight control were higher, and convenience and price lower, among those who had an established diet including beans and soy products, as compared to those who consumed only beef. Those undergoing a dietary change expressed a higher endorsement of natural concerns as well as health, sociability, social image, and price motives than those with an established diet including beans and soy products. The results suggest that eating motives play an important role in changing towards more sustainable food consumption patterns in which meat/beef is replaced with plant proteins. Copyright © 2016 Elsevier Ltd. All rights reserved.

Russia: update on animal experiments and alternatives in education.

Science.gov (United States)

Jukes, Nick

2008-01-01

Progress continues in Russia with growing awareness and implementation of alternatives in education. Further outreach visits and negotiations for replacement have been made by InterNICHE campaigners. Russian language information resources have been complemented by the distribution of translated freeware physiology and pharmacology alternatives; and the InterNICHE Alternatives Loan Systems continue to provide valuable hands-on access to a range of learning tools. Donations of computers and alternatives have established exemplary multimedia laboratories, with software having directly replaced the annual use of several thousand animals. New agreements have been made with institutes to abandon animal experiments for teaching purposes. Work to consolidate the successes is being done, and Russian teachers have begun to present at conferences to share their experiences of implementation. Further development and implementation of alternatives is being achieved through grant funding from the InterNICHE Humane Education Award. Using a different approach, cases of determined conscientious objection have included a campaign against the use of stolen companion animals for surgery practice in the Russian Far East, and a continuing legal challenge to experiments at Moscow State University. This multi-pronged, decentralised and culturally appropriate campaigning strategy has proved to be an effective approach to achieving sustainable change in Russia.

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.

Ankle replacement

Science.gov (United States)

Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... Ankle replacement surgery is most often done while you are under general anesthesia. This means you will ...

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.

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

Nicotine replacement therapy

Science.gov (United States)

Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Before you start using a nicotine replacement product, here are some things to know: The more cigarettes you smoke, the higher the dose you may need to ...

Hip Replacement Surgery

Science.gov (United States)

... Outreach Initiative Breadcrumb Home Health Topics English Español Hip Replacement Surgery Basics In-Depth Download Download EPUB ... PDF What is it? Points To Remember About Hip Replacement Surgery Hip replacement surgery removes damaged or ...

Soil Overconsolidation Changes Caused by Dynamic Replacement

Science.gov (United States)

Piotr, Kanty; Sławomir, Kwiecień; Jerzy, Sękowski

2017-10-01

In the dynamic replacement method (DR) the soil is improved by initially dropping a large weight (typically 8-20 t) pounder from a significant height up to 25 m. The created crater is filled with a stronger material (gravel, rubble, stone aggregate, debris), and the pounder is dropped once or multiple times again. The construction of dynamic replacement pillars influences the parameters of the adjacent soil. It results from the energy generated by dropping a pounder into the soil. In the current practice, these changes are not taken into the account during the design. This paper focuses on the changes of overconsolidation ratio (OCR) and in situ coefficient of lateral earth pressure (K) values estimated base on cone penetration test (CPTU) and Dilatometric test (DMT) performed at a test site. A single column was constructed and the ground around the column was examined using CPTU and DMT, performed at different distances from the column centre (2, 3, 4 and 6 m) and at different time intervals (during construction and 1, 8, 30 days later). The column was constructed in so-called transition soils (between cohesive and non-cohesive). While interpreting the results of the research, the authors addressed the matter of choosing the procedure of OCR and K indication for transition soils (in this case described as silts and/or sandy silts). Overconsolidation changes may differ depending on the chosen analysis procedure (for cohesive or non-cohesive soils). On the basis of the analysis presented in the paper and the observation of soil (acknowledged as cohesive according to macroscopic observations) during column excavation, it was decided that for more detailed analyses methods dedicated to cohesive soils should be applied. Generally, it can be stated that although the changes were complex, DR pillar formation process resulted in the increase of these parameters. The average increases of OCR and K values were 25% and 10% respectively. The post installation values are not

Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats

OpenAIRE

de Jonge, Paul K. J. D.; Sloff, Marije; Janke, Heinz P.; Kortmann, Barbara B. M.; de Gier, Robert P. E.; Geutjes, Paul J.; Oosterwijk, Egbert; Feitz, Wout F. J.

