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

Science.gov (United States)

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

2012-07-01

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

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.

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.

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.

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

Science.gov (United States)

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

2017-10-01

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

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.

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

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

NARCIS (Netherlands)

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

2009-01-01

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

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.

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.

[Alternatives to animal testing].

Science.gov (United States)

Fabre, Isabelle

2009-11-01

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

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

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

Science.gov (United States)

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

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

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...

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

International Nuclear Information System (INIS)

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

2005-01-01

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

Regulatory adequacy of aquatic ecotoxicity testing of nanomaterials

DEFF Research Database (Denmark)

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

2017-01-01

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

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.

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

Science.gov (United States)

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

2014-07-01

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

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

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

Science.gov (United States)

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

2015-12-22

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

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.

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

Alternatives to animal testing: A review.

Science.gov (United States)

Doke, Sonali K; Dhawale, Shashikant C

2015-07-01

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

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 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.

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.

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

International Nuclear Information System (INIS)

Ammerman, D.J.

1997-01-01

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

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.

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

Science.gov (United States)

Roberts, David W; Patlewicz, Grace

2018-01-01

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

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

Science.gov (United States)

Schechtman, Leonard M

2002-01-01

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

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

Science.gov (United States)

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

2015-03-01

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

Non-animal Replacements for Acute Toxicity Testing.

Science.gov (United States)

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

2015-07-01

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

Political incentives towards replacing animal testing in nanotechnology?

Science.gov (United States)

Sauer, Ursula G

2009-01-01

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

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.

Progress Toward Replacing Animals in Toxicity Testing for Cosmetics

OpenAIRE

Nye, Marisa B.

2006-01-01

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

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

Science.gov (United States)

Stokes, William S; Wind, Marilyn

2010-01-01

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

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.

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

Science.gov (United States)

Busquet, Francois; Zurlo, Joanne; Hartung, Thomas

2016-05-01

In the context of the current negotiations between the European Union (EU) and the United States under the Transatlantic Trade Investment Partnership (TTIP), there is the opportunity to look at both legislative frameworks to better pinpoint convergences, synergies, and gaps when it comes to use of laboratory animals for scientific purposes and bring together the best of both worlds. The objectives in this article are to indicate what are the current EU pieces of legislation that are relevant under TTIP regarding the uses of laboratory animals for scientific purposes under the regulations about cosmetics and chemicals, among others. The same approach will be taken to look at the relevant American legal frameworks, that is, the Food and Cosmetics Act and the Toxic Safety Control Act as well as its most recent reauthorization. In conclusion, the authors will identify future frameworks that can contribute to the harmonization of regulatory standards and further steps where TTIP negotiators should strengthen regulatory cooperation. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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...

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

Science.gov (United States)

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

2015-06-01

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

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.

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.

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...

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.

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

Science.gov (United States)

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

2015-10-01

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

9 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...

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

International Nuclear Information System (INIS)

Roberts, J.K.

1976-01-01

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

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.

Evaluation of non-Animal methods for assessing skin Sensitisation hazard

NARCIS (Netherlands)

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

2016-01-01

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

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.

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

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

Science.gov (United States)

Zhang, Y; Du, Y; Wang, S

2000-10-01

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

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

Science.gov (United States)

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

2012-07-01

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

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…

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

Science.gov (United States)

Indans, Ian

2002-02-28

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

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.

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...

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.

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

Science.gov (United States)

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

2010-07-01

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

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

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.

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...

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

Science.gov (United States)

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

2014-11-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Levin, A.E.

1995-09-01

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

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...

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

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

International Nuclear Information System (INIS)

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

1995-01-01

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

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.

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

International Nuclear Information System (INIS)

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

1999-01-01

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

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

Science.gov (United States)

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

2015-02-01

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

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

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

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

Science.gov (United States)

Branson, Bernard M

2015-03-01

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

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

Science.gov (United States)

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

2010-10-05

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

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

Science.gov (United States)

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

2015-11-01

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

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.

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

Science.gov (United States)

2012-02-28

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

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…

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

NARCIS (Netherlands)

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

2014-01-01

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

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

NARCIS (Netherlands)

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

2014-01-01

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

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.

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

Science.gov (United States)

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

2011-07-26

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

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

Science.gov (United States)

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

2016-07-01

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

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)

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

Science.gov (United States)

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

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

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

Science.gov (United States)

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

2012-04-01

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

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.

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).

[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.

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

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

Science.gov (United States)

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

2018-02-07

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

EPA Releases Draft Policy to Reduce Animal Testing for Skin Sensitization

Science.gov (United States)

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

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.

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.

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.

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

Science.gov (United States)

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

2010-02-01

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

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

Science.gov (United States)

2010-03-31

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

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.

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...

Movement of regulatory RNA between animal cells.

Science.gov (United States)

Jose, Antony M

2015-07-01

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

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...

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

Science.gov (United States)

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

Testing and assessment strategies, including alternative and new approaches

DEFF Research Database (Denmark)

Meyer, Otto A.

2003-01-01

The object of toxicological testing is to predict possible adverse effect in humans when exposed to chemicals whether used as industrial chemicals, pharmaceuticals or pesticides. Animal models are predominantly used in identifying potential hazards of chemicals. The use of laboratory animals raises...... ethical concern. However, irrespective of animal welfare it is an important aspect of the discipline of toxicology that the primary object is human health. The ideal testing and assessment strategy is simple to use all the available test methods and preferably more in laboratory animal species from which...... uses and of the absence of health problems involved with their use. Thus, the regulatory toxicology is a cocktail of science and pragmatism added a crucial concern for animal welfare. Test methods are most often used in a testing sequence as bricks in a testing strategy. The main key driving forces...

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.

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.

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

International Nuclear Information System (INIS)

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

1990-01-01

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

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

Animal models of toxicology testing: the role of pigs.

Science.gov (United States)

Helke, Kristi L; Swindle, Marvin Michael

2013-02-01

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

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.

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

Science.gov (United States)

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

2006-08-15

The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

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

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

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

Science.gov (United States)

Hartung, Thomas

2016-01-01

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

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.

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...

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

Science.gov (United States)

Manibusan, M K; Touart, L W

2017-07-01

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

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.

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

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

Science.gov (United States)

Rudenko, Larisa; Matheson, John C

2007-01-01

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

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....

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

Directory of Open Access Journals (Sweden)

Giannakou C

2016-06-01

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

Regulatory changes raise troubling questions for genomic testing.

Science.gov (United States)

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

2014-11-01

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

Regulatory activities

International Nuclear Information System (INIS)

2001-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

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

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

Science.gov (United States)

Schiffelers, Marie-Jeanne W A; Blaauboer, Bas J; Bakker, Wieger E; Beken, Sonja; Hendriksen, Coenraad F M; Koëter, Herman B W M; Krul, Cyrille

2014-06-01

Pharmaceuticals and chemicals are subjected to regulatory safety testing accounting for approximately 25% of laboratory animal use in Europe. This testing meets various objections and has led to the development of a range of 3R models to Replace, Reduce or Refine the animal models. However, these models must overcome many barriers before being accepted for regulatory risk management purposes. This paper describes the barriers and drivers and options to optimize this acceptance process as identified by two expert panels, one on pharmaceuticals and one on chemicals. To untangle the complex acceptance process, the multilevel perspective on technology transitions is applied. This perspective defines influences at the micro-, meso- and macro level which need alignment to induce regulatory acceptance of a 3R model. This paper displays that there are many similar mechanisms within both sectors that prevent 3R models from becoming accepted for regulatory risk assessment and management. Shared barriers include the uncertainty about the value of the new 3R models (micro level), the lack of harmonization of regulatory requirements and acceptance criteria (meso level) and the high levels of risk aversion (macro level). In optimizing the process commitment, communication, cooperation and coordination are identified as critical drivers. Copyright © 2014 Elsevier Inc. All rights reserved.

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

NARCIS (Netherlands)

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

2012-01-01

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

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

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.

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 ...

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

Implementation, availability and regulatory status of an OECD accepted Reconstructed Human Epidermis model in Brazil

Directory of Open Access Journals (Sweden)

Rodrigo De Vecchi

2018-02-01

Full Text Available Introduction: In 2014, Brazil has joined the growing list of countries to ban cosmetic products from being tested on animal models. The new legislation comes into force in 2019. As a result, the interest for validated alternative testing methods for safety assessment has been increasing in academia, industry and associations. However, the lack of specific legislation on the use of biological material of human origin for toxicological tests makes the access to alternative in vitro models difficult. Furthermore, importation to Brazil is not possible on timely manner. Method: In this article, we report the implementation process of a Reconstructed Human Epidermis (SkinEthic™ RHE, an alternative model internationally accepted by OECD, through a technology transfer from EPISKIN® Lyon to Brazil. Regulatory evolution has been motivating the implementation and wide use of alternative methods to animal testing in several industry segments including cosmetic and pharmaceutical. Results: Protocol has been shown to be robust and highly reproducible. Quality control parameters (histological analysis, barrier function test and tissue viability were performed on 24 batches assembled in Brazil. SkinEthic™ RHE model use allows the full replacement of animal test methods for skin hazards identification. It has regulatory acceptance for several toxicological endpoints, such as the Draize test for skin irritation and corrosion. It allows the reduction and refining of pre-clinical protocols through tiered strategies. Implementation of SkinEthic™ RHE protocol is just a first and important step towards a new approach of toxicological safety testing in Brazil. Conclusion: The implementation was successfully done and reported here. However, in order to follow completely the new legislation up to 2019, the availability of validated models is essential. Quality control tests done on RHE batches produced in Brazil demonstrate that the model met OECD acceptance

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

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...

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

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.

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.

Role of human neurobehavioural tests in regulatory activity on chemicals

Science.gov (United States)

Stephens, R.; Barker, P.

1998-01-01

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

Hormonal growth promoting agents in food producing animals.

Science.gov (United States)

Stephany, Rainer W

2010-01-01

In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters ("anabolics") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters ("hormones") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of "legal natural levels" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone

Regulatory dendritic cell therapy: from rodents to clinical application.

Science.gov (United States)

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W

2014-10-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or "tolerogenic" DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

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…

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.

Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function.

Science.gov (United States)

Osborne, Suzanne E; Walthers, Don; Tomljenovic, Ana M; Mulder, David T; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J; Wickham, Mark E; Waller, Ross F; Kenney, Linda J; Coombes, Brian K

2009-03-10

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

Science.gov (United States)

Dunnett, S B; Iversen, S D

1982-02-01

6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

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

Science.gov (United States)

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

2015-11-01

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

A case for increased private sector involvement in Ireland's national animal health services.

Science.gov (United States)

More, Simon J

2008-02-01

Non-regulatory animal health issues, such as Johne's disease, infectious bovine rhinotracheitis (IBR) and mastitis will become increasing important, with ongoing globalisation of markets in animals and animal products. In response, Ireland may need to broaden the scope of its national animal health services. However, there have been concerns about the respective roles and responsibilities (both financial and otherwise) of government and industry in any such moves. This paper argues the case for increased private sector involvement in Ireland's national animal health services, based both on theoretical considerations and country case studies (the Netherlands and Australia). The Dutch and Australian case studies present examples of successful partnerships between government and industry, including systems and processes to address non-regulatory animal health issues. In each case, the roles and responsibilities of government are clear, as are the principles underpinning government involvement. Furthermore, the roles and responsibilities (financial and otherwise) of the Dutch and Australian industry are determined through enabling legislation, providing both legitimacy and accountability. There are constraints on the use of EU and national government funds to support non-regulatory animal health services in EU member states (such as Ireland and the Netherlands).