2017-01-01

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats. Similarly to a previous study in pigs, the ureteral J-stent was blindly inserted until some resistance was met. During evaluation of the goats after three months, perforation of the renal cortex by th...

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.

Opportunities for improving animal welfare in rodent models of epilepsy and seizures.

Science.gov (United States)

Lidster, Katie; Jefferys, John G; Blümcke, Ingmar; Crunelli, Vincenzo; Flecknell, Paul; Frenguelli, Bruno G; Gray, William P; Kaminski, Rafal; Pitkänen, Asla; Ragan, Ian; Shah, Mala; Simonato, Michele; Trevelyan, Andrew; Volk, Holger; Walker, Matthew; Yates, Neil; Prescott, Mark J

2016-02-15

Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important area for application of the 3Rs (replacement, reduction and refinement of animal use). This report provides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality of studies in this area. The report includes practical guidance on principles of choosing a model, induction procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social housing, environmental enrichment, reporting of studies and data sharing. In addition, some model-specific welfare considerations are discussed, and data gaps and areas for further research are identified. The guidance is based upon a systematic review of the scientific literature, survey of the international epilepsy research community, consultation with veterinarians and animal care and welfare officers, and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Performance and hemtochemical parameters of buck-kids fed concentrate partially replaced with tropical Piliostigma thonningii foliage.

Science.gov (United States)

Olafadehan, Olurotimi A; Njidda, Ahmed A; Okunade, Sunday A; Salihu, Sarah O; Balogun, David O; Salem, Abdelfattah Z M

2018-02-01

Fifteen 5-month-old Red Sokoto buck-kids, (6.6 ± 0.71 kg body weight (BW)) randomly distributed into three groups of five animals per group, were used to study the effects of supplementary concentrate partially replaced with Piliostigma thonningii (PT) foliage on the growth performance, economic benefit and blood profile in a completely randomized design using analysis of variance. The goats in group 1 received 100% supplementary concentrates (PT0), groups 2 and 3 received 25% (PT25) and 50% (PT50), respectively, of concentrate replaced with an equal amount (dry matter basis) of Piliostigma foliage. The goats were fed a basal diet of threshed sorghum top (TST). Intake of concentrate, hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, total feeding cost and cost/kg BW were greater (P kids. © 2017 Japanese Society of Animal Science.

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...

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

Science.gov (United States)

Taylor, Katy; Casalegno, Carlotta; Stengel, Wolfgang

2011-01-01

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

Potency testing of veterinary vaccines: the way from in vivo to in vitro.

Science.gov (United States)

Romberg, Judith; Lang, Stefan; Balks, Elisabeth; Kamphuis, Elisabeth; Duchow, Karin; Loos, Daniela; Rau, Henriette; Motitschke, Andreas; Jungbäck, Carmen

2012-01-01

Current quality control of inactivated animal vaccines still focuses on the potency of final products in a batch-wise manner. Animal welfare concerns as well as scientific considerations have led to the '3Rs-concept' that comprises the refinement of animal procedures, the reduction of animal numbers, and the replacement of animal models. Although the 3Rs-concept has been widely accepted as a fundamental principle, the number of approved alternatives for in vivo tests is still limited. To promote further progress, the international scientific workshop 'Potency Testing of Veterinary Vaccines: The Way from in vivo to in vitro' was held at the Paul-Ehrlich-Institut in Langen, Germany, on 01-03 December 2010. More than 130 participants from industry, academia and regulatory authorities discussed the current state of the 3Rs-concept, examples of its successful implementation as well as still existing hurdles. Special emphasis was laid on the 'consistency approach' that aims to ensure relevant quality attributes of vaccine batches by in vitro analyses during production rather than by in vivo potency tests on the final product. This report provides an overview of the insights gained, including the recommendations produced at the end of the workshop. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

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...

Protein Hydrolysates from Non-bovine and Plant Sources Replaces Tryptone in Microbiological Media

Science.gov (United States)

Ranganathan, Yamini; Patel, Shifa; Pasupuleti, Vijai K.; Meganathan, R.

Tryptone (pancreatic digest of casein) is a common ingredient in laboratory and fermentation media for growing wild-type and genetically modified microorganisms. Many of the commercially manufactured products such as human growth hormone, antibiotics, insulin, etc. are produced by recombinant strains grown on materials derived from bovine sources. With the emergence of Bovine Spongiform Encephalopathy (BSE) and the consequent increase in Food and Drug Administration (FDA) regulations, elimination of materials of bovine origin from fermentation media is of paramount importance. To achieve this objective, a number of protein hydrolysates derived from non-bovine animal and plant sources were evaluated. Tryptone in Luria-Bertani (LB) broth was replaced with an equal quantity of alternate protein hydrolysates. Four of the six hydrolysates (one animal and three from plants) were found to efficiently replace the tryptone present in LB-medium as measured by growth rate and growth yield of a recombinant Escherichia coli strain. In addition, we have determined plasmid stability, inducibility and activity of the plasmid encoded β-galactosidase in the recombinant strain grown in the presence of various protein hydrolysates.

BABAR IFR Replacement R and D

CERN Document Server

Berry, M

2003-01-01

The Instrumented Flux Return (IFR) of the BaBar detector will soon need to be replaced by a more robust muon detection system. Scintillator bars with embedded Wavelength Shifting (WLS) fibers and Limited Streamer Tubes are two replacement technology options. The scintillator bars are tested for attenuation length; and causes for the large width of the Photo Multiplier Tube (PMT) signal are analyzed by Monte Carlo simulation. Cooling techniques for Avalanche Photo Diodes (APD) are investigated. The fairly high attenuation length coupled with the narrow PMT signal make the scintillator a viable option for a muon detecting system. Continuing work will focus on increasing timing resolution using an APD to read the signal from the WLS fibers, and investigating the lifetime of the APD. The ability to read a signal from the LST on external copper strips is tested and signals are found to be clearly distinguishable from noise. The voltage is compared to count rate to find that the optimal operating voltage for the LS...

Knee Replacement

Science.gov (United States)

Knee replacement is surgery for people with severe knee damage. Knee replacement can relieve pain and allow you to ... Your doctor may recommend it if you have knee pain and medicine and other treatments are not ...

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

Radioisotopes In Animal Production Research

International Nuclear Information System (INIS)

Eduvie, L.O.

1994-05-01

Animal productivity may be measured among others, in terms of two important physiological processes of reproduction and growth each of which involves a number of integrated disciplines. Both physiological processes are controlled by interactions of genotype and environment. Reproduction essentially involves complex physiological processes controlled by secretions of endocrine glands known as hormones. On the other hand growth is determined largely by availabilty of essential nutrients. In order to achieve good reproductive and growth rates adequate and constant nutrition for livestock include pasture, cereals, tubers and their by-products as well as industrial by-products. While reproduction is essential to provide the required number and replacement of livestock, growth guarantees availability of meat. Another aspect of livestock production is disease control. An animal needs a good health to adequately express its genetic make up and utilize available nutrition. Research in animal production is aimed at improving all aspects of productivity of livestock which include reproduction, growth, milk production, egg production, good semen etc. of livestock. In order to achieve this an understanding of the biochemical and physiological processes occurring in the animal itself, and in the feedstuff fed to the animal as well as the aetiology and control of diseases affecting the animal among other factors, is desirable. A number of methods of investigation have evolved with time. These include colorimetry, spectrophotometry, chromatography, microscopy and raidoisotopic tracer methods. While most of these methods are cumbersome and use equipment with low precision, radioisotopic tracer methods utilize equipment with relatively high precision

21 CFR 58.43 - Animal care facilities.

Science.gov (United States)

2010-04-01

... testing facility shall have a sufficient number of animal rooms or areas, as needed, to assure proper: (1... (4) routine or specialized housing of animals. (b) A testing facility shall have a number of animal... shall exist for the collection and disposal of all animal waste and refuse or for safe sanitary storage...

Perspective on the Ongoing Replacement of Artificial and Animal-Based Dyes with Alternative Natural Pigments in Foods and Beverages.