A case for increased private sector involvement in ireland's national animal health services

Directory of Open Access Journals (Sweden)

More Simon J

2008-02-01

Full Text Available Abstract Non-regulatory animal health issues, such as Johne's disease, infectious bovine rhinotracheitis (IBR and mastitis will become increasing important, with ongoing globalisation of markets in animals and animal products. In response, Ireland may need to broaden the scope of its national animal health services. However, there have been concerns about the respective roles and responsibilities (both financial and otherwise of government and industry in any such moves. This paper argues the case for increased private sector involvement in Ireland's national animal health services, based both on theoretical considerations and country case studies (the Netherlands and Australia. The Dutch and Australian case studies present examples of successful partnerships between government and industry, including systems and processes to address non-regulatory animal health issues. In each case, the roles and responsibilities of government are clear, as are the principles underpinning government involvement. Furthermore, the roles and responsibilities (financial and otherwise of the Dutch and Australian industry are determined through enabling legislation, providing both legitimacy and accountability. There are constraints on the use of EU and national government funds to support non-regulatory animal health services in EU member states (such as Ireland and the Netherlands.

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

Science.gov (United States)

Leonardi, Paul M

2010-04-01

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

[Animal experimentation in the discovery and production of veterinary vaccines].

Science.gov (United States)

Audonnet, J Ch; Lechenet, J; Verschuere, B

2007-08-01

Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development.

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

Regulatory dendritic cell therapy: from rodents to clinical application

OpenAIRE

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W.

2013-01-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or “tolerogenic” DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant...

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....

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

Science.gov (United States)

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

2010-01-01

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

Prediction of skin sensitizers using alternative methods to animal experimentation.

Science.gov (United States)

Johansson, Henrik; Lindstedt, Malin

2014-07-01

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

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

NARCIS (Netherlands)

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

2011-01-01

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

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

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.

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....

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

DEFF Research Database (Denmark)

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

2015-01-01

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

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.

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

Science.gov (United States)

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

2016-01-01

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

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...

Is it possible to replace stimulus animals by scent-filled cups in the social discrimination test?

Science.gov (United States)

van den Bos, Ruud; van der Horst, Klaske J; Baars, Annemarie M; Spruijt, Berry M

2002-01-01

A study in which the rat social discrimination test was refined is described. This test measures social memory by using, in general, juvenile rats as stimulus animals. Rats are offered a first juvenile to investigate (learning trial), and after a specified interval, the rats are offered the same rat and a second juvenile rat to investigate again (retrieval trial). When the rats sniff the second juvenile in the retrieval trial more than the first, social memory for the second juvenile is said to be present. This test is mainly based on scents from the juvenile. Attempts were made to refine the test to reduce the number of animals used, to enhance the scope of the test, and to improve its validity. Firstly, the stimulus animals were replaced by the scent of juveniles, in the form of cups filled with sawdust taken from cages of juvenile rats. Similar results to those in the original test were obtained when using these scents. Furthermore, male and female scents were tested, and showed the same results as for the juvenile scents. Secondly, rats were also given two cups (one scent-filled and one filled with plain sawdust) in the learning trial, to determine which allowed a more-precise delineation of motivational, discriminatory and memory components. Overall, it is possible to replace stimulus animals by scent-filled cups in the social discrimination test, to enhance the scope of the test, and to draw more-valid conclusions with respect to social memory.

Animal cloning: problems and prospects.

Science.gov (United States)

Wells, D N

2005-04-01

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

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

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

Cloned animal products in the human food chain: FDA should protect American consumers.

Science.gov (United States)

Butler, Jennifer E F

2009-01-01

Animal cloning is "complex process that lets one exactly copy the genetic, or inherited, traits of an animal." In 1997, Dolly the sheep was the first animal cloned and since then "scientists have used animal cloning to breed dairy cows, beef cattle, poultry, hogs and other species of livestock." Cloned animals are highly attractive to livestock breeders because "cloning essentially produces an identical copy of an animal with superior traits." The main purpose of cloning livestock is "more focused on efficiency and economic benefits of the producer rather than the overall effect of cloning on an animal's physical and mental welfare." The focus of this article is threefold. First, the science behind animal cloning is explained and some potential uses and risks of this technology are explored. Second, FDA's historical evolution, current regulatory authority, and limitations of that authority, is described. Lastly, a new regulatory vision recognizes the realities of 21st century global markets and the dynamic evolution of scientific discovery and technology.

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

Leak testing United States Nuclear Regulatory Commission type b packaging

International Nuclear Information System (INIS)

Lacy, K.A.

1995-01-01

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

Regulatory activities; Actividades regulatorias

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

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

Laboratory Animal Management: Wild Birds.

Science.gov (United States)

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

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

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.

SIMULATED ANIMAL EXPERIMENTS IN TEACHING AND RESEARCH

Directory of Open Access Journals (Sweden)

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

2015-07-01

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

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

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.

Assessing the satisfaction and burden within an academic animal care and use program.

Science.gov (United States)

Norton, John N; Reynolds, Randall P; Chan, Cliburn; Valdivia, Raphael H; Staats, Herman F

2017-09-01

Although animal research requires adherence to various regulations and standards, the manner in which compliance is maintained and the degree of additional constraints varies between institutions. Regulatory burden, particularly if institutionally imposed, has become a concern for institutions as increased regulatory expectations result in decreased resources available for research efforts. Faculty, research staff, and support staff engaged in animal research were surveyed to determine what institutional animal care and use committee (IACUC) processes were considered burdensome, the perceived value of some suggested modifications, and satisfaction with the IACUC administrative office and the animal resource unit. Although the results revealed overwhelming satisfaction with the IACUC administrative office and the animal resource unit, several IACUC processes were deemed burdensome, and therefore there would be value in modifying IACUC processes. When comparing the value of modifying IACUC processes, different groups within the animal care and use program (ACUP) tended to have different responses on many of the topics. This survey identified several perceived burdensome IACUC processes that would likely benefit individuals if modified. In today's environment of shrinking budgets for biomedical research, minimizing regulatory burden-particularly unnecessary, self-imposed burden-in the ACUP is particularly important to ensure that costs, time, and effort are appropriate to achieve animal welfare and quality of research endeavors.-Norton, J. N., Reynolds, R. P., Chan, C., Valdivia, R. H., Staats, H. F. Assessing the satisfaction and burden within an academic animal care and use program. © FASEB.

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....

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.

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.

On the Concept of Cis-regulatory Information: From Sequence Motifs to Logic Functions

Science.gov (United States)

Tarpine, Ryan; Istrail, Sorin

The regulatory genome is about the “system level organization of the core genomic regulatory apparatus, and how this is the locus of causality underlying the twin phenomena of animal development and animal evolution” (E.H. Davidson. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution, Academic Press, 2006). Information processing in the regulatory genome is done through regulatory states, defined as sets of transcription factors (sequence-specific DNA binding proteins which determine gene expression) that are expressed and active at the same time. The core information processing machinery consists of modular DNA sequence elements, called cis-modules, that interact with transcription factors. The cis-modules “read” the information contained in the regulatory state of the cell through transcription factor binding, “process” it, and directly or indirectly communicate with the basal transcription apparatus to determine gene expression. This endowment of each gene with the information-receiving capacity through their cis-regulatory modules is essential for the response to every possible regulatory state to which it might be exposed during all phases of the life cycle and in all cell types. We present here a set of challenges addressed by our CYRENE research project aimed at studying the cis-regulatory code of the regulatory genome. The CYRENE Project is devoted to (1) the construction of a database, the cis-Lexicon, containing comprehensive information across species about experimentally validated cis-regulatory modules; and (2) the software development of a next-generation genome browser, the cis-Browser, specialized for the regulatory genome. The presentation is anchored on three main computational challenges: the Gene Naming Problem, the Consensus Sequence Bottleneck Problem, and the Logic Function Inference Problem.

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.

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.

[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.

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.

Non-animal methods to predict skin sensitization (I): the Cosmetics Europe database.

Science.gov (United States)

Hoffmann, Sebastian; Kleinstreuer, Nicole; Alépée, Nathalie; Allen, David; Api, Anne Marie; Ashikaga, Takao; Clouet, Elodie; Cluzel, Magalie; Desprez, Bertrand; Gellatly, Nichola; Goebel, Carsten; Kern, Petra S; Klaric, Martina; Kühnl, Jochen; Lalko, Jon F; Martinozzi-Teissier, Silvia; Mewes, Karsten; Miyazawa, Masaaki; Parakhia, Rahul; van Vliet, Erwin; Zang, Qingda; Petersohn, Dirk

2018-05-01

Cosmetics Europe, the European Trade Association for the cosmetics and personal care industry, is conducting a multi-phase program to develop regulatory accepted, animal-free testing strategies enabling the cosmetics industry to conduct safety assessments. Based on a systematic evaluation of test methods for skin sensitization, five non-animal test methods (DPRA (Direct Peptide Reactivity Assay), KeratinoSens TM , h-CLAT (human cell line activation test), U-SENS TM , SENS-IS) were selected for inclusion in a comprehensive database of 128 substances. Existing data were compiled and completed with newly generated data, the latter amounting to one-third of all data. The database was complemented with human and local lymph node assay (LLNA) reference data, physicochemical properties and use categories, and thoroughly curated. Focused on the availability of human data, the substance selection resulted nevertheless resulted in a high diversity of chemistries in terms of physico-chemical property ranges and use categories. Predictivities of skin sensitization potential and potency, where applicable, were calculated for the LLNA as compared to human data and for the individual test methods compared to both human and LLNA reference data. In addition, various aspects of applicability of the test methods were analyzed. Due to its high level of curation, comprehensiveness, and completeness, we propose our database as a point of reference for the evaluation and development of testing strategies, as done for example in the associated work of Kleinstreuer et al. We encourage the community to use it to meet the challenge of conducting skin sensitization safety assessment without generating new animal data.

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

Science.gov (United States)

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

2014-12-01

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

The economics of animal welfare.

Science.gov (United States)

Gibson, T J; Jackson, E L

2017-04-01

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

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.

Team structure and regulatory focus: the impact of regulatory fit on team dynamic.

Science.gov (United States)

Dimotakis, Nikolaos; Davison, Robert B; Hollenbeck, John R

2012-03-01

We report a within-teams experiment testing the effects of fit between team structure and regulatory task demands on task performance and satisfaction through average team member positive affect and helping behaviors. We used a completely crossed repeated-observations design in which 21 teams enacted 2 tasks with different regulatory focus characteristics (prevention and promotion) in 2 organizational structures (functional and divisional), resulting in 84 observations. Results suggested that salient regulatory demands inherent in the task interacted with structure to determine objective and subjective team-level outcomes, such that functional structures were best suited to (i.e., had best fit with) tasks with a prevention regulatory focus and divisional structures were best suited to tasks with a promotion regulatory focus. This contingency finding integrates regulatory focus and structural contingency theories, and extends them to the team level with implications for models of performance, satisfaction, and team dynamics.

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

International Nuclear Information System (INIS)

Levin, A.E.

1993-01-01

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

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.

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...

Regulatory BC1 RNA in Cognitive Control

Science.gov (United States)

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

2017-01-01

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

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.

[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.

75 FR 12804 - Withdrawal of Regulatory Guide 8.6

Science.gov (United States)

2010-03-17

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

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

Science.gov (United States)

Box, Rainer J

2006-01-01

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

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.

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.

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...

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

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)

Regulatory agencies and regulatory risk

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2008-01-01

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

Human-animal chimera: a neuro driven discussion? Comparison of three leading European research countries.

Science.gov (United States)

Cabrera Trujillo, Laura Yenisa; Engel-Glatter, Sabrina

2015-06-01

Research with human-animal chimera raises a number of ethical concerns, especially when neural stem cells are transplanted into the brains of non-human primates (NHPs). Besides animal welfare concerns and ethical issues associated with the use of embryonic stem cells, the research is also regarded as controversial from the standpoint of NHPs developing cognitive or behavioural capabilities that are regarded as "unique" to humans. However, scientists are urging to test new therapeutic approaches for neurological diseases in primate models as they better mimic human physiology than all current animal models. As a response, various countries have issued reports on the topic. Our paper summarizes the ethical issues raised by research with human-animal brain chimeras and compares the relevant regulatory instruments and different recommendations issued in national reports from three important European research nations: Germany, Switzerland and the United Kingdom. We assess and discuss the focus and priorities set by the different reports, review various reasons for and perspectives on the importance of the brain in chimera research, and identify critical points in the reports that warrant further specification and debate.

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...

Transgenic Mouse Models Transferred into the Test Tube: New Perspectives for Developmental Toxicity Testing In Vitro?

Science.gov (United States)

Kugler, Josephine; Luch, Andreas; Oelgeschläger, Michael

2016-10-01

Despite our increasing understanding of molecular mechanisms controlling embryogenesis, the identification and characterization of teratogenic substances still heavily relies on animal testing. Embryonic development depends on cell-autonomous and non-autonomous processes including spatiotemporally regulated extracellular signaling activities. These have been elucidated in transgenic mouse models harboring easily detectable reporter genes under the control of evolutionarily conserved signaling cascades. We propose combining these transgenic mouse models and cells derived thereof with existing alternative toxicological testing strategies. This would enable the plausibility of in vitro data to be verified in light of in vivo data and, ultimately, facilitate regulatory acceptance of in vitro test methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

ENSI’s regulatory framework strategy

International Nuclear Information System (INIS)

2015-03-01

This short brochure issued by the Swiss Federal Nuclear Safety Inspectorate ENSI defines the organisation’s regulatory framework strategy. Six guiding principles are declared and discussed: Comprehensive harmonisation with relevant international requirements, basing the regulatory framework on existing, tried-and-tested regulations, issuing of its own guidelines only when it is necessary to do so, guidelines to be drawn up transparently and with the involvement of all stakeholders and basing the level of detail of its regulatory framework on hazard potential and risk

76 FR 81467 - Availability of an Environmental Assessment for Field Testing Swine Influenza Vaccine, RNA

Science.gov (United States)

2011-12-28

...] Availability of an Environmental Assessment for Field Testing Swine Influenza Vaccine, RNA AGENCY: Animal and... Vaccine, RNA. The environmental assessment, which is based on a risk analysis prepared to assess the risks...: Send your comment to Docket No. APHIS-2011-0114, Regulatory Analysis and Development, PPD, APHIS...

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

International Nuclear Information System (INIS)

Campbell, P.; Colaccino, J.

1994-01-01

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

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

International Nuclear Information System (INIS)

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

1997-01-01

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

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

Science.gov (United States)

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

2006-01-01

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

National biosecurity approaches, plans and programmes in response to diseases in farmed aquatic animals: evolution, effectiveness and the way forward

DEFF Research Database (Denmark)

Håstein, T.; Binde, M.; Hine, M.

2008-01-01

The rapid increase in aquaculture production and trade, and increased attention to the negative effects of disease, are becoming stimuli for developing national biosecurity strategies for farmed fisheries, for which the World Organisation for Animal Health (OIE) Aquatic Animal Health Code...... and Manual of Diagnostic Tests for Aquatic Animals serve as an excellent framework. Using examples from a few countries and selected diseases, this paper provides a general overview of the development of approaches to implementing biosecurity strategies, including those emerging in the national legislation...... and eradication are also discussed. Important to the effectiveness of such strategies are provision of financial, personnel and other resources to implement them, including incentives such as indemnification or compensation in eradication programmes, and practical linkage to regulatory or government policy...

COMPANION ANIMALS SYMPOSIUM: Future aspects and perceptions of companion animal nutrition and sustainability.

Science.gov (United States)

Deng, P; Swanson, K S

2015-03-01

Companion animals play an important role in our lives and are now considered to be and treated as family members in a majority of households in the United States. Because of the high number of pets that now exist, an increasingly stronger pet-human bond, and the importance placed on health and longevity, the pet food industry has realized steady growth over the last few decades. Despite past successes and opportunities that exist in the future, there are also challenges that must be considered. This review will present a brief overview of the current pet food industry and address some of the key issues moving forward. In regards to companion animal research, recent advances and future needs in the areas of canine and feline metabolism, aging, clinical disease, and the gut microbiome using molecular and high-throughput assays; chemical, in vitro, and in vivo testing of feed ingredients; and innovative pet food processing methods is discussed. Training the future workforce for the pet food industry is also of great importance. Recent trends on student demographics and their species and careers of interest, changing animal science department curricula, and technology's impact on instruction are provided. Finally, the sustainability of the pet food industry is discussed. Focus was primarily placed on the disconnect that exists between opinions and trends of consumers and the nutrient recommendations for dogs and cats, the desire for increasing use of animal-based and human-grade products, the overfeeding of pets and the pet obesity crisis, and the issues that involve the evaluation of primary vs. secondary products in terms of sustainability. Moving forward, the pet food industry will need to anticipate and address challenges that arise, especially those pertaining to consumer expectations, the regulatory environment, and sustainability. Given the already strong and increasingly dynamic market for pet foods and supplies, an academic environment primed to supply a

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

Science.gov (United States)

Vaughn, Leigh Ann

2017-03-01

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

Alberta Energy and Utilities Board, regulatory highlights for 1998

International Nuclear Information System (INIS)

1999-01-01

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

Ethical implications of using the minipig in regulatory toxicology studies.

Science.gov (United States)

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

2010-01-01

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

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.

[TNF-α, diabetes type 1 and regulatory T cells].

Science.gov (United States)

Ryba, Monika; Myśliwska, Jolanta

2010-01-01

Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

Practice of Regulatory Science (Development of Medical Devices).

Science.gov (United States)

Niimi, Shingo

2017-01-01

Prototypes of medical devices are made in accordance with the needs of clinical practice, and for systems required during the initial process of medical device development for new surgical practices. Verification of whether these prototypes produce the intended performance specifications is conducted using basic tests such as mechanical and animal tests. The prototypes are then improved and modified until satisfactory results are obtained. After a prototype passes through a clinical trial process similar to that for new drugs, application for approval is made. In the approval application process, medical devices are divided into new, improved, and generic types. Reviewers judge the validity of intended use, indications, operation procedures, and precautions, and in addition evaluate the balance between risk and benefit in terms of efficacy and safety. Other characteristics of medical devices are the need for the user to attain proficiency in usage techniques to ensure efficacy and safety, and the existence of a variety of medical devices for which assessment strategies differ, including differences in impact on the body in cases in which a physical burden to the body or failure of a medical device develops. Regulatory science of medical devices involves prediction, judgment, and evaluation of efficacy, safety, and quality, from which data result which can become indices in the development stages from design to application for approval. A reduction in the number of animals used for testing, improvement in efficiency, reduction of the necessity for clinical trials, etc. are expected through rational setting of evaluation items.

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

Current status of developmental neurotoxicity: regulatory view

DEFF Research Database (Denmark)

Hass, Ulla

2003-01-01

in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US....... Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...

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...

The guinea pig as an animal model for developmental and reproductive toxicology studies.

Science.gov (United States)

Rocca, Meredith S; Wehner, Nancy G

2009-04-01

Regulatory guidelines for developmental and reproductive toxicology (DART) studies require selection of "relevant" animal models as determined by kinetic, pharmacological, and toxicological data. Traditionally, rats, mice, and rabbits are the preferred animal models for these studies. However, for test articles that are pharmacologically inactive in the traditional animal models, the guinea pig may be a viable option. This choice should not be made lightly, as guinea pigs have many disadvantages compared to the traditional species, including limited historical control data, variability in pregnancy rates, small and variable litter size, long gestation, relative maturity at birth, and difficulty in dosing and breeding. This report describes methods for using guinea pigs in DART studies and provides results of positive and negative controls. Standard study designs and animal husbandry methods were modified to allow mating on the postpartum estrus in fertility studies and were used for producing cohorts of pregnant females for developmental studies. A positive control study with the pregnancy-disrupting agent mifepristone resulted in the anticipated failure of embryo implantation and supported the use of the guinea pig model. Control data for reproductive endpoints collected from 5 studies are presented. In cases where the traditional animal models are not relevant, the guinea pig can be used successfully for DART studies. (c) 2009 Wiley-Liss, Inc.

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.

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

Science.gov (United States)

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

2009-07-01

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

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,…

Public morals in private hands? : a study into the evolving path of farm animal welfare governance

NARCIS (Netherlands)

Toschi Maciel, C.

2015-01-01

Executive summary

The advancement of regulatory instruments providing for farm animal welfare measures has been marked by various political and regulatory constraints in both domestic and international settings.In an attempt to overcome some of these constraints, a number of

Perspectives on Regulatory T Cell Therapies.

Science.gov (United States)

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S P; Buer, Jan

2009-01-01

Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (T(reg)) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, T(reg) cell therapies and development of drugs that specifically enhance T(reg) cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human T(reg) cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as T(reg) cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human T(reg) cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease.

Computational and molecular dissection of an X-box cis-Regulatory module

OpenAIRE

Warrington, Timothy Burton

2015-01-01

Ciliopathies are a class of human diseases marked by dysfunction of the cellular organelle, cilia. While many of the molecular components that make up cilia have been identified and studied, comparatively little is understood about the transcriptional regulation of genes encoding these components. The conserved transcription factor Regulatory Factor X (RFX)/DAF-19, which acts through binding to the cis-regulatory motif known as X-box, has been shown to regulate ciliary genes in many animals f...

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...

Regulatory focus affects physician risk tolerance.

Science.gov (United States)

Veazie, Peter J; McIntosh, Scott; Chapman, Benjamin P; Dolan, James G

2014-01-01

Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention-regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (p = 0.01). The Cohen's d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (p = 0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor.

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.

ICH guidelines--implementation of the 3Rs (refinement, reduction, and replacement): incorporating best scientific practices into the regulatory process.

Science.gov (United States)

Ohno, Yasuo

2002-01-01

An overview of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) is described. ICH was established through cooperation of the regulatory agencies and industrial parties of three main regions involved in pharmaceuticals: the European Union, the United States, and Japan. The purpose of the ICH is to make recommendations to achieve greater harmonization regarding interpretation and application of technical guidelines and requirements for product registration in an effort to reduce or obviate the need to duplicate the testing carried out during the research and development of new medicines. The main purpose of ICH was not to foster the 3Rs per se; however, harmonization of guidelines has eliminated duplications of similar tests to satisfy the specific requirements of each region. The ICH process has contributed to mutual understanding of the regulatory requirements and has decreased the number of unnecessary animal experiments. Specific examples of the contributions of ICH harmonization to the 3Rs are described.