Science.gov (United States)

Schweiggert, Ralf M

2018-03-28

This perspective highlights current trends, advances, and challenges related to the replacement of artificial dyes and the insect-based carmine with alternative natural pigments. Briefly reviewing the history of food coloration, key publications and public events leading to diverse concerns about artificial dyes and carmine will be summarized. An overview about promising alternatives in the market and those under development is provided, including a separate section on coloring foodstuffs. The perspective aims at supporting readers to keep abreast with the enormous efforts undertaken by the food and beverage industry to replace certain food dyes.

Hip Joint Replacement Using Monofilament Polypropylene Surgical Mesh: An Animal Model

Directory of Open Access Journals (Sweden)

Jacek Białecki

2014-01-01

Full Text Available Hip joint dysplasia is a deformation of the articular elements (pelvic acetabulum, head of the femur, and/or ligament of the head of the femur leading to laxity of the hip components and dislocation of the femoral head from the pelvic acetabulum. Diagnosis is based on symptoms observed during clinical and radiological examinations. There are two treatment options: conservative and surgical. The classic surgical procedures are juvenile pubic symphysiodesis (JPS, triple pelvic osteotomy (TPO, total hip replacement (THR, and femoral head and neck resection (FHNE. The aim of this experiment was to present an original technique of filling the acetabulum with a polypropylene implant, resting the femoral neck directly on the mesh. The experiment was performed on eight sheep. The clinical value of the new surgical technique was evaluated using clinical, radiological, and histological methods. This technique helps decrease the loss of limb length by supporting the femoral neck on the mesh equivalent to the femoral head. It also reduces joint pain and leads to the formation of stable and mobile pseudarthrosis. The mesh manifested osteoprotective properties and enabled the formation of a stiff-elastic connection within the hip joint. The method is very cost-effective and the technique itself is simple to perform.

Solid-State Thyratron Replacement. Final Report

Energy Technology Data Exchange (ETDEWEB)

Roth, Ian [Diversified Technologies, Inc., Bedford, MA

2017-12-12

Under this SBIR, DTI developed a solid-state switch as an alternative to legacy thyratron equipment. Our Phase II objective was to make a solid-state thyratron replacement that would provide equivalent or better performance, much higher reliability (at least a 20 year lifetime, compared to a thyratron’s two-year lifetime) and would sell for ~3x the cost of a thyratron, or less than $40k. We were successful in building a solid-state switch which could reliably function as a thyratron replacement. The unit was designed to directly replace the thyratrons currently being used at SLAC’s Linac Coherent Light Source (LCLS), and was built in a tank that was small enough to fit into the existing thyratron cabinet, providing a true form-fit-function replacement path. We tested the switch at the full operating specifications: 48 kV, 6.3 kA, and 1 µs risetime. We also demonstrated a peak-to-peak pulse jitter of 1.5 ns, which is five times shorter than is typical for thyratrons. This lower jitter would improve the performance of the LCLS beam. The predicted reliability is more than 80 years, which is 40 times greater than a thyratron.

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.

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.

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

Fat Reduction and Replacement in Dry-Cured Fermented Sausage by Using High Pressure Processing Meat as Fat Replacer and Olive Oil

Directory of Open Access Journals (Sweden)

Bolumar Tomas

2015-09-01

Full Text Available The present paper describes the modification of the lipid fraction of dry-cured fermented sausage through fat reduction (35% and fat replacement of animal fat with olive oil (up to 10%. High pressure processing (HPP treated meat was employed as a novel fat replacer to reduce the fat content and as a new strategy to enable a stable incorporation of olive oil in dry-cured fermented sausages. Chemical (proximate composition and fatty acid profile, physical (water retention, structure formation and colour and sensorial (appearance, texture and flavour properties were evaluated. It is concluded that 35% of fat reduction is possible without reduction of consumer acceptability. Moreover, the addition of HPP-treated meat as a fat replacer resulted in good mimic of the fat particles together with good physical and sensory properties. Therefore, it resulted in an effective and clean alternative (no added-additives for fat reduction. However, the incorporation of olive oil either by direct addition (4.3% oil or within a HPP-created protein network (10% oil resulted in unacceptable products since the oil was not properly retained inside the sausage matrix. Further studies are needed to find processing strategies that permit a stable incorporation of liquid plant oils to dry-cured fermented sausage for the development of healthier and more sustainable dry-cured fermented meat products.