77 FR 22282 - Draft Guidelines on Biologics Quality Monitoring: Testing for the Detection of Mycoplasma...

Science.gov (United States)

2012-04-13

.... Normal reading room hours are 8 a.m. to 4:30 p.m., Monday through Friday, except holidays. To be sure... World Organization for Animal Health that brings together the regulatory authorities of the European... that Mycoplasmas are not present, within the limits of the test, in the final product, working seeds...

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

Science.gov (United States)

2013-01-01

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

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

Science.gov (United States)

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

2013-10-16

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

Evolving PBPK applications in regulatory risk assessment: current situation and future goals

Science.gov (United States)

The presentation includes current applications of PBPK modeling in regulatory risk assessment and discussions on conflicts between assuring consistency with experimental data in current situation and the desire for animal-free model development.

An Organismal Model for Gene Regulatory Networks in the Gut-Associated Immune Response

Directory of Open Access Journals (Sweden)

Katherine M. Buckley

2017-10-01

Full Text Available The gut epithelium is an ancient site of complex communication between the animal immune system and the microbial world. While elements of self-non-self receptors and effector mechanisms differ greatly among animal phyla, some aspects of recognition, regulation, and response are broadly conserved. A gene regulatory network (GRN approach provides a means to investigate the nature of this conservation and divergence even as more peripheral functional details remain incompletely understood. The sea urchin embryo is an unparalleled experimental model for detangling the GRNs that govern embryonic development. By applying this theoretical framework to the free swimming, feeding larval stage of the purple sea urchin, it is possible to delineate the conserved regulatory circuitry that regulates the gut-associated immune response. This model provides a morphologically simple system in which to efficiently unravel regulatory connections that are phylogenetically relevant to immunity in vertebrates. Here, we review the organism-wide cellular and transcriptional immune response of the sea urchin larva. A large set of transcription factors and signal systems, including epithelial expression of interleukin 17 (IL17, are important mediators in the activation of the early gut-associated response. Many of these have homologs that are active in vertebrate immunity, while others are ancient in animals but absent in vertebrates or specific to echinoderms. This larval model provides a means to experimentally characterize immune function encoded in the sea urchin genome and the regulatory interconnections that control immune response and resolution across the tissues of the organism.

Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord.

KAUST Repository

Lovrics, Anna

2014-11-14

We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.

Changing innovation into a registered product: From concept to regulatory approval.

Science.gov (United States)

Rhodes, Linda

2018-05-01

Innovation in animal health pharmaceuticals is important to address unmet and underserved medical needs, and often comes from products initially developed for human medicine. The purpose of the review is to help readers understand how breakthroughs from human biotechnology may be developed for use in veterinary medicine, while understanding the key drivers to success, the difficulties of regulatory approval, and the realistic risks and rewards of developing applications for animals. The types of human drugs which may be useful for veterinary applications are reviewed, including examples. The regulatory path is discussed, with a review of the various oversight agencies, and the categories of data required to be submitted, including safety, efficacy, manufacturing, environmental impact and human food safety. In conclusion, the cost, development time, and barriers to innovation in veterinary medical pharmaceuticals are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

[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.

Alberta Energy and Utilities Board, regulatory highlights for 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-08-01

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

Are animal models useful for studying human disc disorders / degeneration?

NARCIS (Netherlands)

Alini, M.; Eisenstein, S.M.; Ito, K.; Little, C.; Kettler, A.A.; Masuda, K.; Melrose, J.; Ralphs, J.; Stokes, I.; Wilke, H.J.

2008-01-01

Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo

Testing for Cognitive Function in Animals in a Regulatory Context

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

Karen Cristine Ceroni Cazarin

2004-09-01

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

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…

Framework for integrating human and animal data in chemical risk assessment.

Science.gov (United States)

Lavelle, Karlene S; Robert Schnatter, A; Travis, Kim Z; Swaen, Gerard M H; Pallapies, Dirk; Money, Chris; Priem, Peter; Vrijhof, Henk

2012-03-01

Although regulatory agencies formally encourage the integration of all available data in chemical risk assessment, consistent implementation of this practice has been constrained by the lack of a clear, systematic method for doing so. In this paper, we describe a methodology for evaluating, classifying and integrating human and animal data into the risk assessment process that incorporates: (1) a balanced appraisal of human and animal data, (2) relevance to different stages of the risk assessment process, and (3) accommodation for different data quality requirements. The proposed framework offers a flexible, step-wise approach for determining which set of available data best support the chemical risk assessment that involves the rating and relative ranking of human and animal data quality. The evaluation of human data incorporates seven data quality elements, nature and specificity of the lead effect; evaluation of animal data incorporates data quality and relevance to humans. Results of simulations with selected chemicals previously evaluated in a formal risk assessment generally agreed with existing regulatory guidance. Application of the proposed framework across a wider range of chemical agents will improve transparency of the risk assessment process and validity of results, while informing continuous refinements to this evolving methodology. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

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...

Characterizing the rapid spread of porcine epidemic diarrhea virus (PEDV through an animal food manufacturing facility.

Directory of Open Access Journals (Sweden)

Loni L Schumacher

Full Text Available New regulatory and consumer demands highlight the importance of animal feed as a part of our national food safety system. Porcine epidemic diarrhea virus (PEDV is the first viral pathogen confirmed to be widely transmissible in animal food. Because the potential for viral contamination in animal food is not well characterized, the objectives of this study were to 1 observe the magnitude of virus contamination in an animal food manufacturing facility, and 2 investigate a proposed method, feed sequencing, to decrease virus decontamination on animal food-contact surfaces. A U.S. virulent PEDV isolate was used to inoculate 50 kg swine feed, which was mixed, conveyed, and discharged into bags using pilot-scale feed manufacturing equipment. Surfaces were swabbed and analyzed for the presence of PEDV RNA by quantitative real-time polymerase chain reaction (qPCR. Environmental swabs indicated complete contamination of animal food-contact surfaces (0/40 vs. 48/48, positive baseline samples/total baseline samples, positive subsequent samples/total subsequent samples, respectively; P < 0.05 and near complete contamination of non-animal food-contact surfaces (0/24 vs. 16/18, positive baseline samples/total baseline samples, positive subsequent samples/total subsequent samples, respectively; P < 0.05. Flushing animal food-contact surfaces with low-risk feed is commonly used to reduce cross-contamination in animal feed manufacturing. Thus, four subsequent 50 kg batches of virus-free swine feed were manufactured using the same system to test its impact on decontaminating animal food-contact surfaces. Even after 4 subsequent sequences, animal food-contact surfaces retained viral RNA (28/33 positive samples/total samples, with conveying system being more contaminated than the mixer. A bioassay to test infectivity of dust from animal food-contact surfaces failed to produce infectivity. This study demonstrates the potential widespread viral contamination of

The regulatory framework in the UK

International Nuclear Information System (INIS)

O'Sullivan, R.

1984-01-01

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

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.

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

Directory of Open Access Journals (Sweden)

Kazuyoshi eTsutsui

2013-04-01

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

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

International Nuclear Information System (INIS)

Mamani Alegria, Yuri Raul; Salgado Gonzalez, Julio Ricardo

1996-01-01

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

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.

Regulatory difficulties in a developing country

International Nuclear Information System (INIS)

Jacobs, W.R. Jr.

1978-01-01

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

77 FR 65840 - Chrysanthemum White Rust Regulatory Status and Restrictions

Science.gov (United States)

2012-10-31

... Regulatory Status and Restrictions AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Advance... for our advance notice of proposed rulemaking that solicits public comment on whether and how we... importation of plant material that is a host of CWR. This action will allow interested persons additional time...

How long must they suffer? success and failure of our efforts to end the animal tragedy in laboratories.

Science.gov (United States)

Kolar, Roman

2015-05-01

Scientific findings have revealed how much we have dramatically underestimated the intellectual, social and emotional capabilities of non-human animals, including their levels of self-consciousness and ability to suffer from psychological stress. In the 21st century, the field of animal ethics has evolved as a serious scientific discipline, and nowadays largely advocates that the way we treat animals, both legally and in practice, is morally wrong. Politics and legislation have reacted to these facts, to some extent, but neither current legislation nor current practice reflect the scientific and moral state-of-the-art. Too often, the will to change things is watered down in the decision-making process, e.g. in the drafting of legislation. In the field of animal experimentation there have been many genuine efforts by various players, to advance and apply the principles behind the Three Rs. However, the fundamental problem, i.e. the overall number of animals sacrificed for scientific purposes, has increased. Clearly, if we are serious about our will to regard animal experimentation as an ethical and societal problem, we have to put much more emphasis on addressing the question of how to avoid the use of animals in science. To achieve this goal, certain issues need to be considered: a) the present system of ethical evaluation of animal experiments, including testing for regulatory purposes, needs to be reformed and applied effectively to meet the legal and moral requirements; b) animal testing must be avoided in future legislation, and existing legislation has to be revised in that regard; c) resources from animal-based research have to re-allocated toward alternatives; and d) the academic curricula must be reformed to foster and integrate ethical and animal welfare issues. 2015 FRAME.

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.

Regulatory T-cells and autoimmunity.

LENUS (Irish Health Repository)

Ni Choileain, Niamh

2012-02-03

Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

In vitro to in vivo extrapolation of effective dosimetry in developmental toxicity testing : Application of a generic PBK modelling approach

NARCIS (Netherlands)

Fragki, Styliani; Piersma, Aldert H; Rorije, Emiel; Zeilmaker, Marco J

2017-01-01

Incorporation of kinetics to quantitative in vitro to in vivo extrapolations (QIVIVE) is a key step for the realization of a non-animal testing paradigm, in the sphere of regulatory toxicology. The use of Physiologically-Based Kinetic (PBK) modelling for determining systemic doses of chemicals at

In vitro to in vivo extrapolation of effective dosimetry in developmental toxicity testing: Application of a generic PBK modelling approach.

NARCIS (Netherlands)

Fragki, Styliani; Piersma, Aldert H; Rorije, Emiel; Zeilmaker, Marco J

2017-01-01

Incorporation of kinetics to quantitative in vitro to in vivo extrapolations (QIVIVE) is a key step for the realization of a non-animal testing paradigm, in the sphere of regulatory toxicology. The use of Physiologically-Based Kinetic (PBK) modelling for determining systemic doses of chemicals at

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.

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

Science.gov (United States)

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

Perspectives on Regulatory T Cell Therapies

OpenAIRE

Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S.P.; Buer, Jan

2009-01-01

Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (Treg) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, Treg cell therapies and development of drugs that specifically enhance Treg cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human Treg cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 ...

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

Science.gov (United States)

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

2008-01-01

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

75 FR 75678 - Determination of Regulatory Review Period for Purposes of Patent Extension; STELARA

Science.gov (United States)

2010-12-06

..., animal drug product, medical device, food additive, or color additive) was subject to regulatory review... or systemic therapy. Subsequent to this approval, the Patent and Trademark Office received a patent...

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.

Th17 in Animal Models of Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Motomu Hashimoto

2017-07-01

Full Text Available IL-17-secreting helper CD4 T cells (Th17 cells constitute a newly identified subset of helper CD4 T cells that play a key role in the development of rheumatoid arthritis (RA in its animal models. Recently, several models of spontaneous RA, which elucidate the mechanism of RA onset, have been discovered. These animal models shed new light on the role of Th17 in the development of autoimmune arthritis. Th17 cells coordinate inflammation and promote joint destruction, acting on various cells, including neutrophils, macrophages, synovial fibroblasts, and osteoclasts. Regulatory T cells cannot control Th17 cells under conditions of inflammation. In this review, the pathogenic role of Th17 cells in arthritis development, which was revealed by the recent animal models of RA, is discussed.

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.

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.

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals.

Science.gov (United States)

Punt, Ans; Peijnenburg, Ad A C M; Hoogenboom, Ron L A P; Bouwmeester, Hans

2017-01-01

The objective of the present work was to review the availability and predictive value of non-animal toxicokinetic approaches and to evaluate their current use in European risk evaluations of food contaminants, additives and food contact materials, as well as pesticides and medicines. Results revealed little use of quantitative animal or human kinetic data in risk evaluations of food chemicals, compared with pesticides and medicines. Risk evaluations of medicines provided sufficient in vivo kinetic data from different species to evaluate the predictive value of animal kinetic data for humans. These data showed a relatively poor correlation between the in vivo bioavailability in rats and dogs versus that in humans. In contrast, in vitro (human) kinetic data have been demonstrated to provide adequate predictions of the fate of compounds in humans, using appropriate in vitro-in vivo scalers and by integration of in vitro kinetic data with in silico kinetic modelling. Even though in vitro kinetic data were found to be occasionally included within risk evaluations of food chemicals, particularly results from Caco-2 absorption experiments and in vitro data on gut-microbial conversions, only minor use of in vitro methods for metabolism and quantitative in vitro-in vivo extrapolation methods was identified. Yet, such quantitative predictions are essential in the development of alternatives to animal testing as well as to increase human relevance of toxicological risk evaluations. Future research should aim at further improving and validating quantitative alternative methods for kinetics, thereby increasing regulatory acceptance of non-animal kinetic data.

Considerations When Writing and Reviewing a Higher Education Teaching Protocol Involving Animals.

Science.gov (United States)

Vemulapalli, Tracy H; Donkin, Shawn S; Lescun, Timothy B; O'Neil, Peggy A; Zollner, Patrick A

2017-09-01

The targeted use of animals in teaching at institutions of higher learning is fundamental to educating the next generation of professionals in the biologic and animal sciences. As with animal research, universities and colleges that use animals in teaching are subject to regulatory oversight. Instructors must receive approval from their IACUC before using animals in their teaching. However, the questions asked on many institutions' animal care and use protocol (ACUP) are often geared more toward the use of animals for research. These questions may not be wholly appropriate in evaluating a teaching protocol; some questions are not applicable (for example, power analysis to justify animal numbers) whereas other important questions may be missing. This article discusses the issues surrounding the rationale for animal use in teaching; it also proposes a framework that instructors and IACUC members alike can use when writing and reviewing teaching ACUP. We hope this framework will help to ensure the most appropriate IACUC review of the ethical use of animals in higher education.

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

DEFF Research Database (Denmark)

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

2010-01-01

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

Modification of the Genome of Domestic Animals.

Science.gov (United States)

Lotti, Samantha N; Polkoff, Kathryn M; Rubessa, Marcello; Wheeler, Matthew B

2017-07-03

In the past few years, new technologies have arisen that enable higher efficiency of gene editing. With the increase ease of using gene editing technologies, it is important to consider the best method for transferring new genetic material to livestock animals. Microinjection is a technique that has proven to be effective in mice but is less efficient in large livestock animals. Over the years, a variety of methods have been used for cloning as well as gene transfer including; nuclear transfer, sperm mediated gene transfer (SMGT), and liposome-mediated DNA transfer. This review looks at the different success rate of these methods and how they have evolved to become more efficient. As well as gene editing technologies, including Zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the most recent clustered regulatory interspaced short palindromic repeats (CRISPRs). Through the advancements in gene-editing technologies, generating transgenic animals is now more accessible and affordable. The goals of producing transgenic animals are to 1) increase our understanding of biology and biomedical science; 2) increase our ability to produce more efficient animals; and 3) produce disease resistant animals. ZFNs, TALENs, and CRISPRs combined with gene transfer methods increase the possibility of achieving these goals.

Ethical and regulatory problems of molecular imaging

International Nuclear Information System (INIS)

Jeong, Jae Min

2004-01-01

As a molecular imaging is the most up-to-date technology in nuclear medicine, it has complicate ethical and regulatory problems. For animal experiment, we have to follow institutional animal care committee. For clinical experiment, we have to get approval of Institutional Review Board according to Helsinki declaration. In addition, approval from Korea Food and Drug Administration (KFDA) is essential for manufacturing and commercialization. However, too much regulation would suppress development of new technology, which would result in the loss of national competitive power. In addition, most new radioactive ligands for molecular imaging are administered to human at sub-pharmacological and sub-toxicological level. In conclusion, a balanced regulation is essential for the safety of clinical application and development of new technology

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.

The use of whole food animal studies in the safety assessment of genetically modified crops: Limitations and recommendations

Science.gov (United States)

Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve

2013-01-01

There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable. PMID:24164514

The use of whole food animal studies in the safety assessment of genetically modified crops: limitations and recommendations.

Science.gov (United States)

Bartholomaeus, Andrew; Parrott, Wayne; Bondy, Genevieve; Walker, Kate

2013-11-01

There is disagreement internationally across major regulatory jurisdictions on the relevance and utility of whole food (WF) toxicity studies on GM crops, with no harmonization of data or regulatory requirements. The scientific value, and therefore animal ethics, of WF studies on GM crops is a matter addressable from the wealth of data available on commercialized GM crops and WF studies on irradiated foods. We reviewed available GM crop WF studies and considered the extent to which they add to the information from agronomic and compositional analyses. No WF toxicity study was identified that convincingly demonstrated toxicological concern or that called into question the adequacy, sufficiency, and reliability of safety assessments based on crop molecular characterization, transgene source, agronomic characteristics, and/or compositional analysis of the GM crop and its near-isogenic line. Predictions of safety based on crop genetics and compositional analyses have provided complete concordance with the results of well-conducted animal testing. However, this concordance is primarily due to the improbability of de novo generation of toxic substances in crop plants using genetic engineering practices and due to the weakness of WF toxicity studies in general. Thus, based on the comparative robustness and reliability of compositional and agronomic considerations and on the absence of any scientific basis for a significant potential for de novo generation of toxicologically significant compositional alterations as a sole result of transgene insertion, the conclusion of this review is that WF animal toxicity studies are unnecessary and scientifically unjustifiable.

Industrial halal meat production and animal welfare: A review.

Science.gov (United States)

Farouk, M M; Pufpaff, K M; Amir, M

2016-10-01

Islam teaches zero-tolerance to all forms of animal abuse throughout the halal meat production supply chain and demands that when animals are slaughtered, they must be slaughtered in the mindful and attentive way espoused by the Prophet Muhammad. Why then are poor practices and animal welfare abuses still occurring during halal meat production, and how can they be reduced or eliminated? In this review we discuss how improvements might be achieved through: (1) training of staff regarding the religious and regulatory requirements of animal welfare from on-farm to slaughter; (2) empathy and compassion assessment of applicants prior to employment; (3) installation of CCTV cameras around lairage and slaughter sites; (4) regular employee follow-up training to minimise 'compassion fatigue'; (5) incorporating animal welfare requirements in halal certification; (6) using mosque-based sermons by Imams to increase awareness of animal welfare issues; and (7) making portable humane slaughter units available to small cottage operations and home/neighbourhood-kills through mosque-based organizations/structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

As to achieve regulatory action, regulatory approaches

International Nuclear Information System (INIS)

Cid, R.; Encinas, D.

2014-01-01

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

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...

[The design and development of a quality system for the diagnosis of exotic animal diseases at the National Centre for Animal and Plant Health in Cuba].

Science.gov (United States)

de Oca, N Montes; Villoch, A; Pérez Ruano, M

2004-12-01

A quality system for the diagnosis of exotic animal diseases was developed at the national centre for animal and plant health (CENSA), responsible for coordinating the clinical, epizootiological and laboratory diagnosis of causal agents of exotic animal diseases in Cuba. A model was designed on the basis of standard ISO 9001:2000 of the International Organization for Standardization (ISO), standard ISO/IEC 17025:1999 of ISO and the International Electrotechnical Commission, recommendations of the World Organisation for Animal Health (OIE) and other regulatory documents from international and national organisations that deal specifically with the treatment of emerging diseases. Twenty-nine standardised operating procedures were developed, plus 13 registers and a checklist to facilitate the evaluation of the system. The effectiveness of the quality system was confirmed in the differential diagnosis of classical swine fever at an animal virology laboratory in Cuba.

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...

Are innate immune signaling pathways in plants and animals conserved?

Science.gov (United States)

Ausubel, Frederick M

2005-10-01

Although adaptive immunity is unique to vertebrates, the innate immune response seems to have ancient origins. Common features of innate immunity in vertebrates, invertebrate animals and plants include defined receptors for microbe-associated molecules, conserved mitogen-associated protein kinase signaling cascades and the production of antimicrobial peptides. It is commonly reported that these similarities in innate immunity represent a process of divergent evolution from an ancient unicellular eukaryote that pre-dated the divergence of the plant and animal kingdoms. However, at present, data suggest that the seemingly analogous regulatory modules used in plant and animal innate immunity are a consequence of convergent evolution and reflect inherent constraints on how an innate immune system can be constructed.

Anticoccidial efficacy testing: In vitro Eimeria tenella assays as replacement for animal experiments.

Science.gov (United States)

Thabet, Ahmed; Zhang, Runhui; Alnassan, Alaa-Aldin; Daugschies, Arwid; Bangoura, Berit

2017-01-15

Availability of an accurate in vitro assay is a crucial demand to determine sensitivity of Eimeria spp. field strains toward anticoccidials routinely. In this study we tested in vitro models of Eimeria tenella using various polyether ionophores (monensin, salinomycin, maduramicin, and lasalocid) and toltrazuril. Minimum inhibitory concentrations (MIC 95 , MIC 50/95 ) for the tested anticoccidials were defined based on a susceptible reference (Houghton strain), Ref-1. In vitro sporozoite invasion inhibition assay (SIA) and reproduction inhibition assay (RIA) were applied on sensitive laboratory (Ref-1 and Ref-2) and field (FS-1, FS-2, and FS-3) strains to calculate percent of inhibition under exposure of these strains to the various anticoccidials (%I SIA and%I RIA, respectively). The in vitro data were related to oocyst excretion, lesion scores, performance, and global resistance indices (GI) assessed in experimentally infected chickens. Polyether ionophores applied in the RIA were highly effective at MIC 95 against Ref-1 and Ref-2 (%I RIA ≥95%). In contrast, all tested field strains displayed reduced to low efficacy (%I RIA animal model (p89%) against all strains used in this study. However, adjusted GI (GI adj ) for toltrazuril-treated groups exhibited differences between reference and field strains which might indicate varying sensitivity. RIA is a suitable in vitro tool to detect sensitivity of E. tenella towards polyether ionophores, and may thus help to reduce, replace, or refine use of animal experimentation for in vivo sensitivity assays. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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...