Psychosocial determinants of outcomes in knee replacement.

Science.gov (United States)

Lopez-Olivo, Maria A; Landon, Glenn C; Siff, Sherwin J; Edelstein, David; Pak, Chong; Kallen, Michael A; Stanley, Melinda; Zhang, Hong; Robinson, Kausha C; Suarez-Almazor, Maria E

2011-10-01

To identify potential psychosocial and educational barriers to clinical success following knee replacement. The authors evaluated 241 patients undergoing total knee replacement, preoperatively and 6 months after surgery. Outcomes included the Western Ontario McMaster (WOMAC) scale and the Knee Society rating system (KSRS). Independent variables included: the medical outcome study-social support scale; depression, anxiety and stress scale; brief COPE inventory; health locus of control; arthritis self-efficacy scale and the life orientation test-revised. Multiple regression models evaluated associations of baseline demographic and psychosocial variables with outcomes at 6 months, controlling for body mass index, comorbidities and baseline outcome scores. Patients' mean age was 65 ± 9 years; 65% were women. Most patients improved outcomes after surgery. Several psychosocial variables were associated with outcomes. Regression analyses indicated lower education, less tangible support, depression, less problem-solving coping, more dysfunctional coping, lower internal locus of control were associated with worse WOMAC scores (R(2) contribution of psychosocial variables for pain 0.07; for function, 0.14). Older age, lower education, depression and less problem-solving coping were associated with poorer total KSRS scores (R(2) contribution of psychosocial variables to total KSRS model 0.09). Psychosocial variables as a set contributed from 25% to 74% of total explained variance across the models tested. Patients' level of education, tangible support, depression, problem-solving coping, dysfunctional coping and internal locus of control were associated with pain and functional outcomes after knee replacement. The findings suggest that, in addition to medical management, perioperative psychosocial evaluation and intervention are crucial in enhancing knee replacement outcomes.

A low percentage of autologous serum can replace bovine serum to engineer human nasal cartilage

Directory of Open Access Journals (Sweden)

F Wolf

2008-02-01

Full Text Available For the generation of cell-based therapeutic products, it would be preferable to avoid the use of animal-derived components. Our study thus aimed at investigating the possibility to replace foetal bovine serum (FBS with autologous serum (AS for the engineering of cartilage grafts using expanded human nasal chondrocytes (HNC. HNC isolated from 7 donors were expanded in medium containing 10% FBS or AS at different concentrations (2%, 5% and 10% and cultured in pellets using serum-free medium or in Hyaff®-11 meshes using medium containing FBS or AS. Tissue forming capacity was assessed histologically (Safranin O, immunohistochemically (type II collagen and biochemically (glycosaminoglycans -GAG- and DNA. Differences among experimental groups were assessed by Mann Whitney tests. HNC expanded under the different serum conditions proliferated at comparable rates and generated cartilaginous pellets with similar histological appearance and amounts of GAG. Tissues generated by HNC from different donors cultured in Hyaff®-11 had variable quality, but the accumulated GAG amounts were comparable among the different serum conditions. Staining intensity for collagen type II was consistent with GAG deposition. Among the different serum conditions tested, the use of 2% AS resulted in the lowest variability in the GAG contents of generated tissues. In conclusion, a low percentage of AS can replace FBS both during the expansion and differentiation of HNC and reduce the variability in the quality of the resulting engineered cartilage tissues.

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.

Coded Aperture Nuclear Scintigraphy: A Novel Small Animal Imaging Technique

Directory of Open Access Journals (Sweden)