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.

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

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

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.

How "humane" is your endpoint? Refining the science-driven approach for termination of animal studies of chronic infection.

OpenAIRE

Nuno H Franco; Margarida Correia-Neves; I Anna S Olsson

2012-01-01

Public concern on issues such as animal welfare or the scientific validity and clinical value of animal research is growing, resulting in increasing regulatory demands for animal research. Abiding to the most stringent animal welfare standards, while having scientific objectives as the main priority, is often challenging. To do so, endpoints of studies involving severe, progressive diseases need to be established considering how early in the disease process the scientific objectives can be ac...

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.

The origins and evolutionary history of human non-coding RNA regulatory networks.

Science.gov (United States)

Sherafatian, Masih; Mowla, Seyed Javad

2017-04-01

The evolutionary history and origin of the regulatory function of animal non-coding RNAs are not well understood. Lack of conservation of long non-coding RNAs and small sizes of microRNAs has been major obstacles in their phylogenetic analysis. In this study, we tried to shed more light on the evolution of ncRNA regulatory networks by changing our phylogenetic strategy to focus on the evolutionary pattern of their protein coding targets. We used available target databases of miRNAs and lncRNAs to find their protein coding targets in human. We were able to recognize evolutionary hallmarks of ncRNA targets by phylostratigraphic analysis. We found the conventional 3'-UTR and lesser known 5'-UTR targets of miRNAs to be enriched at three consecutive phylostrata. Firstly, in eukaryata phylostratum corresponding to the emergence of miRNAs, our study revealed that miRNA targets function primarily in cell cycle processes. Moreover, the same overrepresentation of the targets observed in the next two consecutive phylostrata, opisthokonta and eumetazoa, corresponded to the expansion periods of miRNAs in animals evolution. Coding sequence targets of miRNAs showed a delayed rise at opisthokonta phylostratum, compared to the 3' and 5' UTR targets of miRNAs. LncRNA regulatory network was the latest to evolve at eumetazoa.

Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

Science.gov (United States)

Gazestani, Vahid H; Salavati, Reza

2015-01-01

Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

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...

Acute physiological impacts of CO2 ocean sequestration on marine animals

International Nuclear Information System (INIS)

Ishimatsu, A.; Hayashi, M.; Lee, K.S.; Murata, K.; Kumagai, E.

2005-01-01

The biological impacts of ocean carbon dioxide (CO 2 ) sequestration must be carefully considered before it is implemented as a mitigation strategy. This paper presented details of a study investigating the effects of high CO 2 concentrations on marine fish, lobster, and octopus. The influence of water temperature on the physiological effects of CO 2 was also discussed. In the first part of the study, eggs and larvae of red seabream were exposed to both CO 2 and HCI-acidified seawater at identical pH levels. Seabream in the CO 2 group showed a much higher mortality rate than fish in the HCI group. Other tests showed that Japanese Flounder died after complete recovery of pH in seawater equilibrated with 5 per cent CO 2 . Cardiac output was rapidly depressed in Yellowtail fish without significant changes in blood oxygen concentrations. Lower temperatures resulted in higher mortality and delayed pH recovery during hypercapnia in all fish. Western rock lobsters were the most tolerant to CO 2 among all species tested. The recovery of hemolymph pH was complete at exposure to CO 2 concentrations of 1 per cent. Changes in hemolymph bicarbonate concentrations indicated that acid-based regulatory mechanisms differed between fish and lobsters. Mortality rates for octopus were significant at CO 2 concentrations of 1 per cent. The results of all tests showed that aquatic animals are more susceptible to increases in ambient CO 2 levels than terrestrial animals. It was concluded that even slight elevations in CO 2 concentration levels adversely affected physiological functioning in the tested species. It was concluded that CO 2 sequestration in deeper, colder waters will have a more pronounced effect on aquatic animals due to the interactions between CO 2 and lower temperatures, as well as the fact that most deep-sea fish are less tolerant to environmental perturbations. 3 refs., 1 tab., 3 figs

Regulatory requirements related to maintenance and compliance monitoring

International Nuclear Information System (INIS)

Ling, A.K.H.

1997-01-01

The maintenance related regulatory requirements are identified in the regulatory documents and licence conditions. Licensee complies with these requirements by operating the nuclear power plant within the safe operating envelope as given in the operating policies and principles and do maintenance according to approved procedures and/or work plans. Safety systems are regularly tested. AECB project officers review and check to ensure that the licensee operates the nuclear power plant in accordance with the regulatory requirements and licence conditions. (author). 6 tabs

Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

Science.gov (United States)

Arenas-Mena, Cesar; Coffman, James A.

2016-01-01

Summary It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis-regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell-cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. PMID:26173445

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.

The political approach of animal rights from the perspective of the rights theory

OpenAIRE

José Luis Rey Pérez

2017-01-01

Traditionally, discussions about animal rights have focused on defending, in different ways, abolitionist or regulatory approaches. Recently, there has been a political change in the way of understanding these rights, which fits better a legal approach that considers that rights –in addition to having a moral dimension- are also effectiveness-oriented legal institutions. This leads to considering that the range of animal rights must be extended to rights linked to the condition of citizenship...

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

EU risk governance of 'cloned food': regulatory uncertainty between trade and non-trade

NARCIS (Netherlands)

Weimer, M.; van Asselt, M.B.A.; Versluis, E.; Vos, E.

2013-01-01

This chapter analyzes the difficulties of creating a viable legal framework for ‘cloned food’ in the EU combining a legal perspective with insights from the interdisciplinary research on risk governance. Animal cloning offers an instructive example for the challenges of designing regulatory

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

Science.gov (United States)

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

Helminth-induced regulatory T cells and suppression of allergic responses.

Science.gov (United States)

Logan, Jayden; Navarro, Severine; Loukas, Alex; Giacomin, Paul

2018-05-28

Infection with helminths has been associated with lower rates of asthma and other allergic diseases. This has been attributed, in part, to the ability of helminths to induce regulatory T cells that suppress inappropriate immune responses to allergens. Recent compelling evidence suggests that helminths may promote regulatory T cell expansion or effector functions through either direct (secretion of excretory/secretory molecules) or indirect mechanisms (regulation of the microbiome). This review will discuss key findings from human immunoepidemiological observations, studies using animal models of disease, and clinical trials with live worm infections, discussing the therapeutic potential for worms and their secreted products for treating allergic inflammation. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

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

USNRC regulatory guidance for engineered safety feature air cleaning systems

International Nuclear Information System (INIS)

Bellamy, R.R.

1991-01-01

The need for clear, technically appropriate, and easily implementable guidance for the design, testing, and maintenance of nuclear air cleaning systems has long been recognized. Numerous industry consensus standards have been issued and revised over the last 30 years. Guidance has also been published by the US Nuclear Regulatory Commission in the form of regulations, regulatory guides, standard review plans, NUREG documents, and information notices. This paper will summarize the latest revisions to these documents and emphasize Regulatory Guide 1.52, Design, Testing, and Maintenance Criteria for Post-Accident Engineered-Safety-Feature Atmosphere Cleanup System Air Filtration and Adsorption Units of Light-Water-Cooled Nuclear Power Plants, which was last revised in 1978. The USNRC has undertaken a project to revise this regulatory guide, and the status of that revision is highlighted

Implications of duplicated cis-regulatory elements in the evolution of metazoans: the DDI model or how simplicity begets novelty.

Science.gov (United States)

Jiménez-Delgado, Senda; Pascual-Anaya, Juan; Garcia-Fernàndez, Jordi

2009-07-01

The discovery that most regulatory genes were conserved among animals from distant phyla challenged the ideas that gene duplication and divergence of homologous coding sequences were the basis for major morphological changes in metazoan evolution. In recent years, however, the interest for the roles, conservation and changes of non-coding sequences grew-up in parallel with genome sequencing projects. Presently, many independent studies are highlighting the importance that subtle changes in cis-regulatory regions had in the evolution of morphology trough the Animal Kingdom. Here we will show and discuss some of these studies, and underscore the future of cis-Evo-Devo research. Nevertheless, we would also explore how gene duplication, which includes duplication of regulatory regions, may have been critical for spatial or temporal co-option of new regulatory networks, causing the deployment of new transcriptome scenarios, and how these induced morphological changes were critical for the evolution of new forms. Forty years after Susumu Ohno famous sentence 'natural selection merely modifies, while redundancy creates', we suggest the alternative: 'natural selection modifies, while redundancy of cis-regulatory elements innovates', and propose the Duplication-Degeneration-Innovation model to explain the increased evolvability of duplicated cis-regulatory regions. Paradoxically, making regulation simpler by subfunctionalization paved the path for future complexity or, in other words, 'to make it simple to make it complex'.

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

Science.gov (United States)

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

2008-10-01

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

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

Science.gov (United States)

Raybould, Alan; Burns, Andrea; Hamer, Mick

2014-01-01

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

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

Assessment of regulatory effectiveness. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-09-01

This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

A Critical Look at Biomedical Journals’ Policies on Animal Research by Use of a Novel Tool: The EXEMPLAR Scale

Directory of Open Access Journals (Sweden)

Ana Raquel Martins

2015-04-01

Full Text Available Animal research is not only regulated by legislation but also by self-regulatory mechanisms within the scientific community, which include biomedical journals’ policies on animal use. For editorial policies to meaningfully impact attitudes and practice, they must not only be put into effect by editors and reviewers, but also be set to high standards. We present a novel tool to classify journals’ policies on animal use—the EXEMPLAR scale—as well as an analysis by this scale of 170 journals publishing studies on animal models of three human diseases: Amyotrophic Lateral Sclerosis, Type-1 Diabetes and Tuberculosis. Results show a much greater focus of editorial policies on regulatory compliance than on other domains, suggesting a transfer of journals’ responsibilities to scientists, institutions and regulators. Scores were not found to vary with journals’ impact factor, country of origin or antiquity, but were, however, significantly higher for open access journals, which may be a result of their greater exposure and consequent higher public scrutiny.

Sound preference test in animal models of addicts and phobias.

Science.gov (United States)

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

2016-08-01

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

Worldwide risks of animal diseases: introduction.

Science.gov (United States)

Pearson, J E

2006-01-01

Animal diseases impact food supplies, trade and commerce, and human health and well-being in every part of the world. Outbreaks draw the attention of those in agriculture, regulatory agencies, and government, as well as the general public. This was demonstrated by the 2000-2001 foot and mouth disease (FMD) outbreaks that occurred in Europe, South America, Asia and Africa and by the recent increased occurrence of emerging diseases transmitted from animals to humans. Examples of these emerging zoonotic diseases are highly pathogenic avian influenza, bovine spongiform encephalopathy, West Nile virus and severe acute respiratory syndrome. There is also the risk of well-known and preventable zoonotic diseases, such as rabies, brucellosis, leishmaniasis, and echinococcosis/hydatidosis, in certain countries; these diseases have a high morbidity with the potential for a very high mortality. Animal agriculturalists should have a global disease awareness of disease risks and develop plans of action to deal with them; in order to better respond to these diseases, they should develop the skills and competencies in politics, media interactions, and community engagement. This issue of Veterinaria Italiana presents information on the risk of animal diseases; their impact on animals and humans at the international, national, industry, and societal levels; and the responses to them. In addition, specific information is provided on national and international disease monitoring, surveillance and reporting, the risk of spread of disease by bioterrorism and on import risk analysis.