Dawid Schellingerhout

2002-10-01

Full Text Available We introduce and demonstrate the utility of coded aperture (CA nuclear scintigraphy for imaging small animals. CA imaging uses multiple pinholes in a carefully designed mask pattern, mounted on a conventional gamma camera. System performance was assessed using point sources and phantoms, while several animal experiments were performed to test the usefulness of the imaging system in vivo, with commonly used radiopharmaceuticals. The sensitivity of the CA system for 99mTc was 4.2 × 103 cps/Bq (9400 cpm/μCi, compared to 4.4 × 104 cps/Bq (990 cpm/μCi for a conventional collimator system. The system resolution was 1.7 mm, as compared to 4–6 mm for the conventional imaging system (using a high-sensitivity low-energy collimator. Animal imaging demonstrated artifact-free imaging with superior resolution and image quality compared to conventional collimator images in several mouse and rat models. We conclude that: (a CA imaging is a useful nuclear imaging technique for small animal imaging. The advantage in signal-to-noise can be traded to achieve higher resolution, decreased dose or reduced imaging time. (b CA imaging works best for images where activity is concentrated in small volumes; a low count outline may be better demonstrated using conventional collimator imaging. Thus, CA imaging should be viewed as a technique to complement rather than replace traditional nuclear imaging methods. (c CA hardware and software can be readily adapted to existing gamma cameras, making their implementation a relatively inexpensive retrofit to most systems.

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.

Guidelines for the welfare and use of animals in cancer research

Science.gov (United States)

Workman, P; Aboagye, E O; Balkwill, F; Balmain, A; Bruder, G; Chaplin, D J; Double, J A; Everitt, J; Farningham, D A H; Glennie, M J; Kelland, L R; Robinson, V; Stratford, I J; Tozer, G M; Watson, S; Wedge, S R; Eccles, S A

2010-01-01

Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice. PMID:20502460

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

OpenAIRE

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

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.

Defining line replaceable units

NARCIS (Netherlands)

Parada Puig, J. E.; Basten, R. J I

2015-01-01

Defective capital assets may be quickly restored to their operational condition by replacing the item that has failed. The item that is replaced is called the Line Replaceable Unit (LRU), and the so-called LRU definition problem is the problem of deciding on which item to replace upon each type of

Reversal learning in gonadectomized marmosets with and without hormone replacement: are males more sensitive to punishment?

Science.gov (United States)

LaClair, Matthew; Lacreuse, Agnès

2016-05-01

This study examined sex differences in executive function in middle-aged gonadectomized marmosets (Callithrix jacchus) with or without hormonal replacement. We tested ten castrated male (mean age 5.5 years) marmosets treated with testosterone cypionate (T, n = 5) or vehicle (n = 5) on Reversal Learning, which contributes to cognitive flexibility, and the Delayed Response task, measuring working memory. Their performance was compared to that of 11 ovariectomized females (mean age = 3.7 years) treated with Silastic capsules filled with 17-β estradiol (E2, n = 6) or empty capsules (n = 5), previously tested on the same tasks (Lacreuse et al. in J Neuroendocrinol 26:296-309, 2014. doi: 10.1111/jne.12147). Behavioral observations were conducted daily. Females exhibited more locomotor behaviors than males. Males and females did not differ in the number of trials taken to reach criterion on the reversals, but males had significantly longer response latencies, regardless of hormone replacement. They also had a greater number of refusals than females. Additionally, both control and T-treated males, but not females, had slower responses on incorrect trials, suggesting that males were making errors due to distraction, lack of motivation or uncertainty. Furthermore, although both males and females had slower responding following an incorrect compared to a correct trial, the sex difference in response latencies was disproportionally large following an incorrect trial. No sex difference was found in the Delayed Response task. Overall, slower response latencies in males than females during Reversal Learning, especially during and following an incorrect trial, may reflect greater sensitivity to punishment (omission of reward) and greater performance monitoring in males, compared to females. Because these differences occurred in gonadectomized animals and regardless of hormone replacement, they may be organized early in life.

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

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.

Deficits in latent inhibition induced by estradiol replacement are ameliorated by haloperidol treatment

Directory of Open Access Journals (Sweden)

Anne eAlmey

2013-10-01

Full Text Available There are sex differences in the symptomatology of schizophrenia, and in the response to antipsychotic treatments. One hallmark symptom of schizophrenia is a deficit in selective attention. Selective attention can be measured using a latent inhibition (LI paradigm in humans; LI can be measured in rodents, and is used as an animal model of the selective attention deficits observed in schizophrenia. In the current experiments LI was used to clarify whether selective attention differs between male rats and ovariectomized (OVX female rats receiving different estradiol (E2 replacement regimens. An additional aim was to determine whether haloperidol's facilitation of LI is enhanced by E2. Males and OVX female rats were trained in a conditioned emotional response LI paradigm. Females received no E2 replacement, a chronic low dose of E2 via silastic capsule, or a high phasic dose of E2 via silastic capsule accompanied by E2 (10 ug/kg SC injections every fourth day. Actual plasma levels of E2 were determined using an enzyme linked immunosorbent assay. Rats were also administered a vehicle treatment, a 0.05mg/kg, or a 0.1mg/kg IP injection of haloperidol. Males and OVX females that did not receive E2 replacement both exhibited LI, but LI was not observed in the low and high E2 replacement groups. Haloperidol restored LI at a lower dose in the females receiving high E2 replacement compared to females receiving low E2 replacement, indicating that E2 replacement facilitates haloperidol in restoring LI.