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

Science.gov (United States)

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

2016-09-01

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. Copyright © 2016 the American Physiological Society.

Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies

Science.gov (United States)

Hooijmans, Carlijn R.; de Vries, Rob B. M.; Ritskes-Hoitinga, Merel; Rovers, Maroeska M.; Leeflang, Mariska M.; IntHout, Joanna; Wever, Kimberley E.; Hooft, Lotty; de Beer, Hans; Kuijpers, Ton; Macleod, Malcolm R.; Sena, Emily S.; ter Riet, Gerben; Morgan, Rebecca L.; Thayer, Kristina A.; Rooney, Andrew A.; Guyatt, Gordon H.; Schünemann, Holger J.

2018-01-01

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE’s indirectness domain as a tool to predict translation from animal models to humans. PMID:29324741

Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies.

Science.gov (United States)

Hooijmans, Carlijn R; de Vries, Rob B M; Ritskes-Hoitinga, Merel; Rovers, Maroeska M; Leeflang, Mariska M; IntHout, Joanna; Wever, Kimberley E; Hooft, Lotty; de Beer, Hans; Kuijpers, Ton; Macleod, Malcolm R; Sena, Emily S; Ter Riet, Gerben; Morgan, Rebecca L; Thayer, Kristina A; Rooney, Andrew A; Guyatt, Gordon H; Schünemann, Holger J; Langendam, Miranda W

2018-01-01

Laboratory animal studies are used in a wide range of human health related research areas, such as basic biomedical research, drug research, experimental surgery and environmental health. The results of these studies can be used to inform decisions regarding clinical research in humans, for example the decision to proceed to clinical trials. If the research question relates to potential harms with no expectation of benefit (e.g., toxicology), studies in experimental animals may provide the only relevant or controlled data and directly inform clinical management decisions. Systematic reviews and meta-analyses are important tools to provide robust and informative evidence summaries of these animal studies. Rating how certain we are about the evidence could provide important information about the translational probability of findings in experimental animal studies to clinical practice and probably improve it. Evidence summaries and certainty in the evidence ratings could also be used (1) to support selection of interventions with best therapeutic potential to be tested in clinical trials, (2) to justify a regulatory decision limiting human exposure (to drug or toxin), or to (3) support decisions on the utility of further animal experiments. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is the most widely used framework to rate the certainty in the evidence and strength of health care recommendations. Here we present how the GRADE approach could be used to rate the certainty in the evidence of preclinical animal studies in the context of therapeutic interventions. We also discuss the methodological challenges that we identified, and for which further work is needed. Examples are defining the importance of consistency within and across animal species and using GRADE's indirectness domain as a tool to predict translation from animal models to humans.

ENSI’s regulatory framework strategy; Regelwerksstrategie des ENSI -- Stratégie réglementaire de l’IFSN -- ENSI’s regulatory framework strategy

Energy Technology Data Exchange (ETDEWEB)

NONE

2015-03-15

This short brochure issued by the Swiss Federal Nuclear Safety Inspectorate ENSI defines the organisation’s regulatory framework strategy. Six guiding principles are declared and discussed: Comprehensive harmonisation with relevant international requirements, basing the regulatory framework on existing, tried-and-tested regulations, issuing of its own guidelines only when it is necessary to do so, guidelines to be drawn up transparently and with the involvement of all stakeholders and basing the level of detail of its regulatory framework on hazard potential and risk.

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

NARCIS (Netherlands)

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

2012-01-01

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

Animal Models for Evaluation of Bone Implants and Devices: Comparative Bone Structure and Common Model Uses.

Science.gov (United States)

Wancket, L M

2015-09-01

Bone implants and devices are a rapidly growing field within biomedical research, and implants have the potential to significantly improve human and animal health. Animal models play a key role in initial product development and are important components of nonclinical data included in applications for regulatory approval. Pathologists are increasingly being asked to evaluate these models at the initial developmental and nonclinical biocompatibility testing stages, and it is important to understand the relative merits and deficiencies of various species when evaluating a new material or device. This article summarizes characteristics of the most commonly used species in studies of bone implant materials, including detailed information about the relevance of a particular model to human bone physiology and pathology. Species reviewed include mice, rats, rabbits, guinea pigs, dogs, sheep, goats, and nonhuman primates. Ultimately, a comprehensive understanding of the benefits and limitations of different model species will aid in rigorously evaluating a novel bone implant material or device. © The Author(s) 2015.

Regulatory compliance guide for DOT-7A type A packaging design

International Nuclear Information System (INIS)

Kelly, D.L.

1996-01-01

The purpose of this guide is to provide instruction for assuring that the regulatory design requirements for a DOT-7A Type A packaging are met. This guide also supports the testing and evaluation activities that are performed on new packaging designs by a DOE-approved test facility through the DOE's DOT-7A Test Program. This Guide was updated to incorporate regulatory changes implemented by HM-169A (49 CFR, 'Transportation')

Acute physiological impacts of CO{sub 2} ocean sequestration on marine animals

Energy Technology Data Exchange (ETDEWEB)

Ishimatsu, A.; Hayashi, M.; Lee, K.S.; Murata, K.; Kumagai, E. [Nagasaki Univ., Nagasaki (Japan). Marine Research Inst.; Kikkawa, T. [Marine Ecology Research Inst., Chiba (Japan). Central Laboratory; Kita, J. [Research Inst. of Innovative Technology for the Earth, Kyoto (Japan)

2005-07-01

The biological impacts of ocean carbon dioxide (CO{sub 2}) sequestration must be carefully considered before it is implemented as a mitigation strategy. This paper presented details of a study investigating the effects of high CO{sub 2} concentrations on marine fish, lobster, and octopus. The influence of water temperature on the physiological effects of CO{sub 2} was also discussed. In the first part of the study, eggs and larvae of red seabream were exposed to both CO{sub 2} and HCI-acidified seawater at identical pH levels. Seabream in the CO{sub 2} group showed a much higher mortality rate than fish in the HCI group. Other tests showed that Japanese Flounder died after complete recovery of pH in seawater equilibrated with 5 per cent CO{sub 2}. Cardiac output was rapidly depressed in Yellowtail fish without significant changes in blood oxygen concentrations. Lower temperatures resulted in higher mortality and delayed pH recovery during hypercapnia in all fish. Western rock lobsters were the most tolerant to CO{sub 2} among all species tested. The recovery of hemolymph pH was complete at exposure to CO{sub 2} concentrations of 1 per cent. Changes in hemolymph bicarbonate concentrations indicated that acid-based regulatory mechanisms differed between fish and lobsters. Mortality rates for octopus were significant at CO{sub 2} concentrations of 1 per cent. The results of all tests showed that aquatic animals are more susceptible to increases in ambient CO{sub 2} levels than terrestrial animals. It was concluded that even slight elevations in CO{sub 2} concentration levels adversely affected physiological functioning in the tested species. It was concluded that CO{sub 2} sequestration in deeper, colder waters will have a more pronounced effect on aquatic animals due to the interactions between CO{sub 2} and lower temperatures, as well as the fact that most deep-sea fish are less tolerant to environmental perturbations. 3 refs., 1 tab., 3 figs.

Enhancing human-animal relationships through veterinary medical instruction in animal-assisted therapy and animal-assisted activities.

Science.gov (United States)

Schaffer, Caroline Brunsman

2008-01-01

Instruction in animal-assisted therapy (AAT) and animal-assisted activities (AAAs) teaches veterinary medical students to confidently and assertively maximize the benefits and minimize the risks of this union of animals and people. Instruction in AAT/AAA also addresses requirements by the American Veterinary Medical Association Council on Education that accredited schools/colleges of veterinary medicine include in their standard curriculum the topics of the human-animal bond, behavior, and the contributions of the veterinarian to the overall public and professional health care teams. Entry-level veterinarians should be prepared to: (1) assure that animals who provide AAT/AAA are healthy enough to visit nursing homes, hospitals, or other institutions; (2) promote behavior testing that selects animals who will feel safe, comfortable, and connected; (3) advise facilities regarding infection control and ways to provide a safe environment where the animals, their handlers, and the people being visited will not be injured or become ill; and (4) advocate for their patients and show compassion for their clients when animals are determined to be inappropriate participants in AAT/AAA programs. This article presents AAT/AAA terminology, ways in which veterinarians can advocate for AAT/AAA, the advantages of being involved in AAT/AAA, a model AAT/AAA practicum from Tuskegee University's School of Veterinary Medicine (TUSVM), and examples of co-curricular activities in AAT/AAA by TUSVM's student volunteers.

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

Science.gov (United States)

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

2011-02-15

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

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation.

Science.gov (United States)

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

2016-01-01

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

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

Science.gov (United States)

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

2015-07-30

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

Animal models in biological and biomedical research - experimental and ethical concerns.

Science.gov (United States)

Andersen, Monica L; Winter, Lucile M F

2017-09-04

Animal models have been used in experimental research to increase human knowledge and contribute to finding solutions to biological and biomedical questions. However, increased concern for the welfare of the animals used, and a growing awareness of the concept of animal rights, has brought a greater focus on the related ethical issues. In this review, we intend to give examples on how animals are used in the health research related to some major health problems in Brazil, as well as to stimulate discussion about the application of ethics in the use of animals in research and education, highlighting the role of National Council for the Control of Animal Experimentation (Conselho Nacional de Controle de Experimentação Animal - CONCEA) in these areas. In 2008, Brazil emerged into a new era of animal research regulation, with the promulgation of Law 11794, previously known as the Arouca Law, resulting in an increased focus, and rapid learning experience, on questions related to all aspects of animal experimentation. The law reinforces the idea that animal experiments must be based on ethical considerations and integrity-based assumptions, and provides a regulatory framework to achieve this. This review describes the health research involving animals and the current Brazilian framework for regulating laboratory animal science, and hopes to help to improve the awareness of the scientific community of these ethical and legal rules.

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.

Animals In Synchrotrons: Overcoming Challenges For High-Resolution, Live, Small-Animal Imaging

International Nuclear Information System (INIS)

Donnelley, Martin; Parsons, David; Morgan, Kaye; Siu, Karen

2010-01-01

Physiological studies in small animals can be complicated, but the complexity is increased dramatically when performing live-animal synchrotron X-ray imaging studies. Our group has extensive experience in high-resolution live-animal imaging at the Japanese SPring-8 synchrotron, primarily examining airways in two-dimensions. These experiments normally image an area of 1.8 mmx1.2 mm at a pixel resolution of 0.45 μm and are performed with live, intact, anaesthetized mice.There are unique challenges in this experimental setting. Importantly, experiments must be performed in an isolated imaging hutch not specifically designed for small-animal imaging. This requires equipment adapted to remotely monitor animals, maintain their anesthesia, and deliver test substances while collecting images. The horizontal synchrotron X-ray beam has a fixed location and orientation that limits experimental flexibility. The extremely high resolution makes locating anatomical regions-of-interest slow and can result in a high radiation dose, and at this level of magnification small animal movements produce motion-artifacts that can render acquired images unusable. Here we describe our experimental techniques and how we have overcome several challenges involved in performing live mouse synchrotron imaging.Experiments have tested different mouse strains, with hairless strains minimizing overlying skin and hair artifacts. Different anesthetics have also be trialed due to the limited choices available at SPring-8. Tracheal-intubation methods have been refined and controlled-ventilation is now possible using a specialized small-animal ventilator. With appropriate animal restraint and respiratory-gating, motion-artifacts have been minimized. The animal orientation (supine vs. head-high) also appears to affect animal physiology, and can alter image quality. Our techniques and image quality at SPring-8 have dramatically improved and in the near future we plan to translate this experience to the

Campylobacter species in animal, food, and environmental sources, and relevant testing programs in Canada.

Science.gov (United States)

Huang, Hongsheng; Brooks, Brian W; Lowman, Ruff; Carrillo, Catherine D

2015-10-01

Campylobacter species, particularly thermophilic campylobacters, have emerged as a leading cause of human foodborne gastroenteritis worldwide, with Campylobacter jejuni, Campylobacter coli, and Campylobacter lari responsible for the majority of human infections. Although most cases of campylobacteriosis are self-limiting, campylobacteriosis represents a significant public health burden. Human illness caused by infection with campylobacters has been reported across Canada since the early 1970s. Many studies have shown that dietary sources, including food, particularly raw poultry and other meat products, raw milk, and contaminated water, have contributed to outbreaks of campylobacteriosis in Canada. Campylobacter spp. have also been detected in a wide range of animal and environmental sources, including water, in Canada. The purpose of this article is to review (i) the prevalence of Campylobacter spp. in animals, food, and the environment, and (ii) the relevant testing programs in Canada with a focus on the potential links between campylobacters and human health in Canada.

The current state of GMO governance: are we ready for GM animals?

Science.gov (United States)

Vàzquez-Salat, Núria; Salter, Brian; Smets, Greet; Houdebine, Louis-Marie

2012-01-01

Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology. Copyright © 2012. Published by Elsevier Inc.

Multi-tissue omics analyses reveal molecular regulatory networks for puberty in composite beef cattle

Science.gov (United States)

Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e., hypothal...

Convergent occurrence of the developmental hourglass in plant and animal embryogenesis?

Science.gov (United States)

Cridge, Andrew G; Dearden, Peter K; Brownfield, Lynette R

2016-04-01

The remarkable similarity of animal embryos at particular stages of development led to the proposal of a developmental hourglass. In this model, early events in development are less conserved across species but lead to a highly conserved 'phylotypic period'. Beyond this stage, the model suggests that development once again becomes less conserved, leading to the diversity of forms. Recent comparative studies of gene expression in animal groups have provided strong support for the hourglass model. How and why might such an hourglass pattern be generated? More importantly, how might early acting events in development evolve while still maintaining a later conserved stage? The discovery that an hourglass pattern may also exist in the embryogenesis of plants provides comparative data that may help us explain this phenomenon. Whether the developmental hourglass occurs in plants, and what this means for our understanding of embryogenesis in plants and animals is discussed. Models by which conserved early-acting genes might change their functional role in the evolution of gene networks, how networks buffer these changes, and how that might constrain, or confer diversity, of the body plan are also discused. Evidence of a morphological and molecular hourglass in plant and animal embryogenesis suggests convergent evolution. This convergence is likely due to developmental constraints imposed upon embryogenesis by the need to produce a viable embryo with an established body plan, controlled by the architecture of the underlying gene regulatory networks. As the body plan is largely laid down during the middle phases of embryo development in plants and animals, then it is perhaps not surprising this stage represents the narrow waist of the hourglass where the gene regulatory networks are the oldest and most robust and integrated, limiting species diversity and constraining morphological space. © The Author 2016. Published by Oxford University Press on behalf of the Annals of

Scientific Knowledge and Technology, Animal Experimentation, and Pharmaceutical Development.

Science.gov (United States)

Kinter, Lewis B; DeGeorge, Joseph J

2016-12-01

Human discovery of pharmacologically active substances is arguably the oldest of the biomedical sciences with origins >3500 years ago. Since ancient times, four major transformations have dramatically impacted pharmaceutical development, each driven by advances in scientific knowledge, technology, and/or regulation: (1) anesthesia, analgesia, and antisepsis; (2) medicinal chemistry; (3) regulatory toxicology; and (4) targeted drug discovery. Animal experimentation in pharmaceutical development is a modern phenomenon dating from the 20th century and enabling several of the four transformations. While each transformation resulted in more effective and/or safer pharmaceuticals, overall attrition, cycle time, cost, numbers of animals used, and low probability of success for new products remain concerns, and pharmaceutical development remains a very high risk business proposition. In this manuscript we review pharmaceutical development since ancient times, describe its coevolution with animal experimentation, and attempt to predict the characteristics of future transformations. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cocombustion of animal meal

International Nuclear Information System (INIS)

Roggen, M.

2001-01-01

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

[Surveillance on severe acute respiratory syndrome associated coronavirus in animals at a live animal market of Guangzhou in 2004].

Science.gov (United States)

Wang, Ming; Jing, Huai-qi; Xu, Hui-fang; Jiang, Xiu-gao; Kan, Biao; Liu, Qi-yong; Wan, Kang-lin; Cui, Bu-yun; Zheng, Han; Cui, Zhi-gang; Yan, Mei-ying; Liang, Wei-li; Wang, Hong-xia; Qi, Xiao-bao; Li, Zhen-jun; Li, Ma-chao; Chen, Kai; Zhang, En-min; Zhang, Shou-yin; Hai, Rong; Yu, Dong-zheng; Xu, Jian-guo

2005-02-01

To study the prevalence of severe acute respiratory syndrome coronavirus (SARS-CoV) like virus in animals at a live animal market of Guanzhou in 2004 before and after culling of wild animal action taken by the local authority, in order to predict the re-emerging of SARS from animal originals in this region. Animals at live animal market were sampled for rectal and throat swabs in triplicate. A single step realtime reverse transcription-polymerase chain reaction (RT-PCR) diagnostic kit was performed for screening SARS-CoV like virus, the manual nested RT- PCR and DNA sequencing were performed for confirmation. Only specimens which tested positive for both of the N and P genes by nested RT-PCR were scored as positive. In 31 animals sampled in January 5 2004 before culling of wild animals at Guangdong Province, including 20 cats (Felis catus), 5 red fox (Vulpes vulpes) and 6 Lesser rice field rats (Rattus losea), 8 (25.8%) animals were tested positive for SARS-CoV like virus by RT-PCR methods, of which 4 cats, 3 red fox and one Lesser rice field rats were included. However, two weeks after culling of animals and disinfection of the market were implemented, in 119 animals sampled in January 20 2004, including 6 rabbits (Oryctolagus cuniculus), 13 cats, 46 red jungle fowl (Gallus gallus), 13 spotbill duck (Anas platyrhynchos), 10 greylag goose (Anser anser), 31 Chinese francolin (Franclinus pintadeanus), only rectal swab from one greylag goose was tested positive for SARS-CoV like virus. Furthermore, in 102 animals that including 14 greylag gooses, 3 cats, 5 rabbits, 9 spotbill duck (Anaspoecilorhyncha), 2 Chinese francolin (Franclinus pintadeanus), 8 common pheasant (Phasianus colchicus), 6 pigeons, 9 Chinese muntjac (Muntiacus reevesi), 19 wild boar (Sus scrofa), 16 Lesser rice field rats, 5 dogs, 1 mink (Mustela vison), 3 goats, 2 green peafowl (Pavo muticus) sampled in April, May, June, July, August and November, only rectal swab from one pig was tested positive

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

OpenAIRE

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

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Sonja Hartnack

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

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

International Nuclear Information System (INIS)

Anon.

1992-01-01

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

Using principles from emergency management to improve emergency response plans for research animals.

Science.gov (United States)

Vogelweid, Catherine M

2013-10-01

Animal research regulatory agencies have issued updated requirements for emergency response planning by regulated research institutions. A thorough emergency response plan is an essential component of an institution's animal care and use program, but developing an effective plan can be a daunting task. The author provides basic information drawn from the field of emergency management about best practices for developing emergency response plans. Planners should use the basic principles of emergency management to develop a common-sense approach to managing emergencies in their facilities.

The murine local lymph node assay: Regulatory and potency considerations under REACH

International Nuclear Information System (INIS)

McGarry, Helen F.

2007-01-01

From June 2007, new chemicals legislation on the registration, evaluation, authorisation and restriction of chemicals (REACH) will come into force across the European Union. This will require the submission of data on human health effects of chemicals, including chemical safety assessments which will require measurements of potency. For skin sensitization hazard identification, REACH states that the first-choice in vivo assay is the local lymph node assay (LLNA). This test has also been the UK competent authority's preferred test for skin sensitization since 2002, and has now replaced guinea pig tests in dossiers submitted to it under the Notification of New Substances Regulations. Advantages of the LLNA over guinea pig tests include improvements in animal welfare, a more scientific approach to hazard identification, and the inclusion of a dose-response element in the endpoint, which enables an estimation of potency. However, notifiers to the UK competent authority have sometimes been reluctant to use the assay because of concerns over false-positive reactions. Across Europe, these concerns have been heightened in the lead-up to the introduction of REACH, since the use of in vivo alternatives to the LLNA will require scientific justification. This review will address some of these concerns from a regulatory perspective

The murine local lymph node assay: regulatory and potency considerations under REACH.

Science.gov (United States)

McGarry, Helen F

2007-09-05

From June 2007, new chemicals legislation on the registration, evaluation, authorization and restriction of chemicals (REACH) will come into force across the European Union. This will require the submission of data on human health effects of chemicals, including chemical safety assessments which will require measurements of potency. For skin sensitization hazard identification, REACH states that the first-choice in vivo assay is the local lymph node assay (LLNA). This test has also been the UK competent authority's preferred test for skin sensitization since 2002, and has now replaced guinea pig tests in dossiers submitted to it under the Notification of New Substances Regulations. Advantages of the LLNA over guinea pig tests include improvements in animal welfare, a more scientific approach to hazard identification, and the inclusion of a dose-response element in the endpoint, which enables an estimation of potency. However, notifiers to the UK competent authority have sometimes been reluctant to use the assay because of concerns over false-positive reactions. Across Europe, these concerns have been heightened in the lead-up to the introduction of REACH, since the use of in vivo alternatives to the LLNA will require scientific justification. This review will address some of these concerns from a regulatory perspective.

Chemokines involved in protection from colitis by CD4+CD25+ regulatory T cells

DEFF Research Database (Denmark)

Kristensen, Nanna Ny; Brudzewsky, Dan; Gad, Monika

2006-01-01

/chemokine receptor-specific gene expression profiling system of 67 genes, the authors have determined the expression profile of chemokine and chemokine receptor genes in the rectum of colitic mice and in mice that have been protected fromcolitis by CD4CD25 regulatory T cells. In mice protected from colitis......, the authors found down regulation of the mRNA expression of the inflammatory chemokine receptors CCR1 and CXCR3 and their ligands CXCL9, CXCL10, CCL5, and CCL7. Also the transcripts for CCR9, CCL25, CCL17, and CXCL1 are found down regulated in protected compared with colitic animals. In addition, the authors......' results suggest that CCL20 is used by CCR6 regulatory T cells in the complex process of controlling colitis because transcripts for this chemokine were expressed to a higher level in protected animals. The chemokine pathways identified in the present study may be of importance for the development of new...

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

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