Effect of sugar beet tubers as a partial replacer to green fodder on production performance and economics of lactating Surti buffaloes in lean period.

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Sorathiya, L M; Patel, M D; Tyagi, K K; Fulsoundar, A B; Raval, A P

2015-01-01

The objective of this study was to evaluate the effects of sugar beet tubers as a replacer to green fodder on production performance and economics of lactating Surti buffaloes. This trial was conducted at the Livestock Research Station, Navsari Agricultural University, Navsari. Twenty lactating Surti buffaloes in a changeover experimental design were selected to assess the effects of replacing green fodder with sugar beet (Beta vulgaris L.) tubers on production performance, economics of feeding sugar beet and blood biochemical profile. Half (50%) of the hybrid Napier was replaced with sliced sugar beet tubers in the ration of experimental animals. Partial replacement of hybrid Napier with that of sugar beet tubers numerically improved dry matter intake, milk yield, 4% fat corrected milk and milk composition parameters such as fat, solid non-fat, protein and lactose, but not significantly. The blood parameters were in normal range and non-significant except that of glucose and triglycerides, which were increased in the sugar beet group. Replacing sugar beet tubers also proved to be cost-effective with improved net profit around Rs. 6.63/day. It can be concluded that 50% hybrid Napier fodder can be replaced with sugar beet tubers without any adverse effect on animal production performance, milk composition blood biochemical profile and economics of feeding.

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

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Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

Animal production and health newsletter. No. 46, July 2007

International Nuclear Information System (INIS)

2007-07-01

In response to many requests from our readers, I will continue to highlight a practical topic related to animal production and health in this section of the newsletter. Increasing the efficiency of animal reproduction is a critical component of a holistic approach to sustainably increase animal productivity in developing Member States. For example, the resources spent to formulate and obtain the ingredients for dairy rations are wasted when a significant proportion of the cows in the herd are dry due to delays in achieving pregnancy. Effective genetic selection to improve productivity is only possible if a regular supply of potential replacements is generated by the females already in the herd or flock. For this reason, improving reproductive efficiency is a key aspect of many of the APH projects

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

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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.

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

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

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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

Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men.

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Srivastava, Rohit K; Bulte, Jeff W M; Walczak, Piotr; Janowski, Miroslaw

2018-05-01

Neurological disorders are a major threat to public health. Stem cell-based regenerative medicine is now a promising experimental paradigm for its treatment, as shown in pre-clinical animal studies. Initial attempts have been on the replacement of neuronal cells only, but glial progenitors (GPs) are now becoming strong alternative cellular therapeutic candidates to replace oligodendrocytes and astrocytes as knowledge accumulates about their important emerging role in various disease processes. There are many examples of successful therapeutic outcomes for transplanted GPs in small animal models, but clinical translation has proved to be challenging due to the 1,000-fold larger volume of the human brain compared to mice. Human GPs transplanted into the mouse brain migrate extensively and can induce global cell replacement, but a similar extent of migration in the human brain would only allow for local rather than global cell replacement. We review here the mechanisms that govern cell migration, which could potentially be exploited to enhance the migratory properties of GPs through cell engineering pre-transplantation. We furthermore discuss the (dis)advantages of the various cell delivery routes that are available, with particular emphasis on intra-arterial injection as the most suitable route for achieving global cell distribution in the larger brain. Now that therapeutic success has proven to be feasible in small animal models, future efforts will need to be directed to enhance global cell delivery and migration to make bench-to-bedside translation a reality. © 2017 Wiley Periodicals, Inc.

Transcatheter aortic valve replacement

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... gov/ency/article/007684.htm Transcatheter aortic valve replacement To use the sharing features on this page, please enable JavaScript. Transcatheter aortic valve replacement (TAVR) is surgery to replace the aortic valve. ...

Reliability and concurrent validity of the Dutch hip and knee replacement expectations surveys.

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van den Akker-Scheek, Inge; van Raay, Jos J A M; Reininga, Inge H F; Bulstra, Sjoerd K; Zijlstra, Wiebren; Stevens, Martin

2010-10-19

Preoperative expectations of outcome of total hip and knee arthroplasty are important determinants of patients' satisfaction and functional outcome. Aims of the study were (1) to translate the Hospital for Special Surgery Hip Replacement Expectations Survey and Knee Replacement Expectations Survey into Dutch and (2) to study test-retest reliability and concurrent validity. Patients scheduled for total hip (N = 112) or knee replacement (N = 101) were sent the Dutch Expectations Surveys twice with a 2 week interval to determine test-retest reliability. To determine concurrent validity, the Expectation WOMAC was sent. The results for the Dutch Hip Replacement Expectations Survey revealed good test-retest reliability (ICC 0.87), no bias and good internal consistency (alpha 0.86) (N = 72). The correlation between the Hip Expectations Score and the Expectation WOMAC score was 0.59 (N = 86). The results for the Dutch Knee Replacement Expectations Survey revealed good test-retest reliability (ICC 0.79), no bias and good internal consistency (alpha 0.91) (N = 46). The correlation with the Expectation WOMAC score was 0.52 (N = 57). Both Dutch Expectations Surveys are reliable instruments to determine patients' expectations before total hip or knee arthroplasty. As for concurrent validity, the correlation between both surveys and the Expectation WOMAC was moderate confirming that the same construct was determined. However, patients scored systematically lower on the Expectation WOMAC compared to the Dutch Expectation Surveys. Research on patients' expectations before total hip and knee replacement has only been performed in a limited amount of countries. With the Dutch Expectations Surveys it is now possible to determine patients' expectations in another culture and healthcare setting.

Virtual reality and 3D animation in forensic visualization.

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Ma, Minhua; Zheng, Huiru; Lallie, Harjinder

2010-09-01

Computer-generated three-dimensional (3D) animation is an ideal media to accurately visualize crime or accident scenes to the viewers and in the courtrooms. Based upon factual data, forensic animations can reproduce the scene and demonstrate the activity at various points in time. The use of computer animation techniques to reconstruct crime scenes is beginning to replace the traditional illustrations, photographs, and verbal descriptions, and is becoming popular in today's forensics. This article integrates work in the areas of 3D graphics, computer vision, motion tracking, natural language processing, and forensic computing, to investigate the state-of-the-art in forensic visualization. It identifies and reviews areas where new applications of 3D digital technologies and artificial intelligence could be used to enhance particular phases of forensic visualization to create 3D models and animations automatically and quickly. Having discussed the relationships between major crime types and level-of-detail in corresponding forensic animations, we recognized that high level-of-detail animation involving human characters, which is appropriate for many major crime types but has had limited use in courtrooms, could be useful for crime investigation. © 2010 American Academy of Forensic Sciences.

Reposição de cães em área endêmica para leishmaniose visceral Dog replacement in an area endemic for visceral leishmaniasis

Directory of Open Access Journals (Sweden)

Andréa Maria Andrade

2007-10-01

Full Text Available Esse trabalho objetivou estimar a reposição de cães em área endêmica para leishmaniose visceral, onde a eutanásia de animais soropositivos é indicada como medida de controle, e avaliar os motivos que levaram a aquisição ou não de novos animais. Houve a reposição em 44,5% dos casos, principalmente devido à necessidade de companhia ou guarda. O principal motivo para a não-reposição foi o temor da leishmaniose visceral.This study aimed to estimate the dog replacement rate in an area endemic for visceral leishmaniasis, in which slaughter of seropositive animals was indicated as a control measure, and to evaluate the reasons why new animals were or were not acquired. The animals were replaced in 44.5% of the cases, and this was done mainly because of the need for a companion or guard dog. The main reason for not replacing the dog was fear of visceral leishmaniasis.